TREA

GENETIC SYSTEMS THAT DEFEND AGAINST FOREIGN DNA AND USES THEREOF

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Information

  • Patent Application
  • 20200109395
  • Publication Number
    20200109395
  • Date Filed
    May 23, 2018
    6 years ago
  • Date Published
    April 09, 2020
    4 years ago
Information
Abstract
Disclosed herein are microbial defense systems, which provide cells protection against phage infection and plasmid transformation. Methods of use of these defense systems for protecting cells from phage infection and plasmid transformation are also disclosed, wherein defense systems may be used individually or in combination. In addition, disclosed herein are methods of making cells that express these defense systems.
Description
SEQUENCE LISTING STATEMENT

The instant application contains a “lengthy” Sequence Listing which has been submitted via CD-R in lieu of a printed paper copy, and is hereby incorporated by reference in its entirety. Said CD-R, recorded on May 15, 2018, are labeled “CRF”, “COPY 1—SEQUENCE LISTING PART,” “COPY 2—SEQUENCE LISTING PART” and “COPY 3—SEQUENCE LISTING PART,” respectively, and each contains only one identical 350,356,650 bytes file (P-573737-PC_SL.txt).


FIELD OF DISCLOSURE

Microbial defense systems providing host cells with anti-phage resistance or resistance against plasmid transformation, or both are disclosed. Methods of identifying these systems, and using these systems for example but not limited, for producing bacterial cells comprising defense systems, for producing food products, and for gene editing, are also disclosed.


BACKGROUND

Bacteria and archaea are often being attacked by viruses (phages), and as a result have developed multiple, sophisticated lines of active defense that can collectively be referred to as the prokaryotic “immune system”. Anti-phage defense strategies include restriction-modification (R/M) systems that target specific sequences on the invading phage, CRISPR-Cas that provides acquired immunity through memorization of past phage attacks, infection systems (Abi) that lead the cell to death or metabolic arrest upon infection, and additional systems whose mechanism of action is not yet clear such as BREX and DISARM. Different bacteria encode different sets of defense systems: CRISPR-Cas systems are found in about 40% of all sequenced bacteria, BREX appears in 10% of sequenced bacteria, and DISARM in about 1%. It has been suggested that many new, currently unknown defense systems reside in the genomes of non-model bacteria and archaea and await discovery.


Anti-phage defense systems have been found to be frequently physically clustered in bacterial and archaeal genomes such that, for example, genes encoding restriction enzymes commonly reside in the vicinity of genes encoding infection systems and other phage resistance systems. The observation that defense systems are clustered in genomic “defense islands” has led to the suggestion that genes of unknown function residing within such defense islands may also participate in anti-phage defense. Indeed, recent studies that anecdotally examined individual genes enriched next to known defense genes yielded the discovery of new systems that protect bacteria against phages.


Anti-phage defense systems are usually composed of multiple genes that work in concert to achieve defense—for example, cas1, cas2, cas3 and the cascade genes in type I CRISPR-Cas systems, and the R, M and S genes in type I restriction systems. Genes functioning within the same defense system are very frequently encoded on the same operon, and the gene order within the operon is highly conserved among distantly related organisms sharing the same system.


Some of these phage-resistance systems have been successfully adapted for biotechnological application; for example, the R/M and the CRISPR/Cas systems have been extensively used for genetic engineering purposes in general and gene therapy in particular.


A broad array of food products, commodity chemicals, and biotechnology products are manufactured industrially by large-scale bacterial fermentation of various substrates. Enormous amounts of bacteria are being cultivated each day in large fermentation vats, thus foreign nucleic acid contamination, for example phage contamination can rapidly bring fermentations to a halt and cause economic setbacks, and is therefore considered a serious threat in these industries. The dairy fermentation industry has openly acknowledged the problem of phages and has been working with academia and starter culture companies to develop defense strategies and systems to curtail the propagation and evolution of phages for decades. There remains a need to provide bacteria that can defend against nucleic acid molecules from foreign sources.


The use of defense systems, for example anti-phage may provide the necessary defense for bacteria in food, chemical, and biotechnology production. Thus, it would be advantageous to both the producers and the consumers to have bacteria resistant to nucleic acid molecules from foreign sources, for example with anti-phage, anti-conjugative element, and or anti-plasmid activity.


Disclosed herein are newly identified anti-phage defense systems, anti-conjugative element systems, and an anti-plasmid system that show strong protection against nucleic acid molecules from foreign sources. These systems could provide protection for fermentation bacteria against phages, for protection of bacteria against viruses, and may also provide biotechnological tools for use with prokaryotic and eukaryotic cells.


SUMMARY

In one aspect, disclosed herein is a method of protecting bacteria from foreign nucleic acid invasion comprising a step of introducing into the bacteria at least one defense system (a) to (o), said at least one defense system comprising:

    • (a) a Defense System IV comprising at least two different polypeptide components selected from
      • a HamA polypeptide comprising a pfam08878 domain or a DUF1837 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 12 rows 2-1782 columns H and I; and
      • a HamB polypeptide comprising COG1204 domain or a pfam00270 domain or a pfam00271 domain or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 12 rows 2-1782 columns L and M; or
    • (b) a Defense System Ia comprising at least two different polypeptide components selected from
      • a ZorA polypeptide comprising a pfam01618 domain, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 8 rows 2-1830 columns J and K;
      • a ZorB polypeptide comprising a pfam13677 domain or a pfam00691 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 8 rows 2-1830 columns N and O;
      • a ZorC polypeptide comprising a pfam15611 domain, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 8 rows 2-1174 columns R and S; and
      • a ZorD polypeptide comprising a pfam00176 domain or a pfam00271 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 8 rows 2-1174 columns V and W;
      • or
    • (c) a Defense System Ib comprising a ZorE polypeptide comprising a pfam01844 domain or a COG3183 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 8 rows 1175-1830 columns Z and AA; and at least one other polypeptide component selected from
      • a ZorA polypeptide comprising a pfam01618 domain, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 8 rows 2-1830 columns J and K; and
      • a ZorB polypeptide comprising a pfam13677 domain or a pfam00691 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 8 rows 2-1830 columns N and O; or
    • (d) a Defense System II comprising at least two different polypeptide components selected from
      • a ThsA polypeptide comprising a pfam13289 domain or a pfam14519 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 9 rows 2-2100 columns I and J; and
      • a ThsB polypeptide comprising a pfam13676 domain or a pfam08937 domain or a pfam08357 domain or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 9 rows 2-2100 columns M and N, Q and R, U and V, Y and Z, and AC and AD; or
    • (e) a Defense System IIIa comprising at least two different polypeptide components selected from
      • a DruA polypeptide comprising a DUF4338 domain or a pfam14236 domain or a combination thereof; or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-123 columns J and K, or a combination thereof;
      • a DruB polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-123 columns N and O;
      • a DruC polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-123 columns R and S;
      • a DruD polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-123 columns V and W; and
      • a DruE polypeptide comprising a pfam00270 domain or a pfam00271 domain or a pfam09369 domain or a DUF1998 domain or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-1343 columns Z and AA; or
    • (f) a Defense System IIIb comprising at least two different polypeptide components selected from
      • a DruM polypeptide comprising a pfam00145 domain or a COG0270 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 124-295 columns AD and AE;
      • a DruF polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 124-295 columns AH and AI;
      • a DruG polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 124-295 columns AL and AM; and
      • a DruE polypeptide comprising a pfam00270 domain or a pfam00271 domain or a pfam09369 domain or a DUF1998 domain or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-1343 column Z and AA; or
    • (g) a Defense System IIIc comprising at least two different polypeptide components selected from
      • a DruH polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 296-1343 columns AP and AQ; and
      • a DruE polypeptide comprising a pfam00270 domain or a pfam00271 domain or a pfam09369 domain or a DUF1998 domain or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-1343 columns Z and AA; or
    • (h) a Defense System V comprising a SduA polypeptide comprising a pfam14082 domain or a pfam01939 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 13 rows 2-1247 columns H and I; or
    • (i) a Defense System VI comprising at least two different polypeptide components selected from
      • a GajA polypeptide comprising a pfam13175 domain or a COG3593 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 14 rows 2-4599 columns H and I; and
      • a GajB polypeptide comprising a pfam04257 domain or a pfam00580 domain or a pfam13361 domain or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 14 rows 2-4599 columns L and M; or
    • (j) a Defense System VII comprising at least two different polypeptide components selected from
      • a PtuA polypeptide comprising a pfam13304 domain or a pfam02463 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 15 rows 2-12507 columns H and I; and
      • a PtuB polypeptide comprising pfam13395 domain or a pfam 01844 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 15 rows 2-2507 columns L and M; or
    • (k) a Defense System VIII comprising at least two different polypeptide components selected from
      • a LmuA polypeptide comprising a pfam14130 domain or a DUF4297 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 16 rows 2-698 columns H and I; and
      • a LmuB polypeptide comprising a pfam02463 domain, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 16 rows 2-698 columns L and M; or
    • (l) a Defense System IX comprising at least two different polypeptide components selected from
      • a KwaA polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 17 rows 2-935 columns H and I; and
      • a KwaB polypeptide comprising a pfam16162 domain or a DUF4868 domain or a combination thereof; or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 17 rows 2-935 columns L and M; or
    • (m) a Defense System Xa comprising at least two different polypeptide components selected from
      • a JetA polypeptide comprising a pfam11855 domain or a DUF3375 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2-2322 columns J and K;
      • a JetB polypeptide comprising a pfam13835 domain or a DUF4194 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2-2322 columns N and O;
      • a JetC polypeptide comprising a pfam13555 domain or a pfam13558 domain or a COG4913 domain or any combination thereof; or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2-2322 columns R and S; and
      • a JetD polypeptide comprising a pfam11795 domain or a DUF3322 domain or a pfam09983 domain or a DUF2220 domain or a COG4924 domain or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2-2322 columns V and W; or
    • (n) a Defense System Xb comprising at least two different polypeptide components selected from
      • a JetAii polypeptide comprising a pfam09660 domain or a DUF2397 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2323-2844 columns J and K;
      • a JetBii polypeptide comprising a pfam09661 domain or a DUF2398 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2323-2844 columns N and O;
      • a JetCii polypeptide comprising a pfam13558 domain, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2323-2844 columns R and S; and
      • a JetDii polypeptide comprising a pfam11796 domain or a DUF3323 domain or a pfam09664 domain or a DUF2399 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2323-2844 columns V and W; or
    • (o) a Defense System Xc comprising at least two different polypeptide components selected from
      • a JetAiii polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2845-3174 columns and K;
      • a JetBiii polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2845-3174 columns N and O;
      • a JetCiii polypeptide comprising a COG1196 domain or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2845-3174 columns R and S; and
      • a JetDiii polypeptide comprising a pfam09983 domain or a pfam09664 domain or a DUF2220 or a DUF2399 domain or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2845-3174 columns V and W; or
    • (p) any combination of Defense Systems Ia-Xc (a)-(o);
    • wherein the introduction of said at least one defense system results in the bacteria being protected from foreign DNA invasion.


In a related aspect, methods of protecting bacteria from foreign nucleic acid invasion comprises protecting from phage infection, protection from plasmid transformation, or protecting from entry of conjugative elements, or any combination thereof. In another related aspect, a phage comprises a single stranded DNA (ssDNA) phage, a double stranded DNA (dsDNA) phage, a single stranded RNA (ssRNA) phage, a double stranded RNA (dsRNA) phage, a lytic phage, or a lysogenic phage, or a combination thereof. In another related aspect, at least one defense system comprises

    • (a) a Defense System IV comprising the HamA polypeptide and the HamB polypeptide; or
    • (b) a Defense System Ia comprising the ZorA polypeptide, the ZorB polypeptide, the ZorC polypeptide, and the ZorD polypeptide; or
    • (c) a Defense System Ib comprising the ZorA polypeptide, the ZorB polypeptide, and the ZorE polypeptide; or
    • (d) a Defense System II comprising the ThsA polypeptide, and the ThsB polypeptide; or
    • (e) a Defense System IIIa comprising the DruA polypeptide, the DruB polypeptide, the DruC polypeptide, the DruD polypeptide, and the DruE polypeptide; or
    • (f) a Defense System IIIb comprising the DruM polypeptide, the DruF polypeptide, the DruG polypeptide, and the DruE polypeptide; or
    • (g) a Defense System IIIc comprising the DruH polypeptide and the DruE polypeptide; or
    • (h) a Defense System V comprising the SduA polypeptide; or
    • (i) a Defense System VI comprising the GajA polypeptide and the GajB polypeptide; or
    • (j) a Defense System VII comprising the PtuA polypeptide and the PtuB polypeptide; or
    • (k) a Defense System VIII comprising the LmuA polypeptide and the LmuB polypeptide; or
    • (l) a Defense System IX comprising the KwaA polypeptide and the KwaB polypeptide; or
    • (m) a Defense System Xa comprising the JetA polypeptide, the JetB polypeptide, the JetC polypeptide, and the JetD polypeptide; or
    • (n) a Defense System Xb comprising the JetAii polypeptide, the JetBii polypeptide, the JetCii polypeptide, and the JetDii polypeptide; or
    • (o) a Defense System Xc comprising the JetAiii polypeptide, the JetBiii polypeptide, the JetCiii polypeptide, and the JetDiii polypeptide; or
    • (p) any combination of Defense Systems Ia-Xc (a)-(o).


In another related aspect, defense systems disclosed herein may be encoded by a nucleic acid sequence, wherein

    • (a) said Defense System IV is encoded by
      • a nucleic acid sequence selected from the group referenced in Table 12, rows 2-1782, columns G, P, and Q or the nucleic acid sequence set forth in SEQ ID NO: 4; or
      • a nucleic acid sequence encoding the at least two different polypeptide sequences as disclosed herein; or
      • a nucleic acid sequence encoding the HamA polypeptide and HamB polypeptide as disclosed herein;
    • (b) said Defense System Ia is encoded by
      • a nucleic acid sequence selected from the group referenced in Table 8 rows 2-1174 columns G, AD, and AE or the nucleic acid sequence set forth in SEQ ID NO: 14; or
      • a nucleic acid sequence encoding the at least two different polypeptide sequences as disclosed herein; or
      • a nucleic acid sequence encoding the ZorA polypeptide, the ZorB polypeptide, the ZorC polypeptide, and ZorD polypeptide as disclosed herein;
    • (c) said Defense System Ib is encoded by
      • a nucleic acid sequence selected from the group referenced in Table 8 rows 1175-1830 columns G, AD, and AE or set forth in SEQ ID NO: 15; or a nucleic acid sequence encoding the at least two different polypeptide sequences as disclosed herein; or
      • a nucleic acid sequence encoding the ZorA polypeptide, the ZorB polypeptide, and ZorE polypeptide as disclosed herein;
    • (d) said Defense System II is encoded by
      • a nucleic acid sequence selected from the group referenced in Table 9 rows 2-2100 columns G, AG, and AH or set forth in the nucleic acid sequence set forth in SEQ ID NO: 10 or SEQ ID NO: 11; or
      • a nucleic acid sequence encoding the at least two different polypeptide sequences as disclosed herein; or
      • a nucleic acid sequence encoding the ThsA polypeptide and the ThsB polypeptide as disclosed herein;
    • (e) said Defense System IIIa is encoded by
      • a nucleic acid sequence selected from the group referenced in Table 10 rows 2-123 columns G, AT, and AU or set forth in SEQ ID NO: 16; or
      • a nucleic acid sequence encoding the at least two different polypeptide sequences as disclosed herein; or
      • a nucleic acid sequence encoding the DruA polypeptide, the DruB polypeptide, the DruC, the DruD, and the DruE polypeptide as disclosed herein;
    • (f) said Defense System IIIb is encoded by
      • a nucleic acid sequence selected from the group referenced in Table 10 rows 124-295 columns G, AT, AU; or
      • a nucleic acid sequence encoding the at least two different polypeptide sequences as disclosed herein; or
      • a nucleic acid sequence encoding the DruM polypeptide, the DruF polypeptide, the DruG polypeptide, and the DruE polypeptide as disclosed herein;
    • (g) said Defense System IIIc is encoded by
      • a nucleic acid sequence selected from the group referenced in Table 10 rows 296-1343 columns G, AT, and AU; or
      • a nucleic acid sequence encoding the at least two different polypeptide sequences as disclosed herein; or
      • a nucleic acid sequence encoding the DruH polypeptide and the DruE polypeptide as disclosed herein;
    • (h) said Defense System V is encoded by
      • a nucleic acid sequence selected from the group referenced in Table 13, rows 2-1247, columns H and J; or
      • a nucleic acid sequence encoding the SduA polypeptide as disclosed herein;
    • (i) said Defense System VI is encoded by
      • a nucleic acid sequence selected from the group referenced in Table 14, rows 2-4599, columns G, P, and Q or the sequences set forth in SEQ ID NO: 5 and SEQ ID NO: 6; or
      • a nucleic acid sequence encoding the at least two different polypeptide sequences as disclosed herein; or
      • a nucleic acid sequence encoding the GajA polypeptide and the GajB polypeptide as disclosed herein;
    • (j) said Defense System VII is encoded by
      • a nucleic acid sequence selected from the group referenced in Table 15, rows 2-2507, columns G, P, and Q or the sequences set forth in SEQ ID NO: 12 and SEQ ID NO: 13; or
      • a nucleic acid sequence encoding the at least two different polypeptide sequences as disclosed herein; or
      • a nucleic acid sequence encoding the Ptu polypeptide and the PtuB polypeptide as disclosed herein;
    • (k) said Defense System VIII is encoded by
      • a nucleic acid sequence selected from the group referenced in Table 16, rows 2-698, columns G, P, and Q or the sequences set forth in SEQ ID NO: 7 and SEQ ID NO: 8; or
      • a nucleic acid sequence encoding the at least two different polypeptide sequences as disclosed herein; or
      • a nucleic acid sequence encoding the LmuA polypeptide and LmuB polypeptide as disclosed herein;
    • (l) said Defense System IX is encoded by
      • a nucleic acid sequence selected from the group referenced in Table 17, rows 2-935, columns G, P, and Q or the sequence set forth in SEQ ID NO: 3; or
      • a nucleic acid sequence encoding the at least two different polypeptide sequences as disclosed herein; or
      • a nucleic acid sequence encoding the KwaA polypeptide and the KwaB polypeptide as disclosed herein;
    • (m) said Defense System Xa is encoded by
      • a nucleic acid sequence selected from the group referenced in Table 11, rows 2-2322, columns G, Z, and AA or the sequence set forth in SEQ ID NO: 17; or
      • a nucleic acid sequence encoding the at least two different polypeptide sequences as disclosed herein; or
      • a nucleic acid sequence encoding the JetA polypeptide, the JetB polypeptide, the JetC polypeptide, and the JetD polypeptide as disclosed herein;
    • (n) said Defense System Xb is encoded by
      • a nucleic acid sequence having at least 80% homology to a sequence selected from the group referenced in Table 11, rows 2323-2844, columns G, Z, and AA or the sequence set forth in SEQ ID NO: 18; or
      • a nucleic acid sequence encoding the at least two different polypeptide sequences as disclosed herein; or
      • a nucleic acid sequence encoding the JetAii polypeptide, the JetBii polypeptide, the JetCii polypeptide, and the JetDii polypeptide as disclosed herein;
    • (o) said Defense System Xc is encoded by
      • a nucleic acid sequence selected from the group referenced in Table 11, rows 2845-3174, columns G, Z, and AA or the sequence set forth in SEQ ID NO: 19; or
      • a nucleic acid sequence encoding the at least two different polypeptide sequences as disclosed herein; or
      • a nucleic acid sequence encoding the JetAiii polypeptide, the JetBiii polypeptide, the JetCiii polypeptide, and the JetDiii polypeptide as disclosed herein.


In another related aspect, methods disclosed herein comprise use of a defense system as disclosed or use of a combination of defense systems wherein

    • (a) for said Defense system IV, said HamA polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 12, rows 2-1782, columns H and J, or
      • said HamB polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 12, rows 2-1782, columns L and N, or a combination thereof;
    • (b) for said Defense system Ia, said ZorA polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 8 rows 2-1830 columns J and L,
      • said ZorB polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 8 rows 2-1830 columns N and P,
      • said ZorC polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 8 rows 2-1174 columns R and T, or
      • said ZorD polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 8 rows 2-1174 columns V and X, or a combination thereof;
    • (c) for said Defense system Ib, said ZorA polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 8 rows 2-1830 columns J and L,
      • said ZorB polypeptide is encoded by a nucleic acid sequence selected from the group Table 8 rows 2-1830 columns N and P,
      • said ZorE polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 8 rows 1175-1830 columns Z and AB, or
      • a combination thereof;
    • (d) for said Defense system II, said ThsA polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 9 rows 2-2100 columns I and K,
      • said ThsB polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 9 rows 2-2100 columns M and O, Q and S, U and W, Y and AA, and AC and AE, or
      • a combination thereof;
    • (e) for said Defense system IIIa, said DruA polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 10 rows 2-123 columns J and L, or
      • said DruB polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 10 rows 2-123 columns N and P, or
      • said DruC polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 10 rows 2-123 columns R and T, or
      • said DruD polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 10 rows 2-123 columns V and X, or
      • said DruE polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 10 rows 2-1343 columns Z and AB, or
      • a combination thereof;
    • (f) for said Defense system IIIb, said DruM polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 10 rows 124-295 columns AD and AF, or
      • said DruF polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 10 rows 124-295 columns AH and AJ, or
      • said DruG polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 10 rows 124-295 columns AL and AN, or
      • said DruE polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 10 rows 2-1343 columns Z and AB, or
      • a combination thereof;
    • (g) for said Defense system IIIc, said DruH polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 10 rows 296-1343 columns AP and AR, or
      • said DruE polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 10 rows 2-1343 columns Z and ZB, or a combination thereof;
    • (h) for said Defense system V, said SduA polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 13; rows 2-1247, columns H and J;
    • (i) for said Defense system VI, said GajA polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 14, rows 2-4599, columns H and J, or
      • said GajB polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 14, rows 2-4599, columns L and N, or a combination thereof;
    • (j) for said Defense system VII, said PtuA polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 15, rows 2-2507, columns H and J, or
      • said PtuB polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 15, rows 2-2507, columns L and N, or a combination thereof;
    • (k) for said Defense system VIII, said LmuA polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 16, rows 2-698, columns H and J, or
      • said LmuB polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 16, rows 2-698, columns L and N, or a combination thereof;
    • (l) for said Defense system IX, said KwaA polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 17, rows 2-935, columns H and J, or
      • said KwaB polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 17, rows 2-935, columns L and N, or a combination thereof;
    • (m) for said Defense system Xa, said JetA polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 11, rows 2-2322, columns J and L, or
      • said JetB polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 11, rows 2-2322, columns N and P, or
      • said JetC polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 11, rows 2-2322, columns R and T, or
      • said JetD polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 11, rows 2-2322, columns V and X, or
      • a combination thereof;
    • (n) for said Defense system Xb, said JetAii polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 11, rows 2323-2844, columns J and L, or
      • said JetBii polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 11, rows 2323-2844, columns N and P, or
      • said JetCii polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 11, rows 2323-2844, columns R and T, or
      • said JetDii polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 11, rows 2323-2844, columns V and X, or
      • a combination thereof;
    • (o) for said Defense system Xc, said JetAiii polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 11, rows 2845-3174, columns J and L, or
      • said JetBiii polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 11, rows 2845-3174, columns N and P, or
      • said JetCiii polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 11, rows 2845-3174, columns R and T, or
      • said JetDiii polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 11, rows 2845-3174, columns V and X, or
      • a combination thereof.


In another aspect, disclosed herein are defense systems encoded by a nucleic acid sequence, comprising at least one defense system (a)-(o), wherein said at least one defense system comprises

    • (a) a Defense System IV comprising at least two different polypeptide components selected from
      • a HamA polypeptide comprising a pfam08878 domain or a DUF1837 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 12 rows 2-1782 columns H and I; and
      • a HamB polypeptide comprising COG1204 domain or a pfam00270 domain or a pfam00271 domain or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 12 rows 2-1782 columns L and M; or
    • (b) a Defense System Ia comprising at least two different polypeptide components selected from
      • a ZorA polypeptide comprising a pfam01618 domain, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 8 rows 2-1830 columns J and K;
      • a ZorB polypeptide comprising a pfam13677 domain or a pfam00691 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 8 rows 2-1830 columns N and O;
      • a ZorC polypeptide comprising a pfam15611 domain, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 8 rows 2-1174 columns R and S; and
      • a ZorD polypeptide comprising a pfam00176 domain or a pfam00271 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 8 rows 2-1174 columns V and W;
        • or
    • (c) a Defense System Ib comprising a ZorE polypeptide comprising a pfam01844 domain or a COG3183 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 8 rows 1175-1830 columns Z and AA; and at least one other polypeptide component selected from
      • a ZorA polypeptide comprising a pfam01618 domain, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 8 rows 2-1830 columns J and K; and
      • a ZorB polypeptide comprising a pfam13677 domain or a pfam00691 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 8 rows 2-1830 columns N and O; or
    • (d) a Defense System II comprising at least two different polypeptide components selected from
      • a ThsA polypeptide comprising a pfam13289 domain or a pfam14519 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 9 rows 2-2100 columns I and J; and
      • a ThsB polypeptide comprising a pfam13676 domain or a pfam08937 domain or a pfam08357 domain or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 9 rows 2-2100 columns M and N, Q and R, U and V, Y and Z, and AC and AD; or
    • (e) a Defense System IIIa comprising at least two different polypeptide components selected from
      • a DruA polypeptide comprising a DUF4338 domain or a pfam14236 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-123 columns J and K, or a combination thereof;
      • a DruB polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-123 columns N and O;
      • a DruC polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-123 columns R and S;
      • a DruD polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-123 columns V and W; and
      • a DruE polypeptide comprising a pfam00270 domain or a pfam00271 domain or a pfam09369 domain or a DUF1998 domain or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-1343 columns Z and AA; or
    • (f) a Defense System IIIb comprising at least two different polypeptide components selected from
      • a DruM polypeptide comprising a pfam00145 domain or a COG0270 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 124-295 columns AD and AE;
      • a DruF polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 124-295 columns AH and AI;
      • a DruG polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 124-295 columns AL and AM; and
      • a DruE polypeptide comprising a pfam00270 domain or a pfam00271 domain or a pfam09369 domain or a DUF1998 domain, or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-1343 columns Z and AA; or
    • (g) a Defense System IIIc comprising at least two different polypeptide components selected from
      • a DruH polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 296-1343 columns AP and AQ; and
      • a DruE polypeptide comprising a pfam00270 domain or a pfam00271 domain or a pfam09369 domain or a DUF1998 domain or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-1343 columns Z and AA; or
    • (h) a Defense System V comprising a SduA polypeptide comprising a pfam14082 domain or a pfam01939 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 13 rows 2-1247 columns H and I; or
    • (i) a Defense System VI comprising at least two different polypeptide components selected from
      • a GajA polypeptide comprising a pfam13175 domain or a COG3593 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 14 rows 2-4599 columns H and I; and
      • a GajB polypeptide comprising a pfam04257 domain or a pfam00580 domain or a pfam13361 domain or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 14 rows 2-4599 columns L and M; or
    • (j) a Defense System VII comprising at least two different polypeptide components selected from
      • a PtuA polypeptide comprising a pfam13304 domain or a pfam02463 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 15 rows 2-12507 columns H and I; and
      • a PtuB polypeptide comprising pfam13395 domain or a pfam 01844 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 15 rows 2-2507 columns L and M; or
    • (k) a Defense System VIII comprising at least two different polypeptide components selected from
      • a LmuA polypeptide comprising a pfam14130 domain or a DUF4297 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 16 rows 2-698 columns H and I; and
      • a LmuB polypeptide comprising a pfam02463 domain, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 16 rows 2-698 columns L and M; or
    • (l) a Defense System IX comprising at least two different polypeptide components selected from
      • a KwaA polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 17 rows 2-935 columns H and I; and
      • a KwaB polypeptide comprising a pfam16162 domain or a DUF4868 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 17 rows 2-935 columns L and M; or
    • (m) a Defense System Xa comprising at least two different polypeptide components selected from
      • a JetA polypeptide comprising a pfam11855 domain or a DUF3375 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2-2322 columns J and K;
      • a JetB polypeptide comprising a pfam13835 domain or a DUF4194 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2-2322 columns N and O;
      • a JetC polypeptide comprising a pfam13555 domain or a pfam13558 domain or a COG4913 domain or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2-2322 columns R and S; and
      • a JetD polypeptide comprising a pfam11795 domain or a DUF3322 domain or a pfam09983 domain or a DUF2220 domain or a COG4924 domain or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2-2322 columns V and W; or
    • (n) a Defense System Xb comprising at least two different polypeptide components selected from
      • a JetAii polypeptide comprising a pfam09660 domain or a DUF2397 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2323-2844 columns J and K;
      • a JetBii polypeptide comprising a pfam09661 domain or a DUF2398 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2323-2844 columns N and O;
      • a JetCii polypeptide comprising a pfam13558 domain comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2323-2844 columns R and S; and
      • a JetDii polypeptide comprising a pfam11796 domain or a DUF3323 domain or a pfam09664 domain or a DUF2399 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2323-2844 columns V and W; or
    • (o) a Defense System Xc comprising at least two different polypeptide components selected from
      • a JetAiii polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2845-3174 columns J and K;
      • a JetBiii polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2845-3174 columns N and O;
      • a JetCiii polypeptide comprising a COG1196 domain or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2845-3174 columns R and S; and
      • a JetDiii polypeptide comprising a pfam09983 domain or a pfam09664 domain or a DUF2220 or a DUF2399 domain or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2845-3174 columns V and W; or
    • (p) any combination of the Defense Systems Ia-Xc (a)-(o);
    • wherein said at least one defense system comprises a non-naturally occurring combination of components.


In a related aspect, a defense system disclosed wherein

    • (a) said Defense System IV comprises the HamA polypeptide and the HamB polypeptide; or
    • (b) said Defense System Ia comprises the ZorA polypeptide, the ZorB polypeptide, the ZorC polypeptide, and the ZorD polypeptide; or
    • (c) said Defense System Ib comprises the ZorA polypeptide, the ZorB polypeptide, and the ZorE polypeptide; or
    • (d) said Defense System II comprises the ThsA polypeptide, and the ThsB polypeptide; or
    • (e) said Defense System IIIa comprises the DruA polypeptide, the DruB polypeptide, the DruC polypeptide, the DruD polypeptide, and the DruE polypeptide; or
    • (f) said Defense System IIIb comprises the DruM polypeptide, the DruF polypeptide, the DruG polypeptide, and the DruE polypeptide; or
    • (g) said Defense System IIIc comprises the DruH polypeptide and the DruE polypeptide; or
    • (h) said Defense System V comprises the SduA polypeptide; or
    • (i) said Defense System VI comprises the GajA polypeptide and the GajB polypeptide; or
    • (j) said Defense System VII comprises the PtuA polypeptide and the PtuB polypeptide; or
    • (k) said Defense System VIII comprises the LmuA polypeptide and the LmuB polypeptide; or
    • (l) said Defense System IX comprises the KwaA polypeptide and the KwaB polypeptide; or
    • (m) said Defense System Xa comprises the JetA polypeptide, the JetB polypeptide, the JetC polypeptide, and the JetD polypeptide; or
    • (n) said Defense System Xb comprises the JetAii polypeptide, the JetBii polypeptide, the JetCii polypeptide, and the JetDii polypeptide; or
    • (o) said Defense System Xc comprises the JetAiii polypeptide, the JetBiii polypeptide, the JetCiii polypeptide, and the JetDiii polypeptide.


In another related aspect, at least one defense system disclosed herein or a combination thereof, provides a host cell with resistance to foreign nucleic acid invasion. In another related aspect, the resistance to foreign nucleic acid invasion comprises resistance to at least one phage infection, or resistance to plasmid transformation, or resistance to entry of a conjugative element, or any combination thereof.


In another aspect, disclosed herein is a nucleic acid construct encoding an at least one defense system (a)-(o), said nucleic acid construct comprising

    • (a) a nucleic acid construct encoding a Defense System IV comprising at least two different polypeptide components selected from
      • a HamA polypeptide comprising a pfam08878 domain or a DUF1837 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 12 rows 2-1782 columns H and I; and
      • a HamB polypeptide comprising COG1204 domain or a pfam00270 domain or a pfam00271 domain or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 12 rows 2-1782 columns L and M; or
    • (b) a nucleic acid construct encoding a Defense System Ia comprising at least two different polypeptide components selected from
      • a ZorA polypeptide comprising a pfam01618 domain, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 8 rows 2-1830 columns J and K;
      • a ZorB polypeptide comprising a pfam13677 domain or a pfam00691 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 8 rows 2-1830 columns N and O;
      • a ZorC polypeptide comprising a pfam15611 domain, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 8 rows 2-1174 columns R and S; and
      • a ZorD polypeptide comprising a pfam00176 domain or a pfam00271 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 8 rows 2-1174 columns V and W;
      • or
    • (c) a nucleic acid construct encoding a Defense System Ib comprising a ZorE polypeptide comprising a pfam01844 domain or a COG3183 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 8 rows 1175-1830 columns Z and AA; and at least one other polypeptide component selected from
      • a ZorA polypeptide comprising a pfam01618 domain, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 8 rows 2-1830 columns J and K; and
      • a ZorB polypeptide comprising a pfam13677 domain or a pfam00691 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 8 rows 2-1830 columns N and O; or
    • (d) a nucleic acid construct encoding a Defense System II comprising at least two different polypeptide components selected from
      • a ThsA polypeptide comprising a pfam13289 domain or a pfam14519 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 9 rows 2-2100 columns I and J; and
      • a ThsB polypeptide comprising a pfam13676 domain or a pfam08937 domain or a pfam08357 domain or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 9 rows 2-2100 columns M and N, Q and R, U and V, Y and Z, and AC and AD; or
    • (e) a nucleic acid construct encoding a Defense System IIIa comprising at least two different polypeptide components selected from
      • a DruA polypeptide comprising a DUF4338 domain or a pfam14236 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-123 columns J and K, or a combination thereof;
      • a DruB polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-123 columns N and O;
      • a DruC polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-123 columns R and S;
      • a DruD polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-123 columns V and W; and
      • a DruE polypeptide comprising a pfam00270 domain or a pfam00271 domain or a pfam09369 domain or a DUF1998 domain or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-1343 columns Z and AA; or
    • (f) a nucleic acid construct encoding a Defense System IIIb comprising at least two different polypeptide components selected from
      • a DruM polypeptide comprising a pfam00145 domain or a COG0270 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 124-295 columns AD and AE;
      • a DruF polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 124-295 columns AH and AI;
      • a DruG polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 124-295 columns AL and AM; and
      • a DruE polypeptide comprising a pfam00270 domain or a pfam00271 domain or a pfam09369 domain or a DUF1998 domain or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-1343 columns Z and AA; or
    • (g) a nucleic acid construct encoding a Defense System IIIc comprising at least two different polypeptide components selected from
      • a DruH polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 296-1343 columns AP and AQ; and
      • a DruE polypeptide comprising a pfam00270 domain or a pfam00271 domain or a pfam09369 domain or a DUF1998 domain or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-1343 columns Z and AA; or
    • (h) a nucleic acid construct encoding a Defense System V comprising a SduA polypeptide comprising a pfam14082 domain or a pfam01939 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 13 rows 2-1247 columns H and I; or
    • (i) a nucleic acid construct encoding a Defense System VI comprising at least two different polypeptide components selected from
      • a GajA polypeptide comprising a pfam13175 domain or a COG3593 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 14 rows 2-4599 columns H and I; and
      • a GajB polypeptide comprising a pfam04257 domain or a pfam00580 domain or a pfam13361 domain or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 14 rows 2-4599 columns L and M; or
    • (j) a nucleic acid construct encoding a Defense System VII comprising at least two different polypeptide components selected from
      • a PtuA polypeptide comprising a pfam13304 domain or a pfam02463 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 15 rows 2-12507 columns H and I; and
      • a PtuB polypeptide comprising pfam13395 domain or a pfam 01844 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 15 rows 2-2507 columns L and M; or
    • (k) a nucleic acid construct encoding a Defense System VIII comprising at least two different polypeptide components selected from
      • a LmuA polypeptide comprising a pfam14130 domain or a DUF4297 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 16 rows 2-698 columns H and I; and
      • a LmuB polypeptide comprising a pfam02463 domain, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 16 rows 2-698 columns L and M; or
    • (l) a nucleic acid construct encoding a Defense System IX comprising at least two different polypeptide components selected from
      • a KwaA polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 17 rows 2-935 columns H and I; and
      • a KwaB polypeptide comprising a pfam16162 domain or a DUF4868 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 17 rows 2-935 columns L and M; or
    • (m) a nucleic acid construct encoding a Defense System Xa comprising at least two different polypeptide components selected from
      • a JetA polypeptide comprising a pfam11855 domain or a DUF3375 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2-2322 columns J and K;
      • a JetB polypeptide comprising a pfam13835 domain or a DUF4194 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2-2322 columns N and O;
      • a JetC polypeptide comprising a pfam13555 domain or a pfam13558 domain or a COG4913 domain or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2-2322 columns R and S; and
      • a JetD polypeptide comprising a pfam11795 domain or a DUF3322 domain or a pfam09983 domain or a DUF2220 domain or a COG4924 domain or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2-2322 columns V and W; or
    • (n) a nucleic acid construct encoding a Defense System Xb comprising at least two different polypeptide components selected from
      • a JetAii polypeptide comprising a pfam09660 domain or a DUF2397 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2323-2844 columns J and K;
      • a JetBii polypeptide comprising a pfam09661 domain or a DUF2398 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2323-2844 columns N and O;
      • a JetCii polypeptide comprising a pfam13558 domain comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2323-2844 columns R and S; and
      • a JetDii polypeptide comprising a pfam11796 domain or a DUF3323 domain or a pfam09664 domain or a DUF2399 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2323-2844 columns V and W; or
    • (o) a nucleic acid construct encoding a Defense System Xc comprising at least two different polypeptide components selected from
      • a JetAiii polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2845-3174 columns J and K;
      • a JetBiii polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2845-3174 columns N and O;
      • a JetCiii polypeptide comprising a COG1196 domain or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2845-3174 columns R and S; and
      • a JetDiii polypeptide comprising a pfam09983 domain or a pfam09664 domain or a DUF2220 or a DUF2399 domain or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2845-3174 columns V and W; or
    • (p) any combination of nucleic acid constructs encoding a Defense Systems Ia-Xc (a)-(o);
    • wherein each nucleic acid construct of each Defense System (a)-(o) further comprises a regulatory element operably linked to said construct comprising a cis-acting regulatory element for directing expression of said nucleic acid sequence, or a transmissible element for directing transfer of said nucleic acid sequence from one cell to another, or a recombination element for integrating said nucleic acid sequence into a genome of a cell transfected with said construct, or an element providing episomal maintenance of said construct within a cell transfected with said construct, or any combination thereof.


In a related aspect, the expressed defense system comprises

    • (a) a Defense System IV comprising the HamA polypeptide, and the HamB polypeptide; or
    • (b) a Defense System Ia comprising the ZorA polypeptide, the ZorB polypeptide, the ZorC polypeptide, and the ZorD polypeptide; or
    • (c) a Defense System Ib comprising the ZorA polypeptide, the ZorB polypeptide, and the ZorE polypeptide; or
    • (d) a Defense System II comprising the ThsA polypeptide, and the ThsB polypeptide; or
    • (e) a Defense System IIIa comprising the DruA polypeptide, the DruB polypeptide, the DruC polypeptide, the DruD polypeptide, and the DruE polypeptide; or
    • (f) a Defense System IIIb comprising the DruM polypeptide, the DruF polypeptide, the DruG polypeptide, and the DruE polypeptide; or
    • (g) a Defense System IIIc comprising the DruH polypeptide and the DruE polypeptide; or
    • (h) a Defense System V comprising the SduA polypeptide; or
    • (i) a Defense System VI comprising the GajA polypeptide and the GajB polypeptide; or
    • (j) a Defense System VII comprising the PtuA polypeptide and the PtuB polypeptide; or
    • (k) a Defense System VIII comprising the LmuA polypeptide and the LmuB polypeptide; or
    • (l) a Defense System IX comprising the KwaA polypeptide and the KwaB polypeptide; or
    • (m) a Defense System Xa comprising the JetA polypeptide, the JetB polypeptide, the JetC polypeptide, and the JetD polypeptide; or
    • (n) a Defense System Xb comprising the JetAii polypeptide, the JetBii polypeptide, the JetCii polypeptide, and the JetDii polypeptide; or
    • (o) a Defense System Xc comprising the JetAiii polypeptide, the JetBiii polypeptide, the JetCiii polypeptide, and the JetDiii polypeptide.


In another related aspect, the nucleic acid construct disclosed herein, wherein


(a) said Defense System IV is encoded by

    • a nucleic acid sequence selected from the group referenced in Table 12, rows 2-1782, columns G, P, and Q or the nucleic acid sequence set forth in SEQ ID NO: 4; or
    • a nucleic acid sequence encoding the at least two different polypeptide sequences as disclosed herein; or
    • a nucleic acid sequence encoding the HamA polypeptide and HamB polypeptide as disclosed herein;


(b) said Defense System Ia is encoded by

    • a nucleic acid sequence selected from the group referenced in Table 8 rows 2-1174 columns G, AD, and AE or the nucleic acid sequence set forth in SEQ ID NO: 14; or
    • a nucleic acid sequence encoding the at least two different polypeptide sequences as disclosed herein; or
    • a nucleic acid sequence encoding the ZorA polypeptide, the ZorB polypeptide, the ZorC polypeptide, and ZorD polypeptide as disclosed herein;


(c) said Defense System Ib is encoded by

    • a nucleic acid sequence selected from the group referenced in Table 8 rows 1175-1830 columns G, AD, and AE or set forth in SEQ ID NO: 15; or
    • a nucleic acid sequence encoding the at least two different polypeptide sequences as disclosed herein; or
      • a nucleic acid sequence encoding the ZorA polypeptide, the ZorB polypeptide, and ZorE polypeptide as disclosed herein;


(d) said Defense System II is encoded by

    • a nucleic acid sequence selected from the group referenced in Table 9 rows 2-2100 columns G, AG, and AH or set forth in the nucleic acid sequence set forth in SEQ ID NO: 10 or SEQ ID NO: 11; or
    • a nucleic acid sequence encoding the at least two different polypeptide sequences as disclosed herein; or
    • a nucleic acid sequence encoding the ThsA polypeptide and the ThsB polypeptide as disclosed herein;


(e) said Defense System IIIa is encoded by

    • a nucleic acid sequence selected from the group referenced in Table 10 rows 2-123 columns G, AT, and AU or set forth in SEQ ID NO: 16; or
    • a nucleic acid sequence encoding the at least two different polypeptide sequences as disclosed herein; or
    • a nucleic acid sequence encoding the DruA polypeptide, the DruB polypeptide, the DruC, the DruD, and the DruE polypeptide as disclosed herein;


(f) said Defense System IIIb is encoded by

    • a nucleic acid sequence selected from the group referenced in Table 10 rows 124-295 columns G, AT, AU; or
    • a nucleic acid sequence encoding the at least two different polypeptide sequences as disclosed herein; or
    • a nucleic acid sequence encoding the DruM polypeptide, the DruF polypeptide, the DruG polypeptide, and the DruE polypeptide as disclosed herein;


(g) said Defense System IIIc is encoded by

    • a nucleic acid sequence selected from the group referenced in Table 10 rows 296-1343 columns G, AT, and AU; or
    • a nucleic acid sequence encoding the at least two different polypeptide sequences as disclosed herein; or
    • a nucleic acid sequence encoding the DruH polypeptide and the DruE polypeptide as disclosed herein;


(h) said Defense System V is encoded by

    • a nucleic acid sequence selected from the group referenced in Table 13; rows 2-1247, columns H and J; or
    • a nucleic acid sequence encoding the SduA polypeptide disclosed herein;


(i) said Defense System VI is encoded by

    • a nucleic acid sequence selected from the group referenced in Table 14, rows 2-4599, columns G, P, and Q or the sequences set forth in SEQ ID NO: 5 and SEQ ID NO: 6; or
    • a nucleic acid sequence encoding the at least two different polypeptide sequences as disclosed herein; or
    • a nucleic acid sequence encoding the GajA polypeptide and the GajB polypeptide as disclosed herein;


(j) said Defense System VII is encoded by

    • a nucleic acid sequence selected from the group referenced in Table 15, rows 2-2507, columns G, P, and Q or the sequences set forth in SEQ ID NO: 12 and SEQ ID NO: 13; or
    • a nucleic acid sequence encoding the at least two different polypeptide sequences as disclosed herein; or
    • a nucleic acid sequence encoding the Ptu polypeptide and the PtuB polypeptide as disclosed herein;


(k) said Defense System VIII is encoded by

    • a nucleic acid sequence selected from the group referenced in Table 16, rows 2-698, columns G, P, and Q or the sequences set forth in SEQ ID NO: 7 and SEQ ID NO: 8; or
    • a nucleic acid sequence encoding the at least two different polypeptide sequences as disclosed herein; or
    • a nucleic acid sequence encoding the LmuA polypeptide and LmuB polypeptide as disclosed herein;


(l) said Defense System IX is encoded by

    • a nucleic acid sequence selected from the group referenced in Table 17, rows 2-935, columns G, P, and Q or the sequence set forth in SEQ ID NO: 3; or
    • a nucleic acid sequence encoding the at least two different polypeptide sequences as disclosed herein; or
    • a nucleic acid sequence encoding the KwaA polypeptide and the KwaB polypeptide as disclosed herein;


(m) said Defense System Xa is encoded by

    • a nucleic acid sequence selected from the group referenced in Table 11, rows 2-2322, columns G, Z, and AA or the sequence set forth in SEQ ID NO: 17; or
    • a nucleic acid sequence encoding the at least two different polypeptide sequences as disclosed herein; or
    • a nucleic acid sequence encoding the JetA polypeptide, the JetB polypeptide, the JetC polypeptide, and the JetD polypeptide as disclosed herein;


(n) said Defense System Xb is encoded by

    • a nucleic acid sequence having at least 80% homology to a sequence selected from the group referenced in Table 11, rows 2323-2844, columns G, Z, and AA or the sequence set forth in SEQ ID NO: 18; or
    • a nucleic acid sequence encoding the at least two different polypeptide sequences as disclosed herein; or
    • a nucleic acid sequence encoding the JetAii polypeptide, the JetBii polypeptide, the JetCii polypeptide, and the JetDii polypeptide as disclosed herein;


(o) said Defense System Xc is encoded by

    • a nucleic acid sequence selected from the group referenced in Table 11, rows 2845-3174, columns G, Z, and AA or the sequence set forth in SEQ ID NO: 19; or
    • a nucleic acid sequence encoding the at least two different polypeptide sequences as disclosed herein; or
    • a nucleic acid sequence encoding the JetAiii polypeptide, the JetBiii polypeptide, the JetCiii polypeptide, and the JetDiii polypeptide as disclosed herein.


Further, in another related aspect, a nucleic acid construct disclosed herein comprises a nucleic acid construct wherein

    • (a) said HamA polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 12, rows 2-1782, columns H and J, or
      • said HamB polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 12, rows 2-1782, columns L and N, or
      • a combination thereof;
    • (b) said ZorA polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 8 rows 2-1830 columns J and L,
      • said ZorB polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 8 rows 2-1830 columns N and P,
      • said ZorC polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 8 rows 2-1174 columns R and T, or
      • said ZorD polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 8 rows 2-1174 columns V and X, or
      • a combination thereof;
    • (c) said ZorA polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 8 rows 2-1830 columns J and L,
      • said ZorB polypeptide is encoded by a nucleic acid sequence selected from the group Table 8 rows 2-1830 columns N and P,
      • said ZorE polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 8 rows 1175-1830 columns Z and AB, or
      • a combination thereof;
    • (d) said ThsA polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 9 rows 2-2100 columns I and K,
      • said ThsB polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 9 rows 2-2100 columns M and O, Q and S, U and W, Y and AA, and AC and AE, or
      • a combination thereof;
    • (e) said DruA polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 10 rows 2-123 columns J and L, or
      • said DruB polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 10 rows 2-123 columns N and P, or
      • said DruC polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 10 rows 2-123 columns R and T, or
      • said DruD polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 10 rows 2-123 columns V and X, or
      • said DruE polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 10 rows 2-1343 columns Z and AB, or
      • a combination thereof;
    • (f) said DruM polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 10 rows 124-295 columns AD and AF, or
      • said DruF polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 10 rows 124-295 columns AH and AJ, or
      • said DruG polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 10 rows 124-295 columns AL and AN, or
      • said DruE polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 10 rows 2-1343 columns Z and AB, or
      • a combination thereof;
    • (g) said DruH polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 10 rows 296-1343 columns AP and AR, or
      • said DruE polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 10 rows 2-1343 columns Z and AB, or
      • a combination thereof;
    • (h) said SduA polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 13; rows 2-1247, columns H and J;
    • (i) said GajA polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 14, rows 2-4599, columns H and J, or
      • said GajB polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 14, rows 2-4599, columns L and N, or
      • a combination thereof;
    • (j) said PtuA polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 15, rows 2-2507, columns H and J, or
      • said PtuB polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 15, rows 2-2507, columns L and N, or
      • a combination thereof;
    • (k) said LmuA polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 16, rows 2-698, columns H and J, or
      • said LmuB polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 16, rows 2-698, columns L and N, or
      • a combination thereof;
    • (l) said KwaA polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 17, rows 2-935, columns H and J, or
      • said KwaB polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 17, rows 2-935, columns L and N, or
      • a combination thereof;
    • (m) said JetA polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 11, rows 2-2322, columns J and L, or
      • said JetB polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 11, rows 2-2322, columns N and P, or
      • said JetC polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 11, rows 2-2322, columns R and T, or
      • said JetD polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 11, rows 2-2322, columns V and X, or
      • a combination thereof;
    • (n) said JetAii polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 11, rows 2323-2844, columns J and L, or
      • said JetBii polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 11, rows 2323-2844, columns N and P, or
      • said JetCii polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 11, rows 2323-2844, columns R and T, or
      • said JetDii polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 11, rows 2323-2844, columns V and X, or
      • a combination thereof;
    • (o) said JetAiii polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 11, rows 2845-3174, column J and L, or
      • said JetBiii polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 11, rows 2845-3174, columns N and O, or
      • said JetCiii polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 11, rows 2845-3174, columns R and T, or
      • said JetDiii polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 11, rows 2845-3174, columns V and X, or
      • a combination thereof.


In another related aspect, disclosed herein is a nucleic acid construct wherein expression of said defense system from the nucleic acid construct in a host cells provides the host cell with resistance to foreign nucleic acid invasion. In another related aspect, resistance to foreign nucleic acid invasion comprises resistance to at least one phage infection, or resistance to plasmid transformation, or resistance to entry of a conjugation element, or any combination thereof.


In another aspect, disclosed herein is a transmissible genetic element or an expression vector comprising a nucleic acid construct as disclosed herein.


In another aspect, disclosed herein is an isolated cell expressing a nucleic acid construct as disclosed herein. In a related aspect, the cell comprises a gram-positive bacterium or a gram-negative bacterium. In another related aspect, the cell comprises resistance to foreign nucleic acid invasion. In still another related aspect, the resistance to foreign nucleic acid invasion comprises resistance to at least one phage infection, or reduced plasmid transformation efficiency, or resistance to entry of a conjugation element, or a combination thereof.


In another aspect, disclosed herein is a food, food additive, feed, nutritional supplement, probiotic supplement, personal care product, health care product, and or a veterinary product comprising any defense system or combination of defense systems as disclosed herein, or the nucleic acid construct or combination of constructs as disclosed herein, or the transmissible genetic element as disclosed herein, or the isolated cell as disclosed herein.


In a related aspect, the defense system or combination of defense systems included in a food, food additive, feed, nutritional supplement, probiotic supplement, personal care product, health care product, and or a veterinary product disclosed herein, comprises a combination of Defense Systems selected from Defense Systems Ia-Xc (a)-(o).


In another aspect, disclosed herein is a method of preparing a food, a food additive, a feed, a nutritional supplements, a probiotic supplement, a personal care product, a health care product or a veterinary product, the method comprising adding to the food, food additive, feed, nutritional supplement, probiotic supplement, personal care product, health care product, or veterinary product at least one defense system as disclosed herein, or the nucleic acid construct as disclosed herein, or the transmissible genetic element disclosed herein, or the isolated cell disclosed herein.


In another aspect, disclosed herein is a method for identifying a defense system in a prokaryotic cell, comprising the steps of:

    • (a) selecting, in-silico, a family of genes that are preferentially located in close proximity to a known defense-related gene family present in a plurality of prokaryotic genomes; and
    • (b) analyzing, in-silico, the DNA upstream and downstream of said gene; and
    • (c) identifying, in-silico, a cassette of genes within the upstream and downstream DNA analyzed in step (b) comprising said gene of step (a), wherein said cassette of genes has conserved synteny in said plurality of prokaryotic genomes.


In a related aspect, in a method of identifying a defense system, the gene of step (a), located in close proximity to a known defense related gene family, is within 10 genes upstream and or 10 genes downstream of the known defense related gene family.


In another aspect, disclosed herein is a method gene editing, said method comprising contacting a nucleic acid sequence comprising a gene to be edited with at least one polypeptide component of a defense system, wherein said defense system component comprises a component selected from the components of the defense system disclosed herein, wherein said method results in the gene being edited.





BRIEF DESCRIPTION OF THE DRAWINGS

The subject matter disclosed herein is particularly pointed out and distinctly claimed in the concluding portion of the specification. The defense systems described, however, both as to organization and method of operation, together with objects, features, and advantages thereof, may best be understood by reference to the following detailed description when read with the accompanying drawings in which:



FIGS. 1A-1C presents the strategy and initial results for the discovery of new anti-phage defense systems in defense islands. FIG. 1A illustrates the computational analysis employed for each pfam found to be enriched in defense islands. Pfams that are enriched in the vicinity of known defense genes are identified, and their neighboring genes are clustered based on sequence homology to identify conserved cassettes that represent putative defense systems. FIG. 1B presents a bar graph showing the tendency of protein families to occur next to defense genes. The genomic neighborhood for each member gene in each pfam is examined, and the fraction of member genes occurring in the vicinity (10 genes on each side) of one or more known defense genes is recorded. A set of 123 pfams known to participate in anti-phage defense (“positive set”) are represented in pink; the remaining 13,960 pfams analyzed in this study are shown in blue. FIG. 1C presents the neighborhood variability score for analyzed pfams. Scores represent the fraction of pfams members occurring in different defense neighborhoods out of total occurrences of pfam members. (Pink, the 123 positive pfams; blue, a set of 576 pfams that passed the 65% threshold for fraction of members occurring with defense genes in proximity.)



FIGS. 2A and 2B present the distribution of predicted functions for pfams genomically associated with known defense genes. FIG. 2A presents the pfams retrieved from prediction cycle #1. FIG. 2B presents the pfams retrieved from prediction cycle #2.



FIGS. 3A-3H show the flowchart and experimentally verified defense systems. (FIG. 3A) Flowchart of the experimental verification strategy. (FIG. 3B) Active defense systems cloned into B. subtilis. (FIG. 3C) Active defense systems cloned into E. coli. For FIGS. 3B and 3C, the fold protection was measured using serial dilution plaque assays, comparing the system-containing strain to a control strain that lacks the system and has an empty vector instead. Data represents average of 3 replicates (FIGS. 3E and 3F). Numbers below phage names represent phage genome size. On the right of FIGS. 3B and 3C, gene organization of the defense systems, with identified domains indicated (DUF, domain of unknown function). Gene sizes are drawn to scale, scale bar represents 400 amino acids. FIG. 3D presents the initial data demonstrating that the ZORYA type I system provides protection against phages as evaluated by serial dilution plaque assay. E. coli MG1655 strain (control) and E. coli MG1655 strain (control) transfected with the ZORYA system I of ZORYA locus of Escherichia coli (E. coli) E24377A and challenged with the indicated phages (phage T4, phage T7, phage lambda vir t [an obligatory lytic mutant of phage lambda], SECphi27, SECphi17, and SECphi18). Columns represent serial 10-fold dilutions of the initial phage stock concentration. The leftmost column represents 10−2 (100 fold) dilution, the second column from the right represents 10−3 (1000 fold dilution), and so on until the leftmost column that represents 10 million fold dilution. FIG. 3E presents the efficiency of plating (EOP) of Bacillus phages on defense systems cloned into B. subtilis BEST7003. Data represent PFU/ml values, average of 3 replicates; error bars are STD. When two representations of the same system are indicated (e.g. Thoeris I and Thoeris II), order of systems is as in FIG. 3B. FIG. 3F presents efficiency of plating (EOP) of coliphages on defense systems cloned into E. coli MG1655. Data represent PFU/ml values, average of 3 replicates; error bars are STD. Order of defense systems in each graph is as in FIG. 3C. FIG. 3G presents efficiency of plating (EOP) of Bacillus phage SpBeta on defense systems mutated in individual genes. Data represent PFU/ml values of SpBeta phage infecting WT and mutated systems. Average of 3 replicates; error bars are STD. Gene deletion results for systems Zorya, Thoeris, Wadjet and Druantia appear in FIGS. 4, 5, 7, and 6, respectively. Gene deletion attempts for the Kiwa system were not successful. FIG. 3H presents distribution of defense systems in sequenced microbial genomes. For each system, phyla in which instances of the system were detected are indicated. Top left pie chart represents the entire set of microbial genomes analyzed, and is shown in order to provide a reference for the phylogenetic distribution of the species whose genomes were sequenced. Data on individual instances of each system are found in Tables 4 and 8-18.



FIGS. 4A-4J present the identified members of the Type I and Type II ZORYA defense systems and analysis thereof. FIG. 4A shows schematic representative instances of the Type I ZORYA system and their defense island context. In the last four embodiments, genes known to be involved in defense are orange. Mobilome genes are in dark grey. RM—restriction modification; TA—toxin-antitoxin; Abi—abortive infection; Wadjet and DISARM are other defense systems identified herein. FIG. 4B presents the domain organization of the Type I ZORYA system comprising zorA (A), zorB (B), zorC (C) and zorD (D). FIG. 4C presents a schematic of the ZORYA type I defense system locus of Escherichia coli (E. coli) E24377A used for cloning. Numbers represent position on the E. coli E24377A genome. Specifically, nucleotides 298890-307639 of the reverse strand were cloned into the E. coli MG1655 genome (SEQ ID NO: 14). FIG. 4D shows multiple schematic representative instances of the Type II ZORYA system and their defense island context. Genes known to be involved in defense are orange. Mobilome genes are in dark grey. RM—restriction modification; TA—toxin-antitoxin; Druantia is another defense systems identified herein. FIG. 4E presents the domain organization of the Type II ZORYA system comprising zorA (A), zorB (B), and zorE (E). Domain organization of zorA and zorB are as in FIG. 4B. FIG. 4F presents a model of the flagellum base. The position of the MotAB complex is indicated. FIG. 4G presents percent phage infection of Zorya-containing cells in solid cultures. FIG. 4H presents optical density (O.D.) versus time post infection of phage infected Zorya Defense System Ia-containing bacteria in liquid cultures. FIG. 4I presents optical density (O.D.) versus time post infection of phage infected Zorya Defense System Ib-containing bacteria in liquid cultures. FIG. 4J presents the efficiency of plating (EOP) of phage SECphi27 infecting WT Type I ZORA, deletion strains, and strains with point mutations. Data represent PFU/ml, average of 3 replicates with error bars representing STD. ZorA:T147A/S184A and ZorB:D26N are predicted to abolish proton flux; ZorC:E400A/H443A are mutations in two conserved residues in pfam15611 (“EH domain”) whose function is unknown; ZorD:D730A/E731A are mutations in the Walker B motif, predicted to abolish ATP hydrolysis.



FIGS. 5A-5E present the identified members of the Thoeris system and analysis thereof. FIG. 5A shows schematic representative instances of the Thoeris (SIR2-TIR) system and their defense island context. In each row of the top set of systems identified, the red gene is the thsA gene (Sir2-domain; pfam13289) gene; the immediately downstream gene is the thsB gene (TIR domain; pfam08937 or pfam13676) gene. In the last four systems presented, the Thoeris genes thsA (containing NAD-binding domain) and thsB (TIR domain) are marked dark and light green, respectively. Genes known to be involved in defense are orange. Mobilome genes are in dark grey. RM, restriction-modification; TA, toxin-antitoxin; Abi, abortive infection. FIG. 5B presents schematic representations of two Thoeris systems identified and analyzed in this study, shown to protect against myophages. Locus tag accessions are indicated for the individual genes. FIG. 5C presents the efficiency of plating (EOP) results of phage SBSphiJ infection with WT and mutated versions of the B. amyloliquefaciens Y2 Thoeris (FIG. 5B top set) or B. cereus MSX-D12 Thoeris (FIG. 5B bottom set) cloned into B. subtilis BEST7003. Average of 3 replicates, error bars represent STD. FIG. 5D shows the initial results demonstrating that the Thoeris system (SIR2-TIR system) provides protection against phages as evaluated by plaque assay. Phage used were SBSphiC, SBSphiJ and SPO1. FIG. 5E presents predictions of the active site in ThsB polypeptide. Shown is an alignment of the ThsB gene from Bacillus amyloliquefaciens Y2 to SARM1 and MliB. Numbers in the alignment represent position in the protein sequence. Positions of verified active sites for MliB and SARM1, and the predicted active site of ThsB, are indicated.



FIGS. 6A-6C present the identified members of the Druantia system and analysis thereof. FIG. 6A presents representative instances of Druantia types I, II and III and their defense island context. The system is characterized by a gene encoding a large (1800aa-2100aa) polypeptide with a DUF1998 domain (druE), preceded by 3, 2, or 1 genes encoding hypothetical proteins with no domain annotation, for Types I, II and III, respectively. In some Type I cases, a gene encoding a polypeptide with a pfam14236 (DUF4338) domain (druA gene; DruA polypeptide) is associated with the system. Type II systems are typically associated with a cytosine methylase gene (DruM). Genes known to be involved in defense are orange. Mobilome genes are in dark grey. RM, restriction-modification; TA, toxin-antitoxin; Zorya, a defense system identified in this study. FIG. 6B presents the Druantia systems that was cloned (Example 6) and experimentally shown to protect against coliphages. Locus tag accessions are indicated for the individual genes. FIG. 6C presents data showing gene deletions render the Druantia defense system inactive. DruA deletion was not tested due to technical reasons. Data represent EOP, average of 3 replicates; error bars are STD.



FIG. 7A-7C present the identified members of the Wadjet system and analysis thereof. The Wadjet system was shown to provide protection against plasmid transformation in B. subtilis. (FIG. 7A) Representative instances of the Wadjet system and their defense island context. Genes known to be involved in defense are orange. RM, restriction-modification; TA, toxin-antitoxin; Abi, abortive infection. (FIG. 7B) Domain organization of the three types of Wadjet. (FIG. 7C) Wadjet reduces plasmid transformation efficiency in B. subtilis. Wadjet systems were taken from B. cereus Q1 (Type I), Bacillus vireti LMG 21834 (Type II) and Bacillus thuringiensis serovar finitimus YBT-020 (Type III) (Table 4) and cloned into B. subtilis BEST7003. Gene deletions and point mutations are of the B. cereus Q1 Type I Wadjet. Transformation efficiency of plasmid pHCMC05 into Wadjet-containing strains is presented as a percentage of the transformation efficiency to B. subtilis BEST7003 carrying an empty vector instead of the Wadjet system. Average of 3 replicates; error bars represent STD.





DETAILED DESCRIPTION

In the following detailed description, numerous specific details are set forth in order to provide a thorough understanding of the defense systems disclosed herein, including cells comprising these systems, methods of producing cells comprising these systems, methods of identifying the defense systems, and products, for example but not limited to food products or probiotic supplements, that may comprise these the defense systems. In some instances, well-known methods, procedures, and components have not been described in detail so as not to obscure the present disclosure.


The evolutionary pressure imposed by phage predation on bacteria has resulted in the development of both anti-phage bacterial resistance systems and counter-resistance mechanisms developed by phages. Harnessing the anti-phage bacterial mechanisms to improve industrial processes by e.g. curtailing the propagation and evolution of phages in fermentation vats in the manufacturing of food products, commodity chemicals, and biotechnology products is a standing goal in biological research. On the counter arm, properly formulated and applied phages or their defense mechanisms have sufficient potential to cure bacterial infections.


In some embodiments, disclosed herein are the defense systems, including but not limited to anti-phage defense systems, methods for producing and using such defense systems, and methods of countering such defense systems. In some embodiments, disclosed herein are defense systems that provide a host cell with resistance to foreign nucleic acid invasion. In some embodiments, a defense system described herein, provides the host cell with resistance to a foreign nucleic acid invasion, wherein the foreign nucleic acid invasion comprises resistance to at least one phage infection, or resistance to plasmid transformation, or a combination of resistance to at least one phage infection and resistance to plasmid transformation. In some embodiments, it is the combination of defense systems that provides a host cell with resistance to a foreign nucleic acid invasion.


Taken together, the disclosure presented herein of anti-phage defense systems or functional portions thereof may in some embodiments be used for conferring phage resistance in microbial cells. Bacteria comprising these anti-phage defense systems can be utilized for example in the dairy industry, where phages cause serious annual losses, as well as in other industries that rely on large-scale bacterial fermentation for biotechnological production. Alternatively, an agent able to antagonize a defense system may in some embodiments can be used as an antibiotic or in conjunction with known antibiotics.


In addition, embodiments disclosed herein include methods of use of defense systems for gene editing, for example but not limited to, for cloning and cutting a nucleic acid sequence leading to specific deletion of a gene, repair of a gene, or replacement of a gene.


Genetic Systems that Defend Against Foreign Nucleic Acid (DNA and RNA)


In some embodiments, disclosed herein is a genetic system that defends a host cell against foreign nucleic acid invasion. One skilled in the art would appreciate that defense against a foreign nucleic acid invasion may encompass, defending against entry of a foreign nucleic acid into the host cell, as well as, defending against the actions of a foreign nucleic acid that has entered the host cell. In some embodiments, defense against a foreign nucleic acid invasion comprises defense from phage infection. In some embodiments, defense against a foreign nucleic acid invasion comprises defense from plasmid transformation. In some embodiments, defense against a foreign nucleic acid invasion comprises defense against entry of a conjugative element. In some embodiments, defense against a foreign nucleic acid invasion comprises defense against any combination of phage infection, plasmid transformation, and entry of a conjugative element.


In some embodiments a foreign nucleic acid comprises a foreign DNA. In some embodiments a foreign nucleic acid comprises a foreign RNA.


In some embodiments, disclosed herein is a genetic system that defends against foreign DNA. (Tables 4, and 6-17) The skilled artisan would appreciate that as used herein the term “defense system” encompasses genetic systems that defend against foreign nucleic acid elements, including foreign DNA elements and foreign RNA elements.


In some embodiments, a defense system described herein functions as an anti-phage defense system, wherein the system provides a microbial cell resistance to phage infection. In some embodiments, a defense system described herein functions as an anti-phage defense system, wherein the system provides bacteria resistance to phage infection. In some embodiments, the defense system functions as an anti-plasmid transformation defense system, wherein the system reduces the transformation of a host cell by plasmid vectors. In some embodiments, the defense system functions as an anti-plasmid transformation defense system, wherein the system reduces the transformation of a microbial cell by plasmid vectors. In some embodiments, the defense system functions as an anti-plasmid transformation defense system, wherein the system reduces the transformation of bacteria by plasmid vectors.


The skilled artisan would appreciate that a defense system may in some embodiments, be introduced into a microbial cell in which such a defense system is not present. In some embodiments, a defense system may be introduced into a bacterium cell in which such a defense system is not present. In some embodiments, a defense system may be introduced into a microbial cell in which such a defense system is not functional. In some embodiments, a defense system may be introduced into a bacterium cell in which such a defense system is not functional. In some embodiments, a defense system may be introduced into a microbial cell in which such a defense system is not expressed. In some embodiments, a defense system may be introduced into a bacterium cell in which such a defense system is not expressed.


In some embodiments, introduction of a defense system into a microbial cell in which such a defense system is not present, provides the microbial cell resistance to foreign nucleic acid invasion. In some embodiments, integration of a defense system into the genome of a microbial cell in which such the defense system is not present, provides the microbial cell resistance to foreign nucleic acid invasion. In some embodiments, integration of functional components of a defense system into the genome of a microbial cell in which such the defense system is not present, provides the microbial cell resistance to foreign nucleic acid invasion. In some embodiments, integration of at least one functional component of a defense system into the genome of a microbial cell in which such the defense system is not present, provides the microbial cell resistance to foreign nucleic acid invasion.


In some embodiments, introduction of a defense system into a microbial cell in which such a defense system is not present, provides the microbial cell resistance to phage infection. In some embodiments, integration of a defense system into the genome of a microbial cell in which such the defense system is not present, provides the microbial cell resistance to phage infection. In some embodiments, integration of functional components of a defense system into the genome of a microbial cell in which such the defense system is not present, provides the microbial cell resistance to phage infection. In some embodiments, integration of at least one functional component of a defense system into the genome of a microbial cell in which such the defense system is not present, provides the microbial cell resistance to phage infection.


In some embodiments, introduction of a defense system into a bacterium cell in which such a defense system is not present, provides the bacterium resistance to foreign nucleic acid invasion. In some embodiments, introduction of a defense system into a bacterium cell in which such a defense system is not present, provides the bacterium resistance to phage infection. In some embodiments, integration of a defense system into the genome of a bacterial cell in which such the defense system is not present, provides the bacterium cell resistance to phage infection. In some embodiments, integration of functional components of a defense system into the genome of a bacterium cell in which such the defense system is not present, provides the bacterium cell resistance to phage infection. In some embodiments, integration of at least one functional component of a defense system into the genome of a bacterium cell in which such the defense system is not present, provides the bacterial cell resistance to phage infection. Resistance to phage infection in bacteria may occur for example, but not limited to, abortive infection of a phage, blocking phage adsorption to the bacterium surface, acquired immunity, preventing phage lysogeny in bacteria, causing degradation of phage genome in bacteria, inhibition of phage replication, and inhibition of phage genome replication. not causing an abortive infection;


In some embodiments, a defense system disclosed herein is not present in a microbial cell species. In some embodiments, a defense system disclosed herein is not present in a bacterial cell species.


In some embodiments, a defense system disclosed herein is not functional in a microbial cell species. In some embodiments, a defense system disclosed herein is not functional in a bacterial cell species. Thus, in some embodiments, introduction of a defense system into a microbial cell lacking a functional version of the defense system disclosed herein, provides resistance to foreign nucleic acid invasion. In some embodiments, introduction of a defense system into a microbial cell lacking a functional version of the defense system disclosed herein, provides resistance to phage infection.


In some embodiments, introduction of a defense system into a microbial cell in which such a defense system is not present, provides the microbial cell resistance to plasmid transformation. In some embodiments, integration of a defense system into the genome of a microbial cell in which such the defense system is not present, provides the microbial cell resistance to plasmid transformation. In some embodiments, integration of functional components of a defense system into the genome of a microbial cell in which such the defense system is not present, provides the microbial cell resistance to plasmid transformation. In some embodiments, integration of at least one functional component of a defense system into the genome of a microbial cell in which such the defense system is not present, provides the microbial cell resistance to plasmid transformation.


In some embodiments, introduction of a defense system into a bacterium cell in which such a defense system is not present, provides the bacterium resistance to plasmid transformation. In some embodiments, integration of a defense system into the genome of a bacterial cell in which such the defense system is not present, provides the bacterium cell resistance to plasmid transformation. In some embodiments, integration of functional components of a defense system into the genome of a bacterium cell in which such the defense system is not present, provides the bacterium cell resistance to plasmid transformation. In some embodiments, integration of at least one functional component of a defense system into the genome of a bacterium cell in which such the defense system is not present, provides the bacterial cell resistance to plasmid transformation. Resistance to plasmid in bacteria may occur for example, but not limited to, reduced transformation efficiency, inhibition of plasmid establishment, and or inhibition of transformation.


In some embodiments, introduction of a defense system into a bacterium cell in which such a defense system is not present, provides the bacterium protection from conjugative elements. In some embodiments, integration of a defense system into the genome of a bacterial cell in which such the defense system is not present, provides the bacterium cell protection from conjugative elements. In some embodiments, integration of functional components of a defense system into the genome of a bacterium cell in which such the defense system is not present, provides the bacterium cell resistance to conjugation with another bacterium. In some embodiments, integration of at least one functional component of a defense system into the genome of a bacterium cell in which such the defense system is not present, provides the bacterial cell resistance to conjugation with another bacterium. The skilled artisan would appreciate that the term “conjugative elements” may encompass mobile genetic elements, plasmids, and transposons.


A skilled artisan would appreciate that a defense system includes but is not limited to a system that defends a cell from foreign nucleic acid. In some embodiments, a defense system includes but is not limited to a system that defends a cell from foreign DNA. In some embodiments, a defense system includes but is not limited to a system that defends a cell from foreign RNA. In some embodiments, a defense system includes but is not limited to an anti-plasmid system. In some embodiments, a defense system includes but is not limited to an anti-transposon system. In some embodiments, a defense system includes but is not limited to an anti-conjugation system. In some embodiments, a defense system includes but is not limited to an anti-phage system.


In some embodiments, the nucleic acid comprises a linear nucleic acid molecule. In some embodiments, the nucleic acid comprises circular nucleic acid molecule. In some embodiments, the nucleic acid comprises a single stranded nucleic acid molecule. In some embodiments, the nucleic acid comprises a double stranded nucleic acid molecule. The skilled artisan would appreciate that foreign nucleic acid may in some embodiments, encompass any nucleic acid molecule foreign to, for example, but not limited to a microbial cell, a bacterium cell, or an archaeal cell.


In some embodiments, a foreign nucleic acid comprises a foreign DNA or foreign RNA. In some embodiments, a foreign DNA or foreign RNA comprises a phage. In some embodiments, a foreign DNA or foreign RNA comprises a plasmid. In some embodiments, a foreign DNA or foreign RNA comprises a conjugative element. In some embodiments, a foreign DNA or foreign RNA comprises a mobile genetic element. In some embodiments, a foreign DNA or foreign RNA comprises a mobile genetic element.


In some embodiments, a defense system protects bacteria from phage infection. In some embodiments, a defense system protects bacteria from plasmid transformation. In some embodiments, a defense system protects bacteria from conjugative elements. In some embodiments, a defense system provides a bacteria resistance to phage infection. In some embodiments, a defense system provides a bacteria resistance to plasmid transformation. In some embodiments, a defense system provides a bacteria resistance to entry of conjugative elements.


Disclosed herein, is the identification of defense systems. In some embodiments, the components of a defense system are located in a gene cluster in a prokaryotic cell. The terms “gene cluster”, “cassette of genes”, “cassette”, and “components of a system”, may in some embodiments herein be used interchangeably having all the same meanings and qualities.


In some embodiments, each gene of a “cassette of genes” comprises a nucleic acid sequence encoding a polypeptide component of the defense system. In some embodiments, a “cassette of genes” comprises nucleic acid sequences encoding components of the defense system including open reading frames encoding defense system polypeptide components, regulatory sequences, and non-coding RNAs. A skilled artisan would appreciate that a “cassette of genes” may encompass an operon. In some embodiments, a cassette of genes comprises regulatory sequences. In some embodiments, a cassette of gene comprises non-coding RNAs.


In some embodiments, disclosed herein is a nucleic acid construct of a Defense System. In some embodiments, a nucleic acid construct of a Defense System comprises at least two nucleic acid constructs each expressing at least one of the polypeptide components of the Defense System. In some embodiments, disclosed herein is a nucleic acid construct of a Defense System comprising at least two nucleic acid constructs each expressing at least one functional polypeptide component of the Defense System.


In some embodiments, the nucleic acid construct comprises a plurality of constructs each expressing a single component of a Defense System described herein. In some embodiments, the nucleic acid construct comprises a plurality of constructs each expressing a single functional component of a Defense System described herein.


In some embodiments, a single nucleic acid construct encodes a number of polypeptide components of a Defense System described herein. In some embodiments, a single construct encodes a number of functional polypeptide components of a Defense System described herein.


A skilled artisan would recognize that the term “anti-phage activity” or “resistant to infection by at least one phage” encompasses an activity providing increased resistance of a host cell to infection by at least one phage in comparison to the host cell of the same species under the same developmental stage (e.g. culture state) which does not express the functional defense system. In some embodiments, a host cell may comprise a microbial cell. In some embodiments, a host comprises a bacterium. Anti-phage activity or resistance of a host cell to infection by at least one phage may be determined by, for example but not limited to, bacterial viability, phage lysogeny, phage genomic replication or phage genomic degradation, or a combination thereof.


A skilled artisan would appreciate that the term “abortive infection (Abi)” encompasses a controlled cell death of an infected bacterial cell which takes place prior to the production of phage progeny, thus protecting the culture from phage propagation. Methods of analyzing Abi include, but are not limited to cell survival assays using high multiplicity of infection, one step growth assays and determination of phage DNA replication by e.g. DNA sequencing and southern blot analysis as further described hereinbelow.


A skilled artisan would appreciate that the phrase “not affecting phage adsorption” encompasses a non-statistically significant difference in phage adsorption to bacteria expressing a functional defense system in comparison to bacteria of the same species under the same developmental stage (e.g. culture state) which does not express a functional defense system.


A skilled artisan would appreciate that the term “adsorption” encompasses the attachment to the host (e.g. bacteria) cell surface via plasma membrane proteins and glycoproteins. Methods of analyzing phage adsorption include, but are not limited to enumerating free phages in bacterial cultures infected with the phages immediately after phage addition and at early time points (e.g. 30 minutes) following phage addition as further described hereinbelow.


A skilled artisan would appreciate that the term “prevent” or “preventing” encompasses a decrease in activity (e.g. phage genomic replication, phage lysogeny, circularization of phage genome) in bacteria expressing a functional defense system in comparison to bacteria of the same species under the same developmental stage (e.g. culture state) which does not express a functional defense system. According to specific embodiments the decrease is at least 1.5 fold, at least 2 fold, at least 3 fold, at least 5 fold, at least 10 fold, or at least 20 fold as compared to same in the absence of the functional defense system.


A skilled artisan would appreciate that the term “resistance” to, for example, foreign nucleic acid invasion, encompasses a decrease in activity (e.g. phage genomic replication, phage lysogeny, circularization of phage genome) in bacteria expressing a functional defense system in comparison to bacteria of the same species under the same developmental stage (e.g. culture state) which does not express a functional defense system. According to specific embodiments the decrease provided by such resistance to foreign nucleic acid invasion is at least 1.5 fold, at least 2 fold, at least 3 fold, at least 5 fold, at least 10 fold, or at least 20 fold as compared to same in the absence of the functional defense system.


A skilled artisan would appreciate that the term “phage genomic replication” encompasses production of new copies of the phage genome which can be dsDNA or ssDNA. Methods of analyzing phage genomic replication are well known in the art, and in the Examples section which follows.


A skilled artisan would appreciate that the term “lysogeny” encompasses the incorporation of the phage genetic material inside the genome of the host (e.g. bacteria). Methods of analyzing phage lysogeny are well known in the art and include, but not limited to, DNA sequencing and PCR analysis. Typically, when a temperate phage infects a bacterium, its genetic material becomes circular before it incorporates into the bacterial genome. Circularization of phage genome can be analyzed by methods well known in the art including, but not limited to, PCR analysis as described e.g. in the Examples section which follows.


When referring to “degradation of phage genome” the meaning is the cleavage of the foreign phage genome by the host bacteria. Method of analyzing genomic degradation are well known in the art including, but not limited to, DNA sequencing and PCR analysis.


A skilled artisan would appreciate that the term “restriction modification system” may encompass a restriction entity having an activity of cleaving a genomic molecule (e.g. DNA)/DNA and a modification entity capable of protecting (e.g., by methylation) the host DNA from the cleavage by the restriction enzyme e.g. by methylating the host DNA. Analyzing restriction modification mode of action include, but is not limited to, evaluation of host specific methylation, presence of degraded foreign DNA and host cell death in the absence of the modification enzyme by methods described herein.


In some embodiments, a functional defense system leads to an abortive infection in bacteria expressing the defense system. In some embodiments, a functional defense system reduces affect phage adsorption to bacteria expressing the defense system. In some embodiments, a functional defense system prevents phage genomic replication in bacteria expressing the defense system. In some embodiments, a functional defense system prevents phage lysogeny in bacteria expressing the defense system. In some embodiments, a functional defense system prevents circularization of a phage genome in bacteria expressing the defense system. In some embodiments, a functional defense system leads to degradation of a phage genome in bacteria expressing the defense system. In some embodiments, a functional defense system comprises a restriction modification system. In some embodiments, a functional defense system comprises a gene editing system.


In some embodiments, a functional defense system does not lead to an abortive infection in bacteria expressing the defense system. In some embodiments, a functional defense system does not affect phage adsorption to bacteria expressing the defense system. In some embodiments, a functional defense system does not prevent phage genomic replication in bacteria expressing the defense system. In some embodiments, a functional defense system does not prevent phage lysogeny in bacteria expressing the defense system. In some embodiments, a functional defense system does not prevent circularization of a phage genome in bacteria expressing the defense system. In some embodiments, a functional defense system does not lead to degradation of a phage genome in bacteria expressing the defense system. In some embodiments, a functional defense system does not comprise a restriction modification system.


A skilled artisan would recognize that the term “anti-plasmid transformation” or “reducing the transformation of a host cell by a plasmid vector” encompasses an activity whereby a host cell, for example but not limited to bacteria, expressing a functional defense system as disclosed herein, has reduced transformation efficiency of an episomal plasmid, in comparison to the host cell of the same species under the same developmental stage (e.g. culture state) which does not express the functional defense system. Anti-plasmid transformation or reduction of transformation efficiency may be determined by, for example but not limited to, measuring plasmid transformation efficiency in the presence or absence of a defense system disclosed herein.


In some embodiments, a plasmid may undergo integration into the bacterial genome or may be episomal. In some embodiments, the plasmid is episomal. In some embodiments, the plasmid is integrative. In some embodiments, a Defense System disclosed herein, provides plasmid resistance.


The skilled artisan would appreciate that “plasmid resistance” or “anti-plasmid activity” encompasses an increase resistance of at least two-fold increased bacterial resistance towards plasmid transformation, in comparison to bacteria of the same species under the same developmental stage (culture state) which does not express the Defense System. In some embodiments, plasmid resistance may be manifested as viability of the bacteria. In some embodiments, plasmid resistance comprises decreased efficiency of transformation of the plasmid. According to a specific embodiment, the plasmid resistance is increased by at least two-fold, five-fold, ten-fold, twenty-fold, fifty-fold, one-hundred-fold, or one-thousand-fold.


Assays for testing plasmid resistance are well known in the art and include, but not limited to, a transformation assay such as described in Itaya and Tsuge [Methods Enzymol (2011) 498:427-47].


As used herein, the terms “the defense system” may in some embodiments be used interchangeably with the term “defense system” or “defense system” or “system”, having all the same meanings and qualities.


In some embodiments, different defense systems may be combined. Combination of defense systems, may in certain embodiments, provide multiple types of defense against foreign nucleic acid. For example, but not limited to defense against phage infection of phage from different families, or defense against phage infection and protection against conjugative elements, or defense against phage infection and resistance to plasmid transformation.


In some embodiments, a nucleic acid construct encodes an at least one defense system, said nucleic acid construct comprising nucleic acid sequences encoding polypeptide components of a defense system. In some embodiments, a nucleic acid construct described herein, encodes at least one defense system described herein. In some embodiments, a nucleic acid construct described herein, encodes at least one functional defense system described herein. In some embodiments, a nucleic acid construct comprises a nucleic acid encoding at least two different polypeptide components of the defense system. In some embodiments, a nucleic acid construct comprises a nucleic acid encoding at least one polypeptide components of the defense system. In some embodiments, a nucleic acid construct comprises a nucleic acid encoding at least three different polypeptide components of the defense system. In some embodiments, a nucleic acid construct comprises a nucleic acid encoding at least four two different polypeptide components of the defense system. In some embodiments, a nucleic acid construct comprises a nucleic acid encoding at least five different polypeptide components of the defense system.


In some embodiments, a nucleic acid construct encodes one component of the defense system, whereby multiple constructs may be used to assemble the functional defense system. In some embodiments, a nucleic acid construct encodes more than one component of the defense system but less than all of the components required for a functionally active defense system, whereby multiple constructs may be used to assemble the functional defense system. In some embodiments, a nucleic acid construct encodes more than one copy of a single component of the defense system, whereby multiple constructs may be used to assemble the functional defense system.


The skilled artisan would recognize that the “components” making up a functional defense system may in some embodiments, be also be referred to herein as the members of the “cassette of genes” identified to represent a defense system, wherein each component is encoded by a different gene. In some embodiments, a construct disclosed herein may comprise less than the full complement of polypeptides required for a functional defense system, whereby multiple constructs may be combined for expression of the functional defense system. In some embodiments, components comprise polypeptide molecules of a defense system. In some embodiments, components comprise non-coding RNAs. In some embodiments, components comprise promoters and other control elements.


In some embodiments, a defense system described herein comprises all of the polypeptide components as described herein. In some embodiments, a defense system comprises one of the polypeptide component as described herein. In some embodiments, a defense system comprises all of the polypeptide component as described herein. In some embodiments, a defense system comprises two of the polypeptide component as described herein. In some embodiments, a defense system comprises three of the polypeptide component as described herein. In some embodiments, a defense system comprises four of the polypeptide component as described herein. In some embodiments, a defense system comprises five of the polypeptide component as described herein. In some embodiments, a defense system comprises more than one copy of a particular polypeptide component of the defense system, as described herein.


A skilled artisan would appreciate that the term “nucleic acid sequence” and “polynucleotide”, which are interchangeably used herein, may encompass a single or double stranded nucleic acid sequence which is isolated and provided in the form of an RNA sequence, a complementary polynucleotide sequence (cDNA), a genomic polynucleotide sequence, and/or a composite polynucleotide sequences (e.g., a combination of the above).


In some embodiments, a nucleic acid construct disclosed herein encodes no more than 20, no more than 15, no more the 10 genes expression products. In some embodiments, a gene expression product comprises a component of a Defense System. In some embodiments, a gene expression product comprises a functional component of a Defense System. In some embodiments, a gene expression product comprises a portion of a component that is functional in a Defense System disclosed herein. In some embodiments, a gene expression product or a portion thereof is isolated. In some embodiments, a gene expression product or a portion thereof is comprised in a Defense System disclosed herein.


A skilled artisan would appreciate that the term “isolated” encompasses an element being at least partially separated from the natural environment, physiological environment e.g., a microorganism e.g., bacteria, e.g., a polypeptide, eg., a nucleic acid sequence.


A skilled artisan would appreciate that the term “polypeptide” encompasses native peptides (either degradation products, synthetically synthesized peptides or recombinant peptides) and peptidomimetics (typically, synthetically synthesized peptides), as well as peptoids and semipeptoids which are peptide analogs, which may have, for example, modifications rendering the peptides more stable while in a body or more capable of penetrating into cells. Such modifications include, but are not limited to N terminus modification, C terminus modification, peptide bond modification, backbone modifications, and residue modification. Methods for preparing peptidomimetic compounds are well known in the art and are specified, for example, in Quantitative Drug Design, C. A. Ramsden Gd., Chapter 17.2, F. Choplin Pergamon Press (1992), which is incorporated by reference as if fully set forth herein.


The polypeptides disclosed herein may be synthesized by any techniques known to those skilled in the art of peptide synthesis, for example but not limited to recombinant DNA techniques or solid phase peptide synthesis.


In some embodiments, a defense system comprises multiple nucleic acid constructs comprising nucleic acid sequences encoding polypeptide components of two or more functional the defense system. In some embodiments, the two or more functional the defense system do not naturally occur together in a cell in nature.


In some embodiments, each nucleic acid construct encoding a defense system or components of a defense system, further comprises a regulatory element or elements operably linked to the construct. In some embodiments, regulatory elements comprise a cis-acting regulatory element for directing expression of said nucleic acid sequence. In some embodiments, regulatory elements comprise a transmissible element for directing transfer of said nucleic acid sequence from one cell to another. In some embodiments, regulatory elements comprise a recombination element for integrating said nucleic acid sequence into a genome of a cell transfected with said construct. In some embodiments, regulatory elements comprise an element providing episomal maintenance of said construct within a cell transfected with said construct. In some embodiments, regulatory elements comprise a combination of a cis-acting regulatory element for directing expression of said nucleic acid sequence, a regulatory element comprising a transmissible element for directing transfer of said nucleic acid sequence from one cell to another, a regulatory element comprising a recombination element for integrating said nucleic acid sequence into a genome of a cell transfected with said construct, a regulatory element comprising an element providing episomal maintenance of said construct within a cell transfected with said construct, in any combination.


Defense Systems


In some embodiments, the defense systems disclosed herein may be a combination of defense systems. In some embodiments, a combination of the defense systems comprises an anti-phage system and an anti-plasmid system. In some embodiments, a combination of the defense systems comprises an anti-phage system and an anti-conjugative element system. In some embodiments, a combination of the defense systems comprises an anti-plasmid system and an anti-conjugative element system. In some embodiments, a combination of the defense systems comprises an anti-phage system, an anti-plasmid system, and an anti-conjugative element system. In some embodiments, a combination of the defense systems comprises an anti-phage system, an anti-plasmid system, or an anti-conjugative element system, or any combination thereof.


In some embodiments, introducing any of the defense systems disclosed herein, into eukaryotic cells, for example but not limited to bacteria cells, where they are not naturally found (therefore the defense system is non-naturally occurring), provides the host cells protection against phage infection.


In some embodiments, nucleic acid sequences or nucleic acid constructs may further include nuclear targeting signals (NLS) so that a nucleic acid sequence encoding a non-naturally polypeptide component, may be directed to the nucleus for expression. In some embodiments, nucleic acid sequences or nucleic acid constructs may further include nuclear targeting signals (NLS) so that multiple nucleic acid sequences encoding non-naturally polypeptide components or a defense system described herein, may be directed to the nucleus for expression. In some embodiments, nucleic acid sequences or nucleic acid constructs may further include nuclear targeting signals (NLS) so that combinations of nucleic acids encoding defense systems (polypeptides) described herein, may be directed to the nucleus for expression.


In some embodiments, introducing any of the defense systems disclosed herein, into eukaryotic cells, for example but not limited to bacteria cells, where they are not naturally found (therefore they are non-naturally occurring), provides the host cells protection against introduction of external DNA. In some embodiments, introducing any of the defense systems disclosed herein, into eukaryotic cells, for example but not limited to bacteria cells, where they are not naturally found, provides the host cells protection against introduction of external plasmid DNA. In some embodiments, introducing any of the defense systems disclosed herein, into eukaryotic cells, for example but not limited to bacteria cells, where they are not naturally found, provides the host cells protection against introduction of external conjugative elements.


In some embodiments, a combination of the defense systems comprises combining an anti-phage system and another anti-phage system. In some embodiments, a combination of the defense systems comprises combining an anti-phage system and more than one other anti-phage system. In some embodiments, a combination of the defense systems comprises combining an anti-phage system and two other anti-phage systems. In some embodiments, a combination of the defense systems comprises combining an anti-phage system and three other anti-phage systems. In some embodiments, a combination of the defense systems comprises combining an anti-phage system and four other anti-phage systems. In some embodiments, a combination of the defense systems comprises combining an anti-phage system and five other anti-phage systems. In some embodiments, a combination of the defense systems comprises combining an anti-phage system and six other anti-phage systems. In some embodiments, a combination of the defense systems comprises combining an anti-phage system and seven other anti-phage systems. In some embodiments, a combination of the defense systems comprises combining an anti-phage system and eight other anti-phage systems. In some embodiments, a combination of the defense systems comprises combining an anti-phage system and nine other anti-phage systems. In some embodiments, a combination of the defense systems comprises combining an anti-phage system and ten other anti-phage systems. In some embodiments, a combination of the defense systems comprises combining an anti-phage system and more than 10 other anti-phage systems. In some embodiments, a combination of the defense systems comprises combining an anti-phage system with between 2-15 other anti-phage systems. In some embodiments, a combination of the defense systems comprises combining an anti-phage system with between 2-7 other anti-phage systems. In some embodiments, a combination of the defense systems comprises combining an anti-phage system with between 7-15 other anti-phage systems.


In some embodiments, an at least one defense system comprises any of the defense systems described herein. In some embodiments, an at least one defense system comprises any combination of the defense systems described herein. In some embodiments, wherein a defense system comprises at least two different polypeptide components (See below and Table 18), an at least one defense system comprises at least two different polypeptide components of the defense system.


Below are non-limiting examples of defense systems, which in some embodiments may be used independently, and in other embodiments may be used in combinations.


The ZORYA Defense System


In some embodiments, a defense system disclosed herein comprises a ZORYA anti-phage defense system. In some embodiments, a ZORYA defense system (Defense System Ia or Defense system Ib) provides a host cell with resistance to entry of foreign nucleic acid invasion. In some embodiments, a host cell expressing a functional ZORYA defense system (Defense System Ia; or Defense System Ib) provides the host cell resistance foreign nucleic acid invasion.


In some embodiments, a ZORYA defense system provides a host cell with resistance to at least one phage. In some embodiments, a ZORYA Type I defense system provides a host cell with resistance to at least one phage. In some embodiments, a ZORYA Type II defense system provides a host cell with resistance to at least one phage. (Table 8)


In some embodiments, expression of a ZORYA defense system in bacteria protects the bacteria from phage infection. In some embodiments, expression of a ZORYA Type I defense system in bacteria protects the bacteria from phage infection. In some embodiments, expression of a ZORYA Type II defense system in bacteria protects the bacteria from phage infection.


In some embodiments, a ZORYA defense system (Defense System Ia or Defense system Ib) provides a host cell with resistance to plasmid transformation. In some embodiments, a host cell expressing a functional ZORYA defense system (Defense System Ia or Defense System Ib) provides a host cells with resistance to plasmid transformation.


In some embodiments, a ZORYA defense system (Defense system Ia or Ib) provides a host cell with resistance to entry of conjugative elements. In some embodiments, a host cell expressing a function ZORYA defense system (Defense System Ia or Ib) provides the host cell resistance from entry of conjugative elements.


As used herein, the term “a ZORYA anti-phage defense system” may be used interchangeably with the term “a Defense System I”, having all the same meanings and qualities. Further, in some embodiments, the term “a ZORYA Type I defense system” may be used interchangeably with the term “a Defense System Ia”, having all the same meanings and qualities. In some embodiments, the term “a ZORYA anti-phage defense system” may be used interchangeably with the term “a Defense System Ia”, having all the same meanings and qualities. Further, in some embodiments, the term “a ZORYA Type I defense system” may be used interchangeably with the term “a Defense System Ia”, having all the same meanings and qualities. In some embodiments, the term “a ZORYA anti-phage defense system” may be used interchangeably with the term “a Defense System Ib”, having all the same meanings and qualities. Further, in some embodiments, the term “a ZORYA Type I defense system” may be used interchangeably with the term “a Defense System Ib”, having all the same meanings and qualities.


In some embodiments, a ZORYA defense system provides a host cell with resistance to plasmid transformation. In some embodiments, a ZORYA Type I defense system provides a host cell with resistance to plasmid transformation. In some embodiments, a ZORYA Type II defense system provides a host cell with resistance to plasmid transformation.


As used herein, the term “ZORYA system” may be used interchangeably in some embodiments with “ZORYA defense system”, “ZORYA the defense system”, “ZORYA defense system”, “ZORYA anti-phage system”, “ZORYA Type I defense system”, “ZORYA Type II defense system”, “Defense System Ia” and “Defense System Ib”.


In some embodiments, a microbial species does not comprise an endogenous Defense System I. In some embodiments, a microbial species does not comprise an endogenous Defense System Ia. In some embodiments, a microbial species does not comprise an endogenous Defense System Ib. In some embodiments, a microbial species does not express an endogenous Defense System I. In some embodiments, a microbial species does not express an endogenous Defense System Ia. In some embodiments, a microbial species does not express an endogenous Defense System Ib. In some embodiments, a microbial species does not express an endogenous functional Defense System I. In some embodiments, a microbial species does not express an endogenous functional Defense System Ia. In some embodiments, a microbial species does not express an endogenous functional Defense System Ib.


In some embodiments, a bacterial species does not comprise an endogenous Defense System I. In some embodiments, a bacterial species does not comprise an endogenous Defense System Ia. In some embodiments, a bacterial species does not comprise an endogenous Defense System Ib. In some embodiments, a bacterial species does not express an endogenous Defense System I. In some embodiments, a bacterial species does not express an endogenous Defense System Ia. In some embodiments, a bacterial species does not express an endogenous Defense System Ib. In some embodiments, a bacterial species does not express an endogenous functional Defense System I. In some embodiments, a bacterial species does not express an endogenous functional Defense System Ia. In some embodiments, a bacterial species does not express an endogenous functional Defense System Ib.


A ZORYA Type I defense system (Defense System Ia) comprises, in some embodiments, a nucleic acid construct comprising a nucleic acid sequence encoding a ZorA polypeptide comprising a pfam01618 domain, a ZorB polypeptide comprising a pfam13677 domain or a pfam00691 domain or a combination thereof, a ZorC polypeptide comprising a pfam15611 domain, and a ZorD polypeptide comprising a pfam00176 domain or a pfam00271 domain or a combination thereof. In some embodiments, a ZORYA Type I defense system comprises a nucleic acid construct comprising a nucleic acid sequence encoding a ZorA polypeptide, a ZorB polypeptide, a ZorC polypeptide, and a ZorD polypeptide. In some embodiments, a ZORYA Type I defense system comprises a nucleic acid construct comprising a nucleic acid sequence comprising a zorA gene, a zorB gene, a zorC gene, and a zorD gene.


In some embodiments, a ZORYA Type I defense system (Defense System Ia) comprises a ZorA polypeptide comprising a pfam01618 domain, a ZorB polypeptide comprising a pfam13677 domain or a pfam00691 domain or a combination thereof, a ZorC polypeptide comprising a pfam15611 domain, and a ZorD polypeptide comprising a pfam00176 domain or a pfam00271 domain or a combination thereof. In some embodiments, a ZORYA Type I defense system (Defense System Ia) having an anti-phage activity comprises a ZorA polypeptide comprising a pfam01618 domain, a ZorB polypeptide comprising a pfam13677 domain or a pfam00691 domain or a combination thereof, a ZorC polypeptide comprising a pfam15611 domain, and a ZorD polypeptide comprising a pfam00176 domain or a pfam00271 domain or a combination thereof.


In some embodiments, a ZORYA Type I defense system (Defense System Ia) comprises at least two polypeptide components selected from a ZorA polypeptide comprising a pfam01618 domain, a ZorB polypeptide comprising a pfam13677 domain or a pfam00691 domain or a combination thereof, a ZorC polypeptide comprising a pfam15611 domain, and a ZorD polypeptide comprising a pfam00176 domain or a pfam00271 domain or a combination thereof. In some embodiments, a ZORYA Type I defense system (Defense System Ia) having an anti-phage activity comprises at least two polypeptide components selected from a ZorA polypeptide comprising a pfam01618 domain, a ZorB polypeptide comprising a pfam13677 domain or a pfam00691 domain or a combination thereof, a ZorC polypeptide comprising a pfam15611 domain, and a ZorD polypeptide comprising a pfam00176 domain or a pfam00271 domain or a combination thereof. In some embodiments, a ZORYA Type I defense system (Defense System Ia) comprises at least three polypeptide components selected from a ZorA polypeptide comprising a pfam01618 domain, a ZorB polypeptide comprising a pfam13677 domain or a pfam00691 domain or a combination thereof, a ZorC polypeptide comprising a pfam15611 domain, and a ZorD polypeptide comprising a pfam00176 domain or a pfam00271 domain or a combination thereof. In some embodiments, a ZORYA Type I defense system (Defense System Ia) having an anti-phage activity comprises at least three polypeptide components selected from a ZorA polypeptide comprising a pfam01618 domain, a ZorB polypeptide comprising a pfam13677 domain or a pfam00691 domain or a combination thereof, a ZorC polypeptide comprising a pfam15611 domain, and a ZorD polypeptide comprising a pfam00176 domain or a pfam00271 domain or a combination thereof. In some embodiments, a ZORYA Type I defense system (Defense System Ia) comprises at least four polypeptide components selected from a ZorA polypeptide comprising a pfam01618 domain, a ZorB polypeptide comprising a pfam13677 domain or a pfam00691 domain or a combination thereof, a ZorC polypeptide comprising a pfam15611 domain, and a ZorD polypeptide comprising a pfam00176 domain or a pfam00271 domain or a combination thereof. In some embodiments, a ZORYA Type I defense system (Defense System Ia) having an anti-phage activity comprises at least four polypeptide components selected from a ZorA polypeptide comprising a pfam01618 domain, a ZorB polypeptide comprising a pfam13677 domain or a pfam00691 domain or a combination thereof, a ZorC polypeptide comprising a pfam15611 domain, and a ZorD polypeptide comprising a pfam00176 domain or a pfam00271 domain or a combination thereof.


In some embodiments, a Defense System Ia comprises a ZorA polypeptide comprising a pfam01618 domain or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 8 rows 2-1830 columns J and K; or a ZorB polypeptide comprising a pfam13677 domain or a pfam00691 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 8 rows 2-1830 columns N and O; or a ZorC polypeptide comprising a pfam15611 domain or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 8 rows 2-1174 columns R and S; or a ZorD polypeptide comprising a pfam00176 domain or a pfam00271 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 8 rows 2-1174 columns V and W; or said Defense System Ia comprises any combination of polypeptide components ZorA, ZorB, ZorC, and ZorD.


A skilled artisan would appreciate that the term “comprising” encompasses inclusion of the recited elements, but not excluding others which may be optional. For example, but not limited to a defense system, a defense system may comprise a single polypeptide component, or may comprise multiple polypeptide components. For example, but not limited to a Defense System Ia, in some embodiments a Defense System Ia comprises at least two different polypeptide components selected from ZorA, ZorB, ZorC, and ZorD. In some embodiments, a Defense System Ia comprises at least three different polypeptide components selected from ZorA, ZorB, ZorC, and ZorD. In some embodiments, a Defense System Ia comprises polypeptide components ZorA, ZorB, ZorC, and ZorD.


A skilled artisan would appreciate that the phrase “consisting essentially of” may encompass, for example but not limited to, a defense system that includes the recited elements but exclude other elements that may have an essential significant effect on the performance of the method. In some embodiments, a Defense System Ia consists essentially of polypeptide components ZorA, ZorB, ZorC, and ZorD.


A skilled artisan would appreciate that the term “consisting of” may encompass, for example but not limited to, a defense system that includes the recited elements but not more than traces of other elements. Thus, in some embodiments, a Defense System Ia consists of a ZorA polypeptide, a ZorB polypeptide, a ZorC polypeptide, and a ZorD polypeptide.


Embodiments defined by each of these transition terms are within the scope of this invention.


A ZORYA Type II defense system (Defense System Ib) comprises, in some embodiments, a nucleic acid construct comprising a nucleic acid sequence encoding a ZorA polypeptide comprising a pfam01618 domain, a ZorB polypeptide comprising a pfam13677 domain or a pfam00691 domain or a combination thereof, and a ZorE polypeptide comprising a pfam01844 domain. In some embodiments, a ZORYA Type II defense system (Defense System Ib) comprises a nucleic acid construct comprising a nucleic acid sequence encoding a ZorA polypeptide, a ZorB polypeptide, and a ZorE polypeptide. In some embodiments, a ZORYA Type II defense system (Defense System Ib) comprises a nucleic acid construct comprising a nucleic acid sequence comprising a zorA gene, a zorB gene, and a zorE gene.


In some embodiments, a ZORYA Type II defense system (Defense System Ib) comprises a ZorA polypeptide comprising a pfam01618 domain, a ZorB polypeptide comprising a pfam13677 domain or a pfam00691 domain or a combination thereof, and a ZorE polypeptide comprising a pfam01844 domain. In some embodiments, a ZORYA Type II defense system (Defense System Ib) having an anti-phage activity comprises a ZorA polypeptide comprising a pfam01618 domain, a ZorB polypeptide comprising a pfam13677 domain or a pfam00691 domain or a combination thereof, and a ZorE polypeptide comprising a pfam01844 domain.


In some embodiments, a Zorya Type II defense system (Defense System Ib) comprises a ZorE polypeptide and ZorA polypeptide. In some embodiments, a Zorya Type II defense system (Defense System Ib) comprises a ZorE polypeptide and ZorB polypeptide. In some embodiments, a Zorya Type II defense system (Defense System Ib) comprises a ZorE polypeptide, ZorA polypeptide, and a ZorB polypeptide. In some embodiments, a Zorya Type II defense system (Defense System Ib) comprises a ZorE polypeptide comprising a pfam01844 domain or a COG3183 domain or a combination thereof. In some embodiments, a Zorya Type II defense system (Defense System Ib) having an anti-phage activity comprises a ZorE polypeptide comprising a pfam01844 domain or a COG3183 domain or a combination thereof.


In some embodiments, a Defense System Ib comprises a ZorA polypeptide comprising a pfam01618 domain or comprises an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 8 rows 2-1830 columns J and K; or a ZorB polypeptide comprises a pfam13677 domain or a pfam00691 domain or a combination thereof, or comprises an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 8 rows 2-1830 columns N and O; or a ZorE polypeptide comprising a pfam01844 domain or a COG3183 domain or a combination thereof or comprises an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 8 rows 1175-1830 columns Z and AA; or any combination thereof.


In some embodiments, a ZORYA Type I defense system having an anti-phage activity comprises a nucleic acid construct comprising a nucleic acid sequence encoding a ZorA polypeptide, a ZorB polypeptide, a ZorC polypeptide, and a ZorD polypeptide. In some embodiments, a ZORYA Type I defense system having an anti-phage activity comprises a nucleic acid construct comprising a nucleic acid sequence comprising a zorA gene, a zorB gene, a zorC gene, and a zorD gene. In some embodiments, a ZORYA Type II defense system having an anti-phage activity comprises a nucleic acid construct comprising a nucleic acid sequence encoding a ZorA polypeptide, a ZorB polypeptide, and a ZorE polypeptide. In some embodiments, a ZORYA defense system having an anti-phage activity comprises a nucleic acid construct comprising a nucleic acid sequence comprising a zorA gene, a zorB gene, and a zorE gene.


In some embodiments, the ZORYA anti-phage defense system comprises a nucleic acid construct comprising nucleic acid sequences encoding a cassette comprising zorA, zorB, zorC, and zorD genes. In some embodiments, a construct comprising the ZORYA defense system encodes one component of the defense system, whereby multiple constructs may be used to assemble the functional defense system. In some embodiments, the components of a ZORYA Type I defense system comprise genes zorA, zorB, zorC, and zorD. In some embodiments, the components of a ZORYA Type I defense system consist of genes zorA, zorB, zorC, and zorD. In some embodiments, the components of a ZORYA Type I defense system comprise nucleic acid sequences encoding a ZorA polypeptide, a ZorB polypeptide, a ZorC polypeptide, and a ZorD polypeptide. In some embodiments, the components of a ZORYA Type I defense system consist of nucleic acid sequences encoding a ZorA polypeptide, a ZorB polypeptide, a ZorC polypeptide, and a ZorD polypeptide.


In some embodiments, a Zorya Type I (Defense System Ia) gene cassette comprises the nucleic acid sequence:












(SEQ ID NO: 14; Construct 49 Table 4)
















1
tgtaaatcct cggggtagat cgcagcgaaa gagcaaccat gccttatcgc aaattcagtt





61
ttggaatgca gttcgcaaaa tgatacccgg tacacttacg attacaaatg cgcggtataa





121
agaagtttgc atttgatcgg tgaataatag gaaactcagt cactgtttcg tctgcaaaat





181
cagccatttc gccttcatac gtagttcttc ggttgaatag taaggtctat catgctgcat





241
cgaacggtga ttttgatgga tgttggaagt gagtagctgt acgtaatttt tgattaaaag





301
taatcaaaat gttgccaatg gttatgctat cgtgtgtttt ttgaatatat aacaggtaaa





361
actatgtcct ggcttaattc tgtcttattg gcgcttacct cggtgcaacc ttatatggta





421
ccggcaaccg ttatcggcct cgtcagtttt gcattcctct gttttatttt cttttatttt





481
tttagagcag ttaaaattat taacggcctg aaaaaatata ctcagtcaat taatggcatc





541
gaaaataatg agcctggtaa tcagcttcag catctgcaaa gtttgtttgt acagcctgag





601
ttaaagcacg cctggaatga attcgaagaa tcgttgcact cacaatatga actggaggac





661
ggggaagaga aaatcgtccg tattagggct actgcaccga gcgccagttt cttctcggag





721
caacaactgg tcgatattcc gctgaacacc gaatttttca aacacctgcc cggtattctg





781
accggtgtgg ggattatcgg taccttctac ggtctgatga ttggtctcaa ccacttcgac





841
cccagcacac cagagcaggt ctccagcagc gtcaataatc tgcttcgcga tgtgctgtac





901
gccttcctcg gttcagcatt tgcgattacg ttctctatcc ttatcacctg gctggagaaa





961
ttctgtctgg cgaaatgcta caaatatctg gaaaaattca ccgcagctct cgacgccctc





1021
tatgacagcg gtgttggcga ggagtacctt gcctcactgg taaaatccag taatgaaagc





1081
gcgacccagg cacgccatct gaaagagagc ctggttaccg atttacgcga tatgctgctg





1141
catctggcca acagccagaa agtggaaaac gagcggctag cgaccaccct cagcaccacc





1201
tatcgcgaaa caggacaaca gtttgccgag caagtcagcg gtgcgattga aaacagcctg





1261
aaatcaccgc tggataaaat agcgggcgcg gttcagaccg ccagtggcga tcaaagcggc





1321
atggtacaaa acatgctgca ggatgtgctg accgcgttta tggcgaaact cgacaccacc





1381
tttggtcagc agtttactaa tctcaacgaa atgatgggac aaaccgttgg cgctattcag





1441
acaatgcaaa ccggtttcgg cgcgttatta caggacatgc gtcaggtgag cgatgattcc





1501
cgccagggca gcgcgcagct catcgagcaa ctgttatcag agatgaaatc tggccagcaa





1561
gctatgcagg ctggcatgaa tgacatgctc accagccttc agacctcggt ggctaaaatt





1621
ggcgcagaag gtgaaggtgc cggcgagcga atggctcgcc aactagagaa aatgttcgct





1681
gatagcgagg cgcgagaaaa agcccaggca gaacatatga ccgcctttat tgaagccatt





1741
cagaattcag tgcagcaggg acaaagcgcc acaatggaaa aaatggcagc ctctgtcgag





1801
tcgcttggtg aacaactggg tagcctgttt gggcagattg ataagggtca gcaacagatt





1861
tcagcaaatc agcaagcgaa tcagcagtcc ctgcacgaac agactcagcg ggtaatgagt





1921
gaggtagacg atcagattaa acaattggtc gaaactgttg ccagccagca tcagggaaca





1981
actgaaacac ttcgtttact cgcagaacaa actaaccgcc agattcagga tatgcatacc





2041
ggcgcggaca aaatgcgtct ggcggccgag cgctttgaac atgccggtga tcgggtgtcg





2101
gaagcaaacc accttaccgc tgacgtgctg aataaagcgc aatcggcagg ttcatcactc





2161
tcccttgcca ccagcgaact cacctctgtg gtggctgatt atcgtaacaa tcgggaagcg





2221
gttagcaaat ccattgccat gctggagttg ctcgccgcaa atacgcagtc tgaacaaacc





2281
acgcgcaccc aattcatcgc cgaccttaag cagcacggtg agcgtctgca gagctataac





2341
cgggaagcac aggcctttat ggaaaatgtc agtgacgtgc tagggaaagg gtttgaagac





2401
ttctctgaag gtgtttcacg cagcctggat aaaacgctgg gcaaactgga cgttgaaatg





2461
gcgaaggctt ctactctgct cgcgggttct gtcgaacaga tcggagaaag cgtcagcgag





2521
cttgatgatg tcctgtcacg cgttcgtgcc taaggggtga cggctgatgt ttggaaatgc





2581
atttggcgtt aaaaaacgcc gcagcgatga agcagagaaa cccttctgga tctcctatgc





2641
cgatttgatg actgccatga tggtgttatt tctggtcgtt atggttgcgt cgctgagttc





2701
cgttacgcag cgtattcaac gtgcggagca aggtgaaaaa acacgggggc aggatatttc





2761
cagattgtgt gagcgcctgg aattgcatgc ccgcaacgtg aacaaaacca ttgtggtgga





2821
ttgccatgat aaccgtatca gttttggtga agccgggcgt ttcgatcaca accaattttt





2881
cctgaacgct gaggggcaaa aagccttgca ggatgtggtt cctcttgtgc tggaagcgtc





2941
caacagtgaa gaaggtaaaa aatggtttaa gcagatcgtt attgaagggt ttaccgacac





3001
cgacggttcg tacttataca acctacatct ctccctgcaa cgttctgagt gggtaatgtg





3061
tagtctgctc gatagccgca gccctctgca aaaaaatatc tccgcagaac agcagctcca





3121
aatccgtaaa cttttcctcg cgggtggtgt ctccttcaat aatgccaagg aaagcaagga





3181
agccagccgc cgcgtcgagt tgcgcatgca gttcttcggg cttaaagata aacgtgataa





3241
ggccgatgag gtggatttcc cccccgtcgt caataaagaa gtttgccagt tggtaatgcc





3301
cctatgacgc ctgcactgaa ttctctttct caacgcattg cagcgaggct ctcttccagc





3361
caacgggatg accattatct gcataatgat ttccacgcgc tggcctcagc tgctctcgac





3421
atggaaaagc ggtttgataa ggcagaaaaa atccctttac cgccacaaaa aatgcgactg





3481
gcagctctgc gtcgccttcg ccttgcacaa gaactcacgg agcgagagtg gcggatggtg





3541
ttttatggtc tcgccgataa tgatccgtca tatcctgacc agccagtact gctggaggat





3601
gatacgtttt tccctgaagt aaacaatgca atcaaaaagc ggcttgaaac taaaaccctg





3661
aaacgccgag actgggccgc actctgttca agctattttg cttaccagaa cccatcacct





3721
gagacaaacc cgcactggtg cgtactgcgt ggtcatatcg ctcagggtta catggtggtg





3781
aaagcggcta tacgacgaga aaaatcgtgg atgaaaacca ttgagtttta tcacgatatt





3841
tttaccccgc aggcgggagg cgtgatctcc agacagttac ttgcgggtga gagcaattca





3901
ctctcgtcat tagaaaaaat cgcgcaaatc cctgatagca gttggttgtg gaaacgtatt





3961
ttcacggtgc ttttagcgca actggacaca ctcgacgatc cccagtttct ggacaaaatt





4021
agctggttgt taggtctggc tgcccagtgg gtacgtttcc gtgatgacat catgactgcg





4081
accttgactc gctattacca ttctatttat cgcgatcagg ctcattcagc tttgaagcag





4141
gccgcgctgg aatactggga taacccgcaa ctgaaaagcc agcagaataa atggcatcag





4201
tatgtctctg agccggtggc tgcgatggtc cggggctggc tggcaaaaca agatctgatg





4261
catttctttg aattgctgcg cggtaatggc gatgttgacc aggcacgatt gcactattgg





4321
ctacgtttcg ccaatcagat gggatttacc cgtatcgtca tggggactga tgcctggcaa





4381
gaccgtggta gtgactttgt gaaattccgc gaggagaata agggacgatt gagttactta





4441
cgaggtggac gtaactttga taacgccatg attatgcaga tcaacgatta tctgttcgtt





4501
gagttttccg ggacagggaa tgcaatgtat gcctatcgaa taggtcacgc gccatttaac





4561
cctgaatcac gcacgcttga tatcaacatt catctaaaag ataaggggcg ctgcgtgctc





4621
cgactgcccc atacaccgcg cgcagaaggg tataacaaag tccggataac cggctggatg





4681
ttgaaatacg acgacgagct gcgtcagttg ggcattcggt ggatggcaga agaagccatc





4741
aagtttgtcg ataagaaagc gtcctctccc gcctctatgt ccgacattaa aatcatcaac





4801
ccgttgcgtg atacggctat acagcatctg gttgaaggta gttcatgtat cgtcagcgat





4861
aatcgacaaa aaggtggcgt actgtccgta caactcaata ctcctgacga caccatagaa





4921
agagagttgt tacggctagg ctttgcgccc gtggctaaag aaccgcatcg ttactggatc





4981
aaataatgct gaaacgtctg ttaagtaaac tgacgggaaa ccgtcagcag atagaacatc





5041
acctaaaaaa tcagtaccag gttgaggaaa acggacttag ctttccgcta tcgctggttg





5101
atgattcgca gctttgggca ctggcatcct ggctagaaca actggctgaa gaagactatc





5161
tgatatcact tacagaccgg tggttgttga gttgggacgc actgtatcgc ctgctggagg





5221
atgaggaaca tgccagcagc ctgcctctta tcggtgtacc tgacgtactg cctttacgcg





5281
caagcctgag ttcacgagga gcattaagcg atagcgattt tcgcgtctgg attgctgaat





5341
gggctacgct tccagcccgc aagccgatcc gtttcagtcg taccggtgcc attttaaccc





5401
atgaaaatca gcaatacctg ttatcgcgtg aaaactgggc actcttacag gcaacagaac





5461
aactcagtgc acagaaaaat cagactcctg gtgaaaccac taaccagttg ggatgggccg





5521
ctatccgcaa atgtgcgaag caagcagccg caaaatttga tgattattta gaaaaaacgc





5581
atgtcgtcaa accaacttca ttgtcattac gtctgcgtaa agcaacggtt gccgatactg





5641
ctgttatcga aattgagccc catttcgagg accagcctgc taactggcta ggcagttttg





5701
acaaaaactc gcaggttcac gatagctacc gcatccctgg agagaatggc gaactcagcc





5761
atgtcattat ccctcccgaa gtgaaagaag tcctgaattc aatacactcg attccaagcc





5821
gtcgagtggc cggaagcgaa gcgctttcct ttgttcgcaa tccttatacc ttcctgggtg





5881
aagatgccgc cagtgttatt gcccctgaag aacatgaaca ggcactgttt gatgccagga





5941
ttttctttca tcatttcagg ttgataccgc aactgaatgc ggaaaataag atcgcagaag





6001
ttacgctggt acttgagcct gtttcacctg ttccccagcc agaaatcact tttgggttct





6061
cagccccccg ggagctggat aaattcatac agcaactcgg tattagcgtc gctgcacaga





6121
tgcctgccgg ttcatggcaa ggttacgagc tggaattaag tcagttcact gaacagcagt





6181
ggcacgattg ccaggcactt ctaactcgct ggcagcaaga aatagaagga aaagaattta





6241
gcgatgtgct ggatattgcg aagtatggcg atcgcgtgat tggcattggt gaatttgaaa





6301
aaatctcctc tccctggctg accaaagcgc agagtgaaaa ctggcttcca gatgacatcg





6361
atttctccgc gttttcagtc gaaacactgt ctggctggca acctgaaaac cttcaccatt





6421
tcgatgaact gcaggagaga attactcagg cagaagctgt aggtgaaacg catatcaccg





6481
caccatggaa tgacagccaa ttaccgttgg atgctgctaa aaccttcagt aagaactggg





6541
aaaaacagca aagcactgca aatgaatctc aaggcaacgt tgcagataaa acggcccgag





6601
ccgtactcaa aattgagcag aatattgaag aaacggccta catcaaacag cgccgcaatt





6661
cactcctcaa tgcgcgtcat gccgagcctg aaattcctct gagccttaaa gagcatatcc





6721
gactcaaaga ccatcaacgt gaaggcgtag cctggctcca gcaactcttc cttcgttcac





6781
ctgaggaaac cgcaggttgc ctgctggcgg atgatatggg gcttgggaaa acgctgcaaa





6841
ttctgagctt cctggtatgg ttcattgaaa aattcccgca agaaccgcca agtctcattg





6901
ttgctcctgt ctctctttta gataactggg aacgtgaact ggacaatttc ttctataccg





6961
caggaatacc ggtattgaaa ttgtatggcg agaccattaa agcggtgaaa tatcccaaac





7021
aggctatccc tgctcatctg caatctcagg ggatcaaaaa cctgcttaaa cctggctggc





7081
agggtgaggc gaaaatcatc ctgacaacct acgaaacgct tcgcgaccag gagttttctc





7141
tggcacgcca gccgtggtcc attatggtgt gcgacgaggc acaaaaaata aaaaacccag





7201
ctgcgttaat cacacatgcg gccaacgcgg tacaagccag gtttaaagtg gcatgtacag





7261
gaacacctgt cgaaaacaca cttgtcgacc tgtggagctt atttgatttt gcccagccag





7321
gattgttagg ggcactaaat gaatttggta aacactatgt tcgccccatc gagaacgaag





7381
atggccgcga tacggaacgg ttggaaagcc tgcgagcgct gatagaacct cagactttac





7441
gccgaaccaa agaagaggtt gcgcgtgatt tacctcagaa aattgaagtg gaaagctgca





7501
agcaattgac gttgtctggc gtgcaaaaac agctctacct ttcgtccgtt gcaaattggc





7561
aacaacagca agcactgagc gaagggatgc agcaggccgg aaccggtatg ttaggtttgt





7621
tacaccgact gaaactcatc tgtgcacacc ctgcagtagt taatccagaa ccacgttttc





7681
gtgataactc acccaagctt aactggctgc tgaaaatact cgcagaacta aaacacacca





7741
cgaaagataa ggtcattatt tttacggagc ttcgagattt acagcgcgaa cttcaacatg





7801
cgatccacca aaagtttggt ttccgccctg tcattatcaa tggtgatacc agcactaaaa





7861
gtcaaagtca aaacagccgc cagcgcctga ttgatgattt tcaggctcag cctgggtttg





7921
gggtgattat tctctctacg gttgccgtcg gattcggcgt taacgtccag aaagccaatc





7981
atgttattca tttcactcgc tgctggaacc cagccaaaga agatcaggca acagaccggg





8041
cgtaccgaat tgggcaaact aaagatgtgt atgtctatta cccgacggtg aaggacactg





8101
aaatcaccac atttgaagaa acactggatg accttctgca gcgtcgacgt gcattggcca





8161
gagatatgct ctgcgctact cccgatttga gtggtgcgga ttttgaggcc attttgaagg





8221
gggcttaacc gatacgagtg gcaataccac cagcagtcga accgattcat ttgaaacgac





8281
acgtagccgc gatggatctg tatcacctac cgacagcttg ggaaagtccc gaattacaaa





8341
tgttcagggg aataccataa cctgccggac ttattcgttt ggaacgacgt gttacgactt





8401
agtccgaggg aaacatgcca ggtaaaaacc gaatatccat cctcagcttt agcaaatacc





8461
tccccatact cgctacttca tattgagaag atattgtgtt gctcatattg ctttgagcat





8521
gctcttcagc gtttacatgt ggatcgtact accctgatga tccgatgcgt tgtttactgc





8581
ttttaacctc tatatacaaa acccccacta aatatttttc tgagactaac ggtaaatcat





8641
tatctatcat gtagttacga tagaattgca tgtatctggc acaaaataag gtttcattac





8701
gttctatctt gttaaatata aagggatcat ttcctcccaa agtcacaatc









The coding regions for each of the zorA, zorB, zorC, and zorD gene sequences within this embodiment of a Zorya Type I cassette (SEQ ID NO: 14) are as follows: nucleotides 364-2553 encode an embodiment of a ZorA polypeptide; nucleotides 2567-3307 encode an embodiment of a ZorB polypeptide; nucleotides 3304-4986 encode an embodiment of a ZorC polypeptide; and nucleotides 4986-8228 encode an embodiment of a ZorD polypeptide.


In some embodiments, a Defense System Ia comprising a ZorA polypeptide, a ZorB polypeptide, a ZorC polypeptide, and a ZorD polypeptide, is encoded by the nucleic acid sequence set forth in SEQ ID NO: 14. In some embodiments, a Defense System Ia comprising a ZorA polypeptide, a ZorB polypeptide, a ZorC polypeptide, and a ZorD polypeptide, is encoded by a nucleic acid sequence having at least 80% homology to the sequence set forth in SEQ ID NO: 14. In some embodiments, a Defense System Ia comprising a ZorA polypeptide, a ZorB polypeptide, a ZorC polypeptide, and a ZorD polypeptide, is encoded by a nucleic acid sequence having at least 85% homology, or 90% homology, or 95% homology, or 97% homology, or 98% homology, or 99% homology to the sequence set forth in SEQ ID NO: 14. In some embodiments, a Defense System Ia comprising a ZorA polypeptide, a ZorB polypeptide, a ZorC polypeptide, and a ZorD polypeptide, is encoded by a nucleic acid sequence having at least 80% identity to the sequence set forth in SEQ ID NO: 14. In some embodiments, a Defense System Ia comprising a ZorA polypeptide, a ZorB polypeptide, a ZorC polypeptide, and a ZorD polypeptide, is encoded by a nucleic acid sequence having at least 85% identity, or 90% identity, or 95% identity, or 97% identity, or 98% identity, or 99% identity to the sequence set forth in SEQ ID NO: 14.


In some embodiments, the ZORYA anti-phage defense system comprises a nucleic acid construct comprising nucleic acid sequences encoding a cassette comprising zorA, zorB, and zorE genes. In some embodiments, a construct comprising the ZORYA defense system encodes one component of the defense system, whereby multiple constructs may be used to assemble the functional defense system. In some embodiments, the components of a ZORYA Type II defense system comprise genes zorA, zorB, and zorE. In some embodiments, the components of a ZORYA Type II defense system consist of genes zorA, zorB, and zorE. In some embodiments, the components of a ZORYA Type II defense system comprise nucleic acid sequences encoding a ZorA polypeptide, a ZorB polypeptide, and a ZorE polypeptide. In some embodiments, the components of a ZORYA Type II defense system consist of nucleic acid sequences encoding a ZorA polypeptide, a ZorB polypeptide, and a ZorE polypeptide.


In some embodiments, a Zorya Type II (Defense System Ib) gene cassette comprises the nucleic acid sequence:












(SEQ ID NO: 15; construct 51 from Table 4)
















1
acctgccttc ctttgataca attcgtaaca ggttactatc atcataaaaa agctcaaccc





61
gatgaactcg ctaaaaatga gacaaatcat ttatatctcg aaaaaacttg ttacaatcat





121
gagcgctaca ccgaacttaa ccatataaat tatgtgtgtt ttgtttattt tttaaacgat





181
tacaactatc cattatttac acaggtatca aaatgttagc gcagcttttt gagcagttgt





241
ttcaatcgat agactctaca ctgatcacca atattttcat ctgggctgtt atattcgtat





301
ttttatcagc gtggtggtgt gacaaaaaaa atatacatag taagtttaga gaatatgctc





361
caaccttaat gggggcatta ggtattctgg gtactttcat tggtattatt attggtttac





421
tcaattttaa taccgaaagt attgatacca gcatccccgt attattaggt ggcctaaaaa





481
cagcattcat tacaagcatt gtaggtatgt tttttgccat tttatttaat ggaatggatg





541
ctttcttttt tgccaataaa cgaagtgcgt tagctgaaaa taaccctgaa tctgttacac





601
ctgaacatat ctatcatgaa ttaaaagagc agaaccagac tctgactaaa ttagtctcgg





661
gtattaacgg tgatagtgaa ggttctctta ttgctcaaat aaaattacta cgtactgaga





721
ttagcgattc ctcgcaggca caattagcta atcacactca tttcagtaat aagctttggg





781
aacaacttga acaatttgca gatctaatgg caaaaggtgc tacagaacaa attattgatg





841
ctttgcgaca agtcattatt gattttaatg aaaatttaac tgaacagttt ggtgaaaact





901
ttaaagctct tgatgcctct gtaaaaaaac ttgttgagtg gcagggaaat tataaaacgc





961
aaattgagca gatgtcagaa caatatcaac aaagtgtcga gtccctggtt gaaacaaaaa





1021
ctgcggttgc agggatttgg gaagaatgta aagaaattcc tctggctatg tctgaactgc





1081
gtgaagtgct tcaggtgaac caacatcaaa tcagcgaact ctcccgccat ttagaaacct





1141
ttgtcgccat ccgcgataaa gctacaaccg tattacctga aatacagaac aaaatggctg





1201
aagtgggtga actgctgaaa tccggagctg caaatgttag tgcatctctt gagcaaacca





1261
gccagcaaat acttcttaat gcagattcaa tgcgcgttgc cctggatgaa ggtaccgaag





1321
gattcagaca atcggttacc caaacacaac aagcatttgc ctcgatggcg catgatgtca





1381
gcaattcctc cgaaacccta accagcacgt taggtgaaac aattactgaa atgaaacaaa





1441
gtggtgaaga attcctgaaa tcactagagt cgcactcgaa agaattgcat agaaatatgg





1501
aacaaaatac gacgaatgtg attgatatgt tcagtaagac tggtgaaaag attaaccatc





1561
aactatccag taatgccgat aatatgtttg attcaatcca gacatcattt gataaggctg





1621
gtgcagggct gacttctcaa gtcagagaat caattgaaaa atttgctcta tccatcaacg





1681
agcagttaca tgcttttgag caagcaactg aacgtgaaat gaaccgtgaa atgcaatcat





1741
taggtaatgc tctgctttca atcagcaaag gttttgtcgg taactatgaa aaacttatta





1801
aagattacca aatagttatg gggcagttac aagcattaat ttctgctaat aaacatcgag





1861
ggtaatcgat catggataag attataggga aacaattacc taaaaaagat caagataatg





1921
aacattgggt atccatgtca gacctaatgg cagggctgat gatggttttt atgttcatat





1981
ctattgctta tatgcactac gtacgtattg aaaaagaaaa aattaaagaa gttgccgtag





2041
cctacgagaa tgctcagtta cagatttata atgctctgga tattgagttt gcaaaggatt





2101
tacaagactg ggatgcagag atcgataaac agactctgga ggttcgattt aaatcaccgg





2161
atgttttatt tggcttagga agcacagagc taaaaccaaa gtttaaactc attcttgacg





2221
acttctttcc tcgctaccta aaagttctag ataattatca ggaacatatt actgaagtcc





2281
gcattgaagg tcacacaagt actgactgga caggaacaac gaatcctgat attgcttatt





2341
ttaataatat ggcactatcg caaggtcgta cacgtgcagt attacaatac gtttatgaca





2401
taaaaaatat cgcgacacac caacaatggg ttaaaagtaa atttgccgca gtaggttatt





2461
catctgcaca tcccattctt gataaaaccg gcaaagagga ccctaatcgc tctcgtcgtg





2521
tcaccttcaa agttgtaaca aatgccgagt tgcagattag aaagattatt caggagtaag





2581
agatgaaatt atctatcgac atttcagaac ttattcaatt agggaagaaa atgttaccag





2641
aaggagtcga tttttttctg gatgaatccc ctattgactt tgatcctata gatattgagt





2701
tatccacggg taaagaagtt agtatcgaag atcttgaccc tggtagcggg cttatctctt





2761
atcatggccg ccaggttctt ttatatattc gggaccattc agggcgttat gatgcggcta





2821
tcgtagatgg cgaaaaagga aaacgttttc atattgcctg gtgcagaact cttgatgaaa





2881
tgcgccataa aaatcgattt gaaaggtatc atgcaactaa ccgcatagat ggtttattcg





2941
aaattgatga tggttcaggt cggagccagg atgttgattt acgggtatgt atgaattgcc





3001
tcgaacgact taattataaa ggaagtattg ataaacaacg aaaaagagag atttttaaat





3061
cattctcatt aaatgagttt ttttcagatt atagtacctg ttttcgtcat atgcctaagg





3121
gtatctatga caaaacaaat agtgggtatg tcgaaaactg gaaggaaata tctaaagaaa





3181
tacgagaaaa ggcaaattat gtttgtaatg attgtggcgt gaatttatca accgccaaaa





3241
acttgtgcca tgtccatcat aaaaatggca tcaaatatga taatcaccat gaaaaccttc





3301
ttgttctgtg caaggattgc catcgaaaac agcccctcca cgaaggtata ttcgttaccc





3361
aagcagagat ggctatcatt caacgtttac gttcccaaca agggttatta aaagcagaat





3421
cctggaatga aatatatgac ctgactgatc catcagtgca tggtgatatt aatatgatgc





3481
aacataaagg ctttcaacct cctgttcctg ggttagatct tcaaaactca gaacatgaaa





3541
ttattgcaac cgtagaagct gcatggccag gccttaaaat tgcagttaac cttactcccg





3601
ccgaagtcga aggatggaga atatataccg tgggtgagct ggttaaagaa atacaaaccg





3661
gagcctttac gccagcaaaa ttgtaaattc taaaactccg tgaaagttaa ggctttcacg





3721
gaagataaat aaagtttccc tgatttgtga ctcaaattac aaaagtagtt tatggcataa





3781
cttgtctgat ttttatggtg taacaggtat aaaagcatat gctatggttc gcctcatact





3841
taaaacttcc ctcatatggg tgaaggttaa agcttggtag acagaagaca gtcacaatga





3901
ataaagcaat aaattga.









The coding regions for each of the zorA, zorB, and zorE gene sequences within this embodiment of a Zorya Type II cassette (SEQ ID NO: 15) are as follows: nucleotides 213-1865 encode an embodiment of a ZorA polypeptide; nucleotides 1872-2579 encode an embodiment of a ZorB polypeptide; and nucleotides 2583-3686 encode an embodiment of a ZorE polypeptide.


In some embodiments, a Defense System Ib comprising a ZorA polypeptide, a ZorB polypeptide, and a ZorE polypeptide, is encoded by the nucleic acid sequence set forth in SEQ ID NO: 15. In some embodiments, a Defense System Ib comprising a ZorA polypeptide, a ZorB polypeptide, and a ZorE polypeptide, is encoded by a nucleic acid sequence having at least 80% homology to the sequence set forth in SEQ ID NO: 15. In some embodiments, a Defense System Ib comprising a ZorA polypeptide, a ZorB polypeptide, and a ZorE polypeptide, is encoded by a nucleic acid sequence having at least 85% homology, or 90% homology, or 95% homology, or 97% homology, or 98% homology, or 99% homology to the sequence set forth in SEQ ID NO: 15. In some embodiments, a Defense System Ib comprising a ZorA polypeptide, a ZorB polypeptide, and a ZorE polypeptide, is encoded by a nucleic acid sequence having at least 80% identity to the sequence set forth in SEQ ID NO: 15. In some embodiments, a Defense System Ib comprising a ZorA polypeptide, a ZorB polypeptide, and a ZorE polypeptide, is encoded by a nucleic acid sequence having at least 85% identity, or 90% identity, or 95% identity, or 97% identity, or 98% identity, or 99% identity to the sequence set forth in SEQ ID NO: 15.


In some embodiments, a construct comprising the ZORYA defense system encodes more than one component of the defense system but less than all of the components required for a functionally active defense system, whereby multiple constructs may be used to assemble the functional defense system. For example, in some embodiments each of ZorA, ZorB, ZorC, and ZorD may be encoded by nucleic acid sequences comprised in different constructs, wherein expression of the combination of constructs produces a functional ZORYA Type I defense system. In some embodiments each of ZorA, ZorB, and ZorE may be encoded by nucleic acid sequences comprised in different constructs, wherein expression of the combination of constructs produces a functional ZORYA Type II defense system.


In some embodiments, the components making up a functional ZORYA Type I anti-phage defense system comprise a ZorA polypeptide, a ZorB polypeptide, a ZorC polypeptide, and a ZorD polypeptide, each encoded by a zorA, a zorB, a zorC, and a zorD gene, respectively.


In some embodiments, the components making up a functional ZORYA Type II anti-phage defense system comprise a ZorA polypeptide, a ZorB polypeptide, and a ZorE polypeptide, each encoded by a zorA, a zorB, and a zorE gene, respectively.


In some embodiments, a ZORYA defense system having an anti-phage activity comprise a nucleic acid encoding a ZorA polypeptide. In some embodiments, a ZORYA defense system having an anti-phage activity comprise a nucleic acid encoding a ZorA polypeptide and a ZorB polypeptide. In some embodiments, a ZORYA defense system having an anti-phage activity comprise a nucleic acid encoding a ZorA polypeptide and a ZorC polypeptide. In some embodiments, a ZORYA defense system having an anti-phage activity comprise a nucleic acid encoding a ZorA polypeptide and a ZorD polypeptide. In some embodiments, a ZORYA defense system having an anti-phage activity comprise a nucleic acid encoding a ZorA polypeptide and a ZorE polypeptide. In some embodiments, a ZORYA defense system having an anti-phage activity comprise a nucleic acid encoding a ZorA polypeptide, a ZorB polypeptide, and a ZorC polypeptide. In some embodiments, a ZORYA defense system having an anti-phage activity comprise a nucleic acid encoding a ZorA polypeptide, a ZorB polypeptide, and a ZorD polypeptide. In some embodiments, a ZORYA defense system having an anti-phage activity comprise a nucleic acid encoding a ZorA polypeptide, a ZorC polypeptide, and a ZorD polypeptide. In some embodiments, a ZORYA defense system having an anti-phage activity comprise a nucleic acid encoding a ZorB polypeptide. In some embodiments, a ZORYA defense system having an anti-phage activity comprise a nucleic acid encoding a ZorB polypeptide and a ZorC polypeptide. In some embodiments, a ZORYA defense system having an anti-phage activity comprise a nucleic acid encoding a ZorB polypeptide and a ZorD polypeptide. In some embodiments, a ZORYA defense system having an anti-phage activity comprise a nucleic acid encoding a ZorB polypeptide and a ZorE polypeptide. In some embodiments, a ZORYA defense system having an anti-phage activity comprise a nucleic acid encoding a ZorC polypeptide. In some embodiments, a ZORYA defense system having an anti-phage activity comprise a nucleic acid encoding a ZorC polypeptide and a ZorD polypeptide. In some embodiments, a ZORYA defense system having an anti-phage activity comprise a nucleic acid encoding a ZorE polypeptide.


In some embodiments, a ZORYA defense system having an anti-phage activity comprise a nucleic acid comprising a zorA gene. In some embodiments, a ZORYA defense system having an anti-phage activity comprise a nucleic acid comprising a zorA gene and a zorB gene. In some embodiments, a ZORYA defense system having an anti-phage activity comprise a nucleic acid comprising a zorA gene and a zorC gene. In some embodiments, a ZORYA defense system having an anti-phage activity comprise a nucleic acid comprising a zorA gene and a zorD gene. In some embodiments, a ZORYA defense system having an anti-phage activity comprise a nucleic acid comprising a zorA gene and a zorE gene. In some embodiments, a ZORYA defense system having an anti-phage activity comprise a nucleic acid comprising a zorA gene, a zorB gene, and a zorC gene. In some embodiments, a ZORYA defense system having an anti-phage activity comprise a nucleic acid comprising a zorA gene, a zorB gene, and a zorD gene. In some embodiments, a ZORYA defense system having an anti-phage activity comprise a nucleic acid comprising a zorA gene, a zorC gene, and a zorD gene. In some embodiments, a ZORYA defense system having an anti-phage activity comprise a nucleic acid comprising a zorB gene. In some embodiments, a ZORYA defense system having an anti-phage activity comprise a nucleic acid comprising a zorB gene and a zorC gene. In some embodiments, a ZORYA defense system having an anti-phage activity comprise a nucleic acid comprising a zorB gene and a zorD gene. In some embodiments, a ZORYA defense system having an anti-phage activity comprise a nucleic acid comprising a zorB gene and a zorE gene. In some embodiments, a ZORYA defense system having an anti-phage activity comprise a nucleic acid comprising a zorC gene. In some embodiments, a ZORYA defense system having an anti-phage activity comprise a nucleic acid comprising a zorC gene and a zorD gene. In some embodiments, a ZORYA defense system having an anti-phage activity comprise a nucleic acid comprising a zorE gene.


In some embodiments, a ZORYA defense system having an anti-phage activity comprises a nucleic acid construct comprising nucleic acids encoding polypeptides in a set order. In one embodiment, the 5′ to 3′ order of polypeptides encoded is ZorA, ZorB, ZorC, and ZorD. In one embodiment, the 5′ to 3′ order of polypeptides encoded is ZorA, ZorB, and ZorE. In some embodiments the 5′ to 3′ order of polypeptides does not affect the anti-phage activity. In some embodiments the 5′ to 3′ order of polypeptides does affect the anti-phage activity.


In some embodiments, the 5′ to 3′ order of polypeptides is random, for example any order of ZorA, ZorB, ZorC, ZorD, and ZorD. In some embodiments, the 5′ to 3′ order of polypeptides is random, for example any order of ZorA, ZorB, and ZorE.


In some embodiments, a ZORYA defense system having an anti-phage activity comprises a nucleic acid construct comprising genes in a set order. In some embodiment, the 5′ to 3′ order of genes is zorA, zorB, zorC, and zorD (Defense System Ia). In some embodiment, the 5′ to 3′ order of genes is zorA, zorB, and zorE (Defense System Ib). In some embodiment, the 5′ to 3′ order of genes in a Defense System Ia is not zorA, zorB, zorC, and zorD. In some embodiment, the 5′ to 3′ order of genes in a Defense System Ib is not zorA, zorB, and zorE. In some embodiments the 5′ to 3′ order of genes does not affect the anti-phage activity. In some embodiments the 5′ to 3′ order of genes does affect the anti-phage activity.


In some embodiments, the 5′ to 3′ order of genes is random, for example any order of zorA, zorB, zorC, zorD, and zorD. In some embodiments, the 5′ to 3′ order of genes is random, for example any order of zorA, zorB, and zorE.


In some embodiments, the ZORYA Type I system (Defense System Ia) composition and order is as shown in FIG. 3C, FIG. 4A, and FIG. 4B. In some embodiments, the ZORYA Type II system (Defense System Ib) composition and order is as shown in FIG. 3C, FIG. 4D, and FIG. 4E.


In some embodiments, a ZORYA defense system having an anti-phage activity originates from a microbial genome (Table 8).


In some embodiments, a functional ZORYA defense system comprises a construct comprising nucleic acid sequences encoding polypeptides, wherein the nucleic acid sequence encoding each polypeptide may originate from a different microbial species. In some embodiments, a Zorya defense system (Defense system Ia; Defense system Ib) comprises a non-naturally occurring combination of polypeptide components. In some embodiments, a Zorya defense system (Defense system Ia; Defense system Ib) comprises a combination of at least two polypeptides that do not naturally occur together. In some embodiments, a Zorya defense system (Defense system Ia; Defense system Ib) comprises a combination of at least three polypeptides that do not naturally occur together. In some embodiments, a Zorya defense system (Defense system Ia) comprises a combination of four polypeptides that do not naturally occur together. In some embodiments, a Zorya defense system (Defense system Ia; Defense system Ib) comprises a non-naturally occurring combination of polypeptide components. In some embodiments, a functional Zorya defense system (Defense system Ia; Defense system Ib) comprises a combination of at least two polypeptides that do not naturally occur together. In some embodiments, a functional Zorya defense system (Defense system Ia; Defense system Ib) comprises a combination of at least three polypeptides that do not naturally occur together. In some embodiments, a functional Zorya defense system (Defense system Ia) comprises a combination of four polypeptides that do not naturally occur together.


A skilled artisan would appreciate that the term “non-naturally occurring” may encompass in one embodiment, polypeptide that do not naturally occur together in nature. For example, polypeptide components that do not naturally occur together, either because they are from the same defense system found in a different strain of bacteria or because they comprise polypeptide components from different defense systems. In some embodiments, polypeptide components that do not naturally occur together, either because they are from the same defense system found in a different strain of a microorganism, or because they comprise polypeptide components from different defense systems. In some embodiments, the term “non-naturally occurring” may encompass a defense system or a functional defense system that is not found within a particular micro-organism in nature. In some embodiments, the term “non-naturally occurring” may encompass a defense system or a functional defense system that is not found within a particular bacteria in nature. In some embodiments, the term “non-naturally occurring” may encompass a combination of defense systems disclosed herein or a functional defense system disclosed herein that are not found within a particular micro-organism in nature. In some embodiments, the term “non-naturally occurring” may encompass a combination of defense systems disclosed herein or a functional defense systems disclosed herein that are not found within a particular bacteria in nature.


In some embodiments, introducing a defense system disclosed herein, or any combination of defense systems, into a bacterial strain that naturally lacks the defense system or system may be advantageous for the bacteria. In some embodiments, introducing a defense system disclosed herein, or any combination of defense systems, into a bacterial strain that naturally lacks the defense system or system may be biotechnologically useful in maintaining healthy bacteria used for example but not limited to, the food industry.


In some embodiments, a functional ZORYA defense system comprises a construct comprising nucleic acid sequences encoding polypeptides, wherein the nucleic acid sequence encoding each polypeptide may originate from a different bacterial species. For example, the source of the nucleic acid sequence encoding a ZorA polypeptide may be one bacterial species from Table 8, the source of the nucleic acid sequence encoding a ZorB polypeptide may be a different bacterial species from Table 8, the source of the nucleic acid sequence encoding a ZorC polypeptide may be yet a different bacterial species from Table 8, and the source of the nucleic acid sequence encoding a ZorD polypeptide may be still a different bacterial species from Table 8. Similarly, the source of the nucleic acid sequence encoding a ZorA polypeptide may be one bacterial species from Table 8, the source of the nucleic acid sequence encoding a ZorB polypeptide may be a different bacterial species from Table 8, and the source of the nucleic acid sequence encoding a ZorE polypeptide may be still a different bacterial species from Table 8.


In some embodiments, the source of the nucleic acid encoding a ZorA polypeptide, a ZorB polypeptide, a ZorC polypeptide, and a ZorD polypeptide is the same. In some embodiments, the source of the nucleic acid encoding a ZorA polypeptide, a ZorB polypeptide, a ZorC polypeptide, and a ZorD polypeptide is the not the same. In some embodiments, the source of some of the components is the same, while the source of other components is not the same. In some embodiments, the source of the nucleic acid sequence of any of the components of a ZORYA Type I defense system comprises any of the species listed in Table 8.


In some embodiments, the source of the nucleic acid encoding a ZorA polypeptide, a ZorB polypeptide, and a ZorE polypeptide is the same. In some embodiments, the source of the nucleic acid encoding a ZorA polypeptide, a ZorB polypeptide, and a ZorE polypeptide is the not the same. In some embodiments, the source of some of the components is the same, while the source of other components is not the same. In some embodiments, the source of the nucleic acid sequence of any of the components of a ZORYA Type II defense system comprises any of the species listed in Table 8.


In some embodiments, a ZORYA defense system having an anti-phage activity comprises a nucleic acid construct comprising non-coding regions between the nucleic acid sequences encoding the polypeptides. In some embodiments, the non-coding regions between the nucleic acid sequences comprises nucleic acid sequence not naturally occurring in the microbial species of origin. In some embodiments, the non-coding regions between the nucleic acid sequences comprises nucleic acid sequence is the naturally occurring in the microbial species of origin.


In some embodiments, a ZORYA system disclosed herein comprises a multi-gene phage resistance system broadly distributed in microbial genomes, for example but not limited to bacteria. A skilled artisan would appreciate that the ZORYA system is not present in the majority of bacterial species.


According to some embodiments, the ZORYA system components are located in a gene cluster in a microbial cell genome. According to some embodiments, the ZORYA system components are located in close proximity (e.g. positioned within 20 genes, 10 genes, 5 genes or less one from the other) in a genome of a prokaryotic cell. According to some embodiments the prokaryotic cell expresses an endogenous ZORYA defense system. According to some embodiments, the prokaryotic cell expresses an endogenous functional ZORYA defense system. According to some embodiments, the species of prokaryotic cell is selected from the group consisting of the species listed in Table 8. According to some embodiments, a prokaryotic cell expresses a non-endogenous ZORYA defense system. According to some embodiments, a prokaryotic cell expresses a non-endogenous functional ZORYA defense system. According to some embodiments, the species of prokaryotic cell expressing a non-endogenous functional ZORYA defense system is selected from the group consisting of the species listed in Table 8.


A skilled artisan would appreciate that the term “endogenous” may encompass the expression of a native gene in its natural location and with its natural expression level in the genome of an organism, for example a prokaryote. In some embodiments, an endogenous anti-nucleic acid defense system is found in bacterial or in archaeal cells. In some embodiments, an endogenous anti-nucleic acid defense system is found in bacterial cells. In some embodiments, an endogenous anti-nucleic acid defense system is found in archaeal cells.


In some embodiments, a ZORYA Type I defense system (Defense System Ia) components comprise ZorA, ZorB, ZorC and ZorD polypeptides. In some embodiments, a ZORYA Type I defense system components comprise functional portions of ZorA, ZorB, ZorC and ZorD polypeptides. In some embodiments, the ZORYA Type I defense system components are encoded by zorA, zorB, zorC and zorD genes.


In some embodiments, a ZORYA Type II defense system (Defense System Ib) components comprise ZorA, ZorB, and ZorE polypeptides. In some embodiments, a ZORYA Type II defense system components comprise functional portions of ZorA, ZorB, and ZorE polypeptides. In some embodiments, the ZORYA Type II defense system components are encoded by zorA, zorB, and zorE genes.


Non-limiting embodiments of endogenous ZORYA systems and the respective location of their components are provided in Table 8 herein.


In some embodiments, the components of a ZORYA system may be identified by the presence of similar domains present within each component. In some embodiments, domains comprise pfam domains and or clusters of orthologous groups (COG) domains.


A skilled artisan would appreciate that the term “pfam” may encompass a large collection of protein domains and protein families maintained by the pfam consortium and available at several sponsored world wide web sites, including for example: pfam.sanger.ac.uk/ (Welcome Trust, Sanger Institute); pfam.sbc.su.se/ (Stockholm Bioinformatics Center); pfam(dot)janelia(dot)org/ (Janelia Farm, Howard Hughes Medical Institute); pfam(dot)jouy(dot)inra(dot)fr/ (Institut national de la Recherche Agronomique); and pfam.ccbb.re.kr/. pfam domains and families are identified using multiple sequence alignments and hidden Markov models (HMMs) (see e.g. R. D. Finnet et al. nucleic Acids Research Database (2010) Issue 38: D211-222). By accessing the pfam database, for example, using any of the above-reference websites, protein sequences can be queried against the hidden Markov models (HMMs) using HMMER homology search software (e.g., HMMER3, hmmer(dot)janelia(dot)org/).


A skilled artisan would appreciate that the term “COG (clusters of orthologous groups)” may encompass a large collection of protein families classified according to their homologous relationships available at e.g. the NCBI COG website (http://www(dot)ncbi(dot)nlm(dot)nih(dot)gov/COG). Each COG consists of a group of proteins found to be orthologous across at least three lineages and likely corresponds to an ancient conserved domain [see e.g. Tatusov et al. Science 1997 Oct. 24; 278(5338):631-7; and Tatusov et al. nucleic Acids Res. 2000 Jan. 1; 28(1): 33-36].


In some embodiments, a Defense System Ia comprises a membrane associated complex. In some embodiments, a Defense System Ib comprises a membrane associated complex.


In some embodiments, the term “ZorA” refers to the polynucleotide or expression product e.g., the polypeptide encoded by the zorA gene. In some embodiments, the term “ZorA” refers to a ZorA polypeptide. In some embodiments, the zorA gene encodes a polypeptide comprising a pfam01618 domain. In some embodiments, the zorA gene encodes a polypeptide comprising a COG0840 domain. In some embodiments, the zorA gene encodes a polypeptide comprising a pfam01618 domain and a COG0840 domain. In some embodiments, the ZorA polypeptide comprises a pfam01618 domain. In some embodiments, the ZorA polypeptide comprises a COG0840 domain. In some embodiments, the ZorA polypeptide comprises a pfam01618 domain and a COG0840 domain.


In some embodiments, the zorA gene encodes a polypeptide member of the MotA/TolQ/EXaB proton channel family. In some embodiments, the zorA gene encodes a polypeptide comprising 3 transmembrane helices.


In some embodiments, the ZorA polypeptide comprises a member of the MotA/TolQ/EXaB proton channel family. In some embodiments, the ZorA polypeptide comprises a member of a family comprising 3 transmembrane helices.


In some embodiments, ZorA polypeptide is encoded by a gene positioned within 5-60 genes of a gene encoding a ZorB, ZorC, ZorD, and or a ZorE polypeptide in a genome of a prokaryotic cell. In some embodiments, ZorA polypeptide is encoded by a gene positioned within 5 genes upstream (5′) or downstream (3′) to a gene encoding a ZorB, ZorC, ZorD, and/or a ZorE polypeptide in a genome of a prokaryotic cell. In some embodiments, ZorA polypeptide is encoded by a gene positioned within 5 genes upstream (5′) and downstream (3′) to a gene encoding a ZorB, ZorC, ZorD, and or ZorE polypeptide, or any combination thereof, in a genome of a prokaryotic cell.


In some embodiments, ZorA and ZorB are encoded by genes positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, ZorA and ZorB are encoded by genes positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, ZorA, ZorB, and ZorC are encoded by genes positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, ZorA, ZorB, and ZorC are encoded by genes positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, ZorA, ZorB, and ZorE are encoded by genes positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, ZorA, ZorB, and ZorE are encoded by genes positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, ZorA, ZorB, ZorC, and ZorD are encoded by genes positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, ZorA, ZorB, ZorC, and ZorD are encoded by genes positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell.


In some embodiments, zorA and zorB genes are positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, zorA, and zorB, genes are positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, zorA, zorB, and zorC genes are positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, zorA, zorB, and zorC genes are positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, zorA, zorB, and zorE genes are positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, zorA, zorB, and zorE genes are positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, zorA, zorB, zorC, and zorD genes are positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, zorA, zorB, zorC, and zorD genes are positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell.


In some embodiments, a ZorA polypeptide is about 550 amino acids long (Median gene size).


In some embodiments, the ZorA polypeptide comprises the amino acid sequence having at least 80% homology to a sequence selected from the group consisting the polypeptides referenced in Table 8, rows 2-1830 columns J and K. In some embodiments, the ZorA polypeptide comprises the amino acid sequence having at least 80% homology within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 8, rows 2-1830 columns J and K.


A skilled artisan would appreciate that the terms “similar domain regions” encompasses but is not limited to pfam domains, COG domains, helices, membrane binding domains, transmembrane domains, structural domains, and enzyme active site domains.


In some embodiments, the ZorA polypeptide comprises a homolog of a polypeptide having the amino acid sequences set forth in the polypeptides referenced in Table 8, rows 2-1830 columns J and K. In some embodiments, a homolog of a ZorA polypeptide comprises a member of the MotA/TolQ/EXaB proton channel family. In some embodiments, a homolog of ZorA polypeptide comprises 3 transmembrane helices. In some embodiments, the ZorA polypeptide comprises the amino acid sequence having at least 80% identity to a sequence selected from the group consisting of the polypeptides referenced in Table 8, rows 2-1830 columns J and K.


A skilled artisan would appreciate that homology encompasses similarity of sequence attributed to descent from a common ancestor. Homologous biological components (genes, proteins, structures) are called homologs. The extent to which nucleotide or protein sequences are related. The similarity between two sequences (DNA, RNA, or amino acid) can be expressed as percent sequence identity and/or percent positive substitutions.


A skilled artisan would appreciate that the term “homolog” encompasses a gene or a polypeptide (a protein) that is related to a second gene or polypeptide (protein), respectively, by descent from a common ancestral DNA or polypeptide (protein) sequence, respectively. Thus, a homolog of a gene, in some embodiments, comprises a similar nucleotide sequence to the gene. In some embodiments, a gene homolog encodes an identical polypeptide as is encoded by the gene. In some embodiments, a gene homolog encodes a polypeptide with the same functional properties as is encoded by the gene. In some embodiments, a gene homolog encodes a polypeptide that comprises a similar amino acid sequence as the polypeptide encoded by the gene. In one embodiment, the polypeptide homolog comprises a similar amino acid sequence as the polypeptide. In some embodiments, the polypeptide homolog comprises the same functional properties as the polypeptide. In some embodiments, the polypeptide homolog comprises similar functional properties as the polypeptide. In some embodiments, the polypeptide homolog comprises a same domain(s) as the polypeptide. In some embodiments, the polypeptide homolog comprises a similar domain(s) as the polypeptide.


A skilled artisan would appreciate that percent homology or percent identity may be determined, for example but no limited to, using BlastP software of the National Center of Biotechnology Information (NCBI) using default parameters. The homolog may also refer to an ortholog, a deletion, insertion, or substitution variant, including an amino acid substitution. In some embodiments, sequence identity or homology can be determined using any protein or nucleic acid sequence alignment algorithm such as Blast, ClustalW, MUSCLE, and HHpred.


In some embodiments, gene homology and/or polypeptide homology can be based on shared motifs, for example but not limited to pfam domains, COG domains, DUF domains, transmembrane domains, and nuclease domains. In some embodiments, similarities of shared motifs are combined with the conserved size of the gene or the expression product in the different subtypes and the location of the gene in the gene cluster.


In some embodiments, the ZorA polypeptide comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polypeptides referenced in Table 8, rows 2-1830 columns J and K. In some embodiments, the ZorA polypeptide comprises the amino acid sequence having at least 80%, at least 85%, at least 95% homology within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 8, rows 2-1830 columns J and K. In some embodiments, the ZorA polypeptide comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polypeptides referenced in Table 8, rows 2-1830 columns J and K. In some embodiments, the ZorA polypeptide comprises the amino acid sequence having at least 80%, at least 85%, at least 95% identity within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 8, rows 2-1830 columns J and K. In some embodiments, the ZorA polypeptide comprises an amino acid sequence selected from the group consisting of the polypeptides referenced in Table 8, rows 2-1830 columns J and K.


In some embodiments, the ZorA polypeptide comprises an amino acid sequence encoded by a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polynucleotides referenced in Table 8, rows 2-1830 columns J and L. In some embodiments, the ZorA polypeptide comprises the amino acid sequence encoded by a nucleic acid sequence having at least 80%, at least 85%, at least 95% homology within similar domain regions within a sequence selected from the group consisting of the polynucleotides referenced in Table 8, rows 2-1830 columns J and L. In some embodiments, the ZorA polypeptide comprises an amino acid sequence encoded by a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polynucleotides referenced in Table 8, rows 2-1830 columns J and L. In some embodiments, the ZorA polypeptide comprises the amino acid sequence encoded by a nucleic acid sequence having at least 80%, at least 85%, at least 95% identity within similar domain regions within a sequence selected from the group consisting of the polynucleotides referenced in Table 8, rows 2-1830 columns J and L. In some embodiments, the ZorA polypeptide comprises an amino acid sequence encoded from a nucleic acid sequence selected from the group consisting of the polynucleotides referenced in Table 8, rows 2-1830 columns J and L.


In some embodiments, the nucleic acid sequence of a zorA gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polynucleotides referenced in Table 8, rows 2-1830 columns J and L. In some embodiments, the nucleic acid sequence of a zorA gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polynucleotides referenced in Table 8, rows 2-1830 columns J and L. In some embodiments, the nucleic acid sequence of a zorA gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology within the nucleotide sequence encoding similar domain regions as a sequence selected from the group consisting of the polynucleotides referenced in Table 8, rows 2-1830 columns J and L. In some embodiments, the nucleic acid sequence of a zorA gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity within the nucleotide sequence encoding similar domain regions as a sequence selected from the group consisting of the polynucleotides referenced in Table 8, rows 2-1830 columns J and L. In some embodiments, the nucleic acid sequence of a zorA gene comprises a nucleic acid sequence selected from the group consisting of the polynucleotides referenced in Table 8, rows 2-1830 columns J and L.


As used herein, the term “ZorB” refers to the polynucleotide or expression product e.g., polypeptide encoded by the zorB gene. In some embodiments, the term “ZorB” refers to a ZorB polypeptide. In some embodiments, the product of the zorB gene comprises a pfam13677 domain. In some embodiments, the product of the zorB gene comprises a pfam00691 domain. In some embodiments, the product of the zorB gene comprises a pfam13677 domain and a pfam00691 domain. In some embodiments, the zorB gene encodes a member of MotB proton channel family. In some embodiments, the zorB gene encodes a polypeptide comprising a transmembrane helix.


In some embodiments, ZorB polypeptide is encoded by a gene positioned within 5-60 genes of a gene encoding a ZorA, ZorC, ZorD, and or a ZorE polypeptide in a genome of a prokaryotic cell. In some embodiments, ZorB polypeptide is encoded by a gene positioned within 5 genes upstream (5′) or downstream (3′) to a gene encoding a ZorA, ZorC, ZorD, and/or a ZorE polypeptide in a genome of a prokaryotic cell.


In some embodiments, ZorA and ZorB are encoded by genes positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments ZorA and ZorB are encoded by genes positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, ZorB and ZorC are encoded by genes positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments ZorB and ZorC are encoded by genes positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, ZorB and ZorE are encoded by genes positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments ZorB and ZorE are encoded by genes positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, ZorB, ZorC, and ZorD are encoded by genes positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, ZorB, ZorC, and ZorD are encoded by genes positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell.


In some embodiments, ZorB polypeptide is encoded by a gene positioned within 5 genes upstream or downstream to a gene encoding zorA, zorC, and zorD, in a genome of a prokaryotic cell. In some embodiments, ZorB polypeptide is encoded by a gene positioned within 5 genes upstream or downstream to a gene encoding zorA and zorE, in a genome of a prokaryotic cell.


In some embodiments, a ZorB polypeptide is about 217 amino acids long (median gene size).


In some embodiments, the ZorB polypeptide comprises an amino acid sequence having at least 80% homology to a sequence selected from the group consisting of the polypeptides referenced in Table 8, rows 2-1830 columns N and O.


In some embodiments, the ZorB polypeptide comprises the amino acid sequence having at least 80% homology within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 8, rows 2-1830 columns N and O. In some embodiments, a homology of the ZorB polypeptide comprises a MotB proton channel family member. In some embodiments, the ZorB polypeptide comprises an amino acid sequence having at least 80% identity to a sequence selected from the group consisting of the polypeptides referenced in Table 8, rows 2-1830 columns N and O.


In some embodiments, the ZorB polypeptide comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polypeptides referenced in Table 8, rows 2-1830 columns N and O. In some embodiments, the ZorB polypeptide comprises the amino acid sequence having at least 80%, at least 85%, at least 95% homology within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 8, rows 2-1830 columns N and O. In some embodiments, the ZorB polypeptide comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polypeptides referenced in Table 8, rows 2-1830 columns N and O. In some embodiments, the ZorB polypeptide comprises the amino acid sequence having at least 80%, at least 85%, at least 95% identity within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 8, rows 2-1830 columns N and O. In some embodiments, the ZorB polypeptide comprises an amino acid sequence selected from the group consisting of the polypeptides referenced in Table 8, rows 2-1830 columns N and O.


In some embodiments, the ZorB polypeptide comprises an amino acid sequence encoded from a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polynucleotides referenced in Table 8, rows 2-1830 columns N and P. In some embodiments, the ZorB polypeptide comprises the amino acid sequence encoded by a nucleic acid sequence having at least 80%, at least 85%, at least 95% homology within similar domain regions within a sequence selected from the group consisting of the polynucleotides referenced in Table 8, rows 2-1830 columns N and P. In some embodiments, the ZorB polypeptide comprises an amino acid sequence encoded from a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polynucleotides referenced in Table 8, rows 2-1830 columns N and P. In some embodiments, the ZorB polypeptide comprises the amino acid sequence encoded by a nucleic acid sequence having at least 80%, at least 85%, at least 95% identity within similar domain regions within a sequence selected from the group consisting of the polynucleotides referenced in Table 8, rows 2-1830 columns N and P. In some embodiments, the ZorB polypeptide comprises an amino acid sequence encoded from a nucleic acid sequence selected from the group consisting of the polynucleotides referenced in Table 8, rows 2-1830 columns N and P.


In some embodiments, the nucleic acid sequence of a zorB gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polynucleotides referenced in Table 8, rows 2-1830 columns N and P. In some embodiments, the nucleic acid sequence of a zorB gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polynucleotides referenced in Table 8, rows 2-1830 columns N and P. In some embodiments, the nucleic acid sequence of a zorB gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology within the nucleotide sequence encoding similar domain regions as a sequence selected from the group consisting of the polynucleotides referenced in Table 8, rows 2-1830 columns N and P. In some embodiments, the nucleic acid sequence of a zorB gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity within the nucleotide sequence encoding similar domain regions as a sequence selected from the group consisting of the polynucleotides referenced in Table 8, rows 2-1830 columns N and P. In some embodiments, the nucleic acid sequence of a zorB gene comprises a nucleic acid sequence selected from the group consisting of the polynucleotides referenced in Table 8, rows 2-1830 columns N and P.


As used herein, the term “ZorC” refers to the polynucleotide or expression product e.g., polypeptide encoded by the zorC gene. In some embodiments, the term “ZorC” refers to a ZorC polypeptide. In some embodiments, the product of a zorC gene comprises a pfam15611 domain. In some embodiments, the product of a zorC gene comprises a EH signature domain.


In some embodiments, ZorC polypeptide is encoded by a gene positioned within 5-60 genes of a gene encoding ZorA, ZorB and/or ZorD in a genome of a prokaryotic cell. In some embodiments, ZorC polypeptide is encoded by a gene positioned within 5 genes upstream (5′) or downstream (3′) to a gene encoding ZorA, ZorB and/or ZorD in a genome of a prokaryotic cell. In some embodiments, ZorC polypeptide is encoded by a gene positioned within 5 genes upstream and downstream to a gene encoding ZorA, ZorB and ZorD in a genome of a prokaryotic cell.


In some embodiments, ZorC and ZorD are encoded by genes positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, ZorC and ZorD are encoded by genes positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell.


In some embodiments, zorC and zorD genes are positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, zorC and zorD genes are positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell.


In some embodiments, a ZorC polypeptide is about 470 amino acids long (median gene size).


In some embodiments, the ZorC polypeptide comprises an amino acid sequence having at least 80% homology to a sequence selected from the group consisting of the polypeptides referenced in Table 8, rows 2-1174 columns R and S. In some embodiments, the ZorC polypeptide comprises the amino acid sequence having at least 80% homology within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 8, rows 2-1174 columns R and S. In some embodiments, the ZorC polypeptide comprises an amino acid sequence having at least 80% identity to a sequence selected from the group consisting of the polypeptides referenced in Table 8, rows 2-1174 columns R and S


In some embodiments, the ZorC polypeptide comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polypeptides referenced in Table 8, rows 2-1174 columns R and S. In some embodiments, the ZorC polypeptide comprises the amino acid sequence having at least 80%, at least 85%, at least 95% homology within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 8, rows 2-1174 columns R and S. In some embodiments, a ZorC homolog comprises an EH signature domain. In some embodiments, the ZorC polypeptide comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polypeptides referenced in Table 8, rows 2-1174 columns R and S. In some embodiments, the ZorC polypeptide comprises the amino acid sequence having at least 80%, at least 85%, at least 95% identity within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 8, rows 2-1174 column N. In some embodiments, the ZorC polypeptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: the polypeptides referenced in Table 8, rows 2-1174 columns R and S.


In some embodiments, the ZorC polypeptide comprises an amino acid sequence encoded from a nucleic acid sequence having at least 80%, at least 85%, at least 90%, at least 95% homology to a sequence selected from the group consisting of the polynucleotides referenced in Table 8, rows 2-1174 columns R and T. In some embodiments, the ZorC polypeptide comprises the amino acid sequence encoded by a nucleic acid sequence having at least 80%, at least 85%, at least 95% homology within similar domain regions within a sequence selected from the group consisting of the polynucleotides referenced in Table 8, rows 2-1174 columns R and T. In some embodiments, the ZorC polypeptide comprises an amino acid sequence encoded from a nucleic acid sequence having at least 80%, at least 85%, at least 90%, at least 95% identity to a sequence selected from the group consisting of the polynucleotides referenced in Table 8, rows 2-1174 columns R and T. In some embodiments, the ZorC polypeptide comprises the amino acid sequence encoded by a nucleic acid sequence having at least 80%, at least 85%, at least 95% identity within similar domain regions within a sequence selected from the group consisting of the polynucleotides referenced in Table 8, rows 2-1174 columns R and T. In some embodiments, the ZorC polypeptide comprises an amino acid sequence encoded from a nucleic acid sequence selected from the group consisting of the polynucleotides referenced in Table 8, rows 2-1174 columns R and T.


In some embodiments, the zorC gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, at least 95% homology to a sequence selected from the group consisting of the polynucleotides referenced in Table 8, rows 2-1174 columns R and T. In some embodiments, the zorC gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, at least 95% identity to a sequence selected from the group consisting of the polynucleotides referenced in Table 8, rows 2-1174 columns R and T. In some embodiments, the nucleic acid sequence of a zorA gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polynucleotides referenced in Table 8, rows 2-1174 columns R and T. In some embodiments, the nucleic acid sequence of a zorA gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polynucleotides referenced in Table 8, rows 2-1174 columns R and T. In some embodiments, the nucleic acid sequence of a zorC gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology within the nucleotide sequence encoding similar domain regions as a sequence selected from the group consisting of the polynucleotides referenced in Table 8, rows 2-1174 columns R and T. In some embodiments, the nucleic acid sequence of a zorC gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity within the nucleotide sequence encoding similar domain regions as a sequence selected from the group consisting of the polynucleotides referenced in Table 8, rows 2-1174 columns R and T. In some embodiments, the zorC gene comprises a nucleic acid sequence selected from the group consisting of the polynucleotides referenced in Table 8, rows 2-1174 columns R and T.


As used herein, the term “ZorD” refers to the polynucleotide or expression product e.g., polypeptide encoded by the zorD gene. In some embodiments, the term “ZorD” refers to a ZorD polypeptide. In some embodiments, the product of the zorD gene comprises a pfam00176 domain. In some embodiments, the product of the zorD gene comprises a pfam00271 domain. In some embodiments, the product of the zorD gene contains a pfam00176 domain and a pfam00271 domain. In some embodiments, the product of the zorD gene comprises, a COG0553 domain. In some embodiments, the product of the zorD gene further contains a pfam04471 domain.


In some embodiments, a ZorD polypeptide comprises a pfam00176 domain. In some embodiments, a ZorD polypeptide comprises a pfam00271 domain. In some embodiments, a ZorD polypeptide comprises a pfam00176 domain and a pfam00271 domain. In some embodiments, a ZorD polypeptide comprises, a COG0553 domain. In some embodiments, a ZorD polypeptide comprises a pfam04471 domain. In some embodiments, a ZorD polypeptide comprises, a pfam00176 domain, a pfam00271 domain, a COG0553 domain, or a pfam04471 domain or any combination thereof. In some embodiments, a ZorD polypeptide comprises, a pfam00176 domain, a pfam00271 domain, a COG0553 domain, and a pfam04471 domain.


In some embodiments, a ZorD polypeptide is encoded by a gene positioned within 5-60 genes of a gene encoding ZorA, ZorB and/or ZorC in a genome of a prokaryotic cell. In some embodiments, a ZorD polypeptide is encoded by a gene positioned within 5 genes upstream (5′) or downstream (3′) to a gene encoding ZorA, ZorB and/or ZorC in a genome of a prokaryotic cell. In some embodiments, ZorD polypeptide is encoded by a gene positioned within 5 genes upstream or downstream to a gene encoding ZorA, ZorB and ZorC in a genome of a prokaryotic cell.


In some embodiments, a ZorD polypeptide is about 1200 amino acids long (median gene size).


In some embodiments, the ZorD polypeptide comprises an amino acid sequence having at least 80% homology to a sequence selected from the group consisting of the polypeptides referenced in Table 8, rows 2-1174 columns V and W. In some embodiments, the ZorD polypeptide comprises the amino acid sequence having at least 80% homology within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 8, rows 2-1174 columns V and W. In some embodiments, a ZorD polypeptide homologue comprises a SW12/SNF2 helicase. In some embodiments, a ZorD polypeptide homologue comprises a Mrr-like nuclease domain. In some embodiments, the ZorD polypeptide comprises an amino acid sequence having at least 80% identity to a sequence selected from the group consisting of the polypeptides referenced in Table 8, rows 2-1174 columns V and W. In some embodiments, the ZorD polypeptide comprises the amino acid sequence having at least 80% identity within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 8, rows 2-1174 columns V and W.


In some embodiments, the ZorD polypeptide comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95% homology to a sequence selected from the group consisting of the polypeptides referenced in Table 8, rows 2-1174 columns V and W. In some embodiments, the ZorD polypeptide comprises the amino acid sequence having at least 80%, 85%, 90%, 95% homology within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 8, rows 2-1174 columns V and W.


In some embodiments, the ZorD polypeptide comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95% identity to a sequence selected from the group consisting of the polypeptides referenced in Table 8, rows 2-1174 columns V and W. In some embodiments, the ZorD polypeptide comprises the amino acid sequence having at least 80%, 85%, 90%, 95% identity within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 8, rows 2-1174 columns V and W. In some embodiments, the ZorD polypeptide comprises an amino acid sequence selected from the group consisting of the polypeptides referenced in Table 8, rows 2-1174 columns V and W.


In some embodiments, the ZorD polypeptide comprises an amino acid sequence encoded from a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polynucleotides referenced in Table 8, rows 2-1174 columns V and X. In some embodiments, the ZorD polypeptide comprises the amino acid sequence encoded by a nucleic acid sequence having at least 80%, 85%, 90%, 95% homology within similar domain regions within a sequence selected from the group consisting of the polynucleotides referenced in Table 8, rows 2-1174 columns V and X. In some embodiments, the ZorD polypeptide comprises an amino acid sequence encoded from a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polynucleotides referenced in Table 8, rows 2-1174 columns V and X. In some embodiments, the ZorD polypeptide comprises the amino acid sequence encoded by a nucleic acid sequence having at least 80%, 85%, 90%, 95% identity within similar domain regions within a sequence selected from the group consisting of the polynucleotides referenced in Table 8, rows 2-1174 columns V and X. In some embodiments, the ZorD polypeptide comprises an amino acid sequence encoded from a nucleic acid sequence selected from the group consisting of the polynucleotides referenced in Table 8, rows 2-1174 columns V and X.


In some embodiments, the zorD gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polynucleotides referenced in Table 8, rows 2-1174 columns V and X. In some embodiments, the zorD gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polynucleotides referenced in Table 8, rows 2-1174 columns V and X. In some embodiments, the nucleic acid sequence of a zorD gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology within the nucleotide sequence encoding similar domain regions as a sequence selected from the group consisting of the polynucleotides referenced in Table 8, rows 2-1174 columns V and X. In some embodiments, the nucleic acid sequence of a zorD gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity within the nucleotide sequence encoding similar domain regions as a sequence selected from the group consisting of the polypeptides referenced in Table 8, rows 2-1174 column P. In some embodiments, the nucleic acid sequence of the zorD gene is selected from the group consisting of the polynucleotides referenced in Table 8, rows 2-1174 columns V and X.


As used herein, the term “ZorE” refers to the polynucleotide or expression product e.g., polypeptide encoded by the zorE gene. In some embodiments, the term “ZorE” refers to a ZorE polypeptide. In some embodiments, the product of the zorE gene comprises a pfam01844 domain. In some embodiments, the product of the zorE gene comprises a COG3183 domain. In some embodiments, the product of the zorE gene contains a pfam01844 domain and a COG3183 domain. In some embodiments, the product of the zorE gene comprises an HNH endonuclease.


In some embodiments, a ZorE polypeptide comprises a pfam01844 domain. In some embodiments, a ZorE polypeptide comprises a COG3183 domain. In some embodiments, a ZorE polypeptide comprises a pfam01844 domain and a COG31383 domain. In some embodiments, a ZorE polypeptide comprises a HNH endonuclease.


In some embodiments, a ZorE polypeptide is encoded by a gene positioned within 5-60 genes of a gene encoding ZorA and/or ZorB in a genome of a prokaryotic cell. In some embodiments, a ZorE polypeptide is encoded by a gene positioned within 5 genes upstream (5′) or downstream (3′) to a gene encoding ZorA and/or ZorB in a genome of a prokaryotic cell. In some embodiments, ZorE polypeptide is encoded by a gene positioned within 5 genes upstream and downstream to a gene encoding ZorA and/or ZorB in a genome of a prokaryotic cell.


In some embodiments, a ZorE polypeptide is about 367 amino acids long (median gene size).


In some embodiments, the ZorE polypeptide comprises an amino acid sequence having at least 80% homology to a sequence selected from the group consisting of the polypeptides referenced in Table 8, rows 1175-1830 columns Z and AA. In some embodiments, the ZorE polypeptide comprises the amino acid sequence having at least 80% homology within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 8, rows 1175-1830 columns Z and AA. In some embodiments, a ZorE polypeptide homologue comprises a HNH endonuclease. In some embodiments, the ZorE polypeptide comprises an amino acid sequence having at least 80% identity to a sequence selected from the group consisting of the polypeptides referenced in Table 8, rows 1175-1830 columns Z and AA. In some embodiments, the ZorE polypeptide comprises the amino acid sequence having at least 80% identity within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 8, rows 1175-1830 columns Z and AA.


In some embodiments, the ZorE polypeptide comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polypeptides referenced in Table 8, rows 1175-1830 columns Z and AA. In some embodiments, the ZorE polypeptide comprises the amino acid sequence having at least 80%, 85%, 90%, 95% homology within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 8, rows 1175-1830 columns Z and AA. In some embodiments, the ZorE polypeptide comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polypeptides referenced in Table 8, rows 1175-1830 columns Z and AA. In some embodiments, the ZorE polypeptide comprises the amino acid sequence having at least 80%, 85%, 90%, 95% identity within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 8, rows 1175-1830 columns Z and AA. In some embodiments, the ZorE polypeptide comprises an amino acid sequence selected from the group consisting of the polypeptides referenced in Table 8, rows 1175-1830 columns Z and AA.


In some embodiments, the ZorE polypeptide comprises an amino acid sequence encoded from a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polynucleotides referenced in Table 8, rows 1175-1830 columns Z and AB. In some embodiments, the ZorE polypeptide comprises the amino acid sequence encoded from a nucleic acid sequence having at least 80%, 85%, 90%, 95% homology within similar domain regions within a sequence selected from the group consisting of the polynucleotides referenced in Table 8, rows 1175-1830 columns Z and AB. In some embodiments, the ZorE polypeptide comprises an amino acid sequence encoded from a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polynucleotides referenced in Table 8, rows 1175-1830 columns Z and AB. In some embodiments, the ZorE polypeptide comprises the amino acid sequence encoded from a nucleic acid sequence having at least 80%, 85%, 90%, 95% identity within similar domain regions within a sequence selected from the group consisting of the polynucleotides referenced in Table 8, rows 1175-1830 columns Z and AB. In some embodiments, the ZorE polypeptide comprises an amino acid sequence encoded from a nucleic acid sequence selected from the group consisting of the polynucleotides referenced in Table 8, rows 1175-1830 columns Z and AB.


In some embodiments, the zorE gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polynucleotides referenced in Table 8, rows 1175-1830 columns Z and AB. In some embodiments, the zorE gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polynucleotides referenced in Table 8, rows 1175-1830 columns Z and AB. In some embodiments, the nucleic acid sequence of a zorE gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology within the nucleotide sequence encoding similar domain regions as a sequence selected from the group consisting of the polynucleotides referenced in Table 8, rows 1175-1830 columns Z and AB. In some embodiments, the nucleic acid sequence of a zorE gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity within the nucleotide sequence encoding similar domain regions as a sequence selected from the group consisting of the polynucleotides referenced in Table 8, rows 1175-1830 columns Z and AB. In some embodiments, the nucleic acid sequence of the zorE gene is selected from the group consisting of the polynucleotides referenced in Table 8, rows 1175-1830 columns Z and AB.


A skilled artisan would appreciate that a “functional portion of a Defense System I component” or “functional fragment of Defense System I component” or “functional portion of a ZORYA defense system component” or “functional fragment of ZORYA defense system component” refers to a functional portion of a ZORYA polynucleotide or polypeptide, as disclosed herein, which expression is sufficient to elicit an anti-phage activity alone or in combination with the at least one of the other ZORYA polynucleotides or polypeptides disclosed herein or functional portions thereof.


As used herein, the terms “ZorA”, “ZorB”, “ZorC”, “ZorD”, “ZorE”, “zorA”, “zorB”, “zorC”, “zorD”, and “zorE”, also refer to functional ZorA, ZorB, ZorC, ZorD, ZorE, zorA, zorB, zorC, zorD, and zorE, homologs, which exhibit the desired activity (i.e., conferring phage resistance). Such homologs can be, for example, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical or homologous to the polypeptides referenced in Table 8, rows 2-1830 columns J and K; rows 2-1830 columns N and O; rows 2-1174 columns R and S; rows 2-1174 columns V and W; and rows 1175-1830 columns Z and AA, respectively, or 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical to the polynucleotide referenced in Table 8, rows 2-1830 columns J and L; rows 2-1830 columns N and P; rows 2-1174 columns R and T; rows 2-1174 columns V and X; and rows 1175-1830 column Z and AB, respectively. In some embodiments, such homologs comprise at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% homology within similar domain regions of the polypeptide referenced in Table 8, rows 2-1830 columns J and K; rows 2-1830 columns N and O; rows 2-1174 columns R and S; rows 2-1174 column V and W; and rows 1175-1830 column Z and AA, respectively, or 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity within nucleotide sequences encoding similar domain regions to the polynucleotide referenced in Table 8, rows 2-1830 columns J and L; rows 2-1830 columns N and P; rows 2-1174 columns R and S; rows 2-1174 columns V and X; and rows 1175-1830 columns Z and AB, respectively.


Table 8 presents embodiments of components of Defense System Ia and Defense System Ib that may be found in a diverse array of bacteria and archaea genomes (referenced in Table 18). Table 8 presents embodiments of nucleic acid sequences encoding gene cassettes of Defense System Ia and Defense System Ib (referenced in Table 18).


The Thoeris Defense System


In some embodiments, a defense system disclosed herein comprises a Thoeris anti-phage defense system. (Table 9)


In some embodiments, a Thoeris defense system provides a host cell with resistance to entry of foreign nucleic acid invasion. In some embodiments, a host cell expressing a functional Thoeris defense system (Defense System II) provides the host cell resistance foreign nucleic acid invasion.


In some embodiments, a Thoeris defense system provides a host cell with resistance to at least one phage. In some embodiments, expression of a Thoeris defense system in bacteria protects the bacteria from phage infection. In some embodiments, expression of a Thoeris defense system in bacteria protects the bacteria from plasmid transformation. In some embodiments, expression of a Thoeris defense system in bacteria protects the bacteria from phage infection and from plasmid transformation.


In some embodiments, a Thoeris defense system provides a host cell with resistance to phage infection. In some embodiments, a Thoeris defense system provides a host cell with resistance to plasmid transformation.


In some embodiments, expression of a Thoeris defense system in bacteria protects the bacteria from phage infection.


As used herein, the term “a Thoeris anti-phage defense system” may be used interchangeably with the term “a Defense System II”, having all the same meanings and qualities. A skilled artisan would appreciate that the term “Thoeris system” may be used interchangeably in some embodiments with “Thoeris defense system”, “Thoeris the defense system”, “Thoeris anti-phage system”, and “Defense System II”, having all the same meanings and qualities.


In some embodiments, a Thoeris defense system (Defense System II) provides a host cell with resistance to plasmid transformation. In some embodiments, a host cell expressing a functional Thoeris defense system (Defense System II) provides a host cells with resistance to plasmid transformation.


In some embodiments, a Thoeris defense system (Defense system II) provides a host cell with resistance to entry of conjugative elements. In some embodiments, a host cell expressing a function Thoeris defense system (Defense System II) provides the host cell resistance from entry of conjugative elements.


In some embodiments, a microbial species does not comprise an endogenous Defense System II. In some embodiments, a microbial species does not express an endogenous Defense System II. In some embodiments, a microbial species does not express an endogenous functional Defense System II.


In some embodiments, a bacterial species does not comprise an endogenous Defense System II. In some embodiments, a bacterial species does not express an endogenous Defense System II. In some embodiments, a bacterial species does not express an endogenous functional Defense System II.


A Thoeris defense system comprises, in some embodiments, a nucleic acid construct comprising a nucleic acid sequence encoding a ThsA polypeptide comprising a pfam13289 domain, and a ThsB polypeptide comprising a pfam13676 domain or a pfam08937 domain or a pfam08357 domain or a pfam13289, or a pfam14519 or a pfam08357 domain or any combination thereof. In some embodiments, a Thoeris defense system comprises a nucleic acid construct comprising a nucleic acid sequence comprising a thsA gene and a thsB gene. In some embodiments, a Thoeris defense system comprises a nucleic acid construct comprising a nucleic acid sequence comprising a thsA gene and multiple copies of a thsB gene. In some embodiments, a Thoeris defense system comprises 2 copies of a thsB gene. In some embodiments, a Thoeris defense system comprises 3 copies of a thsB gene. In some embodiments, a Thoeris defense system comprises 4 copies of a thsB gene. In some embodiments, a Thoeris defense system comprises 5 copies of a thsB gene. In some embodiments, a Thoeris defense system comprises 6 copies of a thsB gene. In some embodiments, a Thoeris defense system comprises 7 copies of a thsB gene. In some embodiments, a Thoeris defense system comprises 8 copies of a thsB gene. In some embodiments, a Thoeris defense system comprises 9 copies of a thsB gene. In some embodiments, a Thoeris defense system comprises 9 copies of a thsB gene. In some embodiments, a Thoeris defense system comprises 1-10 copies of a thsB gene.


In some embodiments, each copy of a thsB gene comprises the same nucleotide sequence. In some embodiments, each copy of a thsB gene comprises a different nucleotide sequence. In some embodiments, each copy of a thsB gene encodes a ThsB polypeptide having the same amino acid sequence. In some embodiments, each copy of a thsB gene encodes a ThsB polypeptide having a different amino acid sequence. In some embodiments, the source of the different nucleotide sequences comprises different donor species. In some embodiments, the source of the difference amino acid sequences comprises different donor species


A Thoeris defense system (Defense System II) comprises, in some embodiments, a nucleic acid construct comprising a nucleic acid sequence encoding a ThsA polypeptide comprising a pfam13289 or a pfam14519 domain or a combination thereof, and a ThsB polypeptide comprising a pfam08937 domain or a pfam13676 domain or a pfam08357 domain or any combination thereof. In some embodiments, a Thoeris defense system comprises a nucleic acid construct comprising a nucleic acid sequence encoding a ThsA polypeptide and a ThsB polypeptide. In some embodiments, a Thoeris defense system comprises a nucleic acid construct comprising a nucleic acid sequence encoding a ThsA polypeptide and 1-10 ThsB polypeptides.


In some embodiments, a Thoeris defense system (Defense System II) comprises a ThsA polypeptide comprising a pfam13289 or a pfam14519 domain or a combination thereof, and a ThsB polypeptide comprising a pfam13676 domain or a pfam08937 domain or a pfam08357 domain or a pfam13289 or a pfam14519 or a pfam08357 domain or any combination thereof. In some embodiments, a Thoeris defense system (Defense System II) comprises a ThsA polypeptide comprising a pfam13289 or a pfam14519 domain or a combination thereof, and 1-10 ThsB polypeptides comprising a pfam13676 domain or a pfam08937 domain or a pfam08357 domain or a pfam13289 or a pfam14519 or a pfam08357 domain or a combination thereof. In some embodiments, a Thoeris defense system (Defense System II) having an anti-phage activity comprises a ThsA polypeptide comprising a pfam13289 or a pfam14519 domain or a combination thereof, and a ThsB polypeptide comprising a pfam13676 domain or a pfam08937 domain or a pfam08357 domain or a pfam13289 or a pfam14519 or a pfam08357 domain or any combination thereof. In some embodiments, a Thoeris defense system (Defense System II) having an anti-phage activity comprises a ThsA polypeptide comprising a pfam13289 or a pfam14519 domain or a combination thereof, and 1-10 ThsB polypeptides comprising a pfam13676 domain or a pfam08937 domain or a pfam08357 domain or a pfam13289, or a pfam14519 or a pfam08357 domain or any combination thereof. In some embodiments, a Thoeris defense system (Defense System II) having an anti-phage activity comprises a ThsA polypeptide comprising a pfam13289 or a pfam14519 domain or a combination thereof, and 1-5 ThsB polypeptides comprising a pfam13676 domain or a pfam08937 domain or a pfam08357 domain or a pfam13289 or a pfam14519 or a pfam08357 domain or any combination thereof. In some embodiments, a Thoeris defense system (Defense System II) having an anti-phage activity comprises a ThsA polypeptide comprising a pfam13289 or a pfam14519 domain or a combination thereof, and 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 ThsB polypeptides comprising a pfam13676 domain or a pfam08937 domain or a pfam08357 domain or a pfam13289 or a pfam14519 or a pfam08357 domain or any combination thereof.


In some embodiments, a Thoeris defense system (Defense System II) comprises at least two different polypeptide components selected from a ThsA polypeptide comprising a pfam13289 or a pfam14519 domain or a combination thereof, and a ThsB polypeptide comprising a pfam13676 domain or a pfam08937 domain or a pfam08357 domain or a pfam13289 or a pfam14519 or a pfam08357 domain or any combination thereof. In some embodiments, a Thoeris defense system (Defense System II) comprises at least two different polypeptide components selected from a ThsA polypeptide comprising a pfam13289 or a pfam14519 domain or a combination thereof, and 1-10 ThsB polypeptides comprising a pfam13676 domain or a pfam08937 domain or a pfam08357 domain or a pfam13289 or a pfam14519 or a pfam08357 domain or a combination thereof. In some embodiments, a Thoeris defense system (Defense System II) having an anti-phage activity comprises at least two different polypeptide components selected from a ThsA polypeptide comprising a pfam13289 or a pfam14519 domain or a combination thereof, and a ThsB polypeptide comprising a pfam13676 domain or a pfam08937 domain or a pfam08357 domain or a pfam13289 or a pfam14519 or a pfam08357 domain or any combination thereof. In some embodiments, a Thoeris defense system (Defense System II) having an anti-phage activity comprises at least two different polypeptide components selected from a ThsA polypeptide comprising a pfam13289 or a pfam14519 domain or a combination thereof, and 1-10 ThsB polypeptides comprising a pfam13676 domain or a pfam08937 domain or a pfam08357 domain or a pfam13289, or a pfam14519 or a pfam08357 domain or any combination thereof. In some embodiments, a Thoeris defense system (Defense System II) having an anti-phage activity comprises at least two different polypeptide components selected from a ThsA polypeptide comprising a pfam13289 or a pfam14519 domain or a combination thereof, and 1-5 ThsB polypeptides comprising a pfam13676 domain or a pfam08937 domain or a pfam08357 domain or a pfam13289 or a pfam14519 or a pfam08357 domain or any combination thereof. In some embodiments, a Thoeris defense system (Defense System II) having an anti-phage activity comprises at least two different polypeptide components selected from a ThsA polypeptide comprising a pfam13289 or a pfam14519 domain or a combination thereof, and 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 ThsB polypeptides comprising a pfam13676 domain or a pfam08937 domain or a pfam08357 domain or a pfam13289 or a pfam14519 or a pfam08357 domain or any combination thereof.


In some embodiments, a Defense System II comprises a ThsA polypeptide comprising a pfam13289 domain or a pfam14519 domain or a combination thereof, or comprises an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 9 rows 2-2100 columns I and J; or a ThsB polypeptide comprising a pfam13676 domain or a pfam08937 domain or a pfam08357 domain or a combination thereof, or comprises an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 9 rows 2-2100 columns M and N, Q and R, U and V, Y and Z, and AC and AD, or a combination thereof; or a combination thereof.


In some embodiments, the amino acid sequences of more than one copy of a Thsb polypeptide present in a Defense System II are identical. In some embodiments, the amino acid sequences of more than one copy of a Thsb polypeptide present in a Defense System II are homologous. In some embodiments, the amino acid sequences of more than one copy of a Thsb polypeptide present in a Defense System II are not identical. In some embodiments, the amino acid sequences of more than one copy of a Thsb polypeptide present in a Defense System II comprise the same functional activity.


In some embodiments, a Thoeris defense system having an anti-phage activity comprises a nucleic acid construct comprising a nucleic acid sequence encoding a ThsA polypeptide and a ThsB polypeptide. In some embodiments, the Thoeris system having an anti-phage activity comprises a nucleic acid construct comprising a nucleic acid sequence encoding a ThsA polypeptide and encoding 1-10 copies of a ThsB polypeptide. In some embodiments, a Thoeris defense system having an anti-phage activity comprises a nucleic acid construct comprising a nucleic acid sequence comprising a thsA gene and a thsB gene. In some embodiments, a Thoeris defense system having an anti-phage activity comprises a nucleic acid construct comprising a nucleic acid sequence comprising a thsA gene and 1-10 copies of a thsB gene.


In some embodiments, the Thoeris anti-phage defense system comprises a nucleic acid construct comprising nucleic acid sequences encoding a cassette comprising thsA and thsB genes. In some embodiments, the Thoeris anti-phage defense system comprises a nucleic acid construct comprising nucleic acid sequences encoding a cassette comprising thsA and 1-10 copies of a thsB genes. In some embodiments, the Thoeris anti-phage defense system comprises a nucleic acid construct comprising nucleic acid sequences encoding a cassette comprising thsA and 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 copies of a thsB genes.


In some embodiments, a Thoeris (Defense System II) gene cassette comprises the nucleic acid sequence:












(SEQ ID NO: 10; construct 31 Table 4)
















1
atgtttttag aaatttataa ttaatttact aatatattgc gataattaga accatttgaa





61
ttacagaagt gccaccaacg aggaagcaat caattaaata gtaagtttaa taattttatt





121
aagaaattga tttgttatac gaaattttat tatatgataa aatatttatg taataaatgt





181
aaatttgtat attaggtaag gggaatgaaa atgaatccaa tagttgaact atttattaaa





241
gattttacaa aagaagttat ggaagagaat gctgcaattt ttgcaggagc gggtttatca





301
atgtctgttg ggtatgttag ttgggcgaag ttattggagc ctattgctca agaaattgga





361
ttagatgtaa ataaagaaaa tgatttagta agcttggcgc aatattattg taatgagaat





421
cagggtaata gaggtagaat taatcaaatt atcctagatg aattttctcg aaaagtagat





481
ttaactgaaa atcacaaaat tttagctcga ttaccaattc atacttattg gacgacaaat





541
tatgataggt taattgaaaa ggcattagaa gaagaaaata agattgctga tgtaaagtat





601
acggtaaaac aattagctac tacaaaggta aaaagagatg cagttgtata taaaatgcat





661
ggagacgtgg aacatccctc tgaggcagtt ttgattaaag atgattatga aaagtattct





721
ataaaaatgg atccgtatat taaggcgttg agtggggatc tagtttctaa gacattttta





781
tttgttggat ttagttttac tgatcccaat ctagattata tattaagtcg agtaaggagt





841
gcttatgaaa gggatcaaag aagacactat tgtttaataa aaaaagaaga gcgaagacca





901
gatgaattag aggcggattt tgagtataga gtaagaaaac aggaattatt tattagtgat





961
ttatcacgtt ttaatataaa gactattgta cttaataatt acaatgagat taccgagata





1021
ttacaacgaa ttgaaaataa tataaaaact aaaacagtat ttttatctgg tagtgcggtt





1081
gaatataatc attgggagac agaacatgct gaacaattca ttcatcagtt aagtaaagaa





1141
ttaattagaa aggattttaa tatagtatct ggttttggac ttggtgtagg gagttttgtt





1201
atcaatggag ttctagaaga attgtatatg aaccagggaa ctatagatga tgatagactt





1261
attctaagac cgtttccaca ggggaaaaag ggcgaagagc aatgggataa atatagacga





1321
gatatgatta caagaactgg ggtaagcatc tttttatatg gaaataaaat agacaaggga





1381
caggttgtta aggctaaggg tgtccaatct gaatttaata tttcttttga acaaaataat





1441
tacgttgttc cggtaggtgc aactggttat attgcaaaag atttatggaa taaagtaaat





1501
gaggaatttg aaacgtatta cccaggtgct gatgcaagga tgaaaaaatt gttcggagaa





1561
ttgaataatg aagcattatc aatagaggaa ctgattaaca ctataataga gtttgtagaa





1621
atcctatcca actaatcatt actgattatt aatcagagag gaactgttaa attatggcga





1681
aaagagtttt ttttagtttc cattatcaag atgtaattga ttttagagta aatgttgtaa





1741
gaaatcattg ggtaacaaaa ttaaatcaaa gtgctgcggg ggtctttgat gcatctcttt





1801
gggaagatgc aaaaaaaaca agtgatatag cacttaaaag attaataaat ggcgggctaa





1861
acaatacctc agttacatgt gttttaattg gatctcagac ttttaataga agatgggtga





1921
gatatgaaat tatgaaaagt atagaaaaag gaaataagat aataggaatt catattaatg





1981
cttttaaaga taaatatgga aatattaaaa gtaaagggcc taatcctttc gattatttag





2041
ggtatcaata tagttcagac ggcaaacagt tacatttgta tgagtggaca gggggaaaat





2101
gggaggaata taaggatttg gcaccatata gggtgaatca aattgctcca gaatcactta





2161
gaggaaaatt ctatagtttg tcatcggttt atcgtgtgta tgattgggtt gctgatgatg





2221
gatataacaa attttcctct tgggtgaact aattaagttt tggataaaat tataaataga





2281
attgctattg ggattagata caaaatgatt aaataagaaa agtacctata aaagtaggtg





2341
cttttttctt tgttatatag aaattacaca ttaatttata tttaggttat tttaaaaaga





2401
aaaagtgatg aatgatggta ttcttacaat taatagttac ttataactat atgtacatga





2461
aaaacatcta tatatgc.









The coding regions for each of the thsA and thsB gene sequences within this embodiment of a Thoeris cassette (SEQ ID NO: 10) are as follows: nucleotides 205-1635 encode a ThsA polypeptide; and nucleotides 1674-2252 encode a ThsB polypeptide.


In some embodiments, a Defense System II comprising a ThsA polypeptide and a ThsB polypeptide is encoded by the nucleic acid sequence set forth in SEQ ID NO: 10. In some embodiments, a Defense System II comprising a ThsA polypeptide and a ThsB polypeptide, is encoded by a nucleic acid sequence having at least 80% homology to the sequence set forth in SEQ ID NO: 10. In some embodiments, a Defense System II comprising a ThsA polypeptide and a ThsB polypeptide, is encoded by a nucleic acid sequence having at least 85% homology, or 90% homology, or 95% homology, or 97% homology, or 98% homology, or 99% homology to the sequence set forth in SEQ ID NO: 10. In some embodiments, a Defense System II comprising a ThsA polypeptide and a ThsB polypeptide, is encoded by a nucleic acid sequence having at least 80% identity to the sequence set forth in SEQ ID NO: 10. In some embodiments, a Defense System II comprising a ThsA polypeptide and a ThsB polypeptide, is encoded by a nucleic acid sequence having at least 85% identity, or 90% identity, or 95% identity, or 97% identity, or 98% identity, or 99% identity to the sequence set forth in SEQ ID NO: 10.


In some embodiments, a Thoeris (Defense System II) gene cassette comprises the nucleic acid sequence:












(SEQ ID NO: 11; construct 32 Table 4)
















1
gttaagcttt aggcggacat cagcaacgat gtccgctttt atcatcttaa cagcaataca





61
aggaggttta cgtggcggat gaaactctga aacagtatat gggcctgtac aaatgttgtt





121
agcaatctca agaaagccca ggagtagata tgattcactg aacagatgtt caatttaaat





181
ctaataatga agagggccta gtcaaaggcg ctcttcatta ttagataaga cataatcatt





241
acacaagatt tatgtcatgg ttctatattc atattttcat tgtaataaat tgaaaatatg





301
aatataatag gtagtgatcg caatactaac attggaggtt ttatgtggaa gtttaaagaa





361
ttaataagag ataagacatt tagaaggtgg gctctgagta taattctgac tattccaact





421
agtgtgagta cattcatttc atttctagac ttggatgctc gttgtagatt aattatttta





481
cttatattag tagggttgtc gctagtcata ataattgttc aattcattag actacttttt





541
atgaataata tcactcttaa tctcaatggt tccgaagttg aaattaaaaa aggtgatatt





601
tttgaagtgc caagaaataa ttataaagtc attgcattta atgagtattt tgacactcaa





661
gtagatgacg taataatcgc ccgcgaaaca ttaaatggtc aatatataaa gcgttattat





721
tcacatcaag atatcactga gttggatcag aaaattaaag atgacgtaaa acttaaaatt





781
gaagaaaaaa atgttgaaag accttttgga ggaaaaacaa cacgttacag cttgggatca





841
gtctttaaag atatggattt ttttctagtt gctttttcga agtttgatag ggaaaatcgt





901
gcccaattaa aactaaatga atatgcaagc tgcatgctta atgtatggaa tgaaatcaat





961
acattacatg caagcaaaga agtgtttatc cccttattag gttctggaat aacaagacat





1021
gtggattctg atgttggagt caatgaacta ttacatataa tgttgtggac atttcagatc





1081
agtaaagtaa agtttagaga accagccaaa gttacaattc ttttgtacaa aaatgatcac





1141
aagaagatca atttttataa gttaaaggag tttgagaaga atgggttata ggaatggaaa





1201
ttatgctgct ttctatgtca gtgaaccgtt tagtgaaagt agtttagggg ctaatgcaac





1261
caaggatttt gtgtcgtata acatgttaag agcatggaaa ggaaaagata ataactaccc





1321
atttaatgac tcccacgata aaacatacaa tgtacgggac ggtagtgatt gggagaaaac





1381
attaaagcca agattaagaa aaagattaga tcaatcaaaa aatataatct tttttttaag





1441
taagcatact gaaaacagca aagctttgcg agaagaaatt gattacggta ttaatgtgaa





1501
ggggctacca gttatcgttg tataccctga actttccgaa aagagtgaca tcatcgactg





1561
cactacaaag gttttcagat cagaagtggt gaatttatgg agtcgagtcc ctgtttttaa





1621
agactctatg ctaaaggtac caactattca tattccttat aaaaaagacc aaattaaaaa





1681
agctttagag aacaaagatt ttatgattaa ttcaaagatt tctgcaggtt cggtttattt





1741
ttatccatgt taatctatta tgggtgaata taatttaaag agaaagaata gattttcagt





1801
ttcgtcctca tggtagctca ttaattcaaa aacctctatg accaatttaa tttattgagg





1861
aggtagaggt tttggtatta aaatgatgaa gatagattat tggatatgaa tttcatttta





1921
tctagtttac ataatatata ttctaggaag ttaaatcttt aatgaaaatt ctgtctcgtt





1981
atcttaagtg tacttagttg gtgagacaga attaaaaaaa taggatgtat tacgatttgt





2041
atttatttct.









The coding regions for each of the thsA and thsB gene sequences within this embodiment of a Thoeris cassette (SEQ ID NO: 11) are as follows: nucleotides 298-1191 encode a ThsA polypeptide; and nucleotides 1181-1753 encode a ThsB polypeptide.


In some embodiments, a Defense System II comprising a ThsA polypeptide and a ThsB polypeptide is encoded by the nucleic acid sequence set forth in SEQ ID NO: 11. In some embodiments, a Defense System II comprising a ThsA polypeptide and a ThsB polypeptide, is encoded by a nucleic acid sequence having at least 80% homology to the sequence set forth in SEQ ID NO: 11. In some embodiments, a Defense System II comprising a ThsA polypeptide and a ThsB polypeptide, is encoded by a nucleic acid sequence having at least 85% homology, or 90% homology, or 95% homology, or 97% homology, or 98% homology, or 99% homology to the sequence set forth in SEQ ID NO: 11. In some embodiments, a Defense System II comprising a ThsA polypeptide and a ThsB polypeptide, is encoded by a nucleic acid sequence having at least 80% identity to the sequence set forth in SEQ ID NO: 11. In some embodiments, a Defense System II comprising a ThsA polypeptide and a ThsB polypeptide, is encoded by a nucleic acid sequence having at least 85% identity, or 90% identity, or 95% identity, or 97% identity, or 98% identity, or 99% identity to the sequence set forth in SEQ ID NO: 11.


In some embodiments, a construct comprising the Thoeris defense system encodes one component of the defense system, whereby multiple constructs may be used to assemble the functional defense system. In some embodiments, the components of a Thoeris defense system comprise genes thsA and thsB. In some embodiments, multiple thsB genes are present in the gene cassette of the defense system locus. In some embodiments, the components of a Thoeris defense system consist of genes thsA and thsB, wherein the copy number of the thsB gene is between 1 and 10. In some embodiments, the components of a Thoeris defense system comprise nucleic acid sequences encoding a ThsA polypeptide and a ThsB polypeptide. In some embodiments, the components of a Thoeris defense system consist of nucleic acid sequences encoding a ThsA polypeptide and a ThsB polypeptide. In some embodiments, the components of a Thoeris defense system consist of nucleic acid sequences encoding a ThsA polypeptide and 1-10 copies of a ThsB polypeptide. In some embodiments, the components of a Thoeris defense system consist of nucleic acid sequences encoding a ThsA polypeptide and 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 copies of a ThsB polypeptide.


In some embodiments, a construct comprising the Thoeris defense system encodes one component of the defense system, whereby a second construct may be used to assemble the functional defense system. In some embodiments, a construct comprising the Thoeris defense system encodes one component of the defense system, whereby additional constructs may be used to assemble the functional defense system. For example, in some embodiments each of ThsA and ThsB may be encoded by nucleic acid sequences comprised in different constructs, wherein expression of the combination of constructs produces a functional Thoeris defense system.


In some embodiments, the components making up a functional Thoeris anti-phage defense system comprise a ThsA polypeptide and a ThsB polypeptide, each encoded by a thsA and a thsB gene, respectively.


In some embodiments, a Thoeris defense system having an anti-phage activity comprise a nucleic acid encoding a ThsA polypeptide. In some embodiments, a Thoeris defense system having an anti-phage activity comprise a nucleic acid encoding a ThsA polypeptide and a ThsB polypeptide.


In some embodiments, a Thoeris defense system having an anti-phage activity comprise a nucleic acid comprising a thsA gene. In some embodiments, a Thoeris defense system having an anti-phage activity comprise a nucleic acid comprising a thsA gene and a thsB gene. In some embodiments, a Thoeris defense system having an anti-phage activity comprise a nucleic acid comprising a thsA gene and 1-10 thsB genes.


In some embodiments, a Thoeris defense system having an anti-phage activity comprises a nucleic acid construct comprising nucleic acids encoding polypeptides in a set order. In one embodiment, the 5′ to 3′ order of polypeptides encoded is ThsA and ThsB. In some embodiments the 5′ to 3′ order of polypeptides does not affect the anti-phage activity. In some embodiments the 5′ to 3′ order of polypeptides does affect the anti-phage activity.


In some embodiments, the 5′ to 3′ order of polypeptides is random, for example any order of ThsA and ThsB. In some embodiments, the 5′ to 3′ order of polypeptides is random, for example any order of ThsA and 1-10 copies of ThsB, wherein ThsB may be encoded both 5′ and 3′ of the gene encoding the ThsA.


In some embodiments, a Thoeris defense system having an anti-phage activity comprises a nucleic acid construct comprising genes in a set order. In some embodiment, the 5′ to 3′ order of genes is thsA and thsB. In some embodiment, the 5′ to 3′ order of genes in a Thoeris defense system is not thsA and thsB. In some embodiments the 5′ to 3′ order of genes does not affect the anti-phage activity. In some embodiments the 5′ to 3′ order of genes does affect the anti-phage activity.


In some embodiments, the 5′ to 3′ order of genes is random, for example any order of thsA and thsB. In some embodiments, the 5′ to 3′ order of polypeptides is random, for example any order of thsA and 1-10 copies of thsB, wherein thsB may be both 5′ and 3′ of thsA.


In some embodiments, the Thoeris system (a Defense System II) composition and order is as shown in FIG. 3B or FIG. 5A.


In some embodiments, a Thoeris defense system having an anti-phage activity originates from a microbial genome (Table 9). A skilled artisan would appreciate that the Thoeris system is not present in the majority of bacteria and or archaea species.


In some embodiments, a functional Thoeris defense system comprises a construct comprising nucleic acid sequences encoding polypeptides, wherein the nucleic acid sequence encoding each polypeptide may originate from a different microbial species. For example, the source of the nucleic acid sequence encoding a ThsA polypeptide may be one microbial species, while the source of the nucleic acid sequence encoding a ThsB polypeptide may be a different microbial species. In some embodiments, a functional Thoeris defense system (Defense system II) comprises a non-naturally occurring combination of polypeptide components. In some embodiments, a functional Thoeris defense system (Defense system II) comprises a combination of at least two polypeptides that do not naturally occur together. In some embodiments, a functional Thoeris defense system (Defense system II) comprises a combination of at least three polypeptides that do not naturally occur together.


In some embodiments, a functional Thoeris defense system comprises a construct comprising nucleic acid sequences encoding polypeptides, wherein the nucleic acid sequence encoding each polypeptide may originate from a different bacterial species. For example, the source of the nucleic acid sequence encoding a ThsA polypeptide may be one bacterial species, while the source of the nucleic acid sequence encoding a ThsB polypeptide may be a different bacterial species.


In some embodiments, the source of the nucleic acid encoding a ThsA polypeptide and a ThsB polypeptide is the same. In some embodiments, the source of the nucleic acid encoding a ThsA polypeptide and a ThsB polypeptide is the not the same. A skilled artisan would appreciate that the term “ThsB polypeptide” may in some embodiments, be used interchangeably with “ThsBi polypeptide”, “ThsBii polypeptide”, “ThsBiii polypeptide”, “ThsBiv polypeptide”, and “ThsBv polypeptide”, wherein the supra numbers I, ii, iii, iv, and v, indicate additional copies of a ThsB polypeptide comprised in embodiments of a Defense System II. Similarly, skilled artisan would appreciate that the term “thsB gene” may in some embodiments, be used interchangeably with “thsBi gene”, “thsBii gene”, “thsBiii gene”, “thsBiv gene”, and “thsBv gene”, wherein the supra numbers i, ii, iii, iv, and v, indicate additional copies of a thsB gene encoding ThsB polypeptides comprised in embodiments of a Defense System II.


In some embodiments, the source of the nucleic acid sequence of any of the components of a Thoeris defense system comprises any of the species listed in Table 9.


In some embodiments, a Thoeris defense system having an anti-phage activity comprises a nucleic acid construct comprising non-coding regions between the nucleic acid sequences encoding the polypeptides. In some embodiments, the non-coding regions between the nucleic acid sequences comprises nucleic acid sequence not naturally occurring in the microbial species of origin. In some embodiments, the non-coding regions between the nucleic acid sequences comprises nucleic acid sequence is the naturally occurring in the microbial species of origin.


In some embodiments, a Thoeris system disclosed herein comprises a multi-gene phage resistance system broadly distributed in microbial genomes, for example but not limited to Proteobacteria, Firmicutes, Bacteriodetes, and Actinobacteria.


According to some embodiments, the Thoeris system components are located in a gene cluster (a cassette of genes) in a microbial cell genome. According to some embodiments, the Thoeris system components are located in close proximity (e.g. positioned within 20 genes, 10 genes, 5 genes or less one from the other) in a genome of a prokaryotic cell. According to some embodiments the prokaryotic cell expresses an endogenous Thoeris defense system. According to some embodiments, the prokaryotic cell expresses an endogenous functional Thoeris defense system. According to some embodiments, the species of prokaryotic cell is selected from the group consisting of the species listed in Table 9. According to some embodiments a prokaryotic cell expresses a non-endogenous Thoeris defense system. According to some embodiments, a prokaryotic cell expresses a non-endogenous functional Thoeris defense system. According to some embodiments, the species of prokaryotic cell expressing a non-endogenous functional Thoeris defense system is selected from the group consisting of the species listed in Table 9.


In some embodiments, Thoeris defense system components comprise ThsA and ThsB polypeptides. In some embodiments, a Thoeris defense system components comprise functional portions of ThsA and ThsB polypeptides. In some embodiments, the Thoeris defense system components are encoded by thsA and thsB genes.


Non-limiting embodiments of endogenous Thoeris systems and the respective location of their components are provided in Table 9 herein.


In some embodiments, the components of a Thoeris system may be identified by the presence of similar domains present within each component. In some embodiments, domains comprise pfam domains and or clusters of orthologous groups (COG) domains.


In some embodiments, a Defense System II comprises a membrane associated complex.


In some embodiments, the term “ThsA” refers to the polynucleotide or expression product e.g., the polypeptide encoded by the thsA gene. In some embodiments, the term “ThsA” refers to a ThsA polypeptide. In some embodiments, the thsA gene encodes a polypeptide comprising a pfam13289 domain. In some embodiments, the thsA gene encodes a polypeptide comprising a pfam14519 domain. In some embodiments, the thsA gene encodes a polypeptide comprising a pfam13289 domain and a pfam14519 domain. In some embodiments, the ThsA polypeptide comprises a pfam13289 domain. In some embodiments, the ThsA polypeptide comprises a pfam14519 domain. In some embodiments, the ThsA polypeptide comprises a pfam13289 domain and a pfam14519 domain.


In some embodiments, the thsA gene encodes a polypeptide comprising a Sir2/Macro domain (NAD binding). In some embodiments, the thsA gene encodes a polypeptide comprising N-terminal transmembrane helices. In some embodiments, the thsA gene encodes a polypeptide comprising a Sir1/Macro domain (NAD binding) and N-terminal transmembrane helices.


In some embodiments, the ThsA polypeptide comprises a Sir2/Macro domain (NAD binding). In some embodiments, the ThsA polypeptide comprises N-terminal transmembrane helices. In some embodiments, the ThsA polypeptide comprises a Sir1/Macro domain (NAD binding) and N-terminal transmembrane helices.


In some embodiments, ThsA polypeptide is encoded by a gene positioned within 5-60 genes of a gene encoding a ThsB polypeptide in a genome of a prokaryotic cell. In some embodiments, ThsA polypeptide is encoded by a gene positioned within 5 genes upstream (5′) or downstream (3′) to a gene encoding a ThsB polypeptide in a genome of a prokaryotic cell. In some embodiments, ThsA polypeptide is encoded by a gene positioned within 5 genes upstream (5′) and downstream (3′) to a gene encoding a ThsB polypeptide in a genome of a prokaryotic cell.


In some embodiments, ThsA and ThsB are encoded by genes positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, ThsA and ThsB are encoded by genes positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, nucleic acid encoding additional copies of ThsB is positions 3′ of the nucleic acid sequence first encoding a ThsB polypeptide.


In some embodiments, thsA and thsB genes are positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, thsA and thsB, genes are positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, additional thsB genes are positions 3′ of the first thsB gene, e.g., the order of a gene cassette with 2 copies of a thsB gene would be thsA, thsB, thsB.


In some embodiments, a ThsA polypeptide is about 477 amino acids long (median gene size).


In some embodiments, the ThsA polypeptide comprises the amino acid sequence having at least 80% homology to a sequence selected from the group consisting of the polypeptides referenced in Table 9, rows 2-2100 columns I and J. In some embodiments, the ThsA polypeptide comprises the amino acid sequence having at least 80% homology within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 9, rows 2-2100 columns I and J. In some embodiments, the ThsA polypeptide comprises a homolog of a polypeptide having the amino acid sequences set forth in the polypeptides referenced in Table 9, rows 2-2100 columns I and J. In some embodiments, a homolog of a ThsA polypeptide comprises a Sir2/Macro domain (NAD binding). In some embodiments, a homolog of ThsA polypeptide comprises N-terminal transmembrane helices. In some embodiments, a homolog of a ThsA polypeptide comprises a Sir1/Macro domain (NAD binding) and N-terminal transmembrane helices.


In some embodiments, the ThsA polypeptide comprises the amino acid sequence having at least 80% identity to a sequence selected from the group consisting of the polypeptides referenced in Table 9, rows 2-2100 columns I and J. In some embodiments, the ThsA polypeptide comprises the amino acid sequence having at least 80% identity within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 9, rows 2-2100 columns I and J. In some embodiments, the ThsA polypeptide comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polypeptides referenced in Table 9, rows 2-2100 columns I and J. In some embodiments, the ThsA polypeptide comprises the amino acid sequence having at least 80%, 85%, 90%, 95% homology within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 9, rows 2-2100 columns I and J. In some embodiments, the ThsA polypeptide comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polypeptides referenced in Table 9, rows 2-2100 columns I and J. In some embodiments, the ThsA polypeptide comprises the amino acid sequence having at least 80%, 85%, 90%, 95% identity within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 9, rows 2-2100 columns I and J. In some embodiments, the ThsA polypeptide comprises an amino acid sequence selected from the group consisting of the polypeptides referenced in Table 9, rows 2-2100 columns I and J.


In some embodiments, the ThsA polypeptide comprises an amino acid sequence encoded by a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polynucleotides referenced in Table 9, rows 2-2100 columns I and K. In some embodiments, the ThsA polypeptide comprises the amino acid sequence encoded from a nucleic acid sequence having at least 80%, 85%, 90%, 95% homology within similar domain regions within a sequence selected from the group consisting of the polynucleotides referenced in Table 9, rows 2-2100 columns I and K. In some embodiments, the ThsA polypeptide comprises an amino acid sequence encoded by a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polynucleotides referenced in Table 9, rows 2-2100 columns I and K. In some embodiments, the ThsA polypeptide comprises the amino acid sequence encoded from a nucleic acid sequence having at least 80%, 85%, 90%, 95% identity within similar domain regions within a sequence selected from the group consisting of the polynucleotides referenced in Table 9, rows 2-2100 columns I and K. In some embodiments, the ThsA polypeptide comprises an amino acid sequence encoded from a nucleic acid sequence selected from the group consisting of the polynucleotides referenced in Table 9, rows 2-2100 columns I and K.


In some embodiments, the nucleic acid sequence of a thsA gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polynucleotides referenced in Table 9, rows 2-2100 columns I and K. In some embodiments, the nucleic acid sequence of a thsA gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polynucleotides referenced in Table 9, rows 2-2100 columns I and K. In some embodiments, the nucleic acid sequence of a thsA gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology within the nucleotide sequences encoding similar domain sequences with a sequence selected from the group consisting of the polynucleotides referenced in Table 9, rows 2-2100 columns I and K. In some embodiments, the nucleic acid sequence of a thsA gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity within nucleotide sequences encoding similar domain regions with a sequence selected from the group consisting of the polynucleotides referenced in Table 9, rows 2-2100 columns I and K. In some embodiments, the nucleic acid sequence of a thsA gene comprises a nucleic acid sequence selected from the group consisting of the polynucleotides referenced in Table 9, rows 2-2100 columns I and K.


As used herein, the term “ThsB” refers to the polynucleotide or expression product e.g., polypeptide encoded by the thsB gene. In some embodiments, the term “ThsB” refers to a ThsB polypeptide. In some embodiments, the product of the thsB gene comprises a pfam08937 domain or a pfam08357 domain. In some embodiments, the thsB gene encodes a Toll/interleukin-1 receptor (TIR) domain.


In some embodiments, ThsB polypeptide is encoded by a gene positioned within 5-60 genes of a gene encoding a ThsA polypeptide in a genome of a prokaryotic cell. In some embodiments, ThsB polypeptide is encoded by a gene positioned within 5 genes upstream (5′) or downstream (3′) to a gene encoding a ThsA polypeptide in a genome of a prokaryotic cell. In some embodiments, ThsB polypeptide is encoded by a gene positioned within 5 genes upstream (5′) and downstream (3′) to a gene encoding a ThsA polypeptide in a genome of a prokaryotic cell.


In some embodiments, ThsA and ThsB are encoded by genes positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments ThsA and ThsB are encoded by genes positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, additional ThsB polypeptides are encoded by genes positioned 3′ of the first gene encoding ThsB. In some embodiments ThsA and ThsB (1-10 copies) are encoded by genes positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell.


In some embodiments, a ThsB polypeptide is about 195 amino acids long (median gene size).


In some embodiments, the ThsB polypeptide comprises an amino acid sequence having at least 80% homology to a sequence selected from the group consisting of the polypeptides referenced in Table 9, rows 2-2100 columns M and N, Q and R, U and V, Y and Z, and AC and AD. In some embodiments, the ThsB polypeptide comprises the amino acid sequence having at least 80%, 85%, 90%, 95% homology within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 9, rows 2-2100 columns M and N, Q and R, U and V, Y and Z, and AC and AD. In some embodiments, a homologue of the ThsB polypeptide comprises a TIR domain. In some embodiments, the ThsB polypeptide comprises an amino acid sequence having at least 80% identity to a sequence selected from the group consisting of the polypeptides referenced in Table 9, rows 2-2100 columns M and N, Q and R, U and V, Y and Z, and AC and AD.


In some embodiments, the ThsB polypeptide comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polypeptides referenced in Table 9, rows 2-2100 columns M and N, Q and R, U and V, Y and Z, and AC and AD. In some embodiments, the ThsB polypeptide comprises the amino acid sequence having at least 80%, 85%, 90%, 95% homology within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 9, rows 2-2100 columns M and N, Q and R, U and V, Y and Z, and AC and AD. In some embodiments, the ThsB polypeptide comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polypeptides referenced in Table 9, rows 2-2100 columns M and N, Q and R, U and V, Y and Z, and AC and AD. In some embodiments, the ThsB polypeptide comprises the amino acid sequence having at least 80%, 85%, 90%, 95% identity within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 9, rows 2-2100 columns M and N, Q and R, U and V, Y and Z, and AC and AD. In some embodiments, the ThsB polypeptide comprises an amino acid sequence selected from the group consisting of the polypeptides referenced in Table 9, rows 2-2100 columns M and N, Q and R, U and V, Y and Z, and AC and AD.


In some embodiments, the ThsB polypeptide comprises an amino acid sequence encoded from a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polynucleotides referenced in Table 9, rows 2-2100 columns M and O, Q and S, U and W, Y and AA, and AC and AE. In some embodiments, the ThsB polypeptide comprises the amino acid sequence encoded by a nucleic acid sequence having at least 80%, 85%, 90%, 95% homology within similar domain regions within a sequence selected from the group consisting of the polynucleotides referenced in Table 9, rows 2-2100 columns M and O, Q and S, U and W, Y and AA, and AC and AE. In some embodiments, the ThsB polypeptide comprises an amino acid sequence encoded from a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polynucleotides referenced in Table 9, rows 2-2100 columns M and O, Q and S, U and W, Y and AA, and AC and AE. In some embodiments, the ThsB polypeptide comprises the amino acid sequence encoded by a nucleic acid sequence having at least 80%, 85%, 90%, 95% identity within similar domain regions within a sequence selected from the group consisting of the polynucleotides referenced in Table 9, rows 2-2100 columns M and O, Q and S, U and W, Y and AA, and AC and AE. In some embodiments, the ThsB polypeptide comprises an amino acid sequence encoded from a nucleic acid sequence selected from the group consisting of the polynucleotides referenced in Table 9, rows 2-2100 columns M and O, Q and S, U and W, Y and AA, and AC and AE.


In some embodiments, the nucleic acid sequence of a thsB gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polynucleotides referenced in Table 9, rows 2-2100 columns M and O, Q and S, U and W, Y and AA, and AC and AE. In some embodiments, the nucleic acid sequence of a thsB gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polynucleotides referenced in Table 9, rows 2-2100 columns M and O, Q and S, U and W, Y and AA, and AC and AE. In some embodiments, the nucleic acid sequence of a thsB gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology within the nucleotide sequences encoding similar domain sequences with a sequence selected from the group consisting of the polynucleotides referenced in Table 9, rows 2-2100 columns M and O, Q and S, U and W, Y and AA, and AC and AE. In some embodiments, the nucleic acid sequence of a thsB gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity within nucleotide sequences encoding similar domain regions with a sequence selected from the group consisting of the polynucleotides referenced in Table 9, rows 2-2100 columns M and O, Q and S, U and W, Y and AA, and AC and AE. In some embodiments, the thsB gene homolog encodes a polypeptide comprising a helicase activity. In some embodiments, the thsB gene homolog encodes a polypeptide comprising a DEAx box helicase activity. In some embodiments, the nucleic acid sequence of a thsB gene comprises a nucleic acid sequence selected from the group consisting of the polynucleotides referenced in Table 9, rows 2-2100 columns M and O, Q and S, U and W, Y and AA, and AC and AE.


A skilled artisan would appreciate that a “functional portion of a Defense System II component” or “functional fragment of Defense System II component” or “functional portion of a Thoeris defense system component” or “functional fragment of Thoeris defense system component” refers to a functional portion of a Thoeris polynucleotide or polypeptide, as disclosed herein, which expression is sufficient to elicit an anti-phage activity alone or in combination with the at least one of the other Thoeris polynucleotides or polypeptides disclosed herein or functional portions thereof.


The terms “ThsA”, “ThsB”, “thsA”, and “thsB”, also refer to functional ThsA, ThsB, thsA, and thsB, homologs, which exhibit the desired activity (i.e., conferring phage resistance). Such homologs can be, for example, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical or homologous to the polypeptide sequences referenced in Table 9, rows 2-2100 columns I and J, M and N, Q and R, U and V, Y and Z, and SAC and AD, respectively, or 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical to the polynucleotide sequences referenced in Table 9, rows 2-2100 columns I and K, M and O, Q and S, U and W, Y and AA, and SAC and AE, respectively. In some embodiments, such homologs comprise at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% homology within similar domain regions of the polypeptide sequences referenced in Table 9, rows 2-2100 columns I and J, M and N, Q and R, U and V, Y and Z, and AC and AD, respectively, or 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity within nucleotide sequences encoding similar domain regions to the polynucleotide sequences referenced in Table 9, rows 2-2100 columns I and K, M and O, Q and S, U and W, Y and AA, and AC and AE, respectively.


Table 9 presents embodiments of components of Defense System II that may be found in a diverse array of bacteria and archaea genomes (referenced in Table 18). Table 9 presents embodiments of nucleic acid sequences encoding gene cassettes of Defense System II (referenced in Table 18).


The Druantia Defense System


In some embodiments, a defense system disclosed herein comprises an Druantia anti-phage defense system. (Table 10) In some embodiments, a Druantia defense system provides a host cell with resistance to entry of foreign nucleic acid invasion. In some embodiments, a host cell expressing a functional Druantia defense system (Defense System IIIa; Defense System IIIb; or Defense System IIIc) provides the host cell resistance foreign nucleic acid invasion.


In some embodiments, a Druantia defense system provides a host cell with resistance to at least one phage.


In some embodiments, a Druantia defense system provides a host cell with resistance to phage infection. In some embodiments, expression of a Druantia defense system in bacteria protects the bacteria from phage infection.


As used herein, the term “a Druantia anti-phage defense system” may be used interchangeably with the term “a Defense System III”, having all the same meanings and qualities. A skilled artisan would appreciate that the term “Druantia system” may be used interchangeably in some embodiments with “Druantia defense system”, “Druantia the defense system”, “Druantia anti-phage system”, and “Defense System III”, having all the same meanings and qualities. Disclosed herein, the Druantia defense system (Defense System III) comprises a Type I Druantia defense system (Defense System IIIa), a Type II Druantia defense system (Defense System IIIb), and a Type III Druantia defense system (Defense system IIIc), as described below.


In some embodiments, expression of a Druantia Type I defense system (Defense System IIIa) in bacteria protects the bacteria from phage infection. In some embodiments, expression of a Druantia Type II defense system (Defense System IIIb) in bacteria protects the bacteria from phage infection. In some embodiments, expression of a Druantia Type III defense system (Defense System IIIc) in bacteria protects the bacteria from phage infection.


In some embodiments, expression of a Druantia defense system in bacteria protects the bacteria from phage infection.


In some embodiments, a Druantia defense system (Defense System IIIa or Defense system IIIb or Defense System IIIc) provides a host cell with resistance to plasmid transformation. In some embodiments, a host cell expressing a functional Druantia defense system (Defense System IIIa or Defense System IIIb or Defense System IIIc) provides a host cells with resistance to plasmid transformation.


In some embodiments, a Druantia defense system (Defense system IIIa or IIIb or IIIc) provides a host cell with resistance to entry of conjugative elements. In some embodiments, a host cell expressing a function Druantia defense system (Defense System IIIa or IIIb or IIIc) provides the host cell resistance from entry of conjugative elements.


In some embodiments, a microbial species does not comprise an endogenous Defense System III. In some embodiments, a microbial species does not express an endogenous Defense System III. In some embodiments, a microbial species does not express an endogenous functional Defense System III.


In some embodiments, a bacterial species does not comprise an endogenous Defense System III. In some embodiments, a bacterial species does not express an endogenous Defense System III. In some embodiments, a bacterial species does not express an endogenous functional Defense System III.


In some embodiments, a microbial species does not comprise an endogenous Defense System IIIa. In some embodiments, a microbial species does not express an endogenous Defense System IIIa. In some embodiments, a microbial species does not express an endogenous functional Defense System IIIa.


In some embodiments, a bacterial species does not comprise an endogenous Defense System IIIA. In some embodiments, a bacterial species does not express an endogenous Defense System IIIa. In some embodiments, a bacterial species does not express an endogenous functional Defense System IIIa.


In some embodiments, a microbial species does not comprise an endogenous Defense System IIIb. In some embodiments, a microbial species does not express an endogenous Defense System IIIb. In some embodiments, a microbial species does not express an endogenous functional Defense System IIIb.


In some embodiments, a bacterial species does not comprise an endogenous Defense System IIIb. In some embodiments, a bacterial species does not express an endogenous Defense System IIIb. In some embodiments, a bacterial species does not express an endogenous functional Defense System IIIb.


In some embodiments, a microbial species does not comprise an endogenous Defense System IIIc. In some embodiments, a microbial species does not express an endogenous Defense System IIIc. In some embodiments, a microbial species does not express an endogenous functional Defense System IIIc.


In some embodiments, a bacterial species does not comprise an endogenous Defense System IIIc. In some embodiments, a bacterial species does not express an endogenous Defense System IIIc. In some embodiments, a bacterial species does not express an endogenous functional Defense System IIIc.


In some embodiments, a Druantia Type I defense system (Defense System IIIa) having an anti-phage activity comprises a nucleic acid construct comprising a nucleic acid sequence encoding a DruA polypeptide comprising a DUF4338 domain or a pfam14236 domain or a combination thereof, a DruB polypeptide, a DruC polypeptide, a DruD polypeptide, and a DruE polypeptide comprising a pfam00270 domain or a pfam00271 domain or a pfam09369 domain or a DUF1998 domain or any combination thereof. In some embodiments, a Druantia Type I defense system (Defense System IIIa) having an anti-phage activity comprises a nucleic acid construct comprising a nucleic acid sequence encoding a DruA polypeptide comprising a DUF4338 domain or a pfam14236 domain or a combination thereof, a DruB polypeptide wherein said DruB polypeptide is encoded by a gene positioned within 5 genes of a gene encoding said DruA polypeptide and said DruE polypeptide, a DruC polypeptide wherein said DruC polypeptide is encoded by a gene positioned within 5 genes of a gene encoding said DruA polypeptide and said DruE polypeptide, a DruD polypeptide wherein said DruD polypeptide is encoded by a gene positioned within 5 genes of a gene encoding said DruA polypeptide and said DruE polypeptide, and a DruE polypeptide comprising a pfam00270 domain or a pfam00271 domain or a pfam09369 domain or a DUF1998 domain or any combination thereof.


In some embodiments, a Druantia Type I defense system (Defense System IIIa) having an anti-phage activity comprises a DruA polypeptide comprising a DUF4338 domain or a pfam14236 domain or a combination thereof, a DruB polypeptide, a DruC polypeptide, a DruD polypeptide, and a DruE polypeptide comprising a pfam00270 domain or a pfam00271 domain or a pfam09369 domain or a DUF1998 domain or any combination thereof. In some embodiments, a Druantia Type I defense system (Defense System IIIa) having an anti-phage activity comprises a DruA polypeptide comprising a DUF4338 domain or a pfam14236 domain or a combination thereof, a DruB polypeptide wherein said DruB polypeptide is encoded by a gene positioned within 5 genes of a gene encoding said DruA polypeptide and said DruE polypeptide, a DruC polypeptide wherein said DruC polypeptide is encoded by a gene positioned within 5 genes of a gene encoding said DruA polypeptide and said DruE polypeptide, a DruD polypeptide wherein said DruD polypeptide is encoded by a gene positioned within 5 genes of a gene encoding said DruA polypeptide and said DruE polypeptide, and a DruE polypeptide comprising a pfam00270 domain or a pfam00271 domain or a pfam09369 domain or a DUF1998 domain or any combination thereof.


In some embodiments, a Defense System IIIa comprises a DruA polypeptide comprising a DUF4338 domain or a pfam14236 domain or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-123 columns J and K; or a DruB polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-123 columns N and O; or a DruC polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-123 columns R and S; or a DruD polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-123 columns V and W; and a DruE polypeptide comprising a pfam00270 domain or a pfam00271 domain or a pfam09369 domain or a DUF1998 domain or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-1343 columns Z and AA; or any combination thereof.


In some embodiments, a Defense System IIIa comprises at least two polypeptide components selected from a DruA polypeptide comprising a DUF4338 domain or a pfam14236 domain or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-123 columns J and K; or a DruB polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-123 columns N and O; or a DruC polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-123 columns R and S; or a DruD polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-123 columns V and W; and a DruE polypeptide comprising a pfam00270 domain or a pfam00271 domain or a pfam09369 domain or a DUF1998 domain or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-1343 columns Z and AA. In some embodiments, a Defense System IIIa comprises at least three polypeptide components selected from a DruA polypeptide comprising a DUF4338 domain or a pfam14236 domain or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-123 columns J and K; or a DruB polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-123 columns N and O; or a DruC polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-123 columns R and S; or a DruD polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-123 columns V and W; and a DruE polypeptide comprising a pfam00270 domain or a pfam00271 domain or a pfam09369 domain or a DUF1998 domain or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-1343 column Z and AA. In some embodiments, a Defense System IIIa comprises at least four polypeptide components selected from a DruA polypeptide comprising a DUF4338 domain or a pfam14236 domain or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-123 columns J and K; or a DruB polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-123 columns N and O; or a DruC polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-123 columns R and S; or a DruD polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-123 columns V and W; and a DruE polypeptide comprising a pfam00270 domain or a pfam00271 domain or a pfam09369 domain or a DUF1998 domain or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-1343 columns Z and AA. In some embodiments, a Defense System IIIa comprises five polypeptide components selected from a DruA polypeptide comprising a DUF4338 domain or a pfam14236 domain or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-123 columns J and K; or a DruB polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-123 columns N and O; or a DruC polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-123 columns R and S; or a DruD polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-123 columns V and W; and a DruE polypeptide comprising a pfam00270 domain or a pfam00271 domain or a pfam09369 domain or a DUF1998 domain or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-1343 columns Z and AA.


In some embodiments, a functional Defense System IIIa comprises at least two polypeptide components selected from a DruA polypeptide comprising a DUF4338 domain or a pfam14236 domain or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-123 columns J and K; or a DruB polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-123 columns N and O; or a DruC polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-123 columns r and S; or a DruD polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-123 columns V and W; and a DruE polypeptide comprising a pfam00270 domain or a pfam00271 domain or a pfam09369 domain or a DUF1998 domain or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-1343 columns Z and AA. In some embodiments, a functional Defense System IIIa comprises at least three polypeptide components selected from a DruA polypeptide comprising a DUF4338 domain or a pfam14236 domain or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-123 columns J and K; or a DruB polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-123 columns N and O; or a DruC polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-123 columns R and S; or a DruD polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-123 columns V and W; and a DruE polypeptide comprising a pfam00270 domain or a pfam00271 domain or a pfam09369 domain or a DUF1998 domain or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-1343 columns Z and AA. In some embodiments, a functional Defense System IIIa comprises at least four polypeptide components selected from a DruA polypeptide comprising a DUF4338 domain or a pfam14236 domain or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-123 columns J and K; or a DruB polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-123 columns N and O; or a DruC polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-123 columns R and S; or a DruD polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-123 columns V and W; and a DruE polypeptide comprising a pfam00270 domain or a pfam00271 domain or a pfam09369 domain or a DUF1998 domain or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-1343 columns Z and AA. In some embodiments, a functional Defense System IIIa comprises five polypeptide components selected from a DruA polypeptide comprising a DUF4338 domain or a pfam14236 domain or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-123 columns J and K; or a DruB polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-123 columns N and O; or a DruC polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-123 columns R and S; or a DruD polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-123 columns V and W; and a DruE polypeptide comprising a pfam00270 domain or a pfam00271 domain or a pfam09369 domain or a DUF1998 domain or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-1343 columns Z and AA.


In some embodiments, a Druantia Type I defense system (Defense System IIIa) having an anti-phage activity comprises a nucleic acid construct comprising a nucleic acid sequence comprising a druA gene, a druB gene, a druC gene, a druD gene, and a druE gene.


In some embodiments, the Druantia Type I anti-phage defense system comprises a nucleic acid construct comprising nucleic acid sequences encoding a gene cassette comprising druA, druB, druC, druD, and druE genes. In some embodiments, a Druantia Type I (Defense System IIIa) gene cassette comprises the nucleic acid sequence:












(SEQ ID NO: 16; construct 56 of Table 4)
















1
tagtaaggca ttatagtgaa acgatgtcta tgaatcacac atctaatgtc cggtgaacgt





61
ttggttgata gggtagtaaa actagtaatc atcctataat tagctatatt cgtggttatt





121
agattgaaaa cagataacat taacaaaatc tataaatcta tttgaatgat ttttttcatc





181
aatgctgttg taacctcctg ctatcaaaag tttttcacaa aatctataag ctcccagaat





241
tgcttgtata aatgctatca ttggcgctgt cccgatcgag ggagcaagga ggggactctc





301
ttgtgccatg cgattaatca cttgggctct aagtgaaatt tagtgggact aaatactaat





361
tggaacgtga gataaaaatg cacaaagatc cctctataat agttaatatc aaccttcgag





421
aagccaaact gaaaaagaag gtacgtgagc atttacaatc cttgggtttt acaagatctg





481
attctggagc gctccaggcc ccgggaaata ccaaagatgt aatacgggct cttcatagtt





541
ctcaacgagc tgagcggata tttgcaaacc aaaagttcat aacgctaaga gcggcaaagc





601
ttattaaatt tttcgcatcc ggcaatgagg tcattccgga taaaatttca ccggtacttg





661
aacgtgtaaa gtcaggaacc tggcaaggag atctctttag gttagcagca ttaacttggt





721
ccgtacctgt ttcaagcgga tttggaaggc gtctccggta tcttgtatgg gatgaaagca





781
acggaaaatt gatagggctg atcgcaattg gtgaccctgt gttcaacctt gcagtccgag





841
ataatttgat tgggtgggat actcatgcca gaagttcccg gcttgttaat ttgatggatg





901
catacgtcct cggtgctctt cccccttata atgccctgct gggaggaaaa ttaattgcat





961
gtctgcttcg tagccgcgat ctttatgatg actttgcaaa ggtctatggt gataccgttg





1021
gagtaatatc tcaaaaaaag aaacaagcac gtcttttggc tattacaaca acatcgtcta





1081
tggggcgctc atcggtatat aaccgtttaa agctggatgg aattcaatat ttaaaatcga





1141
ttggatatac aggcggttgg gggcattttc atatacctga tagcttgttc attgaattac





1201
gtgattactt acgtgatatg gatcacgctt atgcagatca ttatatgttt ggtaatgggc





1261
ctaactggcg tttacgtaca actaaggcag ctttaaatgt actaggattt agagataatt





1321
tgatgaagca tggaattcaa cgtgaagttt ttatcagtca gctagcagaa aatgcaacta





1381
gtattctgca aacaggcaaa ggtgaaccag atctaacctc tttgctttct gctaaagaga





1441
tagctgagtg tgcgatggca cgatggatgg ttccacgatc aattcgcaat ccagaatatc





1501
ggctttggaa agcaagagat ctatttgatt ttattagtaa tgactcgcta aaatttcccc





1561
cgtctgacga gatagcgaaa acagttgtct aatcttaact gaagggggag taagtgaatt





1621
acgctattga taagttcacc gggacactga tattagcagc tcgagcaacg aaatatgctc





1681
aatatgtttg cccagtttgt aaaaaaggtg ttaacctccg taaagggaag gttatacccc





1741
catattttgc tcatttgccc ggacatggta cgtcagactg tgaaaatttt gttcccggaa





1801
attccatcat tatcgaaact attaaaacta tttcaaagcg atatatggat ttgcgcttat





1861
tgattcctgt cggaagtaat agtcgagagt ggtcattaga attagtgttg ccaacctgta





1921
atttatgtag agcaaagata acgttagatg taggaggcag aagccaaacg cttgatatga





1981
ggagtatggt aaagagtcgc cagattggtg ctgaattatc agtaaaatct taccgtattg





2041
tttcatatag tggtgaaccc gatccaaaat ttgtaacaga agttgaaaga gaatgccccg





2101
gtttaccttc tgagggagca gcagttttca ctgctttagg gcgtggggca tcgaagggat





2161
ttccacgagc acaagagtta agatgtactg aaacatttgc ctttctttgg cgacaccctg





2221
ttgctccaga ttttcctgat gaattagaaa taaaaagttt agctagtaaa cagggatgga





2281
atttagctct tgttacaatt cctgaagtcc cttctgtgga gagtatttca tggctaaaat





2341
cttttacata ccttcctgtt gttcctgcca gaacatctat tacagcaatt tggccgttcc





2401
taaatcaaaa aacaagtatt aatcatgtcg aatgtgttca ttctgacaca atattgttgt





2461
cagcaaatat ggcaccaaca tcatcagaaa atgttggacc aactatgtac gcacaaggtt





2521
cctctttatt actttcagcg gttggtgttg aaaaatcacc tgctttcttc attcttaatc





2581
ctggagaaaa tgactttgtg ggcgtttctg gctcaattga gcaggacgta aacttatttt





2641
tttctttcta taaaaaaaac gtttctgtac ccagaaaata tccctcaata gatttggttt





2701
ttactaagag gaataaagaa aagaccatcg tttccttaca tcaaagaaga tgcattgaag





2761
ttatgatgga agcacgaatg tttggccata aattagaata catgtctatg ccttctggtg





2821
ttgaaggagt ggcaagaatt caaagacaaa ctgaaagtag tgttattaag ttagtttcta





2881
atgatgacat tgcagctcat gataagagca tgcggttact atctcctgtt gcgttatctc





2941
aattatctga ttgcttagca aacttaacat gtcatgtaga aatagatttt ttaggtcttg





3001
gtaaaatatt tttacctagt tcttctatgt tatcattaga tgacggggaa tttattgaat





3061
tatctcctaa tcttcgctca cggatattaa gttttatact tcaaatgggg cacaccctcc





3121
atggttttag tttaaataat gattttttat tagttgagaa attagtggat ttgcagccgg





3181
aaccacactt attaccgcat tatagggcat tggtaaaaga agttaagacc aatggatttg





3241
aatgtaaccg ctttagataa ggtgccttcg aatgagttac caatatagcc aagaggcaaa





3301
ggaacggatc tctaagttgg gacaatccga aattgttaac tttatcaatg agatttctcc





3361
aactttacga cgtaaagctt ttggttgttt accaaaagta ccgggattca gggcaggaca





3421
tcccactgaa attaaagaaa aacagaaaag attgattggg tatatgttcc agtcacatcc





3481
ttcctctgag gagagaaaag catggaaaag tttttctctt ttttggcagt tttgggctga





3541
agagaaaatt gacaaatcat ttagtatgat tgataattta ggattaaaag aaaactctgg





3601
ctctattttt attagagagc ttgctaaaaa ctttcctaaa gttgctagag agaatatcga





3661
gcgcctgttt atctttagtg ggtttgctga tgatccagac gttataaatg catttaacct





3721
ttttcctcct gcagttgttc ttgcccgcga tatcgtggtt gatactcttc caattcgttt





3781
agatgagctt gaagcacgta ttagtttaat tgccgataat gtggagaaaa aaaataacca





3841
tattaaagag cttgagttaa aaatagatgc tttttccgaa cggttcgata attactttaa





3901
taatgaaaag agcaatttaa aaataattaa cgaactacaa tccttaataa actcagagac





3961
taaacaatct gatattgcta ataaatctat tgacgagctt tatcatttta atgaaaaaaa





4021
caaacagcta atattatctc ttcaagagaa attagatttt aatgctctgg ctatgaatga





4081
catttctgag catgaaaaat tgataaaaag tatggctaat gaaatttcag agttaaaaaa





4141
tgcattaact atcttgtgtg ataataaaag aaagaataac gagttagatt atatcaatga





4201
attaaaaaaa ctcactgaac gaatagatac acttgaaata aacacatctc aagctagcaa





4261
agtgagtgtc accaatagat ttacaaaatt ccatgaaata gcgcactatg aaaattatga





4321
atatctttca tcctccgaag acatatctaa tagaatttct ttaaatttac aggctgttgg





4381
gttaacaaaa aattcagcag aaacattggc tagattgaca ttagctacct tcgtttctgg





4441
acaaatcatt caattcagtg gctctttggc agatattatc gcggatgcaa ttgccattgc





4501
tattggtgca ccacgttatc acatatggag agttccagtt ggtattattt ctgacatgga





4561
ttcttttgat tttatagaga ctatagctga atcatctcgc tgtctccttt tgaaaggggc





4621
caatctttca gcatttgaga tttatggagc ggcaattaga gatatagttg ttcaacggca





4681
aatacatcca acaaattatg accatctggc attgatagct acttggaaac aaggccctgc





4741
tacattccct gatggaggaa tgttggccga gttgggacca gttattgata ctgatacatt





4801
aaaaatgcgt ggtttatctg ctattttacc ccaattgaaa ccaggttgtc ttgccaagga





4861
taaatggaca aatattgatg gactacagct tgatagtgtt gatgattatg tagatgaatt





4921
aagagcatta ctggacgaag ctggatttga tgggggaact ttgtggaaga gaatggttca





4981
tattttctat acttcactca taagagtccc taatggaaat tatatttatg atctttattc





5041
tgtcttgtct ttttatactc ttacatgggc aaaaattaaa ggtggccccg tccaaaagat





5101
agaagatatt gccaatcgtg aattaaaaaa ttatagtgca aaaatatctt cttgaggagg





5161
tggttaatgg agtggagagc agtatcacga gacaaagcac tggatatgtt atcaactgca





5221
ttaaattgtc gatttgatga tgaagggttg agaatttcag cagtttcaga atgcttaagg





5281
agcgtattat atcaatattc tatatctgaa acagaagaag ctaggcaaac tgtaacctcg





5341
cttcgactca ctagtgcagt aaggcgaaaa ttggtacctt tatggccaga cattgctgat





5401
attgataatg ctatacatcc gggcattatg tctatattga acagcttggc tgaattgggt





5461
gacatgatta agttagaagg tggtaattgg ctcacagctc ccccacatgc agtacgaatt





5521
gacaataaga tggctgtttt ttttggtgga gagccttcct gtacattttc aacgggcgtg





5581
gtagctaaat ctgctggaag agttcgcttg gttgaagaaa aagtgtgtac tggaagtgtt





5641
gaaatctggg atgcaaatga gtggattggt gccccagcag aaggcaatga agaatggtca





5701
tccagactac tatctggaac tatttccggc tttatcgatg cgcctagcaa tatgagtgaa





5761
acgactgcat atgtgcgggg aaaatggctc catttgtcag aactttcttt taataaaaag





5821
caaatctact tatgcagaat gtccgttgat aatcactttt cctattattt aggagaaatt





5881
gaagctggac gcttatgtag aatgaattcg ttagaatcgt ctgatgatgt cagaagatta





5941
cgtttttttc tcgatacaaa agataattgt ccgctaaaga tccgtatcaa aatatctaat





6001
gggctagcaa gattaagatt aaccagaaga ttaccaagac gagaaacgaa ggtactcctg





6061
ctaggctgga gagaatcagg ttttgaaaat gaacattcag gaataacaca ccatgtattc





6121
cccgaggaaa tattacccat agtgcgtagc gcttttgaag ggcttggtat tatttggatt





6181
aacgaattca cgcgacggaa tgaaatatga ttaataaaaa taaagtaact gaacgttcag





6241
gtatacatga taccgtgaaa agccttagtg agaatctgag aaaatacatt gaggcacaat





6301
atcatatccg ggatgaaggg ttaattgctg agcgacgagc gcttttacag caaaatgaaa





6361
ctattgctca agctccttat atagaagcaa ccccaattta tgaacctggt gcgccataca





6421
gtgaattacc tattcccgaa gcagcaagta atgtgctaac tcaactatca gaacttggaa





6481
ttggcctcta tcaacgcccc tataaacacc aatcacaggc acttgagtca tttcttggcg





6541
aagacgcttc tgatctggtc attgcaacag gtacaggctc cggtaagact gaaagctttc





6601
taatgccaat tattggtaaa ttggcgattg aatcttccga gagacctaaa tctgcatccc





6661
ttccaggttg tagagcaatt ttattatatc caatgaatgc attagttaac gatcaacttg





6721
ctcgtatcag acgtcttttt ggtgattctg aagcctctaa aatactgaga tctggaagat





6781
gtgcccctgt acgctttggc gcttatacgg gaagaacgcc ttaccctggt cgtcgtagct





6841
ctagacgaga cgagcttttt atcaaacccc ttttcgatga gttttacaat aaactcgcaa





6901
ataacgcccc tgtacgtgcg gaactgaacc gcattggtcg ctggccaagt aaagatcttg





6961
atgcttttta tgggcaaagc gcatctcagg ctaaaaccta cgtctcaggc aaaaaaacgg





7021
gtaagcaatt tgttttgaac aattgggggg agaggctaat tacccagcct gaggatcgtg





7081
agctaatgac ccggcatgaa atgcagaatc gctgtccaga attactgata acgaactact





7141
ccatgcttga gtatatgctg atgcgaccta tcgagcgtaa tatttttgag cagactaagg





7201
aatggctcaa agctgatgag atgaatgagc ttatcttagt gcttgatgaa gcgcatatgt





7261
atagaggagc agggggagca gaggtagccc ttttaatacg tcgcctctgt gctcggttgg





7321
atattccccg ggaacgtatg cgctgcatcc ttaccagtgc tagtctaggg tccattgagg





7381
atggagaacg ttttgcccaa gacttaactg gcttatcacc aacctcttcg aggaaatttc





7441
gaattattga gggtacaagg gaatcgcgtc ctgagtcaca aattgttacc agtaaagaag





7501
ctaatgcact ggctgaattc gacctaaatt catttcagtg cgtagctgag gatcttgaat





7561
ctgcatatgc agcaatagag tctcttgccg aacgaatggg ctggcaaaag ccgatgataa





7621
aagatcatag tacactacgt aattggttat ttgataattt gactggtttt ggtcctattg





7681
aaacgcttat tgaaatagtt tcaggtaaag cggttaagct aaatatcttg agtgaaaacc





7741
tttttccaga ctctccacag caaattgcag agcgagcgac agatgcatta ctcgcattgg





7801
gttgctatgc tcagagggca tccgatggca gagtgcttat tccaactcgc atgcatcttt





7861
tttatcgggg attaccaggt ctttatgcct gtatagatcc cgattgtaat caacgtttgg





7921
gtaaccatag tgggccaact atacttggcc gcctttatac gaaaccactg gatcaatgta





7981
aatgcgcttc aaaagggcga gtctacgaat tatttaccca ccgtgactgc ggtgcggctt





8041
ttattcgtgg atacgttagt tccgaaatgg actttgtatg gcaccagccg aacggaccat





8101
tatcagaaga tgaggatatc gatcttgttc ccatagatat attggtcgag gaaacacctc





8161
atgtacatag tgattaccag gacagatggc tacatatagc aacaggacgc ctttctaaac





8221
agtgtcaaga tgaggattct ggttatcgta aagtctttat acctgaccga gttaagtctg





8281
gatctgaaat tacatttgat gaatgccctg tttgtatgcg taagacaaga agtgctcaga





8341
atgaaccgtc taaaattatg gatcatgtta caaaagggga agcacctttt acaacgttag





8401
tacgtacaca gatatctcac cagccagcga gtcgtcctat tgatggtaaa catcccaatg





8461
ggggaaaaaa agtacttatt ttttctgatg gccgacaaaa agcagctcgg cttgcacgtg





8521
atattcctag agatattgag cttgatttgt ttcggcaatc cattgctctc gcctgttcta





8581
aactgaaaga tatcaatcgg gaacccaaac caacatcagt actttacctt gctttcctat





8641
cagtcctttc tgaacatgac ttgcttattt ttgatgggga agattcacga aaagttgtaa





8701
tggcccgtga tgaattttat cgtgattata atagcgatct ggctcaagct tttgatgata





8761
acttcagtcc ccaagagtca ccgtcacgat ataaaatagc gttgcttaaa cttttatgta





8821
gcaattacta ttctctttcc ggaacaacag ttggttttgt tgaaccatcg cagcttaaat





8881
caaaaaaaat gtgggaagat gtgcagtcca agaagctaaa tattgagagc aaggatgttc





8941
atgctttagc tgttgcttgg attgatacct tactcactga atttgctttt gatgaatcta





9001
ttgattcgac actacgaatc aaagccgctg gattctacaa acccacttgg ggtagtcaag





9061
gacggtttgg aaaagctctt aggaaaaccc tgatacagca tcctgctatg ggggagcttt





9121
atgtggaagt tttggaggag atttttcgta ctcatctgac attaggaaaa gatggtgtct





9181
actttcttgc tccaaatgca ctacgtctga aaatagatct cttgcatgtc tggaaacaat





9241
gtaatgactg cacggcacta atgccatttg ctttagaaca ttctacttgc cttgcttgtg





9301
gtagtaacag tgtcaaaaca gtcgagccgt cggaaagcag ctatattaat gcacgaaaag





9361
gattctggcg ttcgccggta gaagaagttt tggtttcaaa ttcgcggctt ctaaacctta





9421
gcgttgaaga gcatactgct caactctcac atagagatag ggccagcgtt catgccacta





9481
cagaactcta cgaactgaga ttccaagatg ttcttattaa tgataacgac aagcccattg





9541
atgtacttag ttgtacgacg acgatggaag tgggggttga tattggatct ctggttgctg





9601
ttgctttaag aaacgtccct ccgcaacgag aaaattatca gcaacgtgct gggcgagcag





9661
gccgccgtgg cgcatctgtt tcaacggtgg ttacatattc tcaaaatggc cctcatgata





9721
gttattattt ccttaatcct gaacgcattg ttgcaggttc tcctcgtaca cctgaagtga





9781
aagtaaataa tcccaaaata gccagaagac acgttcattc ttttttagtt cagacctttt





9841
ttcacgagtt aatggaacaa ggaatttata atcccacaga gaaaactgcc atacttgaga





9901
aagcacttgg tactacacga gatttttttc atggagcaaa agatactggc ctaaatctcg





9961
atagctttaa taattgggtt aaaaaccgta ttctatctac taatggtgat ttgagaacaa





10021
gtgttgcagc atggcttcct cctgttcttg aaactggagg gctttctgcc agtgactggt





10081
ttgctaaggt agcagaggaa tttttaaata cactccatgg gctggctgaa attgttccac





10141
aaattgccgc tcttgttgat gaggaaaatg aagatgatga gcagacttct ggtggaatga





10201
aatttgcaca agaagaatta cttgagttcc tgttttacca tggtttatta ccaagttatg





10261
catttcctac aagcctctgt agtttcttgg tagaaaaaat tgtaaagaat attagaggtt





10321
cttttgaggt gcgaacagta caacagcctc agcaatcaat ttctcaggct ctgagtgaat





10381
atgccccggg acgtttgatt gttattgata ggaaaaccta tcgctctggt ggtgtttttt





10441
ctaatgcatt gaaaggcgaa ctaaaccggg caagaaagct tttcaataat cccaaaaagt





10501
ttattcattg cgataagtgc tcttttgtcc gcgatcctca taataatcag aatagcgaaa





10561
atacttgtcc gatctgtggt ggcattctaa aagtagaaat aatgattcag cccgaagtct





10621
ttggacctga aaatgccaag gaacttaatg aggacgacag agagcaagaa atcacctatg





10681
taactgcggc acaatatcca caacctgttg atcctgaaga ttttaagttc aataatggag





10741
gtgctcatat tgtttttact cacgcaatag atcagaaact ggtgacggtg aaccgaggga





10801
aaaatgaggg ggggtccagt ggtttttcag tatgttgcga atgtggtgcg gcctccgttt





10861
atgattccta ctcaccggca aagggggcac atgaaagacc gtataaatat atagcaacta





10921
aggaaacgcc tcgcttatgc tctggcgagt ataaacgcgt ttttctcgga catgatttcc





10981
gtactgattt gcttttatta cgaataaccg ttgggtctcc gcttgtaact gatacttcaa





11041
atgctatcgt tttacggatg tatgaagatg cattatatac aatagcggaa gcactaaggc





11101
ttgcagctag tcgccataaa caactggatc ttgatcctgc tgagtttggc tctggtttca





11161
gaattttacc cactatagag gaagatactc aggcattgga tctcttcctt tatgatactt





11221
tatctggcgg tgcgggttat gcggaagtag cagcagcgaa tctagatgac attcttactg





11281
caacactcgc attgttagaa ggttgtgagt gcgatacctc ctgtacagat tgtctcaatc





11341
atttccacaa ccagcatata caaagccgtc tcgataggaa actaggtgca tctttacttc





11401
gttatgctct atacggaatg gttcctcgtt gtgcttcacc tgatattcag gtagaaaaat





11461
tgtctcaatt gagggcaagt ctggaattgg atggttttca atgcctaatt aagggaactc





11521
aggaggcacc tatgattgtg agtttgaatg accgttctgt tgcagtggga agttaccctg





11581
gtcttattga tcgacccgac tttcaacacg acgtatataa gtcaaagaat actaatgctc





11641
atatagcctt taatgaatat cttcttcgtt caaatctgcc acaagcgcat caaaatatta





11701
gaaaattgtt gcgctgatag cagtattgag tgccctaaag tcctataggg cactcaaggt





11761
tattctcttt taatatttgt taatagcatg tattttaagg ctttcagtcc ttgagctggc





11821
ttttacacaa cgagaaagag gtaattataa taccagccgg atatggcgag aaatggtggc





11881
ccgggggtgt aagtatcccg cataatcgtg ccattcatat ttagagatca tccggcataa





11941
tcaatctgct aacgaaggag atcgcta.









The coding regions for each of the druA, drub, druC, drub, and druE gene sequences within this embodiment of a Druantia Type I cassette (SEQ ID NO: 16) are as follows: nucleotides 378-1592 encode an embodiment of a DruA polypeptide; nucleotides 16614-3260 encode an embodiment of a DruB polypeptide; nucleotides 3272-5155 encode an embodiment of a DruC polypeptide, nucleotides 5167-6210 encode an embodiment of a DruD polypeptide; and nucleotides 6207-11717 encode an embodiment of a DruE polypeptide.


In some embodiments, a Defense System IIIa comprising a DruA polypeptide, a DruB polypeptide, a DruC polypeptide, a DruD polypeptide and a DruE polypeptide is encoded by the nucleic acid sequence set forth in SEQ ID NO: 16. In some embodiments, a Defense System IIIa comprising a DruA polypeptide, a DruB polypeptide, a DruC polypeptide, a DruD polypeptide and a DruE polypeptide, is encoded by a nucleic acid sequence having at least 80% homology to the sequence set forth in SEQ ID NO: 16. In some embodiments, a Defense System IIIa comprising a DruA polypeptide, a DruB polypeptide, a DruC polypeptide, a DruD polypeptide and a DruE polypeptide, is encoded by a nucleic acid sequence having at least 85% homology, or 90% homology, or 95% homology, or 97% homology, or 98% homology, or 99% homology to the sequence set forth in SEQ ID NO: 16. In some embodiments, a Defense System IIIa comprising a DruA polypeptide, a DruB polypeptide, a DruC polypeptide, a DruD polypeptide and a DruE polypeptide, is encoded by a nucleic acid sequence having at least 80% identity to the sequence set forth in SEQ ID NO: 16. In some embodiments, a Defense System IIIa comprising a DruA polypeptide, a DruB polypeptide, a DruC polypeptide, a DruD polypeptide and a DruE polypeptide, is encoded by a nucleic acid sequence having at least 85% identity, or 90% identity, or 95% identity, or 97% identity, or 98% identity, or 99% identity to the sequence set forth in SEQ ID NO: 16.


In some embodiments, the Type I Druantia anti-phage defense system comprises a nucleic acid construct comprising nucleic acid sequences encoding a gene cassette comprising druB, druC, druD, and druE genes. In some embodiments, the Type I Druantia anti-phage defense system comprises a nucleic acid construct comprising nucleic acid sequences encoding a gene cassette comprising druB, druC, druD, druE, and druA genes.


In some embodiments, a construct comprising the Type I Druantia anti-phage defense system encodes one component of the defense system, whereby multiple constructs may be used to assemble the functional defense system. In some embodiments, the components of a Druantia defense system comprise polypeptides DruA, DruB, DruC, DruD, and DruE. In some embodiments, the components of a Druantia Type I defense system comprise polypeptides DruB, DruC, DruD, and DruE.


In some embodiments, a construct comprising the Druantia Type I anti-phage defense system encodes one component of the defense system, whereby multiple constructs may be used to assemble the functional defense system. In some embodiments, the components of a Druantia defense system comprise genes druA, druB, druC, druD, and druE. In some embodiments, the components of a Druantia Type I defense system comprise genes druB, druC, druD, and druE.


In some embodiments, the components of a Druantia Type I defense system consists of genes druA, druB, druC, druD, and druE. In some embodiments, the components of a Druantia Type I defense system consist of genes druB, druC, druD, and druE.


In some embodiments, the components of a Druantia Type I defense system comprise nucleic acid sequences encoding a DruA polypeptide, a DruB polypeptide, a DruC polypeptide, a DruD polypeptide, and a DruE polypeptide. In some embodiments, the components of a Druantia Type I defense system comprise nucleic acid sequences encoding a DruB polypeptide, a DruC polypeptide, a DruD polypeptide, and a DruE polypeptide. In some embodiments, the components of a Druantia Type I defense system comprise nucleic acid sequences encoding a DruB polypeptide, a DruC polypeptide, a DruD polypeptide, a DruE polypeptide, and a DruA polypeptide.


In some embodiments, the components of a Druantia Type I defense system consist of nucleic acid sequences encoding a DruA polypeptide, a DruB polypeptide, a DruC polypeptide, a DruD polypeptide, and a DruE polypeptide. In some embodiments, the components of a Druantia Type I defense system consist of nucleic acid sequences encoding a DruB polypeptide, a DruC polypeptide, a DruD polypeptide, and a DruE polypeptide. In some embodiments, the components of a Druantia Type I defense system consist of nucleic acid sequences encoding a DruB polypeptide, a DruC polypeptide, a DruD polypeptide, a DruE polypeptide, and a DruA polypeptide.


In some embodiments, a construct comprising the Druantia Type I defense system encodes one component of the defense system, whereby a second, third, fourth, or fifth construct may be used to assemble the functional defense system. In some embodiments, a construct comprising the Druantia defense system encodes one component of the defense system, whereby additional constructs may be used to assemble the functional defense system. For example, in some embodiments each of DruA, DruB, DruC, DruD, and DruE may be encoded by nucleic acid sequences comprised in different constructs, wherein expression of the combination of constructs produces a functional Druantia defense system. In some embodiments each of DruB, DruC, DruD, and DruE may be encoded by nucleic acid sequences comprised in different constructs, wherein expression of the combination of constructs produces a functional Druantia defense system.


In some embodiments, the components making up a functional Druantia Type I anti-phage defense system comprise a DruA polypeptide, a DruB polypeptide, a DruC polypeptide, a DruD polypeptide, and a DruE polypeptide, each encoded by a druA, druB, druC, druD, or druE gene, respectively. In some embodiments, the components making up a functional Druantia Type I anti-phage defense system comprise a DruB polypeptide, a DruC polypeptide, a DruD polypeptide, and a DruE polypeptide, each encoded by a druB, druC, druD, or druE gene, respectively.


In some embodiments, a Druantia Type I defense system having an anti-phage activity comprises a nucleic acid encoding a DruA polypeptide. In some embodiments, a Druantia Type I defense system having an anti-phage activity comprises a nucleic acid encoding a DruB polypeptide. In some embodiments, a Druantia Type I defense system having an anti-phage activity comprises a nucleic acid encoding a DruC polypeptide. In some embodiments, a Druantia Type I defense system having an anti-phage activity comprises a nucleic acid encoding a DruD polypeptide. In some embodiments, a Druantia Type I defense system having an anti-phage activity comprises a nucleic acid encoding a DruE polypeptide.


In some embodiments, a Druantia Type I defense system having an anti-phage activity comprises a nucleic acid encoding a DruB polypeptide and a DruE polypeptide. In some embodiments, a Druantia defense system having an anti-phage activity comprises a nucleic acid encoding a DruC polypeptide and a DruE polypeptide. In some embodiments, a Druantia Type I defense system having an anti-phage activity comprises a nucleic acid encoding a DruB polypeptide, a DruC polypeptide, and a DruE polypeptide.


In some embodiments, a Druantia Type I defense system having an anti-phage activity comprise a nucleic acid comprising a druA gene. In some embodiments, a Druantia Type I defense system having an anti-phage activity comprise a nucleic acid comprising a druB gene. In some embodiments, a Druantia Type I defense system having an anti-phage activity comprise a nucleic acid comprising a druC gene. In some embodiments, a Druantia Type I defense system having an anti-phage activity comprise a nucleic acid comprising a druD gene. In some embodiments, a Druantia Type I defense system having an anti-phage activity comprise a nucleic acid comprising a druE gene.


In some embodiments, a Druantia Type I defense system having an anti-phage activity comprises a nucleic acid construct comprising nucleic acids encoding polypeptides in a set order. In one embodiment, the 5′ to 3′ order of polypeptides encoded is DruA, DruB, DruC, DruD, and DruE. In one embodiment, the 5′ to 3′ order of polypeptides encoded is DruB, DruC, DruD, and DruE. In one embodiment, the 5′ to 3′ order of polypeptides encoded is DruB, DruC, DruD, DruE, and DruA.


In some embodiments, the 5′ to 3′ order of polypeptides is random, for example any order of DruA, DruB, DruC, DruD, and DruE. In some embodiments, the 5′ to 3′ order of polypeptides is random, for example any order of DruB, DruC, DruD, and DruE.


In some embodiments the 5′ to 3′ order of polypeptides does not affect the anti-phage activity. In some embodiments the 5′ to 3′ order of polypeptides does affect the anti-phage activity.


In some embodiments, a Druantia Type I defense system having an anti-phage activity comprises a nucleic acid construct comprising genes in a set order. In some embodiment, the 5′ to 3′ order of genes is druA, druB, druC, druD, and druE. In some embodiment, the 5′ to 3′ order of genes is druB, druC, druD, and druE. In some embodiment, the 5′ to 3′ order of genes is druB, druC, druD, druE, and druA.


In some embodiments, the 5′ to 3′ order of genes is random, for example any order of druA, druB, druC, druD, and druE. In some embodiments, the 5′ to 3′ order of genes is random, for example any order of druB, druC, druD, and druE.


In some embodiments the 5′ to 3′ order of genes does not affect the anti-phage activity. In some embodiments the 5′ to 3′ order of genes does affect the anti-phage activity.


In some embodiments, a Druantia Type II defense system (Defense System IIIb) having an anti-phage activity comprises a nucleic acid construct comprising a nucleic acid sequence encoding a DruM polypeptide comprising a COG0270 domain or a pfam00145 domain or a combination thereof, a DruF polypeptide, a DruG polypeptide, and a DruE polypeptide comprising a pfam00270 domain or a pfam00271 domain or a pfam09369 domain or a DUF1998 domain or any combination thereof. In some embodiments, a Druantia Type II defense system (Defense System IIIb) having an anti-phage activity comprises a nucleic acid construct comprising a nucleic acid sequence encoding a DruM polypeptide comprising a COG0270 domain or a pfam00145 domain or a combination thereof, a DruF polypeptide wherein said DruF polypeptide is encoded by a gene positioned within 5 genes of a gene encoding said DruM polypeptide and said DruE polypeptide, a DruG polypeptide wherein said DruG polypeptide is encoded by a gene positioned within 5 genes of a gene encoding said DruM polypeptide and said DruE polypeptide, and a DruE polypeptide comprising a pfam00270 domain or a pfam00271 domain or a pfam09369 domain or a DUF1998 domain or any combination thereof.


In some embodiments, a Druantia Type II defense system (Defense System IIIb) having an anti-phage activity comprises a DruM polypeptide comprising a COG0270 domain or a pfam00145 domain or a combination thereof, a DruF polypeptide, a DruG polypeptide, and a DruE polypeptide comprising a pfam00270 domain or a pfam00271 domain or a pfam09369 domain or a DUF1998 domain or any combination thereof. In some embodiments, a Druantia Type II defense system (Defense System IIIb) having an anti-phage activity comprises a DruM polypeptide comprising a COG0270 domain or a pfam00145 domain or a combination thereof, a DruF polypeptide wherein said DruF polypeptide is encoded by a gene positioned within 5 genes of a gene encoding said DruM polypeptide and said DruE polypeptide, a DruG polypeptide wherein said DruG polypeptide is encoded by a gene positioned within 5 genes of a gene encoding said DruM polypeptide and said DruE polypeptide, and a DruE polypeptide comprising a pfam00270 domain or a pfam00271 domain or a pfam09369 domain or a DUF1998 domain or any combination thereof.


In some embodiments, a Defense System IIIb comprises a DruM polypeptide comprising a pfam00145 domain or a COG0270 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 124-295 columns AD and AE; or a DruF polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 124-295 columns AH and AI; or a DruG polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 124-295 columns AL and AM; or a DruE polypeptide comprising a pfam00270 domain or a pfam00271 domain or a pfam09369 domain or a DUF1998 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-1343 columns Z and AA; or any combination thereof.


In some embodiments a Defense System IIIb comprises at least two different polypeptide components selected from a DruM polypeptide comprising a pfam00145 domain or a COG0270 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 124-295 columns AD and AE; or a DruF polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 124-295 columns AH and AI; or a DruG polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 124-295 columns AL and AM; or a DruE polypeptide comprising a pfam00270 domain or a pfam00271 domain or a pfam09369 domain or a DUF1998 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-1343 columns Z and AA; or any combination thereof. In some embodiments a Defense System IIIb comprises at least three different polypeptide components selected from a DruM polypeptide comprising a pfam00145 domain or a COG0270 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 124-295 columns AD and AE; or a DruF polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 124-295 columns AH and AI; or a DruG polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 124-295 columns AL and AM; or a DruE polypeptide comprising a pfam00270 domain or a pfam00271 domain or a pfam09369 domain or a DUF1998 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-1343 columns Z and AA; or any combination thereof. In some embodiments a Defense System IIIb comprises four different polypeptide components selected from a DruM polypeptide comprising a pfam00145 domain or a COG0270 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 124-295 columns AD and AE; or a DruF polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 124-295 columns AH and AI; or a DruG polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 124-295 columns AL and AM; or a DruE polypeptide comprising a pfam00270 domain or a pfam00271 domain or a pfam09369 domain or a DUF1998 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-1343 columns Z and AA; or any combination thereof.


In some embodiments, a functional Defense System IIIb comprises at least two different polypeptide components selected from a DruM polypeptide comprising a pfam00145 domain or a COG0270 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 124-295 columns AD and AE; or a DruF polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 124-295 columns AH and AI; or a DruG polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 124-295 columns AL and AM; or a DruE polypeptide comprising a pfam00270 domain or a pfam00271 domain or a pfam09369 domain or a DUF1998 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-1343 columns Z and AA; or any combination thereof. In some embodiments, a functional Defense System IIIb comprises at least three different polypeptide components selected from a DruM polypeptide comprising a pfam00145 domain or a COG0270 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 124-295 columns AD and AE; or a DruF polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 124-295 columns AH and AI; or a DruG polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 124-295 columns AL and AM; or a DruE polypeptide comprising a pfam00270 domain or a pfam00271 domain or a pfam09369 domain or a DUF1998 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-1343 columns Z and AA; or any combination thereof. In some embodiments, a functional Defense System IIIb comprises four different polypeptide components selected from a DruM polypeptide comprising a pfam00145 domain or a COG0270 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 124-295 columns AD and AE; or a DruF polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 124-295 columns AH and AI; or a DruG polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 124-295 columns AL and AM; or a DruE polypeptide comprising a pfam00270 domain or a pfam00271 domain or a pfam09369 domain or a DUF1998 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-1343 columns Z and AA; or any combination thereof.


In some embodiments, a Druantia Type II defense system (Defense System IIIb) having an anti-phage activity comprises a nucleic acid construct comprising a nucleic acid sequence comprising a druM gene, a druF gene, a druG gene, and a druE gene.


In some embodiments, the Druantia Type II anti-phage defense system comprises a nucleic acid construct comprising nucleic acid sequences encoding a gene cassette comprising druM, druF, druG, and druE genes. In some embodiments, the Type II Druantia anti-phage defense system comprises a nucleic acid construct comprising nucleic acid sequences encoding a gene cassette comprising druM, druF, druG, and druE genes.


In some embodiments, a construct comprising the Type II Druantia anti-phage defense system encodes one component of the defense system, whereby multiple constructs may be used to assemble the functional defense system. In some embodiments, the components of a Druantia defense system comprise polypeptides DruM, DruF, DruG, and DruE.


In some embodiments, a construct comprising the Druantia Type II anti-phage defense system encodes one component of the defense system, whereby multiple constructs may be used to assemble the functional defense system. In some embodiments, the components of a Druantia defense system comprise genes druM, druF, druG, and druE.


In some embodiments, the components of a Druantia Type II defense system consists of genes druM, druF, druG, and druE.


In some embodiments, the components of a Druantia Type II defense system comprise nucleic acid sequences encoding a DruM polypeptide, a DruF polypeptide, a DruG polypeptide, and a DruE polypeptide.


In some embodiments, the components of a Druantia Type II defense system consist of nucleic acid sequences encoding a DruM polypeptide, a DruF polypeptide, a DruG polypeptide, and a DruE polypeptide.


In some embodiments, a construct comprising the Druantia Type II defense system encodes one component of the defense system, whereby a second, third, or fourth, construct may be used to assemble the functional defense system. In some embodiments, a construct comprising the Druantia defense system encodes one component of the defense system, whereby additional constructs may be used to assemble the functional defense system. For example, in some embodiments each of DruM, DruF, DruG, and DruE may be encoded by nucleic acid sequences comprised in different constructs, wherein expression of the combination of constructs produces a functional Druantia Type II defense system.


In some embodiments, the components making up a functional Druantia Type II anti-phage defense system comprise a DruM polypeptide, a DruF polypeptide, a DruG polypeptide, and a DruE polypeptide, each encoded by a druM, druF, druG, or druE gene, respectively.


In some embodiments, a Druantia Type II defense system having an anti-phage activity comprises a nucleic acid encoding a DruM polypeptide. In some embodiments, a Druantia Type II defense system having an anti-phage activity comprises a nucleic acid encoding a DruF polypeptide. In some embodiments, a Druantia Type II defense system having an anti-phage activity comprises a nucleic acid encoding a DruG polypeptide. In some embodiments, a Druantia Type II defense system having an anti-phage activity comprises a nucleic acid encoding a DruE polypeptide.


In some embodiments, a Druantia Type II defense system having an anti-phage activity comprises a nucleic acid encoding a DruM polypeptide and a DruE polypeptide. In some embodiments, a Druantia defense system having an anti-phage activity comprises a nucleic acid encoding a DruF polypeptide and a DruE polypeptide. In some embodiments, a Druantia Type II defense system having an anti-phage activity comprises a nucleic acid encoding a DruG polypeptide and a DruE polypeptide. In some embodiments, a Druantia defense system having an anti-phage activity comprises a nucleic acid encoding a DruM polypeptide, a DruF polypeptide, and a DruE polypeptide. In some embodiments, a Druantia Type II defense system having an anti-phage activity comprises a nucleic acid encoding a DruM polypeptide, a DruG polypeptide, and a DruE polypeptide. In some embodiments, a Druantia Type II defense system having an anti-phage activity comprises a nucleic acid encoding a DruM polypeptide, a DruF polypeptide, and a DruG polypeptide. In some embodiments, a Druantia Type II defense system having an anti-phage activity comprises a nucleic acid encoding a DruF polypeptide, a DruG polypeptide, and a DruE polypeptide. In some embodiments, a Druantia Type II defense system having an anti-phage activity comprises a nucleic acid encoding a DruF polypeptide and a DruG polypeptide.


In some embodiments, a Druantia Type II defense system having an anti-phage activity comprise a nucleic acid comprising a druM gene. In some embodiments, a Druantia Type II defense system having an anti-phage activity comprise a nucleic acid comprising a druF gene. In some embodiments, a Druantia Type II defense system having an anti-phage activity comprise a nucleic acid comprising a druG gene. In some embodiments, a Druantia Type II defense system having an anti-phage activity comprise a nucleic acid comprising a druE gene.


In some embodiments, a Druantia Type II defense system having an anti-phage activity comprises a nucleic acid construct comprising nucleic acids encoding polypeptides in a set order. In one embodiment, the 5′ to 3′ order of polypeptides encoded is DruM, DruF, DruG, and DruE.


In some embodiments, the 5′ to 3′ order of polypeptides is random, for example any order of DruM, DruF, DruG, and DruE.


In some embodiments the 5′ to 3′ order of polypeptides does not affect the anti-phage activity. In some embodiments the 5′ to 3′ order of polypeptides does affect the anti-phage activity.


In some embodiments, a Druantia Type II defense system having an anti-phage activity comprises a nucleic acid construct comprising genes in a set order. Non-limiting examples of the 5′ to 3′ order or genes comprises druM, druF, druG, and druE; druF, druG, druE, and drum; druG, druE, druM, and druF; and druE, druM, druG, and druF.


In some embodiments, the 5′ to 3′ order of genes is random, for example any order of druM, druF, druG, and druE.


In some embodiments the 5′ to 3′ order of genes does not affect the anti-phage activity. In some embodiments the 5′ to 3′ order of genes does affect the anti-phage activity.


In some embodiments, a Druantia Type III defense system (Defense System IIIc) having an anti-phage activity comprises a nucleic acid construct comprising a nucleic acid sequence encoding a DruH polypeptide and a DruE polypeptide comprising a pfam00270 domain or a pfam00271 domain or a pfam09369 domain or a DUF1998 domain or any combination thereof. In some embodiments, a Druantia Type III defense system (Defense System IIIc) having an anti-phage activity comprises a nucleic acid construct comprising a nucleic acid sequence encoding a DruH polypeptide and said DruE polypeptide, wherein said DruH polypeptide is encoded by a gene positioned within 5 genes of a gene encoding said DruE polypeptide.


In some embodiments, a Druantia Type III defense system (Defense System IIIc) having an anti-phage activity comprises a DruH polypeptide and a DruE polypeptide comprising a pfam00270 domain or a pfam00271 domain or a pfam09369 domain or a DUF1998 domain or any combination thereof. In some embodiments, a Druantia Type III defense system (Defense System IIIc) having an anti-phage activity comprises a DruH polypeptide and a DruE polypeptide comprising a pfam00270 domain or a pfam00271 domain or a pfam09369 domain or a DUF1998 domain or any combination thereof, wherein said DruH polypeptide is encoded by a gene positioned within 5 genes of a gene encoding said DruE polypeptide.


In some embodiments, a Defense System IIIc comprises a DruH polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 296-1343 columns AP and AQ; or a DruE polypeptide comprising a pfam00270 domain or a pfam00271 domain or a pfam09369 domain or a DUF1998 domain or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-1343 columns Z nd AA or a combination thereof; or any combination thereof.


In some embodiments, a Druantia Type IIII defense system (Defense System IIIc) having an anti-phage activity comprises a nucleic acid construct comprising a nucleic acid sequence comprising a druH gene and a druE gene.


In some embodiments, the Druantia Type IIII anti-phage defense system comprises a nucleic acid construct comprising nucleic acid sequences encoding a gene cassette comprising druH and druE genes.


In some embodiments, a construct comprising the Type III Druantia anti-phage defense system encodes one component of the defense system, whereby multiple constructs may be used to assemble the functional defense system. In some embodiments, the components of a Druantia defense system comprise polypeptides DruH and DruE.


In some embodiments, a construct comprising the Druantia Type III anti-phage defense system encodes one component of the defense system, whereby multiple constructs may be used to assemble the functional defense system. In some embodiments, the components of a Druantia defense system comprise genes druH and druE.


In some embodiments, the components of a Druantia Type III defense system consists of genes druH and druE.


In some embodiments, the components of a Druantia Type III defense system comprise nucleic acid sequences encoding a DruH polypeptide and a DruE polypeptide.


In some embodiments, the components of a Druantia Type III defense system consist of nucleic acid sequences encoding a DruH polypeptide and a DruE polypeptide.


In some embodiments, a construct comprising the Druantia Type III defense system encodes one component of the defense system, whereby a second construct may be used to assemble the functional defense system. In some embodiments, a construct comprising the Druantia Type III defense system encodes one component of the defense system, whereby an additional construct may be used to assemble the functional defense system. For example, in some embodiments each of DruH and DruE may be encoded by nucleic acid sequences comprised in different constructs, wherein expression of the combination of constructs produces a functional Druantia defense system.


In some embodiments, the components making up a functional Druantia Type III anti-phage defense system (Defense System IIIc) comprise a DruH polypeptide and a DruE polypeptide, each encoded by a druH and druE gene, respectively. In some embodiments, a Defense System IIIc comprises at least two different polypeptide components selected from DruH and DruE, as described herein. In some embodiments, a functional Defense System IIIc comprises at least two different polypeptide components selected from DruH and DruE, as described herein. In some embodiments, a functional Defense System IIIc having anti-phage activity comprises at least two different polypeptide components selected from DruH and DruE, as described herein.


In some embodiments, a Druantia Type III defense system having an anti-phage activity comprises a nucleic acid encoding a DruH polypeptide. In some embodiments, a Druantia Type III defense system having an anti-phage activity comprises a nucleic acid encoding a DruE polypeptide.


In some embodiments, a Druantia Type III defense system having an anti-phage activity comprises a nucleic acid encoding a DruH polypeptide and a DruE polypeptide.


In some embodiments, a Druantia Type III defense system having an anti-phage activity comprise a nucleic acid comprising a druH gene. In some embodiments, a Druantia Type III defense system having an anti-phage activity comprise a nucleic acid comprising a druE gene.


In some embodiments, a Druantia Type III defense system having an anti-phage activity comprises a nucleic acid construct comprising nucleic acids encoding polypeptides in a set order. In one embodiment, the 5′ to 3′ order of polypeptides encoded is DruH and DruE. In one embodiment, the 5′ to 3′ order of polypeptides encoded is DruE and DruH.


In some embodiments, the 5′ to 3′ order of polypeptides is random, for example any order of DruH and DruE.


In some embodiments the 5′ to 3′ order of polypeptides does not affect the anti-phage activity. In some embodiments the 5′ to 3′ order of polypeptides does affect the anti-phage activity.


In some embodiments, a Druantia Type III defense system having an anti-phage activity comprises a nucleic acid construct comprising genes in a set order. In some embodiment, the 5′ to 3′ order of genes is druH and druE.


In some embodiments, the 5′ to 3′ order of genes is random, for example any order of druH and druE.


In some embodiments the 5′ to 3′ order of genes does not affect the anti-phage activity. In some embodiments the 5′ to 3′ order of genes does affect the anti-phage activity.


In some embodiments, the Druantia system (Defense Systems IIIa, IIIb, and IIIc) composition and order is as shown in FIG. 3C, FIG. 6A, or FIG. 6B.


In some embodiments, a Druantia defense system having an anti-phage activity originates from a microbial genome, for example a bacterial or an archaeal genome (Table 10). A skilled artisan would appreciate that the Druantia system is not present in the majority of bacteria and or archaea species.


In some embodiments, a functional Druantia defense system (Defense System IIIa, Defense System IIIb, and/or Defense System IIIc) comprises a construct comprising nucleic acid sequences encoding polypeptides, wherein the nucleic acid sequence encoding each polypeptide may originate from a different microbial species. In some embodiments, a functional Druantia defense system (Defense System IIIa, Defense System IIIb, and/or Defense System IIIc) comprises a non-naturally occurring combination of polypeptide components. In some embodiments, a functional Druantia defense system (Defense System IIIa, Defense System IIIb, and/or Defense System IIIc) comprises a combination of at least two polypeptides that do not naturally occur together. In some embodiments, a functional Druantia defense system (Defense System IIIa, Defense System IIIb, and/or Defense System IIIc) comprises a combination of at least three polypeptides that do not naturally occur together. In some embodiments, a functional Druantia defense system (Defense System IIIa, Defense System IIIb, and/or Defense System IIIc) comprises a combination of at least four polypeptides that do not naturally occur together. In some embodiments, a functional Druantia defense system (Defense System IIIa, Defense System IIIb, and/or Defense System IIIc) comprises a combination of at least five polypeptides that do not naturally occur together.


For example, the source of the nucleic acid sequence encoding a DruA polypeptide may be one microbial species, the source of the nucleic acid sequence encoding a DruB polypeptide may be a different microbial species, the source of the nucleic acid sequence encoding a DruC polypeptide may be a different microbial species, the source of the nucleic acid sequence encoding a DruD polypeptide may be a different microbial species, and the source of the nucleic acid sequence encoding a DruE polypeptide may be yet a different microbial species. In some embodiments, the source of the nucleic acid sequence encoding some of the components of the Druantia system Type I (Defense System IIIa; DruA, DruB, DruC, DruD, and DruE) are the same, while the source of others is different. In some embodiments, the source of the nucleic acid sequence encoding the components of the Druantia Type I system (DruA, DruB, DruC, DruD, and DruE) is the same.


In other embodiments, the source of the nucleic acid sequence encoding a DruM polypeptide may be one microbial species, the source of the nucleic acid sequence encoding a DruF polypeptide may be a different microbial species, the source of the nucleic acid sequence encoding a DruG polypeptide may be a different microbial species, and the source of the nucleic acid sequence encoding a DruE polypeptide may be a different microbial species. In some embodiments, the source of the nucleic acid sequence encoding some of the components of the Druantia Type II system (Defense System IIIb; DruM, DruF, DruG, and DruE) are the same, while the source of others is different. In some embodiments, the source of the nucleic acid sequence encoding the components of the Druantia Type II system (DruM, DruF, DruG, and DruE) is the same.


In other embodiments, the source of the nucleic acid sequence encoding a DruH polypeptide may be one microbial species, and the source of the nucleic acid sequence encoding a DruE polypeptide may be a different microbial species. In some embodiments, the source of the nucleic acid sequence encoding the components of the Druantia Type III system (Defense System IIIc; DruH and DruE) is the same.


In some embodiments, a functional Druantia Type I defense system comprises a construct comprising nucleic acid sequences encoding polypeptides, wherein the nucleic acid sequence encoding each polypeptide may originate from a different bacterial species. For example, the source of the nucleic acid sequence encoding a DruA polypeptide may be one bacterial species, the source of the nucleic acid sequence encoding a DruB polypeptide may be a different bacterial species, the source of the nucleic acid sequence encoding a DruC polypeptide may be a different bacterial species, the source of the nucleic acid sequence encoding a DruD polypeptide may be a different bacterial species, and the source of the nucleic acid sequence encoding a DruE polypeptide may be yet a different bacterial species. In some embodiments, the source of the nucleic acid sequence encoding some of the components of the Druantia Type I system (DruA, DruB, DruC, DruD, and DruE) are the same, while the source of others is different. In some embodiments, the source of the nucleic acid sequence encoding the components of the Druantia Type I system (DruA, DruB, DruC, DruD, and DruE) is the same.


In other embodiments, the source of the nucleic acid sequence encoding a DruM polypeptide may be one bacterial species, the source of the nucleic acid sequence encoding a DruF polypeptide may be a different bacterial species, the source of the nucleic acid sequence encoding a DruG polypeptide may be a different bacterial species, and the source of the nucleic acid sequence encoding a DruE polypeptide may be a different bacterial species. In some embodiments, the source of the nucleic acid sequence encoding some of the components of a functional Druantia Type II system (DruM, DruF, DruG, and DruE) are the same, while the source of others is different. In some embodiments, the source of the nucleic acid sequence encoding the components of a functional Druantia Type II system (DruM, DruF, DruG, and DruE) is the same.


In other embodiments, in a functional Type III Druantia system, the source of the nucleic acid sequence encoding a DruH polypeptide may be one bacterial species, and the source of the nucleic acid sequence encoding a DruE polypeptide may be a different bacterial species. In some embodiments, the source of the nucleic acid sequence encoding the components of a functional Druantia Type III system (DruH and DruE) is the same.


In some embodiments, the source of the nucleic acid sequence of any of the components of a Druantia defense system (Defense Systems IIIa [Druantia defense system I], IIIb [Druantia defense system II], and IIIc [Druantia defense system III]) comprises any of the species listed in Table 10.


In some embodiments, a Druantia Type I defense system having an anti-phage activity comprises a nucleic acid construct comprising non-coding regions between the nucleic acid sequences encoding the polypeptides. In some embodiments, the non-coding regions between the nucleic acid sequences comprises nucleic acid sequence not naturally occurring in the microbial species of origin. In some embodiments, the non-coding regions between the nucleic acid sequences comprises nucleic acid sequence is the naturally occurring in the microbial species of origin.


In some embodiments, a Druantia Type II defense system having an anti-phage activity comprises a nucleic acid construct comprising non-coding regions between the nucleic acid sequences encoding the polypeptides. In some embodiments, the non-coding regions between the nucleic acid sequences comprises nucleic acid sequence not naturally occurring in the microbial species of origin. In some embodiments, the non-coding regions between the nucleic acid sequences comprises nucleic acid sequence is the naturally occurring in the microbial species of origin.


In some embodiments, a Druantia Type III defense system having an anti-phage activity comprises a nucleic acid construct comprising non-coding regions between the nucleic acid sequences encoding the polypeptides. In some embodiments, the non-coding regions between the nucleic acid sequences comprises nucleic acid sequence not naturally occurring in the microbial species of origin. In some embodiments, the non-coding regions between the nucleic acid sequences comprises nucleic acid sequence is the naturally occurring in the microbial species of origin.


In some embodiments, a Druantia Type I system disclosed herein comprises a multi-gene phage resistance system broadly distributed in microbial genomes, for example but not limited to bacteria and archaea. Yet, the majority of bacterial species do not express a Druantia Type I defense system.


In some embodiments, a Druantia Type II system disclosed herein comprises a multi-gene phage resistance system broadly distributed in microbial genomes, for example but not limited to bacteria and archaea. Yet, the majority of bacterial species do not express a Druantia Type II defense system.


In some embodiments, a Druantia Type III system disclosed herein comprises a multi-gene phage resistance system broadly distributed in microbial genomes, for example but not limited to bacteria and archaea. Yet, the majority of bacterial species do not express a Druantia Type III defense system.


According to some embodiments, the Druantia systems' (Type I) components are located in a gene cluster (a cassette of genes) in a microbial cell genome. According to some embodiments, the Druantia system components are located in close proximity (e.g. positioned within 20 genes, 10 genes, 5 genes or less one from the other) in a genome of a prokaryotic cell. According to some embodiments the prokaryotic cell expresses an endogenous Druantia Type I defense system. According to some embodiments, the prokaryotic cell expresses an endogenous functional Druantia Type I defense system. According to some embodiments, the species of prokaryotic cell is selected from the group consisting of the species listed in Table 10.


According to some embodiments a prokaryotic cell expresses a non-endogenous Druantia Type I defense system. According to some embodiments, a prokaryotic cell expresses a non-endogenous functional Druantia Type I defense system. According to some embodiments, the species of prokaryotic cell expressing a non-endogenous functional Druantia Type I defense system is selected from the group consisting of the species listed in Table 10.


According to some embodiments, the Druantia systems' (Type II) components are located in a gene cluster (a cassette of genes) in a microbial cell genome. According to some embodiments, the Druantia system components are located in close proximity (e.g. positioned within 20 genes, 10 genes, 5 genes or less one from the other) in a genome of a prokaryotic cell. According to some embodiments the prokaryotic cell expresses an endogenous Druantia Type II defense system. According to some embodiments, the prokaryotic cell expresses an endogenous functional Druantia Type II defense system. According to some embodiments, the species of prokaryotic cell is selected from the group consisting of the species listed in Table 10.


According to some embodiments a prokaryotic cell expresses a non-endogenous Druantia Type II defense system. According to some embodiments, a prokaryotic cell expresses a non-endogenous functional Druantia Type II defense system. According to some embodiments, the species of prokaryotic cell expressing a non-endogenous functional Druantia Type II defense system is selected from the group consisting of the species listed in Table 10.


According to some embodiments, the Druantia systems' (Type III) components are located in a gene cluster (a cassette of genes) in a microbial cell genome. According to some embodiments, the Druantia system components are located in close proximity (e.g. positioned within 20 genes, 10 genes, 5 genes or less one from the other) in a genome of a prokaryotic cell. According to some embodiments the prokaryotic cell expresses an endogenous Druantia Type IIII defense system. According to some embodiments, the prokaryotic cell expresses an endogenous functional Druantia Type IIII defense system. According to some embodiments, the species of prokaryotic cell is selected from the group consisting of the species listed in Table 10.


According to some embodiments a prokaryotic cell expresses a non-endogenous Druantia Type III defense system. According to some embodiments, a prokaryotic cell expresses a non-endogenous functional Druantia Type III defense system. According to some embodiments, the species of prokaryotic cell expressing a non-endogenous functional Druantia Type III defense system is selected from the group consisting of the species listed in Table 10.


In some embodiments, Druantia Type I defense system components comprise DruA, DruB, DruC, DruD, and DruE polypeptides. In some embodiments, a Druantia Type I defense system's components comprise functional portions of DruA, DruB, DruC, DruD, and DruE polypeptides.


In some embodiments, Druantia Type II defense system's components comprise DruM, DruF, DruG, and DruE polypeptides. In some embodiments, a Druantia Type II defense system's components comprise functional portions of DruM, DruF, DruG, and DruE polypeptides.


In some embodiments, Druantia Type III defense system components comprise DruH and DruE polypeptides. In some embodiments, a Druantia Type III defense system components comprise functional portions of DruH and DruE polypeptides.


In some embodiments, the Druantia Type I defense system components are encoded by druA, druB, druC, druD, and druE genes. In some embodiments, the Druantia Type I defense system components are encoded by a portion of druA, druB, druC, druD, and druE genes, where the portions of the gene encode functional portions of the respective polypeptides.


In some embodiments, the Druantia Type II defense system components are encoded by druM, druF, druG, and druE genes. In some embodiments, the Druantia Type II defense system components are encoded by a portion of druM, druF, druG, and druE genes, where the portions of the gene encode functional portions of the respective polypeptides.


In some embodiments, the Druantia Type III defense system components are encoded by druH and druE genes. In some embodiments, the Druantia Type III defense system components are encoded by a portion of druH and druE genes, where the portions of the gene encode functional portions of the respective polypeptides.


Non-limiting embodiments of endogenous Druantia systems (Defense Systems IIIa, IIIb, and IIIc) and the respective location of their components are provided in Table 10 herein.


In some embodiments, the components of a Druantia system may be identified by the presence of similar domains present within each component. In some embodiments, domains comprise pfam domains and or clusters of orthologous groups (COG) domains.


In some embodiments, the term “DruA” refers to the polynucleotide or expression product e.g., the polypeptide encoded by the druA gene. In some embodiments, the term “DruA” refers to a DruA polypeptide. In some embodiments, the druA gene encodes a polypeptide comprising a pfam14236 domain. In some embodiments, the druA gene encodes a polypeptide comprising a DUF4338 domain. In some embodiments, the druA gene encodes a polypeptide comprising a pfam14236 domain and a DUF4338 domain. In some embodiments, the DruA polypeptide comprises a pfam14236 domain. In some embodiments, the DruA polypeptide comprises a DUF4338 domain. In some embodiments, the DruA polypeptide comprises a pfam14236 domain and a DUF4338 domain.


In some embodiments, DruA polypeptide is encoded by a gene positioned within 5-60 genes of a gene encoding a DruB, DruC, DruD, or DruE polypeptide, or any combination thereof, in a genome of a prokaryotic cell. In some embodiments, DruA polypeptide is encoded by a gene positioned within 5 genes upstream (5′) or downstream (3′) to a gene encoding a DruB, DruC, DruD, or DruE polypeptide, or any combination thereof, in a genome of a prokaryotic cell. In some embodiments, DruA polypeptide is encoded by a gene positioned within 5 genes upstream (5′) and downstream (3′) to a gene encoding a DruB, DruC, DruD, or DruE, or any combination thereof, polypeptide in a genome of a prokaryotic cell.


In some embodiments, DruA and DruB are encoded by genes positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, DruA and DruB are encoded by genes positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, DruA, DruB, and DruC are encoded by genes positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, DruA, DruB, and DruC are encoded by genes positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, DruA, DruB, DruC, and DruD are encoded by genes positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, DruA, DruB, DruC, and DruD are encoded by genes positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, DruA, DruB, DruC, DruD, and DruE are encoded by genes positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, DruA, DruB, DruC, DruD, and DruE are encoded by genes positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell.


In some embodiments, druA and druB genes are positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, druA and druB genes are positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, druA, druB, and druC genes are positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, druA, druB, and druC genes are positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, druA, druB, druC, and druD genes are positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, druA, druB, druC, and druD genes are positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, druA, druB, druC, druD, and druE genes are positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, druA, druB, druC, druD, and druE genes are positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell.


In some embodiments, a DruA polypeptide is about 404 amino acids long (median gene size).


In some embodiments, the DruA polypeptide comprises the amino acid sequence having at least 80% homology to a sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 2-123, columns J and K. In some embodiments, the DruA polypeptide comprises the amino acid sequence having at least 80% homology within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 2-123, columns J and K. In some embodiments, the DruA polypeptide comprises a homolog of a polypeptide having the amino acid sequences set forth in the polypeptides referenced in Table 10, rows 2-123, columns J and K.


In some embodiments, the DruA polypeptide comprises the amino acid sequence having at least 80% identity to a sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 2-123, columns J and K. In some embodiments, the DruA polypeptide comprises the amino acid sequence having at least 80% identity within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 2-123, columns J and K.


In some embodiments, the DruA polypeptide comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 2-123, columns J and K. In some embodiments, the DruA polypeptide comprises the amino acid sequence having at least 80%, 85%, 90%, 95% homology within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 2-123, columns J and K. In some embodiments, the DruA polypeptide comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 2-123, columns J and K. In some embodiments, the DruA polypeptide comprises the amino acid sequence having at least 80%, 85%, 90%, 95% identity within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 2-123, columns J and K. In some embodiments, the DruA polypeptide comprises an amino acid sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 2-123, columns J and K.


In some embodiments, the DruA polypeptide comprises an amino acid sequence encoded by a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 2-123, columns J and L. In some embodiments, the DruA polypeptide comprises the amino acid sequence encoded by a nucleic acid sequence having at least 80%, 85%, 90%, 95% homology within similar domain regions within a sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 2-123, columns J and L. In some embodiments, the DruA polypeptide comprises an amino acid sequence encoded by a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 2-123, columns J and L. In some embodiments, the DruA polypeptide comprises the amino acid sequence encoded by a nucleic acid sequence having at least 80%, 85%, 90%, 95% homology within similar domain regions within a sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 2-123, columns J and L. In some embodiments, the DruA polypeptide comprises an amino acid sequence encoded from a nucleic acid sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 2-123, columns J and L.


In some embodiments, the nucleic acid sequence of a druA gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 2-123, columns J and L. In some embodiments, the druA gene comprises a nucleic acid sequence having at least 80%, 85%, 90%, 95% homology within encoded similar domain regions in comparison with nucleotide sequence encoding these domain within a sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 2-123, columns J and L. In some embodiments, the nucleic acid sequence of a druA gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 2-123, columns J and L. In some embodiments, the druA gene comprises a nucleic acid sequence having at least 80%, 85%, 90%, 95% identity within encoded similar domain regions in comparison with nucleotide sequence encoding these domain within a sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 2-123, columns J and L. In some embodiments, the nucleic acid sequence of a druA gene comprises a nucleic acid sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 2-123, columns J and L.


As used herein, the term “DruB” refers to the polynucleotide or expression product e.g., polypeptide encoded by the druB gene. In some embodiments, the term “DruB” refers to a DruB polypeptide.


In some embodiments, DruB polypeptide is encoded by a gene positioned within 5-60 genes of a gene encoding a DruC, a DruD, or a DruE polypeptide, or any combination thereof in a genome of a prokaryotic cell. In some embodiments, a DruB-DruC fusion polypeptide is encoded by a gene positioned within 5-60 genes of a gene encoding a DruD or a DruE polypeptide or a combination thereof. In some embodiments, DruB polypeptide is encoded by a gene positioned within 5 genes upstream (5′) or downstream (3′) to a gene encoding a DruC, a DruD, or a DruE polypeptide or any combination thereof in a genome of a prokaryotic cell. In some embodiments, DruB-DruC fusion polypeptide is encoded by a gene positioned within 5 genes upstream (5′) or downstream (3′) to a gene encoding a DruD or a DruE polypeptide or a combination thereof in a genome of a prokaryotic cell. In some embodiments, DruB polypeptide is encoded by a gene positioned within 5 genes upstream (5′) and downstream (3′) to a gene encoding a DruC, a DruD, or a DruE polypeptide or a combination thereof in a genome of a prokaryotic cell.


In some embodiments, DruB and DruC are encoded by genes positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments DruB and DruC are encoded by genes positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, DruB, DruC, and DruD are encoded by genes positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments DruB, DruC, and DruD are encoded by genes positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, DruB, DruC, DruD, and DruE are encoded by genes positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments DruB, DruC, DruD, and DruE are encoded by genes positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, DruB, DruC, and DruD are encoded by genes positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments DruB, DruC, and DruD are encoded by genes positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, DruB, DruC, DruD, DruE, and DruA are encoded by genes positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments DruB, DruC, DruD, DruE, and DruA are encoded by genes positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell.


In some embodiments, druB and druC genes are positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, druB and druC genes are positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, druB, druC, and druD genes are positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, druB, druC, and druD genes are positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, druB, druC, druD, and druE genes are positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, druB, druC, druD, and druE genes are positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, druB, druC, druD, druE, and druA genes are positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, druB, druC, druD, druE, and druA genes are positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell.


In some embodiments, a DruB polypeptide is about 531 amino acids long (median gene size).


In some embodiments, the DruB polypeptide comprises the amino acid sequence having at least 80% homology to a sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 2-123, columns N and O. In some embodiments, the DruB polypeptide comprises the amino acid sequence having at least 80% homology within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 2-123, columns N and O. In some embodiments, the DruB polypeptide comprises a homolog of a polypeptide having the amino acid sequences set forth in the polypeptides referenced in Table 10, rows 2-123, columns N and O.


In some embodiments, the DruB polypeptide comprises the amino acid sequence having at least 80% identity to a sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 2-123, columns N and O. In some embodiments, the DruB polypeptide comprises the amino acid sequence having at least 80% identity within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 2-123, columns N and O.


In some embodiments, the DruB polypeptide comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 2-123, columns N and O. In some embodiments, the DruB polypeptide comprises the amino acid sequence having at least 80%, 85%, 90%, 95% homology within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 2-123, columns N and O. In some embodiments, the DruB polypeptide comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 2-123, columns N and O. In some embodiments, the DruB polypeptide comprises the amino acid sequence having at least 80%, 85%, 90%, 95% identity within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 2-123, columns N and O. In some embodiments, the DruB polypeptide comprises an amino acid sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 2-123, columns N and O.


In some embodiments, the DruB polypeptide comprises an amino acid sequence encoded by a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 2-123, columns N and P. In some embodiments, the DruB polypeptide comprises the amino acid sequence encoded by a nucleic acid sequence having at least 80%, 85%, 90%, 95% homology within similar domain regions within a sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 2-123, columns N and P. In some embodiments, the DruB polypeptide comprises an amino acid sequence encoded by a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 2-123, columns N and P. In some embodiments, the DruB polypeptide comprises the amino acid sequence encoded by a nucleic acid sequence having at least 80%, 85%, 90%, 95% homology within similar domain regions within a sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 2-123, columns N and P. In some embodiments, the DruB polypeptide comprises an amino acid sequence encoded from a nucleic acid sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 2-123, columns N and P.


In some embodiments, the nucleic acid sequence of a druB gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 2-123, columns N and P. In some embodiments, the druB gene comprises a nucleic acid sequence having at least 80%, 85%, 90%, 95% homology within encoded similar domain regions in comparison with nucleotide sequence encoding these domain within a sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 2-123, columns N and P. In some embodiments, the nucleic acid sequence of a druB gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 2-123, columns N and P. In some embodiments, the druB gene comprises a nucleic acid sequence having at least 80%, 85%, 90%, 95% identity within encoded similar domain regions in comparison with nucleotide sequence encoding these domain within a sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 2-123, column L. In some embodiments, the nucleic acid sequence of a druB gene comprises a nucleic acid sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 2-123, columns N and P.


In some embodiments, the term “DruC” refers to the polynucleotide or expression product e.g., the polypeptide encoded by the druC gene. In some embodiments, the term “DruC” refers to a DruC polypeptide.


In some embodiments, DruC polypeptide is encoded by a gene positioned within 5-60 genes of a gene encoding a DruD or DruE polypeptide, or any combination thereof, in a genome of a prokaryotic cell. In some embodiments, DruC polypeptide is encoded by a gene positioned within 5 genes upstream (5′) or downstream (3′) to a gene encoding a DruD or DruE polypeptide, or any combination thereof, in a genome of a prokaryotic cell. In some embodiments, a DruC polypeptide is encoded by a gene positioned within 5 genes upstream (5′) and downstream (3′) to a gene encoding a DruD or DruE polypeptide in a genome of a prokaryotic cell.


In some embodiments, DruC and DruD are encoded by genes positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, DruC and DruD are encoded by genes positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, DruC, DruD, and DruE are encoded by genes positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, DruC, DruD, and DruE are encoded by genes positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, DruC, DruD, DruE, and DruA are encoded by genes positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, DruC, DruD, DruE, and DruA are encoded by genes positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell.


In some embodiments, DruC and DruE polypeptides are encoded by genes positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, DruC and DruE polypeptides are encoded by genes positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell.


In some embodiments, druC and druD genes are positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, druC and druD genes are positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, druC, druD, and druE genes are positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, druC, druD, and druE genes are positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, druC, druD, druE, and druA genes are positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, druC, druD, druE, and druA genes are positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell.


In some embodiments, druC and druE genes are positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, druC and druE genes are positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, druC, druE, and druA genes are positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, druC, druE, and druA genes are positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, druC and druA genes are positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, druC and druA genes are positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell.


In some embodiments, a DruC polypeptide is about 627 amino acids long (median gene size).


In some embodiments, the DruC polypeptide comprises the amino acid sequence having at least 80% homology to a sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 2-123, columns R and S. In some embodiments, the DruC polypeptide comprises the amino acid sequence having at least 80% homology within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 2-123, columns R and S. In some embodiments, the DruC polypeptide comprises a homolog of a polypeptide having the amino acid sequences set forth in the polypeptides referenced in Table 10, rows 2-123, columns R and S.


In some embodiments, the DruC polypeptide comprises the amino acid sequence having at least 80% identity to a sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 2-123, columns R and S. In some embodiments, the DruC polypeptide comprises the amino acid sequence having at least 80% identity within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 2-123, columns R and S.


In some embodiments, the DruC polypeptide comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 2-123, columns R and S. In some embodiments, the DruC polypeptide comprises the amino acid sequence having at least 80%, 85%, 90%, 95% homology within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 2-123, columns R and S. In some embodiments, the DruC polypeptide comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 2-123, columns R and S. In some embodiments, the DruC polypeptide comprises the amino acid sequence having at least 80%, 85%, 90%, 95% identity within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 2-123, columns R and S. In some embodiments, the DruC polypeptide comprises an amino acid sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 2-123, columns R and S.


In some embodiments, the DruC polypeptide comprises an amino acid sequence encoded by a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 2-123, columns R and T. In some embodiments, the DruC polypeptide comprises the amino acid sequence encoded by a nucleic acid sequence having at least 80%, 85%, 90%, 95% homology within similar domain regions within a sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 2-123, columns R and T. In some embodiments, the DruC polypeptide comprises an amino acid sequence encoded by a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 2-123, columns R and T. In some embodiments, the DruC polypeptide comprises the amino acid sequence encoded by a nucleic acid sequence having at least 80%, 85%, 90%, 95% homology within similar domain regions within a sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 2-123, columns R and T. In some embodiments, the DruC polypeptide comprises an amino acid sequence encoded from a nucleic acid sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 2-123, columns R and T.


In some embodiments, the nucleic acid sequence of a druC gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 2-123, columns R and T. In some embodiments, the druC gene comprises a nucleic acid sequence having at least 80%, 85%, 90%, 95% homology within encoded similar domain regions in comparison with nucleotide sequence encoding these domain within a sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 2-123, columns R and T. In some embodiments, the nucleic acid sequence of a druC gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 2-123, columns R and T. In some embodiments, the druC gene comprises a nucleic acid sequence having at least 80%, 85%, 90%, 95% identity within encoded similar domain regions in comparison with nucleotide sequence encoding these domain within a sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 2-123, columns R and T. In some embodiments, the nucleic acid sequence of a druC gene comprises a nucleic acid sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 2-123, columns R and T.


In some embodiments, the term “DruD” refers to the polynucleotide or expression product e.g., the polypeptide encoded by the druD gene. In some embodiments, the term “DruD” refers to a DruD polypeptide.


In some embodiments, DruD polypeptide is encoded by a gene positioned within 5-60 genes of a gene encoding a DruE or DruA polypeptide, or any combination thereof, in a genome of a prokaryotic cell. In some embodiments, DruD polypeptide is encoded by a gene positioned within 5 genes upstream (5′) or downstream (3′) to a gene encoding a DruE or DruA polypeptide, or any combination thereof, in a genome of a prokaryotic cell.


In some embodiments, DruD and DruE are encoded by genes positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, DruD and DruE are encoded by genes positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, DruD, DruE, and DruA are encoded by genes positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, DruD, DruE, and DruA are encoded by genes positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell.


In some embodiments, druD and druE genes are positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, druD and druE genes are positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, druD, druE, and druA genes are positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, druD, druE, and druA genes are positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell.


In some embodiments, druD and druA genes are positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, druD and druA genes are positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell.


In some embodiments, a DruD polypeptide is about 347 amino acids long (median gene size).


In some embodiments, the DruD polypeptide comprises the amino acid sequence having at least 80% homology to a sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 2-123, columns V and W. In some embodiments, the DruD polypeptide comprises the amino acid sequence having at least 80% homology within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 2-123, columns V and W. In some embodiments, the DruD polypeptide comprises a homolog of a polypeptide having the amino acid sequences set forth in the polypeptides referenced in Table 10, rows 2-123, columns V and W.


In some embodiments, the DruD polypeptide comprises the amino acid sequence having at least 80% identity to a sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 2-123, columns V and W. In some embodiments, the DruD polypeptide comprises the amino acid sequence having at least 80% identity within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 2-123, columns V and W.


In some embodiments, the DruD polypeptide comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 2-123, columns V and W. In some embodiments, the DruD polypeptide comprises the amino acid sequence having at least 80%, 85%, 90%, 95% homology within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 2-123, columns V and W. In some embodiments, the DruD polypeptide comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 2-123, columns V and W. In some embodiments, the DruD polypeptide comprises the amino acid sequence having at least 80%, 85%, 90%, 95% identity within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 2-123, columns V and W. In some embodiments, the DruD polypeptide comprises an amino acid sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 2-123, columns V and W.


In some embodiments, the DruD polypeptide comprises an amino acid sequence encoded by a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 2-123, columns V and X. In some embodiments, the DruD polypeptide comprises the amino acid sequence encoded by a nucleic acid sequence having at least 80%, 85%, 90%, 95% homology within similar domain regions within a sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 2-123, columns V and X. In some embodiments, the DruD polypeptide comprises an amino acid sequence encoded by a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 2-123, columns V and X. In some embodiments, the DruD polypeptide comprises the amino acid sequence encoded by a nucleic acid sequence having at least 80%, 85%, 90%, 95% homology within similar domain regions within a sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 2-123, columns V and X. In some embodiments, the DruD polypeptide comprises an amino acid sequence encoded from a nucleic acid sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 2-123, columns V and X.


In some embodiments, the nucleic acid sequence of a druD gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 2-123, column P. In some embodiments, the druD gene comprises a nucleic acid sequence having at least 80%, 85%, 90%, 95% homology within encoded similar domain regions in comparison with nucleotide sequence encoding these domain within a sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 2-123, columns V and X. In some embodiments, the nucleic acid sequence of a druD gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 2-123, columns V and X. In some embodiments, the druD gene comprises a nucleic acid sequence having at least 80%, 85%, 90%, 95% identity within encoded similar domain regions in comparison with nucleotide sequence encoding these domain within a sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 2-123, columns V and X. In some embodiments, the nucleic acid sequence of a druD gene comprises a nucleic acid sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 2-123, columns V and X.


In some embodiments, the term “DruE” refers to the polynucleotide or expression product e.g., the polypeptide encoded by the druE gene. In some embodiments, the term “DruE” refers to a DruE polypeptide. In some embodiments, the druE gene encodes a polypeptide comprising a pfam00270 domain. In some embodiments, the druE gene encodes a polypeptide comprising a pfam00271 domain. In some embodiments, the druE gene encodes a polypeptide comprising a pfam09369 domain. In some embodiments, the druE gene encodes a polypeptide comprising a DUF1998 domain. In some embodiments, the druE gene encodes a polypeptide comprising a pfam00270 domain, a pfam00271 domain, a pfam09369 domain, or a DUF4338 domain, or any combination thereof. In some embodiments, the druE gene encodes a polypeptide comprising a pfam00270 domain, a pfam00271 domain, a pfam09369 domain, and a DUF4338 domain. In some embodiments, a druE gene encodes a polypeptide comprising a helicase activity. In some embodiments, a druE gene encodes a polypeptide comprising a DEAx box helicase activity.


In some embodiments, the DruE polypeptide comprises a pfam00270 domain. In some embodiments, the DruE polypeptide comprises a pfam00271 domain. In some embodiments, the DruE polypeptide comprises a pfam09369 domain. In some embodiments, the DruE polypeptide comprises a DUF1998 domain. In some embodiments, the DruE polypeptide comprises a pfam00270 domain, a pfam00271 domain, a pfam09369 domain, or a DUF4338 domain, or any combination thereof. In some embodiments, the DruE polypeptide comprises a pfam00270 domain, a pfam00271 domain, a pfam09369 domain, and a DUF4338 domain. In some embodiments, a DruE polypeptide comprises a helicase activity. In some embodiments, a DruE polypeptide comprises a DEAx box helicase activity.


In some embodiments, DruE polypeptide is encoded by a gene positioned within 5-60 genes of a gene encoding a DruA polypeptide in a genome of a prokaryotic cell. In some embodiments, DruE polypeptide is encoded by a gene positioned within 5 genes upstream (5′) or downstream (3′) to a gene encoding a DruA polypeptide in a genome of a prokaryotic cell. In some embodiments, DruE polypeptide is encoded by a gene positioned within 5 genes upstream (5′) and downstream (3′) to a gene encoding a DruA polypeptide in a genome of a prokaryotic cell.


In some embodiments, DruE and DruA are encoded by genes positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, DruE and DruA are encoded by genes positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell.


In some embodiments, druE and druA genes are positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, druE and druA genes are positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell.


In some embodiments, a DruE polypeptide is about 2104 amino acids long (median gene size).


In some embodiments, the DruE polypeptide comprises the amino acid sequence having at least 80% homology to a sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 2-1343, columns Z and AA. In some embodiments, the DruE polypeptide comprises the amino acid sequence having at least 80% homology within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 2-1343, columns Z and AA. In some embodiments, the DruE polypeptide comprises a homolog of a polypeptide having the amino acid sequences set forth in the polypeptides referenced in Table 10, rows 2-1343, columns Z and AA.


In some embodiments, a DruE polypeptide homolog comprises a helicase domain. In some embodiments, a DruE polypeptide comprises a helicase activity.


In some embodiments, the DruE polypeptide comprises the amino acid sequence having at least 80% identity to a sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 2-1343, columns Z and AA. In some embodiments, the DruE polypeptide comprises the amino acid sequence having at least 80% identity within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 2-1343, columns Z and AA.


In some embodiments, the DruE polypeptide comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 2-1343, columns Z and AA. In some embodiments, the DruE polypeptide comprises the amino acid sequence having at least 80%, 85%, 90%, 95% homology within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 2-1343, columns Z and AA. In some embodiments, the DruE polypeptide comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 2-1343, columns Z and AA. In some embodiments, the DruE polypeptide comprises the amino acid sequence having at least 80%, 85%, 90%, 95% identity within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 2-1343, columns Z and AA. In some embodiments, the DruE polypeptide comprises an amino acid sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 2-1343, columns Z and AA.


In some embodiments, the DruE polypeptide comprises an amino acid sequence encoded by a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 2-1343, columns Z and AB. In some embodiments, the DruE polypeptide comprises the amino acid sequence encoded by a nucleic acid sequence having at least 80%, 85%, 90%, 95% homology within similar domain regions within a sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 2-1343, columns Z and AB. In some embodiments, the DruE polypeptide comprises an amino acid sequence encoded by a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 2-1343, columns Z and AB. In some embodiments, the DruE polypeptide comprises the amino acid sequence encoded by a nucleic acid sequence having at least 80%, 85%, 90%, 95% homology within similar domain regions within a sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 2-1343, columns Z and AB. In some embodiments, the DruE polypeptide comprises an amino acid sequence encoded from a nucleic acid sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 2-1343, columns Z and AB.


In some embodiments, the nucleic acid sequence of a druE gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 2-1343, columns Z and AB. In some embodiments, the druE gene comprises a nucleic acid sequence having at least 80%, 85%, 90%, 95% homology within encoded similar domain regions in comparison with nucleotide sequence encoding these domain within a sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 2-1343, columns Z and AB. In some embodiments, the nucleic acid sequence of a druE gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 2-1343, columns Z and AB. In some embodiments, the druE gene comprises a nucleic acid sequence having at least 80%, 85%, 90%, 95% identity within encoded similar domain regions in comparison with nucleotide sequence encoding these domain within a sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 2-1343, columns Z and AB. In some embodiments, the nucleic acid sequence of a druE gene comprises a nucleic acid sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 2-1343, columns Z and AB.


In some embodiments, the term “DruM” refers to the polynucleotide or expression product e.g., the polypeptide encoded by the druM gene. In some embodiments, the term “DruM” refers to a DruM polypeptide. In some embodiments, the druM gene encodes a polypeptide.


In some embodiments, DruM polypeptide is encoded by a gene positioned within 5-60 genes of a gene encoding a DruF polypeptide, a DruG polypeptide, and/or a DruE polypeptide in a genome of a prokaryotic cell. In some embodiments, DruM polypeptide is encoded by a gene positioned within 5 genes upstream (5′) or downstream (3′) to a gene encoding a DruF polypeptide, a DruG polypeptide, and/or a DruE polypeptide in a genome of a prokaryotic cell. In some embodiments, DruM polypeptide is encoded by a gene positioned within 5 genes upstream (5′) and downstream (3′) to a gene encoding a DruF polypeptide, a DruG polypeptide, and/or a DruE polypeptide in a genome of a prokaryotic cell.


In some embodiments, DruM. DruF, DruG, and DruE are encoded by genes positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, DruM, DruF, DruG, and DruE are encoded by genes positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell.


In some embodiments, druM, druF, druG, and druE genes are positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, druM, druF, druG, and druE genes are positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell.


In some embodiments, a DruM polypeptide is about 386 amino acids long (median gene size).


In some embodiments, the DruM polypeptide comprises the amino acid sequence having at least 80% homology to a sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 124-295, columns AD and AE. In some embodiments, the DruM polypeptide comprises the amino acid sequence having at least 80% homology within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 124-295, columns AD and AE. In some embodiments, the DruM polypeptide comprises a homolog of a polypeptide having the amino acid sequences set forth in the polypeptides referenced in Table 10, rows 124-295, columns AD and AE.


In some embodiments, a DruM polypeptide homolog comprises a cytosine methylase activity. In some embodiments, a DruM polypeptide homolog comprises a cytosine methylase.


In some embodiments, the DruM polypeptide comprises the amino acid sequence having at least 80% identity to a sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 124-295, columns AD and AE. In some embodiments, the DruM polypeptide comprises the amino acid sequence having at least 80% identity within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 124-295, columns AD and AE.


In some embodiments, the DruM polypeptide comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 124-295, columns AD and AE. In some embodiments, the DruM polypeptide comprises the amino acid sequence having at least 80%, 85%, 90%, 95% homology within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 124-295, columns AD and AE. In some embodiments, the DruM polypeptide comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 124-295, columns AD and AE. In some embodiments, the DruM polypeptide comprises the amino acid sequence having at least 80%, 85%, 90%, 95% identity within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 124-295, columns AD and AE. In some embodiments, the DruM polypeptide comprises an amino acid sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 124-295, columns AD and AE.


In some embodiments, the DruM polypeptide comprises an amino acid sequence encoded by a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 124-295, columns AD and AF. In some embodiments, the DruM polypeptide comprises the amino acid sequence encoded by a nucleic acid sequence having at least 80%, 85%, 90%, 95% homology within similar domain regions within a sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 124-295, columns AD and AF. In some embodiments, the DruM polypeptide comprises an amino acid sequence encoded by a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 124-295, columns AD and AF. In some embodiments, the DruM polypeptide comprises the amino acid sequence encoded by a nucleic acid sequence having at least 80%, 85%, 90%, 95% homology within similar domain regions within a sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 124-295, columns AD and AF. In some embodiments, the DruM polypeptide comprises an amino acid sequence encoded from a nucleic acid sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 124-295, columns AD and AF.


In some embodiments, the nucleic acid sequence of a druM gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 124-295, columns AD and AF. In some embodiments, the druM gene comprises a nucleic acid sequence having at least 80%, 85%, 90%, 95% homology within encoded similar domain regions in comparison with nucleotide sequence encoding these domain within a sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 124-295, columns AD and AF. In some embodiments, a druM gene homolog encodes a cytosine methylase. In some embodiments, the nucleic acid sequence of a druM gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 124-295, columns AD and AF. In some embodiments, the druM gene comprises a nucleic acid sequence having at least 80%, 85%, 90%, 95% identity within encoded similar domain regions in comparison with nucleotide sequence encoding these domain within a sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 124-295, columns AD and AF. In some embodiments, the nucleic acid sequence of a druM gene comprises a nucleic acid sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 124-295, columns AD and AF.


In some embodiments, the term “DruF” refers to the polynucleotide or expression product e.g., the polypeptide encoded by the druF gene. In some embodiments, the term “DruF” refers to a DruF polypeptide. In some embodiments, the druF gene encodes a polypeptide.


In some embodiments, DruF polypeptide is encoded by a gene positioned within 5-60 genes of a gene encoding a DruM polypeptide, a DruG polypeptide, and or a DruE polypeptide in a genome of a prokaryotic cell. In some embodiments, DruF polypeptide is encoded by a gene positioned within 5 genes upstream (5′) or downstream (3′) to a gene encoding a DruM polypeptide, a DruG polypeptide, and or a DruE polypeptide in a genome of a prokaryotic cell. In some embodiments, DruF polypeptide is encoded by a gene positioned within 5 genes upstream (5′) and downstream (3′) to a gene encoding DruM polypeptide, a DruG polypeptide, and or a DruE polypeptide in a genome of a prokaryotic cell.


In some embodiments, DruF, DruG, and DruE are encoded by genes positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, DruF, DruG, and DruE are encoded by genes positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell.


In some embodiments, druF, druG, and druE genes are positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, druF, druG, and druE genes are positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell.


In some embodiments, a DruF polypeptide is about 852 amino acids long (median gene size).


In some embodiments, the DruF polypeptide comprises the amino acid sequence having at least 80% homology to a sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 124-295, columns AH and AI. In some embodiments, the DruF polypeptide comprises the amino acid sequence having at least 80% homology within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 124-295, columns AH and AI. In some embodiments, the DruF polypeptide comprises a homolog of a polypeptide having the amino acid sequences set forth in the polypeptides referenced in Table 10, rows 124-295, columns AH and AI.


In some embodiments, the DruF polypeptide comprises the amino acid sequence having at least 80% identity to a sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 124-295, columns AH and AI. In some embodiments, the DruF polypeptide comprises the amino acid sequence having at least 80% identity within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 124-295, columns AH and AI.


In some embodiments, the DruF polypeptide comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 124-295, columns AH and AI. In some embodiments, the DruF polypeptide comprises the amino acid sequence having at least 80%, 85%, 90%, 95% homology within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 124-295, columns AH and AI. In some embodiments, the DruF polypeptide comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 124-295, columns AH and AI. In some embodiments, the DruF polypeptide comprises the amino acid sequence having at least 80%, 85%, 90%, 95% identity within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 124-295, columns AH and AI. In some embodiments, the DruF polypeptide comprises an amino acid sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 124-295, columns AH and AI.


In some embodiments, the DruF polypeptide comprises an amino acid sequence encoded by a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 124-295, columns AH and AJ. In some embodiments, the DruF polypeptide comprises the amino acid sequence encoded by a nucleic acid sequence having at least 80%, 85%, 90%, 95% homology within similar domain regions within a sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 124-295, columns AH and AJ. In some embodiments, the DruF polypeptide comprises an amino acid sequence encoded by a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 124-295, columns AH and AJ. In some embodiments, the DruF polypeptide comprises the amino acid sequence encoded by a nucleic acid sequence having at least 80%, 85%, 90%, 95% homology within similar domain regions within a sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 124-295, columns AH and AJ. In some embodiments, the DruF polypeptide comprises an amino acid sequence encoded from a nucleic acid sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 124-295, columns AH and AJ.


In some embodiments, the nucleic acid sequence of a druF gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 124-295, columns AH and AJ. In some embodiments, the druF gene comprises a nucleic acid sequence having at least 80%, 85%, 90%, 95% homology within encoded similar domain regions in comparison with nucleotide sequence encoding these domain within a sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 124-295, columns AH and AJ. In some embodiments, the nucleic acid sequence of a druF gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 124-295, columns AH and AJ. In some embodiments, the druF gene comprises a nucleic acid sequence having at least 80%, 85%, 90%, 95% identity within encoded similar domain regions in comparison with nucleotide sequence encoding these domain within a sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 124-295, columns AH and AJ. In some embodiments, the nucleic acid sequence of a druF gene comprises a nucleic acid sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 124-295, columns AH and AJ.


In some embodiments, the term “DruG” refers to the polynucleotide or expression product e.g., the polypeptide encoded by the druG gene. In some embodiments, the term “DruG” refers to a DruG polypeptide. In some embodiments, the druG gene encodes a polypeptide.


In some embodiments, DruG polypeptide is encoded by a gene positioned within 5-60 genes of a gene encoding a DruM polypeptide, a DruF polypeptide, and or a DruE polypeptide in a genome of a prokaryotic cell. In some embodiments, DruG polypeptide is encoded by a gene positioned within 5 genes upstream (5′) or downstream (3′) to a gene encoding a DruM polypeptide, a DruF polypeptide, and or a DruE polypeptide in a genome of a prokaryotic cell. In some embodiments, DruG polypeptide is encoded by a gene positioned within 5 genes upstream (5′) and downstream (3′) to a gene encoding DruM polypeptide, a DruF polypeptide, and or a DruE polypeptide in a genome of a prokaryotic cell.


In some embodiments, DruG and DruE are encoded by genes positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, DruG and DruE are encoded by genes positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell.


In some embodiments, druG and druE genes are positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, druG, and druE genes are positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell.


In some embodiments, a DruG polypeptide is about 711 amino acids long (median gene size).


In some embodiments, the DruG polypeptide comprises the amino acid sequence having at least 80% homology to a sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 124-295, columns AL and AM. In some embodiments, the DruG polypeptide comprises the amino acid sequence having at least 80% homology within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 124-295, columns AL and AM. In some embodiments, the DruG polypeptide comprises a homolog of a polypeptide having the amino acid sequences set forth in the polypeptides referenced in Table 10, rows 124-295, columns AL and AM.


In some embodiments, the DruG polypeptide comprises the amino acid sequence having at least 80% identity to a sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 124-295, columns AL and AM. In some embodiments, the DruG polypeptide comprises the amino acid sequence having at least 80% identity within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 124-295, columns AL and AM.


In some embodiments, the DruG polypeptide comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 124-295, columns AL and AM. In some embodiments, the DruG polypeptide comprises the amino acid sequence having at least 80%, 85%, 90%, 95% homology within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 124-295, columns AL and AM. In some embodiments, the DruG polypeptide comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 124-295, columns AL and AM. In some embodiments, the DruG polypeptide comprises the amino acid sequence having at least 80%, 85%, 90%, 95% identity within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 124-295, columns AL and AM. In some embodiments, the DruG polypeptide comprises an amino acid sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 124-295, columns AL and AM.


In some embodiments, the DruG polypeptide comprises an amino acid sequence encoded by a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 124-295, columns AL and AN. In some embodiments, the DruG polypeptide comprises the amino acid sequence encoded by a nucleic acid sequence having at least 80%, 85%, 90%, 95% homology within similar domain regions within a sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 124-295, columns AL and AN. In some embodiments, the DruG polypeptide comprises an amino acid sequence encoded by a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 124-295, columns AL and AN. In some embodiments, the DruG polypeptide comprises the amino acid sequence encoded by a nucleic acid sequence having at least 80%, 85%, 90%, 95% homology within similar domain regions within a sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 124-295, columns AL and AN. In some embodiments, the DruG polypeptide comprises an amino acid sequence encoded from a nucleic acid sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 124-295, columns AL and AN.


In some embodiments, the nucleic acid sequence of a druG gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 124-295, columns AL and AN. In some embodiments, the druG gene comprises a nucleic acid sequence having at least 80%, 85%, 90%, 95% homology within encoded similar domain regions in comparison with nucleotide sequence encoding these domain within a sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 124-295, columns AL and AN. In some embodiments, the nucleic acid sequence of a druG gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 124-295, columns AL and AN. In some embodiments, the druG gene comprises a nucleic acid sequence having at least 80%, 85%, 90%, 95% identity within encoded similar domain regions in comparison with nucleotide sequence encoding these domain within a sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 124-295, columns AL and AN. In some embodiments, the nucleic acid sequence of a druG gene comprises a nucleic acid sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 124-295, columns AL and AN.


In some embodiments, the term “DruH” refers to the polynucleotide or expression product e.g., the polypeptide encoded by the druH gene. In some embodiments, the term “DruH” refers to a DruH polypeptide. In some embodiments, the druH gene encodes a polypeptide.


In some embodiments, DruH polypeptide is encoded by a gene positioned within 5-60 genes of a gene encoding a DruE polypeptide in a genome of a prokaryotic cell. In some embodiments, DruH polypeptide is encoded by a gene positioned within 5 genes upstream (5′) or downstream (3′) to a gene encoding a DruE polypeptide in a genome of a prokaryotic cell. In some embodiments, DruH polypeptide is encoded by a gene positioned within 5 genes upstream (5′) and downstream (3′) to a gene encoding a DruE polypeptide in a genome of a prokaryotic cell.


In some embodiments, DruH and DruE are encoded by genes positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, DruH and DruE are encoded by genes positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell.


In some embodiments, druH and druE genes are positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, druH, and druE genes are positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell.


In some embodiments, a DruH polypeptide is about 1079 amino acids long (median gene size).


In some embodiments, the DruH polypeptide comprises the amino acid sequence having at least 80% homology to a sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 296-1343, columns AP and AQ. In some embodiments, the DruH polypeptide comprises the amino acid sequence having at least 80% homology within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 296-1343, columns AP and AQ. In some embodiments, the DruH polypeptide comprises a homolog of a polypeptide having the amino acid sequences set forth in the polypeptides referenced in Table 10, rows 296-1343, columns AP and AQ.


In some embodiments, the DruH polypeptide comprises the amino acid sequence having at least 80% identity to a sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 296-1343, columns AP and AQ. In some embodiments, the DruH polypeptide comprises the amino acid sequence having at least 80% identity within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 296-1343, columns AP and AQ.


In some embodiments, the DruH polypeptide comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 296-1343, columns AP and AQ. In some embodiments, the DruH polypeptide comprises the amino acid sequence having at least 80%, 85%, 90%, 95% homology within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 296-1343, columns AP and AQ. In some embodiments, the DruH polypeptide comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 296-1343, columns AP and AQ. In some embodiments, the DruH polypeptide comprises the amino acid sequence having at least 80%, 85%, 90%, 95% identity within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 296-1343, columns AP and AQ. In some embodiments, the DruH polypeptide comprises an amino acid sequence selected from the group consisting of the polypeptides referenced in Table 10, rows 296-1343, columns AP and AQ.


In some embodiments, the DruH polypeptide comprises an amino acid sequence encoded by a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 296-1343, columns AP and AR. In some embodiments, the DruH polypeptide comprises the amino acid sequence encoded by a nucleic acid sequence having at least 80%, 85%, 90%, 95% homology within similar domain regions within a sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 296-1343, columns AP and AR. In some embodiments, the DruH polypeptide comprises an amino acid sequence encoded by a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 296-1343, columns AP and AR. In some embodiments, the DruH polypeptide comprises the amino acid sequence encoded by a nucleic acid sequence having at least 80%, 85%, 90%, 95% homology within similar domain regions within a sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 296-1343, columns AP and AR. In some embodiments, the DruH polypeptide comprises an amino acid sequence encoded from a nucleic acid sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 296-1343, columns AP and AR.


In some embodiments, the nucleic acid sequence of a druH gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 296-1343, columns AP and AR. In some embodiments, the druH gene comprises a nucleic acid sequence having at least 80%, 85%, 90%, 95% homology within encoded similar domain regions in comparison with nucleotide sequence encoding these domain within a sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 296-1343, columns AP and AR. In some embodiments, the nucleic acid sequence of a druH gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 296-1343, columns AP and AR. In some embodiments, the druH gene comprises a nucleic acid sequence having at least 80%, 85%, 90%, 95% identity within encoded similar domain regions in comparison with nucleotide sequence encoding these domain within a sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 296-1343, columns AP and AR. In some embodiments, the nucleic acid sequence of a druH gene comprises a nucleic acid sequence selected from the group consisting of the polynucleotides referenced in Table 10, rows 296-1343, columns AP and AR.


A skilled artisan would appreciate that the terms a “functional portion of a Defense System IIIa component” or “functional fragment of Defense System IIIa component” or “functional portion of a Druantia Type I defense system component” or “functional fragment of Druantia Type I defense system component” refers to a functional portion of a Druantia polynucleotide or polypeptide, as disclosed herein, which expression is sufficient to elicit an anti-phage activity alone or in combination with the at least one of the other Druantia polynucleotides or polypeptides disclosed herein or functional portions thereof.


A skilled artisan would appreciate that the terms a “functional portion of a Defense System IIIb component” or “functional fragment of Defense System IIIb component” or “functional portion of a Druantia Type II defense system component” or “functional fragment of Druantia Type II defense system component” refers to a functional portion of a Druantia polynucleotide or polypeptide, as disclosed herein, which expression is sufficient to elicit an anti-phage activity alone or in combination with the at least one of the other Druantia polynucleotides or polypeptides disclosed herein or functional portions thereof.


A skilled artisan would appreciate that the terms a “functional portion of a Defense System IIIc component” or “functional fragment of Defense System IIIc component” or “functional portion of a Druantia Type III defense system component” or “functional fragment of Druantia Type III defense system component” refers to a functional portion of a Druantia polynucleotide or polypeptide, as disclosed herein, which expression is sufficient to elicit an anti-phage activity alone or in combination with the at least one of the other Druantia polynucleotides or polypeptides disclosed herein or functional portions thereof.


The terms “DruA”, “DruB”, “DruC”, “DruD”, “DruE”, “DruF”, “DruG”, “DruH”, “DruM”, “druA”, “druB”, “druC”, “druD”, “druE”, “druF”, “druG”, “druH”, and “druM”, also refer to functional DruA, DruB, DruC, DruD, DruE, DruF, DruG, DruH, DruM, druA, druB, druG, druD, druE, druF, druG, druH, and druM, homologs, which exhibit the desired activity (i.e., conferring phage resistance). Such homologs can be, for example, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical or homologous to the polypeptide referenced in Table 10 rows 2-123, columns J and K; rows 2-123, columns N and O; rows 2-123, columns R and S; rows 2-123, columns V and W; rows 2-1343, columns Z and AA; rows 124-295, columns AD and AE; rows 124-295, columns AH and AI; rows 124-295, columns AL and AM, and rows 296-1343, columns AP and AQ, respectively, or 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% homologous or identical to the polynucleotide sequences referenced in Table 10 rows 2-123, columns J and L; rows 2-123, columns N and P; rows 2-123, columns R and T; rows 2-123, columns V and X; rows 2-1343, columns Z and AB; rows 124-295, columns AD and AF; rows 124-295, columns AH and AJ; rows 124-295, columns AL and AN, and rows 296-1343, columns AP and AR, respectively. In some embodiments, such homologs comprise at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% homology within similar domain regions of the polypeptide sequences referenced in Table 10 rows 2-123, columns J and K; rows 2-123, columns N and O; rows 2-123, columns R and S; rows 2-123, columns V and W; rows 2-1343, columns Z and AA; rows 124-295, columns ad and AE; rows 124-295, columns AH and AI; rows 124-295, columns AL and AN, and rows 296-1343, columns AP and AQ, respectively, or 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity within nucleotide sequences encoding similar domain regions to the polynucleotide sequences referenced in Table 10 rows 2-123, columns J and L; rows 2-123, columns N and P; rows 2-123, columns R and T; rows 2-123, columns V and X; rows 2-1343, columns Z and AB; rows 124-295, columns AD and AF; rows 124-295, columns AH and AJ; rows 124-295, columns AL and AN, and rows 296-1343, column AP and AR, respectively.


Table 10 presents embodiments of components of Defense System III (IIIa; IIIb; and IIIc) that may be found in a diverse array of bacteria and archaea genomes (referenced in Table 18). Table 10 presents embodiments of nucleic acid sequences encoding gene cassettes of Defense System III (IIIa; IIIb; and IIIc; referenced in Table 18).


The Hachiman Defense System


In some embodiments, a defense system disclosed herein comprises a Hachiman anti-phage defense system. (Table 12) In some embodiments, a Hachiman defense system provides a host cell with resistance to at least one phage.


In some embodiments, a Hachiman defense system provides a host cell with resistance to entry of foreign nucleic acid invasion. In some embodiments, a host cell expressing a functional Hachiman defense system (Defense System IV) provides the host cell resistance foreign nucleic acid invasion.


In some embodiments, a bacterial cell expressing a Hachiman defense system (Defense System IV) protects the bacteria from phage infection. In some embodiments, a bacterial cell expressing a functional Hachiman defense system (Defense System IV) protects the bacteria from phage infection.


In some embodiments, a Hachiman defense system provides a host cell with resistance to plasmid transformation. In some embodiments, a host cell expressing a functional Hachiman defense system (Defense System IV) provides a host cells with resistance to plasmid transformation.


In some embodiments, a Hachiman defense system provides a host cell with resistance to entry of conjugative elements. In some embodiments, a host cell expressing a function Hachiman defense system (Defense System IV) provides the host cell resistance from entry of conjugative elements.


As used herein, the term “a Hachiman anti-phage defense system” may be used interchangeably with the term “a Defense System IV”, having all the same meanings and qualities. A skilled artisan would appreciate that the term “Hachiman system” may be used interchangeably in some embodiments with “Hachiman defense system”, “Hachiman the defense system”, “Hachiman anti-phage system”, and “Defense System IV”, having all the same meanings and qualities.


In some embodiments, a microbial species does not comprise an endogenous Defense System IV. In some embodiments, a microbial species does not express an endogenous Defense System IV. In some embodiments, a microbial species does not express a functional Defense System IV.


In some embodiments, a bacterial species does not comprise an endogenous Defense System IV. In some embodiments, a bacterial species does not express an endogenous Defense System IV. In some embodiments, a bacterial species does not endogenously express a functional Defense System IV.


A Hachiman defense system comprises, in some embodiments, a nucleic acid construct comprising a nucleic acid sequence encoding a HamA polypeptide comprising a pfam08878 domain or a DUF1837 domain or a combination thereof, and a HamB polypeptide comprising COG1204 domain or a pfam00270 domain or a pfam00271 domain or any combination thereof. In some embodiments, a Hachiman defense system comprises a nucleic acid construct comprising a nucleic acid sequence comprising a hamA gene and a hamB gene.


A Hachiman defense system comprises, in some embodiments, a nucleic acid construct comprising a nucleic acid sequence encoding a HamA polypeptide comprising a pfam08878 or a DUF1837 domain or a combination thereof, and a HamB polypeptide comprising a COG1204 domain or a pfam00270 domain or a pfam00271 domain, or any combination thereof. In some embodiments, a Hachiman defense system comprises a nucleic acid construct comprising a nucleic acid sequence encoding a HamA polypeptide and a HamB polypeptide.


In some embodiments, a Hachiman defense system comprises, a HamA polypeptide comprising a pfam08878 or a DUF1837 domain or a combination thereof, and a HamB polypeptide comprising a COG1204 domain or a pfam00270 domain or a pfam00271 domain or any combination thereof. In some embodiments, a Hachiman defense system comprises a HamA polypeptide and a HamB polypeptide.


In some embodiments, a Defense System IV comprising a HamA polypeptide comprising a pfam08878 domain or a DUF1837 domain or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 12 rows 2-1782 columns H and I; or a HamB polypeptide comprising COG1204 domain or a pfam00270 domain or a pfam00271 domain or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 12 rows 2-1782 columns L and M; any combination thereof.


In some embodiments, a Defense System IV comprises at least two different polypeptide components selected from a HamA polypeptide comprising a pfam08878 domain or a DUF1837 domain or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 12 rows 2-1782 columns H and I; and a HamB polypeptide comprising COG1204 domain or a pfam00270 domain or a pfam00271 domain or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 12 rows 2-1782 columns L and M.


In some embodiments, a Hachiman defense system having an anti-phage activity comprises a nucleic acid construct comprising a nucleic acid sequence encoding a HamA polypeptide and a HamB polypeptide. In some embodiments, a Hachiman defense system having an anti-phage activity comprises a nucleic acid construct comprising a nucleic acid sequence comprising a hamA gene and a hamB gene.


In some embodiments, the Hachiman anti-phage defense system comprises a nucleic acid construct comprising nucleic acid sequences encoding a cassette comprising hamA and hamB genes.


In some embodiments, a construct comprising the Hachiman defense system encodes one component of the defense system, whereby multiple constructs, for example but not limited to, two constructs may be used to assemble the functional defense system. In some embodiments, the components of a Hachiman defense system comprise genes hamA and hamB. In some embodiments, the components of a Hachiman defense system consist of genes hamA and hamB. In some embodiments, the components of a Hachiman defense system comprise nucleic acid sequences encoding a HamA polypeptide and a HamB polypeptide. In some embodiments, the components of a Hachiman defense system consist of nucleic acid sequences encoding a HamA polypeptide and a HamB polypeptide.


In some embodiments, a construct comprising the Hachiman defense system encodes one component of the defense system, whereby a second construct may be used to assemble the functional defense system. In some embodiments, a construct comprising the Hachiman defense system encodes one component of the defense system, whereby additional constructs may be used to assemble the functional defense system. For example, in some embodiments each of HamA and HamB may be encoded by nucleic acid sequences comprised in different constructs, wherein expression of the combination of constructs produces a functional Hachiman defense system.


In some embodiments, the components making up a functional Hachiman anti-phage defense system comprise a HamA polypeptide and a HamB polypeptide, each encoded by a hamA and a hamB gene, respectively.


In some embodiments, a Hachiman defense system having an anti-phage activity comprises a nucleic acid encoding a HamA polypeptide. In some embodiments, a Hachiman defense system having an anti-phage activity comprises a nucleic acid encoding a HamA polypeptide and a HamB polypeptide. In some embodiments, a Hachiman defense system having an anti-phage activity comprises a nucleic acid encoding a HamB polypeptide.


In some embodiments, a Hachiman defense system having an anti-phage activity comprises a nucleic acid comprising a hamA gene. In some embodiments, a Hachiman defense system having an anti-phage activity comprises a nucleic acid comprising a hamA gene and a hamB gene. In some embodiments, a Hachiman defense system having an anti-phage activity comprises a nucleic acid comprising hamB gene.


In some embodiments, a Hachiman defense system having an anti-phage activity comprises a nucleic acid construct comprising nucleic acids encoding polypeptides in a set order. In one embodiment, the 5′ to 3′ order of polypeptides encoded is HamA and HamB. In some embodiments the 5′ to 3′ order of polypeptides does not affect the anti-phage activity. In some embodiments the 5′ to 3′ order of polypeptides does affect the anti-phage activity.


In some embodiments, the 5′ to 3′ order of polypeptides is random, for example any order of nucleic acid sequences encoding HamA and HamB.


In some embodiments, a Hachiman defense system having an anti-phage activity comprises a nucleic acid construct comprising genes in a set order. In some embodiment, the 5′ to 3′ order of genes is hamA and hamB. In some embodiment, the 5′ to 3′ order of genes in a Hachiman defense system is not hamA and hamB. In some embodiments the 5′ to 3′ order of genes does not affect the anti-phage activity. In some embodiments the 5′ to 3′ order of genes does affect the anti-phage activity.


In some embodiments, the 5′ to 3′ order of genes is random, for example any order of hamA and hamB.


In some embodiments, the Hachiman system (Defense System IV) composition and order is as shown in FIG. 3B.


In some embodiments, a Hachiman defense system having an anti-phage activity originates from a microbial genome, for example a bacterial and or an archaeal genome (Table 12). A skilled artisan would appreciate that the Hachiman system is not present in the majority of bacteria and or archaea species.


In some embodiments, introducing a combination of polypeptide components within a defense system disclosed herein, for example taking HamA from one bacterium and HamB from another bacterium and combining them into HamA-HamB functional defense system that defends against foreign elements that are not naturally occurring is advantageous to the host cell comprising the non-naturally occurring polypeptide components. In some embodiments, introducing a combination of polypeptide components within any defense system disclosed herein, and combining them to form a functional defense system that defends against foreign elements that are not naturally occurring, is advantageous to the host cell comprising the combination of non-naturally occurring polypeptide components.


In some embodiments, a functional Hachiman defense system comprises a construct comprising nucleic acid sequences encoding polypeptides, wherein the nucleic acid sequence encoding each polypeptide may originate from a different microbial species. For example, the source of the nucleic acid sequence encoding a HamA polypeptide may be one microbial species, while the source of the nucleic acid sequence encoding a HamB polypeptide may be a different microbial species. In some embodiments, a functional Hachiman defense system comprises a non-naturally occurring combination of polypeptide components. In some embodiments, a functional Hachiman defense system comprises a combination of at least two polypeptides that do not naturally occur together.


In some embodiments, a functional Hachiman defense system comprises a construct comprising nucleic acid sequences encoding polypeptides, wherein the nucleic acid sequence encoding each polypeptide may originate from a different bacterial species. For example, the source of the nucleic acid sequence encoding a HamA polypeptide may be one bacterial species, while the source of the nucleic acid sequence encoding a HamB polypeptide may be a different bacterial species.


In some embodiments, the source of the nucleic acid encoding a HamA polypeptide and a HamB polypeptide is the same. In some embodiments, the source of the nucleic acid encoding a HamA polypeptide and a HamB polypeptide is the not the same. In some embodiments, the source of the nucleic acid sequence of any of the components of a Hachiman defense system comprises any of the species listed in Table 12.


In some embodiments, a Hachiman defense system having an anti-phage activity comprises a nucleic acid construct comprising non-coding regions between the nucleic acid sequences encoding the polypeptides. In some embodiments, the non-coding regions between the nucleic acid sequences comprises nucleic acid sequence not naturally occurring in the microbial species of origin. In some embodiments, the non-coding regions between the nucleic acid sequences comprises nucleic acid sequence is the naturally occurring in the microbial species of origin.


In some embodiments, a Hachiman system disclosed herein comprises a multi-gene phage resistance system broadly distributed in microbial genomes, for example but not limited to bacteria and archaea. According to some embodiments, the Hachiman system components are located in a gene cluster (a cassette of genes) in a microbial cell genome. According to some embodiments, the Hachiman system components are located in close proximity (e.g. positioned within 20 genes, 10 genes, 5 genes or less one from the other) in a genome of a prokaryotic cell. According to some embodiments the prokaryotic cell expresses an endogenous Hachiman defense system. According to some embodiments, the prokaryotic cell expresses an endogenous functional Hachiman defense system. According to some embodiments, the species of prokaryotic cell is selected from the group consisting of the species listed in Table 12. According to some embodiments a prokaryotic cell expresses a non-endogenous Hachiman defense system. According to some embodiments, a prokaryotic cell expresses a non-endogenous functional Hachiman defense system. According to some embodiments, the species of prokaryotic cell expressing a non-endogenous functional Hachiman defense system is selected from the group consisting of the species listed in Table 12.


In some embodiments, a Hachiman (Defense System IV) gene cassette comprises the nucleic acid sequence:












(SEQ ID NO: 4; construct 3 Table 4)
















1
taaaagctgc ttcaggtaaa tatcctgaag cagcttttgt ggttaaaaga gaaagtaggt





61
aatagtcatt tgtagtgtat taaagaagat ggaggtgaat aaaacgatgt aatttaagcc





121
ataagttggc cgctttggcc aatgttttct ttattttata tatggtaaaa ttataattag





181
tttagatagt acatttgctt agtaaagatg tactttaaaa aaaaataaat ttatttttgt





241
ggctcttaac gaaatgaata tgctattttg atgtatctta ggtagaaatc taaaaatatt





301
aagaagttgt taaacagcgt taagctagga ggaaatatat gactatacaa gatgatatgg





361
ttggaaaaca tcctatcgag aatgattttt ggaaatggtt gcagcatgaa gatacagaat





421
cctcggattt aaaacggcat cgttacttag aagtggattc tagtaatcgt gatgaagcta





481
ttaaatctgt tgcagcttgg ctaattaagt atcatttgtc ggaaggtaaa aagagagtga





541
taagaaaaaa acaagaaata cttgaaaaac atgattttgc tgaatatgca caatcgcttc





601
atgtttttcc taaaagtgat aaaacacaga aaggaaattt aggagaaata tttttatcgg





661
aatatttgag tcagacatca ggagttcaaa tcctagtgta taaattacac tacaacccca





721
acatagatca atcgatgaaa ggggatgacg ttttacttgt taacccagat aaagttttat





781
taggagaaag taaatttcgt tctactccaa ataaacgtgc tgttgaagag gcttctgaac





841
ttatgaaaga taagttaact ttgcctatgt ctcttggttt tattgcagat agattatttg





901
aacaaggaaa agatgaatta ggtgaagtga ttttcgatct tcaatttaag atgagtagta





961
tagaaataga tattaaaaat atagggtttt tattatctac taaaaaggtt cgtagtatcg





1021
tagaaaataa cctttcttct ccaaattctg attttatttt tatttcatta ggaatggatg





1081
acccagcagc ttttttgaaa agtgtatttg actatgcaga aagtaatctt ctggagggat





1141
cttatgaaac ttgaaacagc atataattat tttgaaaagc ttgaaaaaga tgaacgtctt





1201
caaaactata tttcacaggc taattcaaga tatatccttt acatagcaaa tgaaccattg





1261
gaaaatttcc cacattacac tgtaaatcta gatgaaaaat gtacacatat agcatttagt





1321
tatctcaatt gtggatggcg ctttttttta gagaaaatca gtgatgaagc tacaaaatgt





1381
atggaaaagg cttctgaaat attggagtat ttgtatgcct atagtgattg cgaaaagtta





1441
tataaagagt attaccgttt agtatgctca ttagcgtatt atatatctgc acagtattct





1501
aaatctttta ttatcttggg gaaatataat tctgattcat atatagggaa aataacaaaa





1561
ttatttttaa ctagaaactt tatagaatta gaaaggcaac tggaaattaa gtacttgaag





1621
aacgatgaag aaacttcaag tgagaataag gataacataa tatatgaaaa aattttatct





1681
aatgcatttt tacatataat taattttatt cgcacaggga agatggaatc tttggaaagt





1741
tctaaagata tggttcgaga tttaattact ttggctgata taaataatga accacatatg





1801
tggtggtact ttagactact atatttggtt tttgaagaat atgaagatgg gtctttgtgg





1861
aaagtggttc caccgctttt agataatgat gatatatcag ctaaatatat ttatgctaat





1921
ttatacaaaa agaagccaat aactgaattt tttaagtcgc aaagggaatg tttggacgga





1981
gagttattaa agaacgatgg tttcgtaatt ggaatgccta ctagttcagg aaaaacaaag





2041
gttgctgaag taacaatatt aaaaacttta actaaatctc caggtgcact ttgtatttat





2101
attgcacctt atcgatcttt ggctaatgaa gtggaattta gcctatctag tatgtttgag





2161
attatgggtt atcaggtttc gcagttatat gggggatctc aaacgtctcc gctggatcgg





2221
caattgacta agcaagctaa tgtcataatt gttactccgg aaaaagctaa atcgatgttg





2281
agatctaata aagacttaaa ggatagaatt caacttgtaa tcattgatga aggtcattta





2341
gtcgggtttc agccaagata tattacagga gaattgctta ttgaagaact aaagattgtt





2401
ttgaaaaaaa ataatggtca acttgtacta ctatctgctg ttcttcctaa tatttctgat





2461
ttttctttgt ggattggtga ggatgataaa gctaaaagaa tgtctgtctg gagaccatca





2521
agtcaaagat ttggagaatt atctttagca agaaatactg tgaatataaa ttgggaggga





2581
gaaacaccat catataataa gaactttata acaccaaaat tagtaaaacc agaacggatt





2641
acaaaaacag gaaggaaata tgcagctaaa tattttccag cagataaaaa agaaggtgtt





2701
gctgcaaccg caacaaaaat gctagatgtg ggatccgttt tgatttatgt aggaagatcg





2761
aatatggtat tgtctcaagc taggattgtt tcgaaactct ttgaggaaaa gggaatagaa





2821
catgagtgga ggaataaaaa cgattggttg tttgtggaat tagcttgtat agaagaatat





2881
ggggaagatt cagaaatatt atctttatta aaacaaggta tagtacccca tagttctaaa





2941
ttaccaacag aagtacgtca gagcatagag aaattaatgg ctaatgataa tcctaagata





3001
ataattgcga catccacact tggacaaggg gttaatattg gtgtttcgac agttattgta





3061
tctaatgttc gtttagatga gagtaatact gtaaaagtaa atgatttttg gaatattgct





3121
ggtagagcgg ggagggcatt tacagataca gagggtaaaa ttctatacgc aattgataga





3181
aataaaagcc agtggtctat ttataatcaa attcaaatga aagaaatgta tttcaaatat





3241
agaaatattg aaaaagctac aagtggtctc tatcttcttc ttcgttatct atttatatta





3301
tcggaagaat tcgagataga atacagctta tttttagaac ttctagcaga aaatagagaa





3361
tccattgatg aacagaaagc tgtggagttt ttttctgagg cagatcagtt ccttgagtta





3421
ttagatgata ctctaatttc catggatatt atgaatgagg caaacgtttt ggaaaattcc





3481
tcttcttgga tagacgatgt ctttcgttct tcgctagctt ttattcaagc aaaacaagat





3541
caatcatttt ctgaagaaaa aatgattgaa atcttaaaag caagaaattc aggtgtaata





3601
aagttggctg gagaagaaac aaaatggcat tcaatagcat catcaagtgt accattgaga





3661
gcaagtcttg taattgaaca taggatagat gagctactaa agtatgtacg aaaatacatt





3721
gactcagata agagttttga agagttatta tctcttgtga tggaacttga tatatttatt





3781
gatagtctac cgatatctaa aatagaagga atagaaatag gtgctaattt ttctgaaatt





3841
cgtgagggat ggtttagtgg tactagcata cacatattgg aaaaaaggca cgaaaatgta





3901
agaagtatct gtaatgaata ttattctttt cattttcctt ggattgtaaa tgcgatagct





3961
caaaagatca aattaattga ttgccaagag gaatcaaagg tgttggagca aatttcttta





4021
tttgctgaaa tagggttaaa caataataaa agtgtaaaaa tctatttggc aggtataaag





4081
tcaagaaatt gtgccactga attatctgag aaaataggca tggataatga tttggtgacg





4141
cctgttaagg agctacttct agagtttttc aatttatgtg tagtgaaaaa agaggattgt





4201
tcagaaattt gtttcaattg gttaaagctt ttaaatgatg aaaaagaagc taaagagtat





4261
gtaaaggtaa aaagacggtc tttccaattt aatattcctt ttgatttaca tgacaatctt





4321
ttatatataa agaaagtaca gagtgaaata tggctgtgct catttgatta taaaattaaa





4381
attcctgtat taaaagagaa ggcgttattt aatgagtgct cggatatacc tgatattttc





4441
ttgagaaagg aaaaaggaga tgtctggatt ttagattctc ataatcctta tattattttt





4501
tattaattta tttgaattta atattttgga taaggcagat tgttcaacta tttggaggaa





4561
ataaaaaaac ggattattaa gggtgaacta aatttaatca aactttttac aaatctgcat





4621
ctttctcatt ttcaccttta aaaatgccaa ggaactcaat gaaatttggt atgcagatac





4681
cttcaagagc caccaatcct aaagtgaaat ctccatagtt tttacgatat tcttcataaa





4741
ttaatctggc tatatcttca ccaaaagaaa acatttcttt tgttatttcg gaaagataag





4801
gtagaagtgg tatatactca tctggtttac ctttttcatt tgaaggtact tttactgcat





4861
acccttgatc aagtgtcata atgttaattt gatgaccact atgtacaata gaatcgcgta





4921
tttctctatt cttatgaaag ctttctataa tagataatag ttttttttct aaggattcag





4981
gtaatttatc cttggttgtt cctttttcaa cggaagtaat taaactattt aaggaatcaa





5041
aactgagttg tccaacaaat ttaggagcta ctgttaatcg taggattttt gccatgaaat





5101
cataaattga acgaatatcc at.









The coding regions for each of the hamA and hamB gene sequences within this embodiment of a Hachiman cassette (SEQ ID NO: 4) are as follows: nucleotides 339-1154 encode an embodiment of a HamA polypeptide, and nucleotides 1114-4506 encode an embodiment of a HamB polypeptide.


In some embodiments, a Defense System IV comprising a HamA polypeptide and a HamB polypeptide is encoded by the nucleic acid sequence set forth in SEQ ID NO: 4. In some embodiments, a Defense System IV comprising a HamA polypeptide and a HamB polypeptide, is encoded by a nucleic acid sequence having at least 80% homology to the sequence set forth in SEQ ID NO: 4. In some embodiments, a Defense System IV comprising a HamA polypeptide and a HamB polypeptide, is encoded by a nucleic acid sequence having at least 85% homology, or 90% homology, or 95% homology, or 97% homology, or 98% homology, or 99% homology to the sequence set forth in SEQ ID NO: 4. In some embodiments, a Defense System IV comprising a HamA polypeptide and a HamB polypeptide, is encoded by a nucleic acid sequence having at least 80% identity to the sequence set forth in SEQ ID NO: 4. In some embodiments, a Defense System IV comprising a HamA polypeptide and a HamB polypeptide, is encoded by a nucleic acid sequence having at least 85% identity, or 90% identity, or 95% identity, or 97% identity, or 98% identity, or 99% identity to the sequence set forth in SEQ ID NO: 4.


In some embodiments, Hachiman defense system components comprise HamA and HamB polypeptides. In some embodiments, Hachiman defense system components comprise functional portions of HamA and HamB polypeptides. In some embodiments, the Hachiman defense system components are encoded by hamA and hamB genes.


Non-limiting embodiments of endogenous Hachiman systems and the respective location of their components are provided in Table 12 herein.


In some embodiments, the components of a Hachiman system may be identified by the presence of similar domains present within each component. In some embodiments, domains comprise pfam domains and or clusters of orthologous groups (COG) domains.


In some embodiments, the term “HamA” refers to the polynucleotide or expression product e.g., the polypeptide encoded by the hamA gene. In some embodiments, the term “HamA” refers to a HamA polypeptide. In some embodiments, the hamA gene encodes a polypeptide comprising a pfam08878 domain. In some embodiments, the hamA gene encodes a polypeptide comprising a DUF1837 domain. In some embodiments, the hamA gene encodes a polypeptide comprising a pfam08878 domain and a DUF1837 domain. In some embodiments, the HamA polypeptide comprises a pfam08878 domain. In some embodiments, the HamA polypeptide comprises a DUF1837 domain. In some embodiments, the HamA polypeptide comprises a pfam08878 domain and a DUF1837 domain.


In some embodiments, HamA polypeptide is encoded by a gene positioned within 5-60 genes of a gene encoding a HamB polypeptide in a genome of a prokaryotic cell. In some embodiments, HamA polypeptide is encoded by a gene positioned within 5 genes upstream (5′) or downstream (3′) to a gene encoding a HamB polypeptide in a genome of a prokaryotic cell. In some embodiments, HamA polypeptide is encoded by a gene positioned within 5 genes upstream (5′) and downstream (3′) to a gene encoding a HamB polypeptide in a genome of a prokaryotic cell.


In some embodiments, HamA and HamB are encoded by genes positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, HamA and HamB are encoded by genes positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell.


In some embodiments, hamA and hamB genes are positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, hamA and hamB, genes are positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell.


In some embodiments, a HamA polypeptide is about 269 amino acids long (median gene size).


In some embodiments, the HamA polypeptide comprises the amino acid sequence having at least 80% homology to a sequence selected from the group consisting of the polypeptides referenced in Table 12, rows 2-1782, columns H and I. In some embodiments, the HamA polypeptide comprises the amino acid sequence having at least 80% homology within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 12, rows 2-1782, columns H and I. In some embodiments, the HamA polypeptide comprises a homolog of a polypeptide having the amino acid sequences set forth in the polypeptides referenced in Table 12, rows 2-1782, columns H and I.


In some embodiments, the HamA polypeptide comprises the amino acid sequence having at least 80% identity to a sequence selected from the group consisting of the polypeptides referenced in Table 12, rows 2-1782, columns H and I. In some embodiments, the HamA polypeptide comprises the amino acid sequence having at least 80% identity within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 12, rows 2-1782, columns H and I.


In some embodiments, the HamA polypeptide comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polypeptides referenced in Table 12, rows 2-1782, columns H and I. In some embodiments, the HamA polypeptide comprises the amino acid sequence having at least 80%, 85%, 90%, 95% homology within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 12, rows 2-1782, columns H and I. In some embodiments, the HamA polypeptide comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polypeptides referenced in Table 12, rows 2-1782, columns H and I. In some embodiments, the HamA polypeptide comprises the amino acid sequence having at least 80%, 85%, 90%, 95% identity within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 12, rows 2-1782, columns H and I. In some embodiments, the HamA polypeptide comprises an amino acid sequence selected from the group consisting of the polypeptides referenced in Table 12, rows 2-1782, columns H and I.


In some embodiments, the HamA polypeptide comprises an amino acid sequence encoded by a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polynucleotides referenced in Table 12, rows 2-1782, columns H and J. In some embodiments, the HamA polypeptide comprises the amino acid sequence encoded by a nucleic acid sequence having at least 80%, 85%, 90%, 95% homology within similar domain regions within a sequence selected from the group consisting of the polynucleotides referenced in Table 12, rows 2-1782, columns H and J. In some embodiments, the HamA polypeptide comprises an amino acid sequence encoded by a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polynucleotides referenced in Table 12, rows 2-1782, columns H and J. In some embodiments, the HamA polypeptide comprises the amino acid sequence encoded by a nucleic acid sequence having at least 80%, 85%, 90%, 95% homology within similar domain regions within a sequence selected from the group consisting of the polynucleotides referenced in Table 12, rows 2-1782, columns H and J. In some embodiments, the HamA polypeptide comprises an amino acid sequence encoded from a nucleic acid sequence selected from the group consisting of the polynucleotides referenced in Table 12, rows 2-1782, columns H and J.


In some embodiments, the nucleic acid sequence of a hamA gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polynucleotides referenced in Table 12, rows 2-1782, columns H and J. In some embodiments, the hamA gene comprises a nucleic acid sequence having at least 80%, 85%, 90%, 95% homology within encoded similar domain regions in comparison with nucleotide sequence encoding these domain within a sequence selected from the group consisting of the polynucleotides referenced in Table 12, rows 2-1782, columns H and J. In some embodiments, the nucleic acid sequence of a hamA gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polynucleotides referenced in Table 12, rows 2-1782, columns H and J. In some embodiments, the hamA gene comprises a nucleic acid sequence having at least 80%, 85%, 90%, 95% identity within encoded similar domain regions in comparison with nucleotide sequence encoding these domain within a sequence selected from the group consisting of the polynucleotides referenced in Table 12, rows 2-1782, columns H and J. In some embodiments, the nucleic acid sequence of a hamA gene comprises a nucleic acid sequence selected from the group consisting of the polynucleotides referenced in Table 12, rows 2-1782, columns H and J.


As used herein, the term “HamB” refers to the polynucleotide or expression product e.g., polypeptide encoded by the hamB gene. In some embodiments, the term “HamB” refers to a HamB polypeptide. In some embodiments, the product of the hamB gene comprises a COG1204 domain. In some embodiments, the hamB gene encodes a pfam00270 domain. In some embodiments, the hamB gene encodes a pfam00271 domain. In some embodiments, the hamB gene encodes a helicase.


In some embodiments, HamB polypeptide is encoded by a gene positioned within 5-60 genes of a gene encoding a HamA polypeptide in a genome of a prokaryotic cell. In some embodiments, HamB polypeptide is encoded by a gene positioned within 5 genes upstream (5′) or downstream (3′) to a gene encoding a HamA polypeptide in a genome of a prokaryotic cell. In some embodiments, HamB polypeptide is encoded by a gene positioned within 5 genes upstream (5′) and downstream (3′) to a gene encoding a HamA polypeptide in a genome of a prokaryotic cell.


In some embodiments, HamA and HamB are encoded by genes positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments HamA and HamB are encoded by genes positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell.


In some embodiments, a HamB polypeptide is about 867 amino acids long (median gene size).


In some embodiments, the HamB polypeptide comprises the amino acid sequence having at least 80% homology to a sequence selected from the group consisting of the polypeptides referenced in Table 12, rows 2-1782, columns L and M. In some embodiments, the HamB polypeptide comprises the amino acid sequence having at least 80% homology within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 12, rows 2-1782, columns L and M. In some embodiments, the HamB polypeptide comprises a homolog of a polypeptide having the amino acid sequences set forth in the polypeptides referenced in Table 12, rows 2-1782, columns L and M.


In some embodiments, a HamB polypeptide homolog comprises a helicase domain.


In some embodiments, a HamB polypeptide homolog comprises a helicase activity.


In some embodiments, the HamB polypeptide comprises the amino acid sequence having at least 80% identity to a sequence selected from the group consisting of the polypeptides referenced in Table 12, rows 2-1782, columns L and M. In some embodiments, the HamB polypeptide comprises the amino acid sequence having at least 80% identity within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 12, rows 2-1782, columns L and M.


In some embodiments, the HamB polypeptide comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polypeptides referenced in Table 12, rows 2-1782, columns L and M. In some embodiments, the HamB polypeptide comprises the amino acid sequence having at least 80%, 85%, 90%, 95% homology within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 12, rows 2-1782, columns L and M. In some embodiments, the HamB polypeptide comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polypeptides referenced in Table 12, rows 2-1782, columns L and M. In some embodiments, the HamB polypeptide comprises the amino acid sequence having at least 80%, 85%, 90%, 95% identity within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 12, rows 2-1782, columns L and M. In some embodiments, the HamB polypeptide comprises an amino acid sequence selected from the group consisting of the polypeptides referenced in Table 12, rows 2-1782, columns L and M.


In some embodiments, the HamB polypeptide comprises an amino acid sequence encoded by a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polynucleotides referenced in Table 12, rows 2-1782, columns L and N. In some embodiments, the HamB polypeptide comprises the amino acid sequence encoded by a nucleic acid sequence having at least 80%, 85%, 90%, 95% homology within similar domain regions within a sequence selected from the group consisting of the polynucleotides referenced in Table 12, rows 2-1782, columns L and N. In some embodiments, the HamB polypeptide comprises an amino acid sequence encoded by a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polynucleotides referenced in Table 12, rows 2-1782, columns L and N. In some embodiments, the HamB polypeptide comprises the amino acid sequence encoded by a nucleic acid sequence having at least 80%, 85%, 90%, 95% homology within similar domain regions within a sequence selected from the group consisting of the polynucleotides referenced in Table 12, rows 2-1782, columns L and N. In some embodiments, the HamB polypeptide comprises an amino acid sequence encoded from a nucleic acid sequence selected from the group consisting of the polynucleotides referenced in Table 12, rows 2-1782, columns L and N.


In some embodiments, the nucleic acid sequence of a hamB gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polynucleotides referenced in Table 12, rows 2-1782, columns L and N. In some embodiments, the hamB gene comprises a nucleic acid sequence having at least 80%, 85%, 90%, 95% homology within encoded similar domain regions in comparison with nucleotide sequence encoding these domain within a sequence selected from the group consisting of the polynucleotides referenced in Table 12, rows 2-1782, columns L and N. In some embodiments, the nucleic acid sequence of a hamB gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polynucleotides referenced in Table 12, rows 2-1782, columns L and N. In some embodiments, the hamB gene comprises a nucleic acid sequence having at least 80%, 85%, 90%, 95% identity within encoded similar domain regions in comparison with nucleotide sequence encoding these domain within a sequence selected from the group consisting of the polynucleotides referenced in Table 12, rows 2-1782, columns L and N. In some embodiments, the nucleic acid sequence of a hamB gene comprises a nucleic acid sequence selected from the group consisting of the polynucleotides referenced in Table 12, rows 2-1782, columns L and N.


A skilled artisan would appreciate that the terms a “functional portion of a Defense System IV component” or “functional fragment of Defense System IV component” or “functional portion of a Hachiman defense system component” or “functional fragment of Hachiman defense system component” refers to a functional portion of a Hachiman polynucleotide or polypeptide, as disclosed herein, which expression is sufficient to elicit an anti-phage activity alone or in combination with the at least one of the other Hachiman polynucleotides or polypeptides disclosed herein or functional portions thereof.


The terms “HamA”, “HamB”, “hamA”, and “hamB”, also refer to functional HamA, HamB, hamA, and hamB, homologs, which exhibit the desired activity (i.e., conferring phage resistance). Such homologs can be, for example, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical or homologous to the polypeptide sequences referenced in Table 12 rows 2-1782 columns H and I and L and M, respectively, or 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% homologous or identical to the polynucleotide sequences referenced in Table 12 rows 2-1782 columns H and J and L and N, respectively. In some embodiments, such homologs comprise at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% homology or identity within similar domain regions of the polypeptide sequences referenced in Table 12 rows 2-1782 columns H and I and L and M, respectively, or 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% homology or identity within nucleotide sequences encoding similar domain regions to the polynucleotide sequences referenced in Table 12 rows 2-1782 columns H and J and L and N, respectively.


Table 12 presents embodiments of components of Defense System IV that may be found in a diverse array of bacteria and archaea genomes (referenced in Table 18). Table 12 presents embodiments of nucleic acid sequences encoding gene cassettes of Defense System IV (referenced in Table 18).


The Shedu Defense System


In some embodiments, a defense system disclosed herein comprises a Shedu anti-phage defense system. (Table 13)


In some embodiments, a Shedu defense system provides a host cell with resistance to entry of foreign nucleic acid invasion. In some embodiments, a host cell expressing a functional Shedu defense system (Defense System V) provides the host cell resistance foreign nucleic acid invasion.


In some embodiments, a Shedu defense system provides a host cell with resistance to at least one phage. In some embodiments, a microbial cell comprising a Shedu defense system is protected from phage infection. In some embodiments, a microbial cell expressing a Shedu defense system is protected from phage infection. In some embodiments, a microbial cell expressing a functional Shedu defense system is protected from phage infection. In some embodiments, a bacterial cell comprising a Shedu defense system is protected from phage infection. In some embodiments, a bacterial cell expressing a Shedu defense system is protected from phage infection. In some embodiments, a bacterial cell expressing a functional Shedu defense system is protected from phage infection.


In some embodiments, a Shedu defense system provides a host cell with resistance to a plasmid.


In some embodiments, a Shedu defense system (Defense System V) provides a host cell with resistance to plasmid transformation. In some embodiments, a host cell expressing a functional Shedu defense system (Defense System V) provides a host cells with resistance to plasmid transformation.


In some embodiments, a Shedu defense system (Defense system V) provides a host cell with resistance to entry of conjugative elements. In some embodiments, a host cell expressing a function Shedu defense system (Defense System V) provides the host cell resistance from entry of conjugative elements.


As used herein, the term “a Shedu anti-phage defense system” may be used interchangeably with the term “a Defense System V”, having all the same meanings and qualities. A skilled artisan would appreciate that the term “Shedu system” may be used interchangeably in some embodiments with “Shedu defense system”, “Shedu the defense system”, “Shedu anti-phage system”, and “Defense System V”, having all the same meanings and qualities.


In some embodiments, a microbial species does not comprise an endogenous Defense System V. In some embodiments, a microbial species does not express an endogenous Defense System V. In some embodiments, a microbial species does not express a functional Defense System V.


In some embodiments, a bacterial species does not comprise an endogenous Defense System V. In some embodiments, a bacterial species does not express an endogenous Defense System V. In some embodiments, a bacterial species does not express an endogenous functional Defense System V.


A Shedu defense system comprises, in some embodiments, a nucleic acid construct comprising a nucleic acid sequence encoding a SduA polypeptide comprising a pfam14082 domain or a DUF4263 domain or a pfam01939 domain, or a combination thereof. In some embodiments, a Shedu defense system comprises a SduA polypeptide comprising an endonuclease NucS activity. A skilled artisan would appreciate that an endonuclease NucS activity encompasses an enzymatic activity cleaving both 3′ and 5′ ssDNA extremities of branched DNA structures, wherein the NucS endonuclease may bind to ssDNA. In some embodiments, a Shedu defense system comprises a nucleic acid construct comprising a nucleic acid sequence comprising a sduA gene.


A Shedu defense system comprises, in some embodiments, a nucleic acid construct comprising a nucleic acid sequence comprising a sduA gene encoding a pfam14082 domain or a DUF4263 domain or a pfam01939 domain, or a combination thereof. In some embodiments, a Shedu defense system comprising a sduA gene encodes a polypeptide comprising an endonuclease NucS activity.


In some embodiments, a Defense System V comprises a SduA polypeptide comprising a pfam14082 domain or a pfam01939 domain or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 13 rows 2-1247 columns H and I or a combination thereof.


In some embodiments, a Shedu defense system having an anti-phage activity comprises a nucleic acid construct comprising a nucleic acid sequence encoding a SduA polypeptide. In some embodiments, a Shedu defense system having an anti-phage activity comprises a nucleic acid construct comprising a nucleic acid sequence comprising a sduA gene.


In some embodiments, the Shedu anti-phage defense system comprises a nucleic acid construct comprising nucleic acid sequences encoding a cassette comprising a sduA gene.


In some embodiments, a construct comprising the Shedu defense system encodes one component of the defense system. In some embodiments, the components of a Shedu defense system comprise a sduA gene. In some embodiments, the components of a Shedu defense system consist of a sduA gene. In some embodiments, the components of a Shedu defense system comprise nucleic acid sequences encoding a SduA polypeptide. In some embodiments, the components of a Shedu defense system consist of nucleic acid sequences encoding a SduA polypeptide.


In some embodiments, a construct comprising the Shedu defense system encodes one component of the defense system, whereby a second construct may be used to assemble the functional defense system. In some embodiments, a construct comprising the Shedu defense system encodes one component of the defense system, whereby additional constructs may be used to assemble the functional defense system. In some embodiments, the Shedu defense system comprises non-coding RNA.


In some embodiments, the components making up a functional Shedu anti-phage defense system comprise a SduA polypeptide encoded by a sduA gene.


In some embodiments, a Shedu defense system having an anti-phage activity comprises a nucleic acid encoding a SduA polypeptide.


In some embodiments, a Shedu defense system having an anti-phage activity comprises a nucleic acid comprising a sduA gene.


In some embodiments, the Shedu system (Defense System V) composition and order is as shown in FIG. 3B.


In some embodiments, a Shedu defense system having an anti-phage activity originates from a microbial genome, for example a bacterial and or an archaeal genome (Table 13). A skilled artisan would appreciate that the Shedu system is not present in the majority of bacteria and or archaea species.


In some embodiments, a Shedu defense system having an anti-phage activity comprises a nucleic acid construct comprising non-coding regions. In some embodiments, the non-coding regions comprises nucleic acid sequence not naturally occurring in the microbial species of origin. In some embodiments, the non-coding regions comprises nucleic acid sequence is the naturally occurring in the microbial species of origin.


In some embodiments, Shedu defense system components comprise functional portions of a SduA polypeptides. In some embodiments, the Shedu defense system functional portions of a SduA polypeptide component is encoded by a sduA gene.


Non-limiting embodiments of endogenous Shedu systems and the respective location of their component are provided in Table 13 herein. In some embodiments, a Shedu (Defense System V) gene cassette comprises the nucleic acid sequence:












(SEQ ID NO: 9; construct 28 Table 4)
















1
aatgaaattt gaacgccttt cggcagtgat atttgtacac ctcattttta cgtgccagcg





61
tgatgtacat gaaaagtggt gaaaagattc ctattgtggc tgagagtagt agcatgatga





121
tggtgtttct tttttctttt ttgatggttt tcatgagtga tttggccccc tttttgtttt





181
gtcttcttta aattaggggt gacgttgggg gagatgcaag gggaatctgt agaaaaattg





241
attgagaccg atatagataa attccatatt tttatttatg aaatcctata ctgtcaatat





301
taatcaaaac aattaatgag atcaaatttt tttgttcatc agacattaat agaatgattg





361
tatggataat agtagtttct ttatcacaac aacgcattat catgaagctc cacaatagga





421
ttgtagaata acctcaaatt caatcctatg ttcattgaaa agggggcggg gaactcttta





481
aacatctcca cgaggtattt tgagtgtatg tgctttatta attctacatg cttaggctaa





541
ctaatcatta atagactaca aaaaacattc atgcctagta cagaaacaca cccttctcat





601
tgaagaagac taaccagtgg tattcgcaaa agaagaaaag aggattacct caacagccac





661
ctaccttttt atattgtaaa tatgtcctat ttaattcgga gtagtgtata ctattagtag





721
aaaattccaa gcgtagctat cgaggagtgt taacaaaata tgagtgacaa aattaatgta





781
tggacaacat caagagactc tgctgtatgt ggtgacattg aattaaaaaa aacatctact





841
actagactta tttttaggcc tgaaatagtg aacaataata aaaatcctaa ggcatctgtt





901
agaggatgct ttatctttca aaagaaaggt agaaatgccc tttgggatga ttataaggaa





961
ttagatatga ataagttaaa agcagaggaa tggattaaac tagagataaa ctctgatgct





1021
atgctgactc ttactaaaga aattcagaag cattatgcag tgcatgaaaa gtatggggtt





1081
aggtatggag catttcacct tttcaaggat aaccctgata tcgagaaact gattgaaatg





1141
tttgagagta acactgattt gcttactcaa ttaatggagg atgacaagag tgaagctcta





1201
gagaaaacat tagaatggat tgttacaaat gataatccag ataaaataat tgacaggctt





1261
aaaaatctaa aagagcaaga tttagaccaa cttaatactc ttattgggat agctaatcta





1321
aaaaaggtat tgtctgtttg ggaaagcaac aaactcacta atacctctga gaagttttgg





1381
caaagtgtct taaaagaaaa cacttggatt ttgagtcaga ttttctctaa cccgactgtt





1441
ttgataaatg atgaagccta tgtaggcgga aagactgtca aaaatgatag tggtaagtta





1501
gtagatttct tatatgcaaa ccctttctca aaagatgctg tacttattga gattaagact





1561
ccatcaacgc ctctaattac tcccactgaa tacagaacag gagtatattc cgcacataaa





1621
gacttgacag gagcagttac gcaagtgttg acttataaga caaccctaca gagggagtat





1681
cagaatatag actataacaa ttatagacag ggaatcaaaa ctgattttga cattattact





1741
ccttgttgtg ttgttatagc aggcatgttt gatacattaa ctgatacagc tcatagacat





1801
tcctttgaac tgtacagaaa agagttaaaa aatgtaactg taattacttt tgatgaactg





1861
tttgaaaggg ttaaggggtt aatcaagcta ttggaaggat aaacccttgc cttctttttt





1921
tactgcctct aaatttatag aatgcatccg ttaaagctaa gtagaaatat tagaagaaag





1981
ggcaaaattt aaagagagaa atttgccttt tctttttatc aaactgatca aaaaatttta





2041
tatttcaatc actttatttc gccacctgaa tttttttatt ttttaaaagt gccttgcctc





2101
tcaccaattc aggtcattat aaaacaaaaa aagaaccgtt tatcaacaac aaacggtccg





2161
attaaaaatc ttgtgcgtat ctattaaaaa taacttaata aaacatgctt att.









The coding region for the sduA gene sequence within this embodiment of a Shedu cassette (SEQ ID NO: 9) is as follows: nucleotides 760-1902 encode an embodiment of a SduA polypeptide.


In some embodiments, a Defense System V comprising a SduA polypeptide is encoded by the nucleic acid sequence set forth in SEQ ID NO: 9. In some embodiments, a Defense System V comprising a SduA polypeptide, is encoded by a nucleic acid sequence having at least 80% homology to the sequence set forth in SEQ ID NO: 9. In some embodiments, a Defense System V comprising a SduA polypeptide, is encoded by a nucleic acid sequence having at least 85% homology, or 90% homology, or 95% homology, or 97% homology, or 98% homology, or 99% homology to the sequence set forth in SEQ ID NO: 9. In some embodiments, a Defense System V comprising a SduA polypeptide, is encoded by a nucleic acid sequence having at least 80% identity to the sequence set forth in SEQ ID NO: 9. In some embodiments, a Defense System V comprising a SduA polypeptide, is encoded by a nucleic acid sequence having at least 85% identity, or 90% identity, or 95% identity, or 97% identity, or 98% identity, or 99% identity to the sequence set forth in SEQ ID NO: 9.


In some embodiments, the components of a Shedu system may be identified by the presence of similar domains present within each component. In some embodiments, domains comprise pfam domains and or clusters of orthologous groups (COG) domains.


In some embodiments, the term “SduA” refers to the polynucleotide or expression product e.g., the polypeptide encoded by the sduA gene. In some embodiments, the term “SduA” refers to a SduA polypeptide. In some embodiments, the sduA gene encodes a polypeptide comprising a pfam14082 domain. In some embodiments, the sduA gene encodes a polypeptide comprising a DUF4263 domain. In some embodiments, the sduA gene encodes a polypeptide comprising a pfam01939 domain. In some embodiments, the sduA gene encodes a polypeptide comprising a pfam14082 domain, a DUF4236 domain, or a pfam01939 domain, or any combination thereof. In some embodiments, the SduA polypeptide comprises a pfam14082 domain. In some embodiments, the SduA polypeptide comprises a DUF4263 domain. In some embodiments, the SduA polypeptide comprises a pfam01939 domain. In some embodiments, the SduA polypeptide comprises a pfam14082 domain, a DUF4263 domain, or pfam01939 domain, or any combination thereof.


In some embodiments, a SduA polypeptide is about 367 amino acids long (median gene size).


In some embodiments, the SduA polypeptide comprises the amino acid sequence having at least 80% homology to a sequence selected from the group consisting of the polypeptides referenced in Table 13, rows 2-1247, columns H and I. In some embodiments, the SduA polypeptide comprises the amino acid sequence having at least 80% homology within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 13, rows 2-1247, columns H and I. In some embodiments, the SduA polypeptide comprises a homolog of a polypeptide having the amino acid sequences set forth in the polypeptides referenced in Table 13, rows 2-1247, columns H and I.


In some embodiments, a SduA polypeptide homolog comprises an endonuclease NucS domain. In some embodiments, a SduA polypeptide homolog comprises an endonuclease NucS activity. In some embodiments, a SduA polypeptide homolog comprises an activity that cleaves both 3′ and 5′ ssDNA extremities of branched DNA structures. In some embodiments, a SduA polypeptide homolog binds to ssDNA. In some embodiments, a SduA polypeptide homolog comprises an activity that cleaves both 3′ and 5′ ssDNA extremities of branched DNA structures and it binds to ssDNA. In some embodiments, an SduA polypeptide comprises a member of the PD-(D/E)XK superfamily.


In some embodiments, the SduA polypeptide comprises the amino acid sequence having at least 80% identity to a sequence selected from the group consisting of the polypeptides referenced in Table 13, rows 2-1247, columns H and I. In some embodiments, the SduA polypeptide comprises the amino acid sequence having at least 80% identity within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 13, rows 2-1247, columns H and I.


In some embodiments, the SduA polypeptide comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polypeptides referenced in Table 13, rows 2-1247, columns H and I. In some embodiments, the SduA polypeptide comprises the amino acid sequence having at least 80%, 85%, 90%, 95% homology within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 13, rows 2-1247, columns H and I. In some embodiments, the SduA polypeptide comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polypeptides referenced in Table 13, rows 2-1247, columns H and I. In some embodiments, the SduA polypeptide comprises the amino acid sequence having at least 80%, 85%, 90%, 95% identity within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 13, rows 2-1247, columns H and I. In some embodiments, the SduA polypeptide comprises an amino acid sequence selected from the group consisting of the polypeptides referenced in Table 13, rows 2-1247, columns H and I.


In some embodiments, the SduA polypeptide comprises an amino acid sequence encoded by a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polynucleotides referenced in Table 13, rows 2-1247, columns H and J. In some embodiments, the SduA polypeptide comprises the amino acid sequence encoded by a nucleic acid sequence having at least 80%, 85%, 90%, 95% homology within similar domain regions within a sequence selected from the group consisting of the polynucleotides referenced in Table 13, rows 2-1247, columns H and J. In some embodiments, the SduA polypeptide comprises an amino acid sequence encoded by a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polynucleotides referenced in Table 13, rows 2-1247, columns H and J. In some embodiments, the SduA polypeptide comprises the amino acid sequence encoded by a nucleic acid sequence having at least 80%, 85%, 90%, 95% homology within similar domain regions within a sequence selected from the group consisting of the polynucleotides referenced in Table 13, rows 2-1247, columns H and J. In some embodiments, the SduA polypeptide comprises an amino acid sequence encoded from a nucleic acid sequence selected from the group consisting of the polynucleotides referenced in Table 13, rows 2-1247, columns H and J.


In some embodiments, the nucleic acid sequence of a sduA gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polynucleotides referenced in Table 13, rows 2-1247, columns H and J. In some embodiments, the sduA gene comprises a nucleic acid sequence having at least 80%, 85%, 90%, 95% homology within encoded similar domain regions in comparison with nucleotide sequence encoding these domain within a sequence selected from the group consisting of the polynucleotides referenced in Table 13, rows 2-1247, columns H and J. In some embodiments, the nucleic acid sequence of a sduA gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polynucleotides referenced in Table 13, rows 2-1247, columns H and J. In some embodiments, the sduA gene comprises a nucleic acid sequence having at least 80%, 85%, 90%, 95% identity within encoded similar domain regions in comparison with nucleotide sequence encoding these domain within a sequence selected from the group consisting of the polynucleotides referenced in Table 13, rows 2-1247, columns H and J. In some embodiments, the nucleic acid sequence of a sduA gene comprises a nucleic acid sequence selected from the group consisting of the polynucleotides referenced in Table 13, rows 2-1247, columns H and J.


A skilled artisan would appreciate that the terms a “functional portion of a Defense System V component” or “functional fragment of Defense System V component” or “functional portion of a Shedu defense system component” or “functional fragment of Shedu defense system component” refers to a functional portion of a Shedu polynucleotide or polypeptide, as disclosed herein, which expression is sufficient to elicit an anti-phage activity alone.


The terms “SduA” and “sduA”, also refer to functional SduA and sduA, homologs, which exhibit the desired activity (i.e., conferring phage resistance). Such homologs can be, for example, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical or homologous to the polypeptide sequences referenced in Table 13 rows 2-1247 columns H and I, respectively, or 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical or homologous to the polynucleotide sequences referenced in Table 13 rows 2-1247 columns H and J, respectively. In some embodiments, such homologs comprise at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% homology or identity within similar domain regions of the polypeptide sequences referenced in Table 13 rows 2-1247 columns H and I, respectively, or 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity or homology within nucleotide sequences encoding similar domain regions to the sequences referenced in Table 13 rows 2-1247 columns H and J, respectively.


Table 13 presents embodiments of components of Defense System V that may be found in a diverse array of bacteria and archaea genomes (referenced in Table 18). Table 13 presents embodiments of nucleic acid sequences encoding gene cassettes of Defense System V (referenced in Table 18).


The Gabija Defense System


In some embodiments, a defense system disclosed herein comprises a Gabija anti-phage defense system. (Table 14)


In some embodiments, a Gabija defense system provides a host cell with resistance to entry of foreign nucleic acid invasion. In some embodiments, a host cell expressing a functional Gabija defense system (Defense System VI) provides the host cell resistance foreign nucleic acid invasion.


In some embodiments, a Gabija defense system provides a host cell with resistance to at least one phage.


In some embodiments, a microbial cell comprising a Gabija defense system protects the microbial cell from phage infection. In some embodiments, a microbial cell expressing a Gabija defense system protects the microbial cell from phage infection. In some embodiments, a microbial cell expressing a functional Gabija defense system protects the microbial cell from phage infection. In some embodiments, a bacterial cell comprising a Gabija defense system protects the bacterial cell from phage infection. In some embodiments, a bacterial cell expressing a Gabija defense system protects the bacterial cell from phage infection. In some embodiments, a bacterial cell expressing a functional Gabija defense system protects the bacterial cell from phage infection.


In some embodiments, a Gabija defense system (Defense System VI) provides a host cell with resistance to plasmid transformation In some embodiments, a host cell expressing a functional Gabija defense system (Defense System VI) provides a host cells with resistance to plasmid transformation.


In some embodiments, a Gabija defense system (Defense system VI) provides a host cell with resistance to entry of conjugative elements. In some embodiments, a host cell expressing a function Gabija defense system (Defense System VI) provides the host cell resistance from entry of conjugative elements.


As used herein, the term “a Gabija anti-phage defense system” may be used interchangeably with the term “a Defense System VI”, having all the same meanings and qualities. A skilled artisan would appreciate that the term “Gabija system” may be used interchangeably in some embodiments with “Gabija defense system”, “Gabija defense system”, “Gabija anti-phage system”, and “Defense System VI”, having all the same meanings and qualities.


In some embodiments, a microbial species does not comprise an endogenous Defense System VI. In some embodiments, a microbial species does not express an endogenous Defense System VI. In some embodiments, a microbial species does not express an endogenous functional Defense System VI.


In some embodiments, a bacterial species does not comprise an endogenous Defense System VI. In some embodiments, a bacterial species does not express an endogenous Defense System VI. In some embodiments, a bacterial species does not express an endogenous functional Defense System VI.


A Gabija defense system comprises, in some embodiments, a nucleic acid construct comprising a nucleic acid sequence encoding a GajA polypeptide comprising a pfam13175 domain or a COG3593 domain or a combination thereof, and a GajB polypeptide comprising a pfam04257 domain or a pfam00580 domain or a pfam13361 domain or a combination thereof. In some embodiments, a Gabija defense system comprises a nucleic acid construct comprising a nucleic acid sequence comprising a gajA gene and a gajB gene.


In some embodiments, a Gabija defense system comprises, a GajA polypeptide comprising a pfam13175 domain or a COG3593 domain or a combination thereof, and a GajB polypeptide comprising a pfam04257 domain or a pfam00580 domain or a pfam13361 domain or any combination thereof. In some embodiments, a Gabija defense system comprises a GajA polypeptide and a GajB polypeptide.


In some embodiments, a Defense System VI comprises a GajA polypeptide comprising a pfam13175 domain or a COG3593 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 14 rows 2-4599 columns H and I; or a GajB polypeptide comprising a pfam04257 domain or a pfam00580 domain or a pfam13361 domain or any combination thereof or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 14 rows 2-4599 columns L and M; or a combination thereof.


In some embodiments, a Defense System VI comprises at least two different polypeptide components selected from a GajA polypeptide comprising a pfam13175 domain or a COG3593 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 14 rows 2-4599 columns H and I; and a GajB polypeptide comprising a pfam04257 domain or a pfam00580 domain or a pfam13361 domain or any combination thereof or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 14 rows 2-4599 columns L and M.


In some embodiments, a Gabija defense system having an anti-phage activity comprises a nucleic acid construct comprising a nucleic acid sequence encoding a GajA polypeptide and a GajB polypeptide. In some embodiments, a Gabija defense system having an anti-phage activity comprises a nucleic acid construct comprising a nucleic acid sequence encoding a GajA polypeptide comprising an ATPase domain, and a GajB polypeptide comprising a helicase activity. In some embodiments, a Gabija defense system having an anti-phage activity comprises a nucleic acid construct comprising a nucleic acid sequence encoding a GajA polypeptide comprising an ATPase domain. In some embodiments, a Gabija defense system having an anti-phage activity comprises a nucleic acid construct comprising a nucleic acid sequence encoding a GajB polypeptide comprising a helicase activity. In some embodiments, a Gabija defense system having an anti-phage activity comprises a nucleic acid construct comprising a nucleic acid sequence encoding a GajA polypeptide comprising an ATP-dependent endonuclease, and a GajB polypeptide comprising a UvrD helicase activity. In some embodiments, a Gabija defense system having an anti-phage activity comprises a nucleic acid construct comprising a nucleic acid sequence encoding a GajA polypeptide comprising an ATP-dependent endonuclease activity. In some embodiments, a Gabija defense system having an anti-phage activity comprises a nucleic acid construct comprising a nucleic acid sequence encoding a GajB polypeptide comprising a UvrD helicase activity.


In some embodiments, the Gabija anti-phage defense system comprises a nucleic acid construct comprising nucleic acid sequences encoding a cassette comprising gajA and gajB genes.


In some embodiments, a Gabija (Defense System VI) gene cassette comprises the nucleic acid sequence:












(SEQ ID NO: 5; construct 7 of Table 4)
















1
gatcaaacaa tttattccta ttggaatggg ggaagagtcc caaactctca aagagctagt





61
tgatattgtt tggctgctgt gatggattta tttctaagaa aatagtgtgg gctattcatt





121
tttatgttgg atgtttgcag acttaataat gatagcttta gggaacactt actctgtaaa





181
atcggttatt ccctaaaccg ggatttaggt tcacagtata caagctctgg ggttacagaa





241
tacacttaat cttacagcat cattcaacca aaagagtctc tttatgataa tgcctgtgtc





301
gagtcatttt acggtattaa aaaaagaaga agtaaattat gtgcaatatc tagactacca





361
attttccaag ataagaaata tatgttttac gtttcggaaa tattagttgt atcaatggtt





421
tatagagcat tctacatttt cttgtgcaaa tcatgtaaca cagaaaaatg aagtttatga





481
aaaatattta tttatttttc actggtgaat actgaaatag tattcattta ttttttgttt





541
attttacaaa tttttttgaa agtcgttcaa tagcagagaa tttctagtat aattttggta





601
aataattcta tagattgatc ggaattatga atttaattta cagatatttt agagtaacat





661
tggagctatt atattaaaaa agaatgcttc aagattgagc gaacgatagc tttgggataa





721
attagctttt tggcggatag tgaagcagta acgagtaagt tagtaaataa agtgttaaat





781
agaataacag aagaatagga gagggcttta tgtatttaaa aagtttaaaa atctacaact





841
ttagaaaatt tggaacaaat aacaacaaga tagaatttgt tgatgctaaa agttttcaag





901
aacaaagaaa taaaaaagaa gtaaatattg ctccaacaac aactttaatt gtaggaaaga





961
ataactgtgg aaaaacaacg attattaaat cgttagataa tcttattaat aataataaag





1021
acgcttttaa agcaaatgat tttaattttt tatacttaaa aaaactaatt gagtattatg





1081
aacaagcaat tccaaaatta gatgatgaat taaaagaaaa aattaaaaca ccgtatcttc





1141
aatttaatat ttgtattgga attgagaata atagtaatga cttagttacc aatatagttc





1201
gttttatgaa attagatgat attaataatt ctgaattaaa aattgttata aaagtagaat





1261
tggagaacga agaagttttc attagagatg tgaaaaaact gttagagaaa aatgataatt





1321
cgagtcttcg gtttaatagc tttttggaat tgataaatga ttcggatttt aaaataaatt





1381
attataatac agataatgat aaaatagata attttaacat aaaaaattta attgaattga





1441
gaccgattaa agcaaataac attgaaagcg aaaaatgcct ttcaaaagct tttagtaaaa





1501
taattgaata tcgctataaa acattattcg aagaggaaag cgataatctt aattcgacaa





1561
tcataaatat taatcgaaca cttaccaaat taattagtga aaaacatacg gttagtataa





1621
ataagtcttt agaagaaatt gaatcaaatg aaaaacttca agtattgcta agggcagatt





1681
tgacttttca aaatgtgatg aataatttaa tcaaatatga atacgtcgaa cgtaatatga





1741
atatacctga gaatcaattt ggtttaggtt atacaaattt gatgatgata atagcggatt





1801
taattgatta tatggaaaaa tacccagaaa actcatttaa cagtaaggtt aatttaattt





1861
caattgaaga acctgaaaca tttatgcatc cacaaatgca ggagttattt ataaaaaata





1921
taaatgaagc gattgcttct ttattgaaaa gtaaaaataa aaacgtaaat agccagttga





1981
taattacaac acactcatca catatactaa atagtaaaat acacagtggt aatactttta





2041
ataatataaa ttacgttact accaaaaata attatactca tgtagtgaat ttgcatgatg





2101
atataattat ccctaaaagt gaaaaaaaag ctcataaaag agagcaggat cttaagttct





2161
taaaaaaaca tattaagtat aaagtttctg agttgttttt ttcagatgct attatttttg





2221
ttgaaggtgt gactgaagaa acgcttctta aatattatat tgatgataat aataagctca





2281
ataaatatta tatatcggtt ttcaatattg atggggctca cggaatggtt tatcacaatt





2341
taattgaaat actacaagta cctgctttga taattacgga tttagatata gaaagagatg





2401
atgatgaaaa gaaaaatttc aagcaaatct ctgatttaac gggaaaattc acaactaata





2461
aaacaattaa aaagtataat gatgactcta atagtttaga ggaattacag catgagcagc





2521
ttaaaataaa taatatgtat attgcatatc aaggtaaaat cgaagaatat tatgcaacaa





2581
gttttgaaga agcatttatc ttaacaaatt acaaaaatga acttttaaat agtgtactaa





2641
aaaaaatgaa acctcagatt tatgaaaata ttatgggtga gggagatgat ttcacaaaga





2701
taaaggaaaa ttcctataaa ctccaaaaaa agttatcaaa tgataaaagt gattttgcga





2761
atgagctact ctataagttt ataacggagg atataacaat tccttctttg ccaaagtata





2821
ttaagagtgg cctttcatgg ttagctaaaa aattagaagg ggaggaataa gggtgagttt





2881
atccaaaata atcccatcta ataagaaaga agagcagaaa tcaataaatg caatttttaa





2941
ttctattgat aaaagtgaag gtatcatttt taattctggt gctggtgctg gaaaaacata





3001
cgctcttatt gaaagtttga aatacataat aagaaactac gagaagagct taaaacaaca





3061
taatcaacaa attatctgta tcacatatac gaatgttgca actaaagaag taaaagagag





3121
attaggaaac acagatttag tattagtttc tacaattcat gaaagaatgt ggggactcat





3181
taaagattat caaaaagaat tagttgagat tcacaaagaa aagttggaag atgaaatctc





3241
aagtttaaaa caaaaattag aaaaaggtca gggatacgaa aaatttcaag aattagaaga





3301
ggacttaaag ggaaatttta aaaaaataat gattgagaat agggaactat tttttcaaaa





3361
ttatagtgct aaagcagcag aggtaaaaaa atcatttaaa atactcttaa acgattaccc





3421
taatatgctg aaaaatgttg gaaattttaa gagaatagta aatgcaattt acaaattaga





3481
tcagtatagt aaatgctatg aaaatataag cttaaataaa cagggttata aatctgtaga





3541
gtacaattcg atttataata acgatcaact ttataaaatg agaataagcc atgatacttt





3601
gttagattat ggtctgaaaa taattaagaa atatgacttg ttaaaacaaa taatcattga





3661
taaatatcca tttattttta ttgatgagta tcaggatacg gatgaaaaag ttatattaat





3721
aatgagttat ttagagcaat atgcaaaaaa aattgatcac aaaattttta taggttattt





3781
tggtgatact gctcaaaata tttatgatga tggagtagga agtgaaataa caaagattca





3841
ctcaggatta aaacagatag ataaagtgtt taatagaaga tctacaaaag aagtcattga





3901
ggttataaac aaaattagaa acgatagcat cgaacaaata tcaatttatg atgattgtga





3961
aggcggtagt gtaaagtttt ataaagggac ttcaggtaat gttaaggact taatagagcg





4021
gtatatatat gaatggaaaa taactacgga aaatcaacta cattgtctag ttttaactaa





4081
taagattgtt gcagaatata gtggttttaa aaacatatac gaagctttca aagagacaga





4141
taaatataaa gggagcaatt ataatcaact taatacggaa ctcttaagta atgatttatc





4201
taagcttggt gaaattccta agttgttatt taatatagtt agattacaga ataatcttgt





4261
ggataaaacg acttcagtta ttgatattac acctaaagaa agcctattcg atgagatgag





4321
tatagaaggg ttaaggaatt taattaaact attaaaacaa taccaaggga aaacattagg





4381
tgaatatata gaatcgatat caactgttta ttctcaagtt aatgatgaaa attataaaaa





4441
aataatagat tggacttttg gttttgaaaa tatcacattc gaactattta aaaatcatct





4501
tatagaaaag ttatttaata atatattaga tgatgatgtt gatcgtgcaa ccgcaactat





4561
acaaaaaata ctagaagttg atattgttga gtatggattg tggtataaat ttattatgga





4621
taaacaagaa gagaaggtta tttatcatac ttatcatggt acaaagggac gagagtttga





4681
taatgttatt attattatgg aaaatgcttt tggaagaaat cacaattatt ttaatttctt





4741
ttttgaaaat ttcttgcatc cagatgtatt agaaggtgaa aagaaactga acttcgagaa





4801
aataaagaat ttgttatatg tttcttgctc tagagctatt aagaatttaa gagttttata





4861
tattgatgat gttaccgatt ttgaaagtga aattaaggaa atgtttggag aagtatatcc





4921
tttttagtaa taattgaatg aagatatttt tcatgaataa aaaaatgttg tgttgatggg





4981
aagcatcata aaaaaacact cttaaccttt ttacaaagaa acaccccact cgttaggctt





5041
aattattaag tttatgtatt attttattat tcaaaacctt atttttgcta ttgattagcc





5101
gctcataata tttaattatg agcggtttta taacatccga gcacaagttt taaaaatgaa





5161
aattcaggac taggtttatt attcaagacg atgattacat atcatttaag gtgcaggaaa





5221
ataattaaag cattataagt aatatcgata tttcagtttg ttaagatttt ctaagggaaa





5281
tttgttcttt tatctagaaa ataattggat tatctaattc atcat.









The coding regions for each of the gajA and gajB gene sequences within this embodiment of a Gabija cassette (SEQ ID NO: 5) are as follows: nucleotides 810-2870 encode an embodiment of a GajA polypeptide, and nucleotides 2873-4927 encode an embodiment of a GajB polypeptide.


In some embodiments, a Defense System VI comprising a GajA polypeptide and a GajB polypeptide is encoded by the nucleic acid sequence set forth in SEQ ID NO: 5. In some embodiments, a Defense System VI comprising a GajA polypeptide and a GajB polypeptide, is encoded by a nucleic acid sequence having at least 80% homology to the sequence set forth in SEQ ID NO: 5. In some embodiments, a Defense System VI comprising a GajA polypeptide and a GajB polypeptide, is encoded by a nucleic acid sequence having at least 85% homology, or 90% homology, or 95% homology, or 97% homology, or 98% homology, or 99% homology to the sequence set forth in SEQ ID NO: 5. In some embodiments, a Defense System VI comprising a GajA polypeptide and a GajB polypeptide, is encoded by a nucleic acid sequence having at least 80% identity to the sequence set forth in SEQ ID NO: 5. In some embodiments, a Defense System VI comprising a GajA polypeptide and a GajB polypeptide, is encoded by a nucleic acid sequence having at least 85% identity, or 90% identity, or 95% identity, or 97% identity, or 98% identity, or 99% identity to the sequence set forth in SEQ ID NO: 5.


In some embodiments, a Gabija (Defense System VI) gene cassette comprises the nucleic acid sequence:












(SEQ ID NO: 6; construct 8 of Table 4)
















1
ataatagtac tatttaacga tacctgtcaa aaaacataat cgatatttta tcaaaattaa





61
aaaaagaaac cattttattt aacttttctt taaaatggtt tcttggatta tgggacttag





121
ttttttgtct ggaaaatata atgggaattt attgtataat aaaactatgt agaaatacat





181
ggttttttta tttattgagg atgggattct agtgaagggg aacagcttgc ttaactattt





241
ataaaataca gggataagaa cagaattaaa gaaggtatat gttaaaagta aaataattaa





301
gaagataagg tgatgaataa tgaaattcag taatattaca ataaagaact tcaggaattt





361
tgaaaaagta aatataaatt tagataataa aaatgtgatt ttcgggatga atgatattgg





421
aaaaacaaat tttttatatg cattgagatt tcttttagat aaagagataa gaaaattcgg





481
ttttaataaa tctgattatc ataaacatga cacttctaaa aaaattgaaa ttattttaac





541
acttgatttg tctaattatg aaaaggatga agatacaaaa aaacttattt cagtggttaa





601
gggtgctaga acatcggcaa atgcagatgt tttttatatc gcactagaat ctaaatatga





661
tgataaagaa ttatatggga acataatttt aaaatgggga tcggaactag ataatttaat





721
agatatacca gggagaggga acataaacgc gttagataat gtatttaagg tgatttatat





781
aaatccgctt gttgatttag acaaattgtt cgcacaaaat aaaaaatata tttttgaaga





841
gtcacagggt aatgaatcag atgaagggat tttaaataat attaaatctt taacagatca





901
agtaaatcaa caaataggag aaatgacaat tattaagggt ttccagcaag agataacaag





961
tgaatatagg tctttaaaaa aagaagaggt ttctattgag ctgaagtccg aaatggcaat





1021
taaaggattt ttctcagata ttattccata tataaaaaaa gacggtgatt ctaattacta





1081
tccaacctca ggggatggta gaagaaaaat gctttcttac tctatatata actatctggc





1141
taagaaaaaa tatgaggata aaattgttat ttatttaatt gaggaacccg aaattagtct





1201
acatagatca atgcaaattg ctttatcaaa acagttattt gaacaatcta catataaata





1261
ttttttctta tccactcact ctcctgaact tctttatgaa atggataata caagattaat





1321
aagagtgcat tcaactgaaa aggttgtatg ttcttcccat atgtataatg tggaagaagc





1381
ctatggaagt gtcaagaaaa agctaaataa agctttatca tcggctctat ttgctgaaag





1441
agtactttta atagaaggtc cttcagaaaa aatattattt gaaaaggttt tagacgaagt





1501
agaaccagaa tatgaattaa atggaggttt cttgcttgaa gtaggaggga cgtactttaa





1561
tcattatgtg tgtacattaa atgatttagg tataacccat ataattaaaa cagataatga





1621
tttgaaatca aaaaaaggta aaaaaggtgt atacgaatta ctaggattaa atagatgctt





1681
aaacttatta ggacgtgaaa atctagatga gattactatt gacatccctg aagatataaa





1741
aggtaagaag aaaaaagaga gacttaatga aagaaaaaaa gagattttta aacaatataa





1801
aaatgaggta ggggaattct taggggaacg aatatattta tcggaaatcg atctggaaaa





1861
tgatttatat tctgcaattg gtgaaagcat gaaaagaatt tttgaaaacg aagatcccgt





1921
gcactattta cagaaaagta aactatttaa catggtcgag ctagtaaata atttaagtac





1981
taaagattgt tttgatgttt ttgagcacga aaaatttgca tgcctaaagg agttggtggg





2041
tagtgataga ggatgaaatg tctagagaac aaataataaa ggatgggggt aatattcttg





2101
ttaccgctgg agcaggttcg ggtaaaacaa caatattagt tagtaaaatt gaagctgatt





2161
taaaagaaaa taaaactcat tactcaattg cagctgttac ttttacaaat aaggcagcaa





2221
aagaaatcga gggaagatta gggtattcat caagagggaa ttttattggc actaacgatg





2281
gttttgtcga gtctgaaatt attaggccgt ttattaaaga tgcatttgga aatgattatc





2341
cagacaattt cactgctgaa tattttgata accaatttgc ttcatacgat aagggattgc





2401
aagtgctaaa atatcaaaat atattaggga cttatagtaa tcctaaaaag aattttaagt





2461
ttcaattggc tttagatatt ttaaaaaaat cacttgtcgc tagacaatat atattttcaa





2521
aatacttcaa gatatttata gacgagtacc aagattcgga taaggatatg cataatttat





2581
ttatgtattt aaaggatcag cttaaaatta agttatttat tgttggtgac ccaaaacaat





2641
ctatttatat ctggagggga gcagaacctg aaaattttaa tggtcttata gaaaattcta





2701
cggattttaa taaatatcat ttaacttcca actttcgatg ctgtcaggat attcaaaatt





2761
actctaattt atttaatgaa gaaactagaa gcttaattaa agaaaaaaat gaggttcaaa





2821
atgtaatcag tatagcagac gatatgccaa tttcagatat tttattaaaa ttaacagaag





2881
aaaagcaggt attaaacata gaagcggaat tagtgatttt agtccggaga cgtaatcaag





2941
ccattgaaat aatgaaagaa ctaaatgaag aagggtttaa ttttattttt attccccaaa





3001
ccccattaga tagggcaact ccaaatgcaa ctcttttaaa agaggtaatt aaatatgtta





3061
aaaatgatag atattcaata tatgatttag ctgctgaaat tgtaggtaat ctaagttcac





3121
gagaaattaa ggagatacaa aaaataatta atgaattact agtacctaat attaatcagg





3181
tactaattaa tcaggtatta attaatttat ttgctaaatt agaaattact ttagatacta





3241
gagaaattac agcatttaca gaagtaatga tgacgaatga atttgacata gcatttgata





3301
caaatgaata tttacataaa atatttactg tacattctgc aaaaggatta gaatttaatc





3361
aagtcattat tactgcaagt gattacaatg tacactataa tagagatact aacgaacatt





3421
atgttgctac aactagagca aaagataaat taattgtcat tatggataat aagaagtact





3481
cagattatat tgagacgcta atgaaagaac ttaaaattaa aaatattatt aagtcaatat





3541
aaggaaactt aagtttgaca taataacgat gaaatataaa agtttgtttt cgtaaatagc





3601
caatgtcact aagttatcaa gacttaaatt ttaaaacctt taaaaataaa gactctaaca





3661
tattagtcat aattaatatg ttagggtctt ttgttttatt tgaaatgtta ttttcaactt





3721
tataagacaa tgaatattat ttttgtttaa taatatccag agtgctcaaa ataaatatca





3781
gaaggtaatt cctaataata ttgcgtgtgt agttaatagt taaaataata aaataaaaaa





3841
agatggtata atttagtata ccatcttttt ttattttatt aggaggttca aaa.









The coding regions for each of the gajA and gajB gene sequences within this embodiment of a Gabija cassette (SEQ ID NO: 6) are as follows: nucleotides 320-2056 encode an embodiment of a GajA polypeptide, and nucleotides 2058-3542 encode an embodiment of a GajB polypeptide.


In some embodiments, a Defense System VI comprising a GajA polypeptide and a GajB polypeptide is encoded by the nucleic acid sequence set forth in SEQ ID NO: 6. In some embodiments, a Defense System VI comprising a GajA polypeptide and a GajB polypeptide, is encoded by a nucleic acid sequence having at least 80% homology to the sequence set forth in SEQ ID NO: 6. In some embodiments, a Defense System VI comprising a GajA polypeptide and a GajB polypeptide, is encoded by a nucleic acid sequence having at least 85% homology, or 90% homology, or 95% homology, or 97% homology, or 98% homology, or 99% homology to the sequence set forth in SEQ ID NO: 6. In some embodiments, a Defense System VI comprising a GajA polypeptide and a GajB polypeptide, is encoded by a nucleic acid sequence having at least 80% identity to the sequence set forth in SEQ ID NO: 6. In some embodiments, a Defense System VI comprising a GajA polypeptide and a GajB polypeptide, is encoded by a nucleic acid sequence having at least 85% identity, or 90% identity, or 95% identity, or 97% identity, or 98% identity, or 99% identity to the sequence set forth in SEQ ID NO: 6.


In some embodiments, a construct comprising the Gabija defense system encodes one component of the defense system, whereby multiple constructs, for example but not limited to, two constructs may be used to assemble the functional defense system. In some embodiments, the components of a Gabija defense system comprise genes gajA and gajB. In some embodiments, the components of a Gabija defense system consist of genes gajA and gajB. In some embodiments, the components of a Gabija defense system comprise nucleic acid sequences encoding a GajA polypeptide and a GajB polypeptide. In some embodiments, the components of a Gabija defense system consist of nucleic acid sequences encoding a GajA polypeptide and a GajB polypeptide.


In some embodiments, a construct comprising the Gabija defense system encodes one component of the defense system, whereby a second construct may be used to assemble the functional defense system. In some embodiments, a construct comprising the Gabija defense system encodes one component of the defense system, whereby additional constructs may be used to assemble the functional defense system. For example, in some embodiments each of GajA and GajB may be encoded by nucleic acid sequences comprised in different constructs, wherein expression of the combination of constructs produces a functional Gabija defense system.


In some embodiments, the components making up a functional Gabija anti-phage defense system comprise a GajA polypeptide and a GajB polypeptide, each encoded by a gajA and a gajB gene, respectively. In some embodiments, a gajA gene encodes a polypeptide comprising an ATPase activity. In some embodiments, a gajB gene encodes a polypeptide comprising a helicase activity.


In some embodiments, a Gabija defense system having an anti-phage activity comprises a nucleic acid encoding a GajA polypeptide. In some embodiments, a Gabija defense system having an anti-phage activity comprises a nucleic acid encoding a GajA polypeptide and a GajB polypeptide. In some embodiments, a Gabija defense system having an anti-phage activity comprises a nucleic acid encoding a GajB polypeptide.


In some embodiments, a Gabija defense system having an anti-phage activity comprises a nucleic acid comprising a gajA gene. In some embodiments, a Gabija defense system having an anti-phage activity comprises a nucleic acid comprising a gajA gene and a gajB gene. In some embodiments, a Gabija defense system having an anti-phage activity comprises a nucleic acid comprising gajB gene.


In some embodiments, a Gabija defense system having an anti-phage activity comprises a nucleic acid construct comprising nucleic acids encoding polypeptides in a set order. In one embodiment, the 5′ to 3′ order of polypeptides encoded is GajA and GajB. In some embodiments the 5′ to 3′ order of polypeptides does not affect the anti-phage activity. In some embodiments the 5′ to 3′ order of polypeptides does affect the anti-phage activity.


In some embodiments, the 5′ to 3′ order of polypeptides is random, for example any order of nucleic acid sequences encoding GajA and GajB.


In some embodiments, a Gabija defense system having an anti-phage activity comprises a nucleic acid construct comprising genes in a set order. In some embodiment, the 5′ to 3′ order of genes is gajA and gajB. In some embodiment, the 5′ to 3′ order of genes in a Gabija defense system is not gajA and gajB. In some embodiments the 5′ to 3′ order of genes does not affect the anti-phage activity. In some embodiments the 5′ to 3′ order of genes does affect the anti-phage activity.


In some embodiments, the 5′ to 3′ order of genes is random, for example any order of gajA and gajB.


In some embodiments, the Gabija system (Defense System VI) composition and order is as shown in FIG. 3B.


In some embodiments, a Gabija defense system having an anti-phage activity originates from a microbial genome, for example a bacterial or an archaeal genome (Table 14). A skilled artisan would appreciate that the Gabija system is not present in the majority of bacteria and or archaea species.


In some embodiments, a functional Gabija defense system comprises a construct comprising nucleic acid sequences encoding polypeptides, wherein the nucleic acid sequence encoding each polypeptide may originate from a different microbial species. For example, the source of the nucleic acid sequence encoding a GajA polypeptide may be one microbial species, while the source of the nucleic acid sequence encoding a GajB polypeptide may be a different microbial species. In some embodiments, a functional Gabija defense system comprises a non-naturally occurring combination of polypeptide components. In some embodiments, a functional Gabija defense system comprises a combination of at least two polypeptides that do not naturally occur together.


In some embodiments, a functional Gabija defense system comprises a construct comprising nucleic acid sequences encoding polypeptides, wherein the nucleic acid sequence encoding each polypeptide may originate from a different bacterial species. For example, the source of the nucleic acid sequence encoding a GajA polypeptide may be one bacterial species, while the source of the nucleic acid sequence encoding a GajB polypeptide may be a different bacterial species.


In some embodiments, the source of the nucleic acid encoding a GajA polypeptide and a GajB polypeptide is the same. In some embodiments, the source of the nucleic acid encoding a GajA polypeptide and a GajB polypeptide is the not the same. In some embodiments, the source of the nucleic acid sequence of any of the components of a Gabija defense system comprises any of the species listed in Table 14.


In some embodiments, a Gabija defense system having an anti-phage activity comprises a nucleic acid construct comprising non-coding regions between the nucleic acid sequences encoding the polypeptides. In some embodiments, the non-coding regions between the nucleic acid sequences comprises nucleic acid sequence not naturally occurring in the microbial species of origin. In some embodiments, the non-coding regions between the nucleic acid sequences comprises nucleic acid sequence is the naturally occurring in the microbial species of origin.


In some embodiments, a Gabija system disclosed herein comprises a multi-gene phage resistance system broadly distributed in microbial genomes, for example but not limited to bacteria and archaea. According to some embodiments, the Gabija system components are located in a gene cluster (a cassette of genes) in a microbial cell genome. According to some embodiments, the Gabija system components are located in close proximity (e.g. positioned within 20 genes, 10 genes, 5 genes or less one from the other) in a genome of a prokaryotic cell. According to some embodiments the prokaryotic cell expresses an endogenous Gabija defense system. According to some embodiments, the prokaryotic cell expresses an endogenous functional Gabija defense system. According to some embodiments, the species of prokaryotic cell is selected from the group consisting of the species listed in Table 14. According to some embodiments a prokaryotic cell expresses a non-endogenous Gabija defense system. According to some embodiments, a prokaryotic cell expresses a non-endogenous functional Gabija defense system. According to some embodiments, the species of prokaryotic cell expressing a non-endogenous functional Gabija defense system is selected from the group consisting of the species listed in Table 14.


In some embodiments, Gabija defense system components comprise GajA and GajB polypeptides. In some embodiments, Gabija defense system components comprise functional portions of GajA and GajB polypeptides. In some embodiments, the Gabija defense system functional components are encoded by gajA and gajB genes.


Non-limiting embodiments of endogenous Gabija systems and the respective location of their components are provided in Table 14 herein.


In some embodiments, the components of a Gabija system may be identified by the presence of similar domains present within each component. In some embodiments, domains comprise pfam domains and or clusters of orthologous groups (COG) domains.


In some embodiments, the term “GajA” refers to the polynucleotide or expression product e.g., the polypeptide encoded by the gajA gene. In some embodiments, the term “GajA” refers to a GajA polypeptide. In some embodiments, the gajA gene encodes a polypeptide comprising a pfam13175 domain. In some embodiments, the gajA gene encodes a polypeptide comprising a COG3593 domain. In some embodiments, the gajA gene encodes a polypeptide comprising a pfam13175 domain and a COG3593 domain. In some embodiments, the GajA polypeptide comprises a pfam13175 domain. In some embodiments, the GajA polypeptide comprises a COG3593 domain. In some embodiments, the GajA polypeptide comprises a pfam13175 domain and a COG3593 domain.


In some embodiments, GajA polypeptide is encoded by a gene positioned within 5-60 genes of a gene encoding a GajB polypeptide in a genome of a prokaryotic cell. In some embodiments, GajA polypeptide is encoded by a gene positioned within 5 genes upstream (5′) or downstream (3′) to a gene encoding a GajB polypeptide in a genome of a prokaryotic cell. In some embodiments, GajA polypeptide is encoded by a gene positioned within 5 genes upstream (5′) and downstream (3′) to a gene encoding a GajB polypeptide in a genome of a prokaryotic cell.


In some embodiments, GajA and GajB are encoded by genes positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, GajA and GajB are encoded by genes positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell.


In some embodiments, gajA and gajB genes are positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, gajA and gajB, genes are positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell.


In some embodiments, a GajA polypeptide is about 670 amino acids long (median gene size).


In some embodiments, the GajA polypeptide comprises the amino acid sequence having at least 80% homology to a sequence selected from the group consisting of the polypeptides referenced in Table 14, rows 2-4599, columns H and I. In some embodiments, the GajA polypeptide comprises the amino acid sequence having at least 80% homology within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 14, rows 2-4599, column H. In some embodiments, the GajA polypeptide comprises a homolog of a polypeptide having the amino acid sequences set forth in the polypeptides referenced in Table 14, rows 2-4599, columns H and I.


In some embodiments, a GajA polypeptide homolog comprises an ATPase domain. In some embodiments, a GajA polypeptide homolog comprises an ATPase activity. In some embodiments, a GajA polypeptide homolog comprises an ATP-dependent endonuclease domain. In some embodiments, a GajA polypeptide homolog comprises an ATP-dependent endonuclease activity.


In some embodiments, the GajA polypeptide comprises the amino acid sequence having at least 80% identity to a sequence selected from the group consisting of the polypeptides referenced in Table 14, rows 2-4599, columns H and I. In some embodiments, the GajA polypeptide comprises the amino acid sequence having at least 80% identity within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 14, rows 2-4599, columns H and I.


In some embodiments, the GajA polypeptide comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polypeptides referenced in Table 14, rows 2-4599, columns H and I. In some embodiments, the GajA polypeptide comprises the amino acid sequence having at least 80%, 85%, 90%, 95% homology within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 14, rows 2-4599, columns H and I. In some embodiments, the GajA polypeptide comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polypeptides referenced in Table 14, rows 2-4599, columns H and I. In some embodiments, the GajA polypeptide comprises the amino acid sequence having at least 80%, 85%, 90%, 95% identity within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 14, rows 2-4599, columns H and I. In some embodiments, the GajA polypeptide comprises an amino acid sequence selected from the group consisting of the polypeptides referenced in Table 14, rows 2-4599, columns H and I.


In some embodiments, the GajA polypeptide comprises an amino acid sequence encoded by a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polynucleotides referenced in Table 14, rows 2-4599, columns H and J. In some embodiments, the GajA polypeptide comprises the amino acid sequence encoded by a nucleic acid sequence having at least 80%, 85%, 90%, 95% homology within similar domain regions within a sequence selected from the group consisting of the polynucleotides referenced in Table 14, rows 2-4599, columns H and J. In some embodiments, the GajA polypeptide comprises an amino acid sequence encoded by a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polynucleotides referenced in Table 14, rows 2-4599, columns H and J. In some embodiments, the GajA polypeptide comprises the amino acid sequence encoded by a nucleic acid sequence having at least 80%, 85%, 90%, 95% homology within similar domain regions within a sequence selected from the group consisting of the polynucleotides referenced in Table 14, rows 2-4599, columns H and J. In some embodiments, the GajA polypeptide comprises an amino acid sequence encoded from a nucleic acid sequence selected from the group consisting of the polynucleotides referenced in Table 14, rows 2-4599, columns H and J.


In some embodiments, the nucleic acid sequence of a gajA gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polynucleotides referenced in Table 14, rows 2-4599, columns H and J. In some embodiments, the gajA gene comprises a nucleic acid sequence having at least 80%, 85%, 90%, 95% homology within encoded similar domain regions in comparison with nucleotide sequence encoding these domain within a sequence selected from the group consisting of the polynucleotides referenced in Table 14, rows 2-4599, columns H and J. In some embodiments, the nucleic acid sequence of a gajA gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polynucleotides referenced in Table 14, rows 2-4599, columns H and J. In some embodiments, the gajA gene comprises a nucleic acid sequence having at least 80%, 85%, 90%, 95% identity within encoded similar domain regions in comparison with nucleotide sequence encoding these domain within a sequence selected from the group consisting of the polynucleotides referenced in Table 14, rows 2-4599, columns H and J. In some embodiments, the nucleic acid sequence of a gajA gene comprises a nucleic acid sequence selected from the group consisting of the polynucleotides referenced in Table 14, rows 2-4599, columns H and J.


As used herein, the term “GajB” refers to the polynucleotide or expression product e.g., polypeptide encoded by the gajB gene. In some embodiments, the term “GajB” refers to a GajB polypeptide. In some embodiments, the product of the gajB gene comprises a pfam04257 domain. In some embodiments, the gajB gene encodes a pfam00580 domain. In some embodiments, the gajB gene encodes a pfam13361 domain. In some embodiments, the product of the gajB gene comprises a pfam04257 domain or a pfam00580 domain or a pfam13361 domain, or any combination thereof. In some embodiments, the product of the gajB gene comprises a pfam04257 domain, a pfam00580 domain, and a pfam13361 domain. In some embodiments, the gajB gene encodes a helicase. In some embodiments, the gajB gene encodes a UvrD helicase.


In some embodiments, GajB polypeptide is encoded by a gene positioned within 5-60 genes of a gene encoding a GajA polypeptide in a genome of a prokaryotic cell. In some embodiments, GajB polypeptide is encoded by a gene positioned within 5 genes upstream (5′) or downstream (3′) to a gene encoding a GajA polypeptide in a genome of a prokaryotic cell. In some embodiments, GajB polypeptide is encoded by a gene positioned within 5 genes upstream (5′) and downstream (3′) to a gene encoding a GajA polypeptide in a genome of a prokaryotic cell.


In some embodiments, a GajB polypeptide is about 598 amino acids long (median gene size).


In some embodiments, the GajB polypeptide comprises the amino acid sequence having at least 80% homology to a sequence selected from the group consisting of the polypeptides referenced in Table 14, rows 2-4599, columns L and M. In some embodiments, the GajB polypeptide comprises the amino acid sequence having at least 80% homology within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 14, rows 2-4599, columns L and M. In some embodiments, the GajB polypeptide comprises a homolog of a polypeptide having the amino acid sequences set forth in the polypeptides referenced in Table 14, rows 2-4599, columns L and M.


In some embodiments, a GajB polypeptide homolog comprises a UvrD helicase domain. In some embodiments, a GajB polypeptide homolog comprises a UvrD helicase activity.


In some embodiments, the GajB polypeptide comprises the amino acid sequence having at least 80% identity to a sequence selected from the group consisting of the polypeptides referenced in Table 14, rows 2-4599, columns L and M. In some embodiments, the GajB polypeptide comprises the amino acid sequence having at least 80% identity within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 14, rows 2-4599, columns L and M.


In some embodiments, the GajB polypeptide comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polypeptides referenced in Table 14, rows 2-4599, columns L and M. In some embodiments, the GajB polypeptide comprises the amino acid sequence having at least 80%, 85%, 90%, 95% homology within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 14, rows 2-4599, columns L and M. In some embodiments, the GajB polypeptide comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polypeptides referenced in Table 14, rows 2-4599, columns L and M. In some embodiments, the GajB polypeptide comprises the amino acid sequence having at least 80%, 85%, 90%, 95% identity within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 14, rows 2-4599, columns L and M. In some embodiments, the GajB polypeptide comprises an amino acid sequence selected from the group consisting of the polypeptides referenced in Table 14, rows 2-4599, columns L and M.


In some embodiments, the GajB polypeptide comprises an amino acid sequence encoded by a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polynucleotides referenced in Table 14, rows 2-4599, columns L and N. In some embodiments, the GajB polypeptide comprises the amino acid sequence encoded by a nucleic acid sequence having at least 80%, 85%, 90%, 95% homology within similar domain regions within a sequence selected from the group consisting of the polynucleotides referenced in Table 14, rows 2-4599, columns L and N. In some embodiments, the GajB polypeptide comprises an amino acid sequence encoded by a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polynucleotides referenced in Table 14, rows 2-4599, columns L and N. In some embodiments, the GajB polypeptide comprises the amino acid sequence encoded by a nucleic acid sequence having at least 80%, 85%, 90%, 95% homology within similar domain regions within a sequence selected from the group consisting of the polynucleotides referenced in Table 14, rows 2-4599, columns L and N. In some embodiments, the GajB polypeptide comprises an amino acid sequence encoded from a nucleic acid sequence selected from the group consisting of the polynucleotides referenced in Table 14, rows 2-4599, columns L and N.


In some embodiments, the nucleic acid sequence of a gajB gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polynucleotides referenced in Table 14, rows 2-4599, columns L and N. In some embodiments, the gajB gene comprises a nucleic acid sequence having at least 80%, 85%, 90%, 95% homology within encoded similar domain regions in comparison with nucleotide sequence encoding these domain within a sequence selected from the group consisting of the polynucleotides referenced in Table 14, rows 2-4599, columns L and N. In some embodiments, the nucleic acid sequence of a gajB gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polynucleotides referenced in Table 14, rows 2-4599, columns L and N. In some embodiments, the gajB gene comprises a nucleic acid sequence having at least 80%, 85%, 90%, 95% identity within encoded similar domain regions in comparison with nucleotide sequence encoding these domain within a sequence selected from the group consisting of the polynucleotides referenced in Table 14, rows 2-4599, columns L and N. In some embodiments, the nucleic acid sequence of a gajB gene comprises a nucleic acid sequence selected from the group consisting of the polynucleotides referenced in Table 14, rows 2-4599, columns L and N.


A skilled artisan would appreciate that the terms a “functional portion of a Defense System VI component” or “functional fragment of Defense System VI component” or “functional portion of a Gabija defense system component” or “functional fragment of Gabija defense system component” refers to a functional portion of a Gabija polynucleotide or polypeptide, as disclosed herein, which expression is sufficient to elicit an anti-phage activity alone or in combination with the at least one of the other Gabija polynucleotides or polypeptides disclosed herein or functional portions thereof.


The terms “GajA”, “GajB”, “gajA” and “gajB”, also refer to functional GajA, GajB, gajA and gajB, homologs, which exhibit the desired activity (i.e., conferring phage resistance). Such homologs can be, for example, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical or homologous to the polypeptide sequences references in Table 14 rows 2-4599 columns H and I and L and M, respectively, or 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical or homologous to the polynucleotide sequences references in Table 14 rows 2-4599 columns H and J and L and N, respectively. In some embodiments, such homologs comprise at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% homology or identity within similar domain regions of the polypeptide sequences references in Table 14 rows 2-4599 columns H and I and L and M, respectively, or 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity or homology within nucleotide sequences encoding similar domain regions to the polynucleotide sequences references in Table 14 rows 2-4599 columns H and J and L and N, respectively.


Table 14 presents embodiments of components of Defense System VI that may be found in a diverse array of bacteria and archaea genomes (referenced in Table 18). Table 14 presents embodiments of nucleic acid sequences encoding gene cassettes of Defense System VI (referenced in Table 18).


The Septu Defense System


In some embodiments, a defense system disclosed herein comprises a Septu anti-phage defense system (Table 15).


In some embodiments, a Septu defense system provides a host cell with resistance to entry of foreign nucleic acid invasion. In some embodiments, a host cell expressing a functional Septu defense system (Defense System VII) provides the host cell resistance foreign nucleic acid invasion.


In some embodiments, a Septu defense system provides a host cell with resistance to at least one phage.


In some embodiments, a microbial cell comprising a Septu defense system protects the microbial cell from phage infection. In some embodiments, a microbial cell expressing a Septu defense system protects the microbial cell from phage infection. In some embodiments, a microbial cell expressing a functional Septu defense system protects the microbial cell from phage infection. In some embodiments, a bacterial cell comprising a Septu defense system protects the bacterial cell from phage infection. In some embodiments, a bacterial cell expressing a Septu defense system protects the bacterial cell from phage infection. In some embodiments, a bacterial cell expressing a functional Septu defense system protects the bacterial cell from phage infection.


In some embodiments, a Septu defense system provides a host cell with resistance to plasmid transformation. In some embodiments, a Septu defense system (Defense System VII) provides a host cell with resistance to plasmid transformation. In some embodiments, a host cell expressing a functional Septu defense system (Defense System VII) provides a host cells with resistance to plasmid transformation.


In some embodiments, a Septu defense system (Defense system VII) provides a host cell with resistance to entry of conjugative elements. In some embodiments, a host cell expressing a function Septu defense system (Defense System VII) provides the host cell resistance from entry of conjugative elements.


As used herein, the term “a Septu anti-phage defense system” may be used interchangeably with the term “a Defense System VII”, having all the same meanings and qualities. A skilled artisan would appreciate that the term “Septu system” may be used interchangeably in some embodiments with “Septu defense system”, “Septu the defense system”, “Septu anti-phage system”, and “Defense System VII”, having all the same meanings and qualities.


In some embodiments, a microbial species does not comprise an endogenous Defense System VII. In some embodiments, a microbial species does not express an endogenous Defense System VII. In some embodiments, a microbial species does not express an endogenous functional Defense System VII.


In some embodiments, a bacterial species does not comprise an endogenous Defense System VII. In some embodiments, a bacterial species does not express an endogenous Defense System VII. In some embodiments, a bacterial species does not express an endogenous functional Defense System VII.


A Septu defense system comprises, in some embodiments, a nucleic acid construct comprising a nucleic acid sequence encoding a PtuA polypeptide comprising a pfam13304 domain or a pfam02463 domain or a combination thereof, and a PtuB polypeptide comprising pfam13395 domain or a pfam01844 domain or a combination thereof. In some embodiments, a Septu defense system comprises a nucleic acid construct comprising a nucleic acid sequence comprising a ptuA gene and a ptuB gene.


In some embodiments, a Septu defense system comprises, a PtuA polypeptide comprising a pfam13304 domain or a pfam02463 domain or a combination thereof, and a PtuB polypeptide comprising pfam13395 domain or a pfam01844 domain or a combination thereof. In some embodiments, a Septu defense system comprising anti-phage activity comprises a PtuA polypeptide and a PtuB polypeptide.


In some embodiments, a Defense System VII comprises a PtuA polypeptide comprising a pfam13304 domain or a pfam02463 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 15 rows 2-12507 columns H and I; or a PtuB polypeptide comprising pfam13395 domain or a pfam 01844 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 15 rows 2-2507 columns L and M; or combination thereof.


In some embodiments, a Defense System VII comprises at least two different polypeptides selected from a PtuA polypeptide comprising a pfam13304 domain or a pfam02463 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 15 rows 2-12507 columns H and I; and a PtuB polypeptide comprising pfam13395 domain or a pfam 01844 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 15 rows 2-2507 columns L and M.


In some embodiments, a Septu defense system having an anti-phage activity comprises a nucleic acid construct comprising a nucleic acid sequence encoding a PtuA polypeptide and a PtuB polypeptide. In some embodiments, a Septu defense system having an anti-phage activity comprises a nucleic acid construct comprising a nucleic acid sequence encoding a PtuA polypeptide comprising an AAA domain (“ATPases Associated with diverse cellular Activities” domain) or a RecF/RecN/SMC N-terminal domain (a domain found at the N terminus of structural maintenance of chromosomes (SMC) proteins) or an N-terminal HNH nuclease domain, or any combination thereof, and a PtuB polypeptide comprising a HNH endonuclease activity.


In some embodiments, a Septu defense system having an anti-phage activity comprises a nucleic acid construct comprising a nucleic acid sequence encoding a PtuA polypeptide comprising an AAA domain (“ATPases Associated with diverse cellular Activities” domain). In some embodiments a PtuA polypeptide comprises a RecF/RecN/SMC N-terminal domain (a domain found at the N terminus of structural maintenance of chromosomes (SMC) proteins). In some embodiments, a PtuA polypeptide comprises an N-terminal HNH nuclease domain. In some embodiments, a PtuA polypeptide comprises an AAA domain (“ATPases Associated with diverse cellular Activities” domain) and a RecF/RecN/SMC N-terminal domain (a domain found at the N terminus of structural maintenance of chromosomes (SMC) proteins) and an N-terminal HNH nuclease domain. In some embodiments, a Septu defense system having an anti-phage activity comprises a nucleic acid construct comprising a nucleic acid sequence encoding a PtuB polypeptide comprising a HNH endonuclease. In some embodiments, a Septu defense system having an anti-phage activity comprises a nucleic acid construct comprising a nucleic acid sequence encoding a PtuA polypeptide comprising an AAA domain (“ATPases Associated with diverse cellular Activities” domain) and a RecF/RecN/SMC N-terminal domain (a domain found at the N terminus of structural maintenance of chromosomes (SMC) proteins). In some embodiments, a Septu defense system having an anti-phage activity comprises a nucleic acid construct comprising a nucleic acid sequence encoding a PtuA polypeptide comprising an AAA domain (“ATPases Associated with diverse cellular Activities” domain) and a RecF/RecN/SMC N-terminal domain (a domain found at the N terminus of structural maintenance of chromosomes (SMC) proteins) and an N-terminal HNH nuclease domain, and a PtuB polypeptide comprising a HNH endonuclease. In some embodiments, a Septu defense system having an anti-phage activity comprises a nucleic acid construct comprising a nucleic acid sequence encoding a PtuA polypeptide comprising an AAA domain (“ATPases Associated with diverse cellular Activities” domain) and a RecF/RecN/SMC N-terminal domain (a domain found at the N terminus of structural maintenance of chromosomes (SMC) proteins), and a PtuB polypeptide comprising a HNH endonuclease.


In some embodiments, the Septu anti-phage defense system comprises a nucleic acid construct comprising nucleic acid sequences encoding a cassette comprising ptuA and ptuB genes.


In some embodiments, a Septu (Defense System VII) gene cassette comprises the nucleic acid sequence:












(SEQ ID NO: 12; Table 4 construct 42)
















1
gggaatgcaa aaaggaggcg ggacttgagt gcgagttctg cctctttttt gctgaattta





61
gaaatctttt aagttttatc taaaaaagca ttcactttat tgttatttat gtagtaagag





121
taaaatttta ttaaaaattc taaagctgta ttggtttata agctagtgct atatctacta





181
tttgttctgg agtaagatct tcatcattaa aagaaaggca ttattatttt tggtgaatgt





241
tatttagtat aaaccatagg ggaatggaat attttatgat aaaattgagt ggagtaaata





301
attgtaaaga taaataaacg gatagcatgt aaaaaaaggg ttgaccttga gccttattaa





361
gacgggtgtt gtagtaataa atgaattaag agaaaaacat ttgtaattag tcaacaaaaa





421
gggagttgct tgaatgttag ttataaaaga attaaaaatt gatgggattg gcggtattaa





481
tagccttaaa cttaatttta acgaggggtt aaatttgatt tgcggtccaa atggtgtagg





541
gaaaaccaca attcttgaaa gtattggcca tatgtttagt aatggtagtc gtagtaaggt





601
taagagaaat gttaaatttg atcaggggag ttgtgaaatt agctattcaa cattcctaga





661
tactatacat acacagtcat gtattttaag gaattatgaa gaaaatgatt cgctggattg





721
gcatggtgga aatgcaaatt tggctaaaga ggtcattgtc ttcaaagctc aaagatcatt





781
cacttatacg caattagatt ctcttcgtaa agatacggaa acaagtgatg gtaaatttct





841
ggatgattct atgaatggaa ttcaattttt cgactttaag aattggttta tccatcgttt





901
tttatttagt catgtagata atgaattaac aacagtacaa aaagagaatt ttaaacttgc





961
gacagattgt tttggtattt tagataatag cattcgtttt agtagtgtta aaagtgatac





1021
attcgatata attataagta cctcaaatgg tgaaatctat tttgagtatc tatcatcagg





1081
attcaaatca tgtatctata ttattcatgg gttaattaaa gaaatagagt atcgttttaa





1141
aaacgatggt ggtattaaag ttcaagatta tgaagggcta atactaatcg atgagttgga





1201
ccttcattta catccacagt ggcaagcgaa aatgatttat ttaataaagc atatattacc





1261
taaagctcaa attattgcaa caacacatag tcctcatatg gtacaagctg cagcaattaa





1321
tgaacttata gctttaggaa tcgatgaaga tgcggatgta tatgtaagac aactacctaa





1381
tgttcaatat ggatttcagg gatggactgt tgaggaaata ttggaagacg ttatggggtt





1441
agatgaaaca cggtctccaa tgtacataga ggctataact gaatttgaaa aatctctaga





1501
tgaagaaaat gaggagaaga tatttgaagc ttattataag ttagatttaa tgctacaccc





1561
aagtaatcca cttcgcaagt tgttaaagtt acaagtagct caattcggga gggttataga





1621
gtgattcatt taaaacgccc taatagtcct agtaaactta taaatgaaga agcaaaacta





1681
actcaagaat ttcttcaaaa tggtaatagt gtttggggaa agccttatat taagcttgct





1741
cttctagaga tgtcaaataa caaatgtgta tactgtgaat gtagactaga tgaagagagt





1801
aagtatatgg aggtagagca ctttctacca aaagatactt atcctaatct agttgtcaat





1861
tggagaaatt tattaccaag ttgtaaaaga tgtaatggaa aaaaagggac acatgattca





1921
aaaaaagaac ctattatcaa tcctactgtt gatactccaa gtaatcatat aaaaatgttt





1981
aactattgcc taaagggaaa agatttaaaa gggaaaacaa cagttgatgt attgcaccta





2041
aaccaacttg atagattagt atacccaaga atgttaattg gaacaaaaac tatagaaaca





2101
gtagaaaaac ttttagaaat ggcagagaac tttaatttga atattaatgc tactgggcgt





2161
atcaaaagtc gtattataca tggcactaca cagttgctca tagaagctca accgcattcc





2221
gaatattctg cgacagttgc ctcggtttta tttaacaatg aagattttgt taagttaaaa





2281
gagattatga ttaagtgcac aatctggaat acagaacatc aaaagttact gtctaatgca





2341
gaaagaaata ttttggtaga gccactttac aattgcctca ataataagaa ttaatgattc





2401
taacgtatac tctagctgaa agtatatagt tagtgtattc cttggggtag cttcaaccta





2461
tttgatatta gatgtagaat tagagttaca attgatgtga aagtaagtgt caatggttca





2521
caaattataa agtacacaac agtaaaggta agccatacta tgtaacagca aatgaggtct





2581
atgtatatgg gaagtaaaaa aagcggtctg ctcaaattat gagtagaccg cttttttact





2641
taagtatgct atttatcact tcataaatat aaaattacat atcaattact tttttacgac





2701
tttaccggca acacctgttt accgaattag ttgatgaaga ctcatcaatt aattcaatgc





2761
ttttatttgc aatatattgc ctcgcgttct tattaaaatc aatcagtgta gagaaaagaa





2821
gctggaagag ttagagggga tatatgatgt gtttgtgaag ggatatataa tagaggaaat





2881
ataaaaagtg ctaacaagtt tgcaaacgaa cttgctaaca cctatacaga atagacataa





2941
aatatcgctg atatgtcatc tttgaaatag ctttaatcag ttaaatcaca cttatacgaa





3001
atgcttatag taacagtctt aatatcaaga atataatcat ccagatattc ctttactttt





3061
cagacgaaaa cgagggatga tat.









The coding regions for each of the ptuA and ptuB gene sequences within this embodiment of a Septu cassette (SEQ ID NO: 12) are as follows: nucleotides 434-1624 encode an embodiment of a PtuA polypeptide, and nucleotides 1621-2394 encode an embodiment of a PtuB polypeptide.


In some embodiments, a Defense System VII comprising a PtuA polypeptide and a PtuB polypeptide is encoded by the nucleic acid sequence set forth in SEQ ID NO: 12. In some embodiments, a Defense System VII comprising a PtuA polypeptide and a PtuB polypeptide, is encoded by a nucleic acid sequence having at least 80% homology to the sequence set forth in SEQ ID NO: 12. In some embodiments, a Defense System VII comprising a PtuA polypeptide and a PtuB polypeptide, is encoded by a nucleic acid sequence having at least 85% homology, or 90% homology, or 95% homology, or 97% homology, or 98% homology, or 99% homology to the sequence set forth in SEQ ID NO: 12. In some embodiments, a Defense System VII comprising a PtuA polypeptide and a PtuB polypeptide, is encoded by a nucleic acid sequence having at least 80% identity to the sequence set forth in SEQ ID NO: 12. In some embodiments, a Defense System VII comprising a PtuA polypeptide and a PtuB polypeptide, is encoded by a nucleic acid sequence having at least 85% identity, or 90% identity, or 95% identity, or 97% identity, or 98% identity, or 99% identity to the sequence set forth in SEQ ID NO: 12.


In some embodiments, a Septu (Defense System VII) gene cassette comprises the nucleic acid sequence:












(SEQ ID NO: 13; construct 43 of Table 4)
















1
ggctttttaa gtgtacattt ttattgaaga ttggatagaa ttcaacaaga tgaatttgat





61
gtttattaaa cataagatgg aaaggctatg tgttaaataa aaagatgaaa taattaccat





121
tagtgtataa aataataagt aactagtttg gtaatgattt taaggatatg aagtatatta





181
accgtgacat attatagttg aaattcagtt ttatatcatg tgaaaatatg cttttgagga





241
gggtaaagat atgattcgaa tacataaaga taaatatttt gattcaatat atgatgaatt





301
gttagaacaa gcaactcaag aaaagtatat ggatgagtat ttactagaaa agtttatgaa





361
aagatacttt aatggtaaat gttcatactg tgaaattcga atgaaagagt tacgactaac





421
aattgacttt tatagaccta taaatggatc gttaaacacg atggatggtg aatttcatcc





481
tgatcattat aaatggttaa aaaatgaaga tgataatata ctttcaattt gtgtagaatg





541
taagcgagcg aaaagtaatc gttttccagt agatggcgat gtcgcttcta ttaatgctga





601
taagaataaa ttagtgaaag aaagacgttt attgatacat ccttgtagag attatcctga





661
aaggcatttt gattacgatg aaagtggaat ggtttattat aaaagtaaaa aaggcgaggt





721
tactgtagat gttttaaatt tgaatcgcgg tatgttggta gaaatgcgtg cccaagtata





781
tagtgaattt aataatcttt gttatttatt ctcaatggag caaagtccct actatttaaa





841
gcaaattcta caagaagttc agttggattc aatatttatt ggtttaaaaa agtttatact





901
ttctgaatgg gtaatcttaa atgagaaaat tccatttctt caagaatttg agccattatt





961
aggtaagaga ttgcaggaag aagaagtgag agttttatca gttagaaata ataagattag





1021
tcaaattgat attgataata atatccttta tgttgataat gataagcgga gaaagcgtgt





1081
tcctgcaagg aaaattaatg attattacga tgtatccgac gagaacgctt tagaaaaata





1141
ttatggaaaa cagcgtttta ttgaaaaaat tgaaatttat aactttaaaa gtattagaaa





1201
tatgaaaatt gattttactc tcagtaaaag cagtaatgct ccttggctaa tgttattagg





1261
agaaaatggt gtgggcaaaa gctcaatttt acaagcaatt gcattaacac taatgggaaa





1321
cgaacaacgg caaaaaatta taaaaaagaa accttatgaa tatttaacaa aaggctttga





1381
tgaaggttct ataaagataa aattatcagg catgcaagag cctattagta tttatttaaa





1441
ttcgaattca tttgaattta caggtgaaaa tcatcaaagg cctagggttc taattttagg





1501
ttatggctca acgcgattac ttcctagaga agaaatgtta tcaaattata aggtgacttg





1561
ggcaagaata gaaaatctat ttaatccttt tattccatta gttaatgtaa gagagtatct





1621
cttatcttta aataatgaag attttaataa tgttaaaaaa gctattgagt ccttattttt





1681
agatgaagta ataattgatc gggatcagat atatgaagaa gtatattttg gatttgcgaa





1741
ttcttacagt aaactagaag atttaagtga tggctatcag acaattattg ctctggctac





1801
tgatattatg atggttatga agaatagatg gcgaaatttt gatgctgaag gaattgtttt





1861
aatagatgaa attgatgcac atcttcatcc aaggtggaat atagaaattg tttctcgatt





1921
aaaaaatgct tttccgaaaa ttcaatttat tgcaactacc cataacccgc tatcacttcg





1981
tggtttaata gatggagaag ttgcagtatt actagaaaat gaggaaagag aagcgtatat





2041
tactcaaaag ttaccttctc aaaaaggatt taatgtagaa ggattattaa cttctaaatt





2101
ttttggattg tatgacacca tgccagattt aaatgaatta tttgatcgat attatttact





2161
tttatctaat cctagtccta atgaaaggca aaaggaagaa ataaaaaatt tacaagataa





2221
attgtcaaaa tatgaaaaag taggtaccac attaagagaa caaaaattct atgaagcagt





2281
ggattactat tttgcacagt acagaaaaaa taatgtggaa ttaagtgatg aagagtttaa





2341
caatattata gaagatgcta ttaaatattt tgaaaggtaa gattttttat gataaaagtt





2401
caaagagaag cagaaccagc tgtattaaat ctaactgact cagattctat tggttttaaa





2461
gaattggaag cggcaaaaaa aactactttt acaaaagata cgaaatttcc gttcgaggca





2521
tataaggatg aaagtgtaaa aaatctttta aaaaaaatgt ttaatggtaa atgtggatat





2581
tgtgaaagta ttattaatgt gacttcgtat gaagaaattg aacattttag acctaaaaaa





2641
gctattaata tagaaggtat acaaggattg acttatcctg gttactattg gttggctatg





2701
agttggaata atttgttgat ttcttgtcaa aggtgcaata ggtcgcataa aaaaaattat





2761
tttccaatag aaaacgaaag taatcgtgca aaagctcccg gtgaagaaag tggagaggag





2821
gtattactat taaacccttg tgaagatgac ccgagtgaac atttggaatt taaggataca





2881
ggtattattg aatttaaaga gggatctaaa aagggagaaa aatctataaa agtttatgct





2941
cttcatagga gagaacttac tgaagaaaga gcgaaagttg ctaaggatat tgagctgaag





3001
aaagtacaaa tacttgacgg attaagtact ctaaaggtgc ttttacgcta tcaagaagat





3061
agtgatcttc aaaaagagat tgaaaaaact gtatcaaata taatatcatt atatgatttt





3121
atatttgaat atgaaaatga tcctaacagg ccttatcagg caatggtaac tcagattact





3181
tcggattttc tgagtgaacg taaagaatta atcaataaat tgaagacaac atccaatcgg





3241
aaaaattcct gtgaacaaag tcatatttca agttaagtta atttaggata agagctataa





3301
aaaagctctt atcctattta ttatgaagtt tagcgagata gtaaaagtaa cataattaat





3361
atttaaaaaa ttattttttc ttgagtaacg gtattaactc tgctacattt aatatttttt





3421
gtctttataa aatgccttat gtcaattata aaaaaatcat gatgctttct aatttagtcc





3481
tagcgtcttc tttaaattaa gatactataa atatgaggtc cctcaatgct gttgtttata





3541
aagtattttt gctaactgga ttactttgtt gttacgttca tctgacttag tgttccagct





3601
ccacctaact caattaatat ttctatgttt atcatcagtc tatcttttta aaattagtat





3661
atctaaattt ttgcaatgga agcaattggt tttatataat tgtagaagga tttaccaatg





3721
gacaatagcg ggaggattca aaaaa.









The coding regions for each of the ptuA and ptuB gene sequences within this embodiment of a Septu cassette (SEQ ID NO: 13) are as follows: nucleotides 251-2380 encode an embodiment of a PtuA polypeptide, and nucleotides 2389-3276 encode an embodiment of a PtuB polypeptide.


In some embodiments, a Defense System VII comprising a PtuA polypeptide and a PtuB polypeptide is encoded by the nucleic acid sequence set forth in SEQ ID NO: 13. In some embodiments, a Defense System VII comprising a PtuA polypeptide and a PtuB polypeptide, is encoded by a nucleic acid sequence having at least 80% homology to the sequence set forth in SEQ ID NO: 13. In some embodiments, a Defense System VII comprising a PtuA polypeptide and a PtuB polypeptide, is encoded by a nucleic acid sequence having at least 85% homology, or 90% homology, or 95% homology, or 97% homology, or 98% homology, or 99% homology to the sequence set forth in SEQ ID NO: 13. In some embodiments, a Defense System VII comprising a PtuA polypeptide and a PtuB polypeptide, is encoded by a nucleic acid sequence having at least 80% identity to the sequence set forth in SEQ ID NO: 13. In some embodiments, a Defense System VII comprising a PtuA polypeptide and a PtuB polypeptide, is encoded by a nucleic acid sequence having at least 85% identity, or 90% identity, or 95% identity, or 97% identity, or 98% identity, or 99% identity to the sequence set forth in SEQ ID NO: 13.


In some embodiments, a construct comprising the Septu defense system encodes one component of the defense system, whereby multiple constructs, for example but not limited to, two constructs may be used to assemble the functional defense system. In some embodiments, the components of a Septu defense system comprise genes ptuA and ptuB. In some embodiments, the components of a Septu defense system consist of genes ptuA and ptuB. In some embodiments, the components of a Septu defense system comprise nucleic acid sequences encoding a PtuA polypeptide and a PtuB polypeptide. In some embodiments, the components of a Septu defense system consist of nucleic acid sequences encoding a PtuA polypeptide and a PtuB polypeptide.


In some embodiments, a construct comprising the Septu defense system encodes one component of the defense system, whereby a second construct may be used to assemble the functional defense system. In some embodiments, a construct comprising the Septu defense system encodes one component of the defense system, whereby additional constructs may be used to assemble the functional defense system. For example, in some embodiments each of PtuA and PtuB may be encoded by nucleic acid sequences comprised in different constructs, wherein expression of the combination of constructs produces a functional Septu defense system.


In some embodiments, the components making up a functional Septu anti-phage defense system comprise a PtuA polypeptide and a PtuB polypeptide, each encoded by a ptuA and a ptuB gene, respectively. In some embodiments, a ptuA gene encodes a polypeptide comprising an AAA domain (“ATPases Associated with diverse cellular Activities” domain). In some embodiments, a ptuA gene encodes a polypeptide comprising a RecF/RecN/SMC N-terminal domain (a domain found at the N terminus of structural maintenance of chromosomes (SMC) proteins). In some embodiments, a ptuA gene encodes a polypeptide comprising an N-terminal HNH nuclease domain. In some embodiments, a ptuA gene encodes a polypeptide comprising a AAA domain (“ATPases Associated with diverse cellular Activities” domain) or a RecF/RecN/SMC N-terminal domain (a domain found at the N terminus of structural maintenance of chromosomes (SMC) proteins) or an N-terminal HNH nuclease domain, or any combination thereof. In some embodiments, a ptuA gene encodes a polypeptide comprising a AAA domain (“ATPases Associated with diverse cellular Activities” domain) and a RecF/RecN/SMC N-terminal domain (a domain found at the N terminus of structural maintenance of chromosomes (SMC) proteins). In some embodiments, a ptuA gene encodes a polypeptide comprising a AAA domain (“ATPases Associated with diverse cellular Activities” domain) and a RecF/RecN/SMC N-terminal domain (a domain found at the N terminus of structural maintenance of chromosomes (SMC) proteins) and an N-terminal HNH nuclease domain.


In some embodiments, a ptuB gene encodes a polypeptide comprising a HNH endonuclease.


In some embodiments, a Septu defense system having an anti-phage activity comprises a nucleic acid encoding a PtuA polypeptide. In some embodiments, a Septu defense system having an anti-phage activity comprises a nucleic acid encoding a PtuA polypeptide and a PtuB polypeptide. In some embodiments, a Septu defense system having an anti-phage activity comprises a nucleic acid encoding a PtuB polypeptide.


In some embodiments, a Septu defense system having an anti-phage activity comprises a nucleic acid comprising a ptuA gene. In some embodiments, a Septu defense system having an anti-phage activity comprises a nucleic acid comprising a ptuA gene and a ptuB gene. In some embodiments, a Septu defense system having an anti-phage activity comprises a nucleic acid comprising ptuB gene.


In some embodiments, a Septu defense system having an anti-phage activity comprises a nucleic acid construct comprising nucleic acids encoding polypeptides in a set order. In one embodiment, the 5′ to 3′ order of polypeptides encoded is PtuA and PtuB. In some embodiments the 5′ to 3′ order of polypeptides does not affect the anti-phage activity. In some embodiments the 5′ to 3′ order of polypeptides does affect the anti-phage activity.


In some embodiments, the 5′ to 3′ order of polypeptides is random, for example any order of nucleic acid sequences encoding PtuA and PtuB.


In some embodiments, a Septu defense system having an anti-phage activity comprises a nucleic acid construct comprising genes in a set order. In some embodiment, the 5′ to 3′ order of genes is ptuA and ptuB. In some embodiment, the 5′ to 3′ order of genes in a Septu defense system is not ptuA and ptuB. In some embodiments the 5′ to 3′ order of genes does not affect the anti-phage activity. In some embodiments the 5′ to 3′ order of genes does affect the anti-phage activity.


In some embodiments, the 5′ to 3′ order of genes is random, for example any order of ptuA and ptuB.


In some embodiments, the Septu system (Defense System VII) composition and order is as shown in FIG. 3B.


In some embodiments, a Septu defense system having an anti-phage activity originates from a microbial genome, for example a bacterial or an archaeal genome (Table 15). A skilled artisan would appreciate that the Septu system is not present in the majority of bacteria and or archaea species.


In some embodiments, a functional Septu defense system comprises a construct comprising nucleic acid sequences encoding polypeptides, wherein the nucleic acid sequence encoding each polypeptide may originate from a different microbial species. For example, the source of the nucleic acid sequence encoding a PtuA polypeptide may be one microbial species, while the source of the nucleic acid sequence encoding a PtuB polypeptide may be a different microbial species. In some embodiments, a functional Septu defense system comprises a non-naturally occurring combination of polypeptide components. In some embodiments, a functional Septu defense system comprises a combination of at least two polypeptides that do not naturally occur together.


In some embodiments, a functional Septu defense system comprises a construct comprising nucleic acid sequences encoding polypeptides, wherein the nucleic acid sequence encoding each polypeptide may originate from a different bacterial species. For example, the source of the nucleic acid sequence encoding PtuA polypeptide may be one bacterial species, while the source of the nucleic acid sequence encoding a PtuB polypeptide may be a different bacterial species.


In some embodiments, the source of the nucleic acid encoding a PtuA polypeptide and a PtuB polypeptide is the same. In some embodiments, the source of the nucleic acid encoding a PtuA polypeptide and a PtuB polypeptide is the not the same. In some embodiments, the source of the nucleic acid sequence of any of the components of a Septu defense system comprises any of the species listed in Table 15.


In some embodiments, a Septu defense system having an anti-phage activity comprises a nucleic acid construct comprising non-coding regions between the nucleic acid sequences encoding the polypeptides. In some embodiments, the non-coding regions between the nucleic acid sequences comprises nucleic acid sequence not naturally occurring in the microbial species of origin. In some embodiments, the non-coding regions between the nucleic acid sequences comprises nucleic acid sequence is the naturally occurring in the microbial species of origin.


In some embodiments, a Septu system disclosed herein comprises a multi-gene phage resistance system broadly distributed in microbial genomes, for example but not limited to bacteria and archaea. According to some embodiments, the Septu system components are located in a gene cluster (a cassette of genes) in a microbial cell genome. According to some embodiments, the Septu system components are located in close proximity (e.g. positioned within 20 genes, 10 genes, 5 genes or less one from the other) in a genome of a prokaryotic cell. According to some embodiments the prokaryotic cell expresses an endogenous Septu defense system. According to some embodiments, the prokaryotic cell expresses an endogenous functional Septu defense system. According to some embodiments, the species of prokaryotic cell is selected from the group consisting of the species listed in Table 15. According to some embodiments a prokaryotic cell expresses a non-endogenous Septu defense system. According to some embodiments, a prokaryotic cell expresses a non-endogenous functional Septu defense system. According to some embodiments, the species of prokaryotic cell expressing a non-endogenous functional Septu defense system is selected from the group consisting of the species listed in Table 15.


In some embodiments, Septu defense system components comprise PtuA and PtuB polypeptides. In some embodiments, Septu defense system components comprise functional portions of PtuA and PtuB polypeptides. In some embodiments, the Septu defense system functional components are encoded by ptuA and ptuB genes.


Non-limiting embodiments of endogenous Septu systems and the respective location of their components are provided in Table 15 herein.


In some embodiments, the components of a Septu system may be identified by the presence of similar domains present within each component. In some embodiments, domains comprise pfam domains and or clusters of orthologous groups (COG) domains.


In some embodiments, the term “PtuA” refers to the polynucleotide or expression product e.g., the polypeptide encoded by the ptuA gene. In some embodiments, the term “PtuA” refers to a PtuA polypeptide. In some embodiments, the ptuA gene encodes a polypeptide comprising a pfam13304 domain. In some embodiments, the ptuA gene encodes a polypeptide comprising a pfam02463 domain. In some embodiments, the ptuA gene encodes a polypeptide comprising a pfam13304 domain and a pfam02463 domain. In some embodiments, the PtuA polypeptide comprises a pfam13304 domain. In some embodiments, the PtuA polypeptide comprises a pfam02463 domain. In some embodiments, the PtuA polypeptide comprises a pfam13304 domain and a pfam02463 domain.


In some embodiments, PtuA polypeptide is encoded by a gene positioned within 5-60 genes of a gene encoding a PtuB polypeptide in a genome of a prokaryotic cell. In some embodiments, PtuA polypeptide is encoded by a gene positioned within 5 genes upstream (5′) or downstream (3′) to a gene encoding a PtuB polypeptide in a genome of a prokaryotic cell. In some embodiments, PtuA polypeptide is encoded by a gene positioned within 5 genes upstream (5′) and downstream (3′) to a gene encoding a PtuB polypeptide in a genome of a prokaryotic cell.


In some embodiments, PtuA and PtuB are encoded by genes positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, PtuA and PtuB are encoded by genes positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell.


In some embodiments, ptuA and ptuB genes are positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, ptuA and ptuB, genes are positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell.


As used herein, the term “PtuA” refers to the polynucleotide or expression product e.g., polypeptide encoded by the ptuA gene. In some embodiments, the term “PtuA” refers to a PtuA polypeptide. In some embodiments, the product of the ptuA gene comprises a pfam13304 domain. In some embodiments, the ptuA gene encodes a pfam02463 domain. In some embodiments, the product of the ptuA gene comprises a pfam13304 domain or a pfam02463 domain, or any combination thereof. In some embodiments, the product of the ptuA gene comprises a pfam13304 domain and a pfam02463 domain. In some embodiments, the ptuA gene encodes a AAA domain. In some embodiments, the ptuA gene encodes a RecF/RecN/SMC N-terminal domain (a domain found at the N terminus of structural maintenance of chromosomes (SMC) proteins). In some embodiments, the ptuA gene encodes an N-terminal HNH nuclease domain. In some embodiments, the ptuA gene encodes a AAA domain, or a RecF/RecN/SMC N-terminal domain (a domain found at the N terminus of structural maintenance of chromosomes (SMC) proteins), or an N-terminal HNH nuclease domain, or any combination thereof. In some embodiments, the ptuA gene encodes a AAA domain and a RecF/RecN/SMC N-terminal domain (a domain found at the N terminus of structural maintenance of chromosomes (SMC) proteins) and an N-terminal HNH nuclease domain. In some embodiments, the ptuA gene encodes a AAA domain and a RecF/RecN/SMC N-terminal domain (a domain found at the N terminus of structural maintenance of chromosomes (SMC) proteins). In some embodiments, the ptuA gene encodes a RecF/RecN/SMC N-terminal domain (a domain found at the N terminus of structural maintenance of chromosomes (SMC) proteins) and an N-terminal HNH nuclease domain.


In some embodiments, PtuA polypeptide is encoded by a gene positioned within 5-60 genes of a gene encoding a PtuB polypeptide in a genome of a prokaryotic cell. In some embodiments, PtuA polypeptide is encoded by a gene positioned within 5 genes upstream (5′) or downstream (3′) to a gene encoding a PtuB polypeptide in a genome of a prokaryotic cell. In some embodiments, PtuA polypeptide is encoded by a gene positioned within 5 genes upstream (5′) and downstream (3′) to a gene encoding a PtuB polypeptide in a genome of a prokaryotic cell.


In some embodiments, a PtuA polypeptide is about 452 amino acids long (median gene size).


In some embodiments, the PtuA polypeptide comprises the amino acid sequence having at least 80% homology to a sequence selected from the group consisting of the polypeptides referenced in Table 15, rows 2-2507, columns H and I. In some embodiments, the PtuA polypeptide comprises the amino acid sequence having at least 80% homology to similar domain regions in a sequence selected from the group consisting of the polypeptides referenced in Table 15, rows 2-2507, columns H and I. In some embodiments, a PtuA polypeptide homologue comprises an AAA domain (“ATPases Associated with diverse cellular Activities” domain). In some embodiments, a PtuA polypeptide homologue comprises a RecF/RecN/SMC N-terminal domain (a domain found at the N terminus of structural maintenance of chromosomes (SMC) proteins). In some embodiments, a PtuA polypeptide homologue comprises an N-terminal HNH nuclease domain. In some embodiments, a PtuA polypeptide homologue comprises an AAA domain (“ATPases Associated with diverse cellular Activities” domain) and a RecF/RecN/SMC N-terminal domain (a domain found at the N terminus of structural maintenance of chromosomes (SMC) proteins). In some embodiments, a PtuA polypeptide homologue comprises an AAA domain (“ATPases Associated with diverse cellular Activities” domain) and a RecF/RecN/SMC N-terminal domain (a domain found at the N terminus of structural maintenance of chromosomes (SMC) proteins) and an HNH nuclease domain. In some embodiments, the PtuA polypeptide comprises a homolog of a polypeptide having the amino acid sequences set forth in the polypeptides referenced in Table 15, rows 2-2507, columns H and I.


In some embodiments, the PtuA polypeptide comprises the amino acid sequence having at least 80% identity to a sequence selected from the group consisting of the polypeptides referenced in Table 15, rows 2-2507, columns H and I. In some embodiments, the PtuA polypeptide comprises the amino acid sequence having at least 80% homology to a sequence selected from the group consisting of the polypeptides referenced in Table 15, rows 2-2507, columns H and I. In some embodiments, the PtuA polypeptide comprises the amino acid sequence having at least 80% homology to similar domain regions in a sequence selected from the group consisting of the polypeptides referenced in Table 15, rows 2-2507, columns H and I. In some embodiments, the PtuA polypeptide comprises the amino acid sequence having at least 80% identity to similar domain regions in a sequence selected from the group consisting of the polypeptides referenced in Table 15, rows 2-2507, columns H and I.


In some embodiments, the PtuA polypeptide comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polypeptides referenced in Table 15, rows 2-2507, columns H and I. In some embodiments, the PtuA polypeptide comprises the amino acid sequence having at least 80%, at least 85%, at least 90%, or at least 95%, homology to similar domain regions in a sequence selected from the group consisting of the polypeptides referenced in Table 15, rows 2-2507, columns H and I. In some embodiments, the PtuA polypeptide comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polypeptides referenced in Table 15, rows 2-2507, columns H and I. In some embodiments, the PtuA polypeptide comprises the amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95% identity to similar domain regions in a sequence selected from the group consisting of the polypeptides referenced in Table 15, rows 2-2507, columns H and I. In some embodiments, the PtuA polypeptide comprises an amino acid sequence selected from the group consisting of the polypeptides referenced in Table 15, rows 2-2507, columns H and I.


In some embodiments, the PtuA polypeptide comprises an amino acid sequence encoded by a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polynucleotides referenced in Table 15, rows 2-2507, columns H and J. In some embodiments, the PtuA polypeptide comprises the amino acid sequence encoded by a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95%, homology to similar domain regions in a sequence selected from the group consisting of the polynucleotides referenced in Table 15, rows 2-2507, columns H and J. In some embodiments, the PtuA polypeptide comprises an amino acid sequence encoded by a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polynucleotides referenced in Table 15, rows 2-2507, columns H and J. In some embodiments, the PtuA polypeptide comprises the amino acid sequence encoded by a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95%, homology to similar domain regions in a sequence selected from the group consisting of the polynucleotides referenced in Table 15, rows 2-2507, columns H and J. In some embodiments, the PtuA polypeptide comprises an amino acid sequence encoded from a nucleic acid sequence selected from the group consisting of the polynucleotides referenced in Table 15, rows 2-2507, columns H and J.


In some embodiments, the nucleic acid sequence of a ptuA gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polynucleotides referenced in Table 15, rows 2-2507, columns H and J. In some embodiments, the nucleic acid sequence of a ptuA gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology within regions encoding similar domain sequences to a sequence selected from the group consisting of the polynucleotides referenced in Table 15, rows 2-2507, columns H and J.


In some embodiments, the nucleic acid sequence of a ptuA gene encodes a polypeptide comprising an AAA domain (“ATPases Associated with diverse cellular Activities” domain). In some embodiments, the nucleic acid sequence of a ptuA gene encodes a polypeptide comprising a RecF/RecN/SMC N-terminal domain (a domain found at the N terminus of structural maintenance of chromosomes (SMC) proteins). In some embodiments, the nucleic acid sequence of a ptuA gene encodes a polypeptide comprising an HNH nuclease domain. In some embodiments, the nucleic acid sequence of a ptuA gene encodes a polypeptide comprising an AAA domain (“ATPases Associated with diverse cellular Activities” domain) and a RecF/RecN/SMC N-terminal domain (a domain found at the N terminus of structural maintenance of chromosomes (SMC) proteins). In some embodiments, the nucleic acid sequence of a ptuA gene encodes a polypeptide comprising an AAA domain (“ATPases Associated with diverse cellular Activities” domain) and a RecF/RecN/SMC N-terminal domain (a domain found at the N terminus of structural maintenance of chromosomes (SMC) proteins) and an HNH nuclease domain. In some embodiments, the nucleic acid sequence of a ptuA gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polynucleotides referenced in Table 15, rows 2-2507, columns H and J. In some embodiments, the nucleic acid sequence of a ptuA gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity within regions encoding similar domain sequences to a sequence selected from the group consisting of the polynucleotides referenced in Table 15, rows 2-2507, columns H and J. In some embodiments, the nucleic acid sequence of a ptuA gene comprises a nucleic acid sequence selected from the group consisting of the polynucleotides referenced in Table 15, rows 2-2507, columns H and J.


As used herein, the term “PtuB” refers to the polynucleotide or expression product e.g., polypeptide encoded by the ptuB gene. In some embodiments, the term “PtuB” refers to a PtuB polypeptide. In some embodiments, the product of the ptuB gene comprises a pfam13395 domain. In some embodiments, the ptuB gene encodes a pfam01844 domain. In some embodiments, the product of the ptuB gene comprises a pfam13395 domain or a pfam01844 domain, or any combination thereof. In some embodiments, the product of the ptuB gene comprises a pfam13395 domain and a pfam01844 domain. In some embodiments, the ptuB gene encodes a HNH endonuclease.


In some embodiments, PtuB polypeptide is encoded by a gene positioned within 5-60 genes of a gene encoding a PtuA polypeptide in a genome of a prokaryotic cell. In some embodiments, PtuB polypeptide is encoded by a gene positioned within 5 genes upstream (5′) or downstream (3′) to a gene encoding a PtuA polypeptide in a genome of a prokaryotic cell. In some embodiments, PtuB polypeptide is encoded by a gene positioned within 5 genes upstream (5′) and downstream (3′) to a gene encoding a PtuA polypeptide in a genome of a prokaryotic cell.


In some embodiments, a PtuB polypeptide is about 219 amino acids long (median gene size).


In some embodiments, the PtuB polypeptide comprises an amino acid sequence having at least 80% homology to a sequence selected from the group consisting of the polypeptides referenced in Table 15, rows 2-2507, columns L and M. In some embodiments, the PtuB polypeptide comprises the amino acid sequence having at least 80% homology to similar domain regions in a sequence selected from the group consisting of the polypeptides referenced in Table 15, rows 2-2507, columns L and M. In some embodiments, a homologue of the PtuB polypeptide comprises an HNH endonuclease. In some embodiments, the PtuB polypeptide comprises an amino acid sequence having at least 80% identity to a sequence selected from the group consisting of the polypeptides referenced in Table 15, rows 2-2507, columns L and M. In some embodiments, the PtuB polypeptide comprises the amino acid sequence having at least 80% identity to similar domain regions in a sequence selected from the group consisting of the polypeptides referenced in Table 15, rows 2-2507, columns L and M.


In some embodiments, the PtuB polypeptide comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polypeptides referenced in Table 15, rows 2-2507, columns L and M. In some embodiments, the PtuB polypeptide comprises the amino acid sequence having at least 80%, at least 85%, at least 90%, or at least 95%, homology to similar domain regions in a sequence selected from the group consisting of the polypeptides referenced in Table 15, rows 2-2507, columns L and M. In some embodiments, the PtuB polypeptide comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polypeptides referenced in Table 15, rows 2-2507, columns L and M. In some embodiments, the PtuB polypeptide comprises the amino acid sequence having at least 80%, at least 85%, at least 90%, or at least 95%, identity to similar domain regions in a sequence selected from the group consisting of the polypeptides referenced in Table 15, rows 2-2507, columns L and M. In some embodiments, the PtuB polypeptide comprises an amino acid sequence selected from the group consisting of the polypeptides referenced in Table 15, rows 2-2507, columns L and M.


In some embodiments, the PtuB polypeptide comprises an amino acid sequence encoded from a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polynucleotides referenced in Table 15, rows 2-2507, columns L and N. In some embodiments, the PtuB polypeptide comprises the amino acid sequence encoded by a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95%, homology to similar domain regions in a sequence selected from the group consisting of the polynucleotides referenced in Table 15, rows 2-2507, columns L and N. In some embodiments, the PtuB polypeptide comprises an amino acid sequence encoded from a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polynucleotides referenced in Table 15, rows 2-2507, columns L and N. In some embodiments, the PtuB polypeptide comprises the amino acid sequence encoded by a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95%, identity to similar domain regions in a sequence selected from the group consisting of the polynucleotides referenced in Table 15, rows 2-2507, columns L and N. In some embodiments, the PtuB polypeptide comprises an amino acid sequence encoded from a nucleic acid sequence selected from the group consisting of the polynucleotides referenced in Table 15, rows 2-2507, columns L and N.


In some embodiments, the nucleic acid sequence of a ptuB gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polynucleotides referenced in Table 15, rows 2-2507, columns L and N. In some embodiments, the nucleic acid sequence of a ptuB gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polynucleotides referenced in Table 15, rows 2-2507, columns L and N. In some embodiments, the nucleic acid sequence of a ptuB gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology within the nucleotide sequence encoding similar domain regions to regions with a sequence selected from the group consisting of the polynucleotides referenced in Table 15, rows 2-2507, columns L and N. In some embodiments, the nucleic acid sequence of a ptuB gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence encoding similar domain regions selected from the group consisting of the polynucleotides referenced in Table 15, rows 2-2507, columns L and N. In some embodiments, the ptuB gene homolog encodes a polypeptide comprising a HNH endonuclease. In some embodiments, the nucleic acid sequence of a ptuB gene comprises a nucleic acid sequence selected from the group consisting of the polynucleotides referenced in Table 15, rows 2-2507, columns L and N.


A skilled artisan would appreciate that the terms a “functional portion of a Defense System VII component” or “functional fragment of Defense System VII component” or “functional portion of a Septu defense system component” or “functional fragment of Septu defense system component” refers to a functional portion of a Septu polynucleotide or polypeptide, as disclosed herein, which expression is sufficient to elicit an anti-phage activity alone or in combination with the at least one of the other Septu polynucleotides or polypeptides disclosed herein or functional portions thereof.


The terms “PtuA”, “PtuB”, “ptuA” and “ptuB”, also refer to functional PtuA, PtuB, ptuA and ptuB, homologs, which exhibit the desired activity (i.e., conferring phage resistance). Such homologs can be, for example, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical or homologous to the polypeptide sequences referenced in Table 15 rows 2-2507 columns H and I and L and M, respectively, or 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical or homologous to the polynucleotide sequences referenced in Table 15 rows 2-2507 columns H and J and L and N, respectively. In some embodiments, such homologs comprise at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% homology or identity within similar domain regions of the polypeptide sequences referenced in Table 15 rows 2-2507 columns H and I and L and M, respectively, or 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity or homology within nucleotide sequences encoding similar domain regions to the polynucleotide sequences referenced in Table 15 rows 2-2507 columns H and J and L and N, respectively.


Table 15 presents embodiments of components of Defense System VII that may be found in a diverse array of bacteria and archaea genomes (referenced in Table 18). Table 15 presents embodiments of nucleic acid sequences encoding gene cassettes of Defense System VII (referenced in Table 18).


The Lamassu Defense System


In some embodiments, a defense system disclosed herein comprises a Lamassu anti-phage defense system. (Table 16)


In some embodiments, a Lamassu defense system provides a host cell with resistance to entry of foreign nucleic acid invasion. In some embodiments, a host cell expressing a functional Lamassu defense system (Defense System VIII) provides the host cell resistance foreign nucleic acid invasion.


In some embodiments, a Lamassu defense system provides a host cell with resistance to at least one phage.


In some embodiments, a microbial cell comprising a Lamassu defense system protects the microbial cell from phage infection. In some embodiments, a microbial cell expressing a Lamassu defense system protects the microbial cell from phage infection. In some embodiments, a microbial cell expressing a functional Lamassu defense system protects the microbial cell from phage infection. In some embodiments, a bacterial cell comprising a Lamassu defense system protects the bacterial cell from phage infection. In some embodiments, a bacterial cell expressing a Lamassu defense system protects the bacterial cell from phage infection. In some embodiments, a bacterial cell expressing a functional Lamassu defense system protects the bacterial cell from phage infection.


In some embodiments, a Lamassu defense system provides a host cell with resistance to a plasmid.


As used herein, the term “a Lamassu anti-phage defense system” may be used interchangeably with the term “a Defense System VII”, having all the same meanings and qualities. A skilled artisan would appreciate that the term “Lamassu system” may be used interchangeably in some embodiments with “Lamassu defense system”, “Lamassu the defense system”, “Lamassu anti-phage system”, and “Defense System VIII”, having all the same meanings and qualities.


In some embodiments, a Lamassu defense system (Defense System VIII) provides a host cell with resistance to plasmid transformation. In some embodiments, a host cell expressing a functional Lamassu defense system (Defense System VIII) provides a host cells with resistance to plasmid transformation.


In some embodiments, a Lamassu defense system (Defense system VIII) provides a host cell with resistance to entry of conjugative elements. In some embodiments, a host cell expressing a function Lamassu defense system (Defense System VIII) provides the host cell resistance from entry of conjugative elements.


In some embodiments, a microbial species does not comprise an endogenous Defense System VIII. In some embodiments, a microbial species does not express an endogenous Defense System VIII. In some embodiments, a microbial species does not express an endogenous functional Defense System VIII.


In some embodiments, a bacterial species does not comprise an endogenous Defense System VIII. In some embodiments, a bacterial species does not express an endogenous Defense System VIII. In some embodiments, a bacterial species does not express an endogenous functional Defense System VIII.


A Lamassu defense system comprises, in some embodiments, a nucleic acid construct comprising a nucleic acid sequence encoding a LmuA polypeptide comprising a pfam14130 domain or a DUF4297 domain or a combination thereof, and a LmuB polypeptide comprising a pfam02463 domain. In some embodiments, a Lamassu defense system comprises a nucleic acid construct comprising a nucleic acid sequence comprising a lmuA gene and a lmuB gene.


In some embodiments, a Lamassu defense system comprises, a LmuA polypeptide comprising a pfam14130 domain or a DUF4297 domain or a combination thereof, and a LmuB polypeptide comprising a pfam02463 domain. In some embodiments, a Lamassu defense system comprises a LmuA polypeptide and a LmuB polypeptide.


In some embodiments, a Defense System VIII comprises a LmuA polypeptide comprising a pfam14130 domain or a DUF4297 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 16 rows 2-698 columns H and I; or a LmuB polypeptide comprising a pfam02463 domain or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 16 rows 2-698 columns L and M; or a combination thereof.


In some embodiments, a Defense System VIII comprises at least two different polypeptide components selected from a LmuA polypeptide comprising a pfam14130 domain or a DUF4297 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 16 rows 2-698 column H and I; and a LmuB polypeptide comprising a pfam02463 domain or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 16 rows 2-698 columns L and M.


In some embodiments, a Lamassu defense system having an anti-phage activity comprises a nucleic acid construct comprising a nucleic acid sequence encoding a LmuA polypeptide and a LmuB polypeptide. In some embodiments, a Lamassu defense system having an anti-phage activity comprises a nucleic acid construct comprising a nucleic acid sequence encoding a LmuA polypeptide and a LmuB polypeptide comprising a RecF/RecN/SMC N-terminal domain.


In some embodiments, a Lamassu defense system having an anti-phage activity comprises a nucleic acid construct comprising a nucleic acid sequence encoding a LmuB polypeptide comprising a RecF/RecN/SMC N-terminal domain.


In some embodiments, the Lamassu anti-phage defense system comprises a nucleic acid construct comprising nucleic acid sequences encoding a cassette comprising lmuA and lmuB genes.


In some embodiments, a Lamassu (Defense System VIII) gene cassette comprises the nucleic acid sequence:












(SEQ ID NO: 7; construct 13 of Table 4)
















1
tgcatattta taattgtgtg ttgaggcgag tgttaatcta ttgcaaatag ttttgcaatt





61
ctccactagt caattatatc tcttgatatc catcttgata aaaaactttt aaagacactt





121
tctcatttgg gaggtgtctt tatttattgg tatcatagtt tttttatggg agctaataaa





181
agtaacataa gatccgctca tgcattctgt gtctgataat gaaaaaaatt aggtatttat





241
atttgatagt tcaaaatcta tattattgaa aacataataa aattttcctg ataaatagta





301
ccattttttt gaaaatcctg atatcatata aataagagag aggatatcag gaggagcgca





361
atgattgaaa ttgacaacgg gggagccatc gcactaaaag gatttaacta tcaaaaagct





421
tccatcatac ttgtaatgat tcataatttt gaaaaagata attttatagt catacctgaa





481
tcgcaagaag attttgaaat tcatcttgga caagatactt attttataca agtgaaagga





541
acaaaaaaac tttccatagg taagttgaag tcaaggccta gcggaaaagc ttcaatcata





601
gagaaaaatc tttctcctgg taatgttgga gatataagga aaatatttct ctgggatata





661
gcggagttaa caaaaaacga attgataagc caagaaggaa cgcttattcc tatgaaacac





721
agcctttcat tgaaacaaaa gacagagatt ataaatactc ttgatttaga tgaagaacag





781
aaaaatagaa tgaacaatca atatatatat ataacccctt ttccaaacga tataaatttg





841
gctttaacat ttttaaaagg agaaatggtt aatgaaaact tgctggtttc taacgatcga





901
gctaaattag ttttaggaga actatcattg gaaatagatc gtaaaagtga aatagtagtt





961
tctactgaaa gtgatgtaga aaggaaaaaa atcgacggga attatcttaa gcaggtattc





1021
attaatatta agcaaaaaga gatgtttgat gaaattttag ataatctctc tatcaacaca





1081
attatgaaaa aaaaagtaaa gaaggagaaa ttaagaatac cactcttgta tcaaaatatt





1141
aaagagcaaa cgaagcaaaa ggcagatatt aatttactta tgagggagaa tgatgagggt





1201
gctattaact atctcagaga tctattggta gagatagtgc cagatatgaa gcctacagaa





1261
ctatctattg ctttagcaat agactgtttt tgtgagttgg gagaataaaa tctatgataa





1321
taattgcttt ttctattctt gattttaaaa ataaagaagc acaaaatttt gactttaaag





1381
ctgggactaa tctaattgtt agtaaaggaa ataccaaagg taaatcaagt cttttaaaat





1441
caatgtatta tacattagga tttgatgtgc atcaatttcc tagtaactgg aacataaatt





1501
ttatgtattt ccaaatagaa gtcttaataa ataatgttaa atataatata actagacaaa





1561
aaaatatttt tagagtaagt gatgtagaag tacctttgaa tgtaaaagag tattcagagt





1621
ggcttcaaca taaacttgag attaaaatgc agttagctaa tactcatact aagcacttat





1681
acgaggcata ttcttcggca gtaattttac cattttacat agatcaagac gattcttggg





1741
atggcggaat ttatagaaat gtaactaata ctctgaatca atatactcgc ataccggcag





1801
atattttcaa aagtgttttt aatctctcca attacgaact tctggagttg caaaattcgc





1861
ttactaatta tagtaaagaa aagaatacgg tagtgtctac aataaagagt ttattaaatg





1921
ttttggaaga ttatagacat gaaaacgcag atgtccctac tgtttcaaaa attgataaaa





1981
tagccttaaa taaagatatc gatcgctact tgcagatgca aaatgaatta aatgaacaaa





2041
tagtaaaata taaaatgaag ctattaaaca agcaagaaat gttggattta caaaagcaag





2101
aattgtctga attagagcag cttttaaaaa tgaacaaaaa gagatataac tctattgaaa





2161
cagaatgtca atattgtcat tctaaattaa caaaagaaca atctttaaca agacttgatt





2221
tatcgaataa ttattttgaa atatcgcttt tgaaagagga aatagaaaaa gaagtagtaa





2281
aattgactaa tgaaattata atattcgaat cacaacaaaa ttctattgaa tctaaaattg





2341
atgaaattca tcgtaggatt caaaattcta aagatctact tacgattgat gattatgtaa





2401
aagcaactgc taaaaaagaa gcatcaaatg aattggaaag tttagttgat aaacaagttc





2461
tttctaaata taatttagaa gaaaaaatta aagtattaag aagggaaatt aataaactga





2521
agaaagagaa agaaagttta agagagatta ttgagcgaga ttacactgat ttggtatttg





2581
aaataaaaaa agtgttgaat gatttaaatg atacaaagct ggatttatct gaattaaatc





2641
tggatgaact taaatttctt gaatttaaga aaatatcggg gagtggtatg gataaaaata





2701
aaaaattttt agcttactat ttaatttatt ttagtttgtt gagaaagtat agctcttata





2761
taattccctt ttgtatggat tcgtttatta aaaatgaaat tacgggtgag actgcaaaaa





2821
agatgtttga agcaatagaa aaatattttt ttgacactaa tcagtctttc ttttcaatcg





2881
tttctgaaaa ccttaaacat ttagagtttg tagatagtta caataagatt aatgttgagg





2941
gtaagctgtt ggttagagat aaatatgatg agattgcttt gaaattcaaa tttgatagtt





3001
aaaattatta aagggccttg aatgacattt gatagttcaa actttcaaat gcctgaagag





3061
aaaaatgatt atccgaaaga aattaactca tatagaatta tgcacttaat attcttaatt





3121
ttttagtaga atactcaatc ctttgatttt ttttggaata taataacatt tttcatcaga





3181
aaacaacaag gggaaaagcc aatttcttta cagtaggagt tggctttatt gtgcagaaac





3241
taaattaaat attatatgtt ttttcgatct taaccatatg aaaggataaa taaacaaaga





3301
gttgattgac ttcgttcttc gcttcataga ttgaggagtt gattcaactt tccattct









The coding regions for each of the lmuA and lmuB gene sequences within this embodiment of a Lamassu cassette (SEQ ID NO: 7) are as follows: nucleotides 361-1308 encode an embodiment of a LmuA polypeptide, and nucleotides 1314-3002 encode an embodiment of a LmuB polypeptide.


In some embodiments, a Defense System VIII comprising a LmuA polypeptide and a LmuB polypeptide is encoded by the nucleic acid sequence set forth in SEQ ID NO: 7. In some embodiments, a Defense System VIII comprising a LmuA polypeptide and a LmuB polypeptide, is encoded by a nucleic acid sequence having at least 80% homology to the sequence set forth in SEQ ID NO: 7. In some embodiments, a Defense System VIII comprising a LmuA polypeptide and a LmuB polypeptide, is encoded by a nucleic acid sequence having at least 85% homology, or 90% homology, or 95% homology, or 97% homology, or 98% homology, or 99% homology to the sequence set forth in SEQ ID NO: 7. In some embodiments, a Defense System VIII comprising a LmuA polypeptide and a LmuB polypeptide, is encoded by a nucleic acid sequence having at least 80% identity to the sequence set forth in SEQ ID NO: 7. In some embodiments, a Defense System VIII comprising a LmuA polypeptide and a LmuB polypeptide, is encoded by a nucleic acid sequence having at least 85% identity, or 90% identity, or 95% identity, or 97% identity, or 98% identity, or 99% identity to the sequence set forth in SEQ ID NO: 7.


In some embodiments, a Lamassu (Defense System VIII) gene cassette comprises the nucleic acid sequence:












(SEQ ID NO: 8; construct 14 of Table 4)
















1
gaagatgcgg ttaacaaaat agaagagatt ttgttggtaa tgtgaccaat tttgtgatca





61
ctggttttgt atagtatagg aatagaaaaa taacaaccgt atcaaacgtt aatttgacac





121
ggtttctaca actatgccct cggagaggct cgaactcatg gccttcatcc tgtcaaagtg





181
taaatagaag tcgttagttt aacgtaagtc aaatcggaaa tcggcactat ttacggatac





241
cgttatatca acgtttgcag ctaaatagtt atacgtccgt cttgttttct attattaatt





301
aaagcgtgta gtaccgccat actgcaagat ataaaaccgt taattgtcat tttaggatcc





361
ttcacattca ttgattatta cgaagctgca ggaatggcta tgtaaacagt acatgtttgg





421
aaagaaatga agatgatagg agaaaatctt catgaaattt atcatcgagc gaattaaatg





481
gacgtatgta aaaggtgatg aacaacccac gatgaaaatt aaatacaagt aaacgagcca





541
cgctcgtcac tgggcgtggt tttaatgtgt gtaattggaa actgtatgta aaaaagaaat





601
taacaagttt gttagtactg gatgatttag gataaaaaat gaaatttata acaaattata





661
gcttaaaatt gatataatat gataagaagg atgttttgct attgtaattt aagaaacaag





721
aattttgaac agaaaaaatt cactatataa atgaaattgt aaaattgcct ttgggattta





781
aaggagggat ggctagtgga tataagttct tatcctagct tggaaactta tgaagcacgt





841
gagaatacag gttcaaggtc ttcaaacaga ttagctatgc aaattagttt tgctatgtgg





901
aagatttttg aattatatca aaatgaagat tttactgtgg ctatggattg tattgatgat





961
gtagtcatat ttaaaacatc aaatgaaaat ccaactattg tgacttatca attgaaaaca





1021
aaggatgcta ctacggggaa ctttgaactg agaaagctaa ttggtgataa tgtatttttg





1081
aaaatgtatg atcacattga aaaaatagat gcagatgttg aagaaatata tttaataact





1141
aacaatcctt tgaaatttag aaagaaaacg gttaatgcag aacggatttt atttgaaaaa





1201
ttagatgaag atataaaaga gttaattgaa gaaaatatgt ctcagagtaa agtttttgca





1261
gataaaggat tatcatctaa gtttatatat tctttggtag atatgtcttt tcataatcat





1321
agagaaatca gtcaatataa attaaattct ttattaatga aagaaaaaat agatattagt





1381
ataacagctg cagatgcact ttttaatgca ttgcaagata ttttaacaac taagcaaaat





1441
tatgagttta gtttacaaga tgaatttaat acggtactaa agaaaaaaag ttactcgaaa





1501
acggaattta catcactatt ggataactcg aaaaaaatta atgcctatgt tttatctttc





1561
gaggatattc gtaccaacta taaaagcaaa cctttaaagc tgaaagaaga aagtttatac





1621
aggagagcga tggctagtgt taaagaaaaa tgcaataaat ctcctaatat attacaaaat





1681
ataaatgaag atatttttca atatgctaaa gagcagattg atatcaatga cgaaataacg





1741
agaattgagc tagtcatact tttacaaagt gtttttgacg acaagataaa tgttgagtta





1801
tctaaagaag aaaaagaaat tctatatatg caaaatatcg aattagccct aagggaggga





1861
taaactcatg aataaaataa taattcgtaa gttatttata tttgatgtga ttgaaaaaaa





1921
agccaaaagt gtagattttg aagatggtat caatattgtt acaagtaaag gaaatcaact





1981
gggtaaatca actataatga aatctattta ttatacattg ggtgcagaag tgttttttgc





2041
cgacagatta aatgtaaaga gtaaaatcca tatgttagag acagacgtta atgataagaa





2101
atataccttt attagacatg gcgatgttgt tgtgataaaa gatggtaaag gaatttttaa





2161
gacgtcgaac gcttctgaat tatcatctaa gttgcatgat atatttggat ttagcgtttt





2221
tctagaagat aaacagaaaa aatatgtgat agctccacct gtatttcgtt acattcctta





2281
ttatattgac caagaccatg gttggacatc agaattgaaa tcttttgata aattaggtca





2341
attcgataaa aaaagcaggg atttattatt ttattatcat ttaaatattc ttgatgaaga





2401
ttatggagta aagttgaaag agaaaaaaga actagatgct tcaatgactg atttgaaaac





2461
taggaaaaaa gagattttag gcctactcgc atacataaga gagaatatta cagcttttaa





2521
tttagaaatg gatattacag cgttacaaat tcaaaagaga gaaatactta ataaatataa





2581
aaagtattca tatgatttga ataacatacg aagaaaaatt ttagaatatc aagaagaaat





2641
atttaaaatt gacaatgtaa ttgataattt aaatagtact ttgaaacaaa atgataaagt





2701
aagagaacat ataaaacatc aatttgatgt agagtgcccg tattgtaata atcattttga





2761
aatacaggcg aaagatatat taagaattaa ttataatatt gtagacttag aggcatcaaa





2821
attagaaatg ctagatataa aagaaaaatt attggggaaa atgaaaaaag tacaaaaaga





2881
gtatgaagat tatcaagcta cgttgaaagc tattgaagaa gaaaaagttg attcagaaaa





2941
tacacttgaa gacatactga aatttaaagg gttacaagaa actcaaaatc aactaaatac





3001
ggaacttgtc aaaaatactg gtgatataga agaaaagtca gaagacttaa aagaaataag





3061
acgagattta aaaaaatggc aggatgaaat agataaagtt aacagtaggt ataaggatat





3121
cttaaattta aatctaatta gatttaatac gaatgaacat gcactccctg aaaaatataa





3181
tattggaaaa aacctcaaag catctggtag cggtcaagtt cgagttaatt tagctagagt





3241
atattcattt ataaagcttc ttgaagaata taatcctaca ggattaaaat atccattagt





3301
aattgactct cctaaaggcg gagaacagag tactacaaat agtgaattga ttttaagatt





3361
gttgacggag aaagcgcaaa tttcaaatca aattatttta gctacaattg attttgaaag





3421
tttttataat ggagatacta aaaaattcaa cataatctct ttagaaaatg aaccttatca





3481
tttattatct gctgaagatt atcaaaataa tcaagtgata attgatgact ttgtttcttt





3541
atattttgaa gcaaatcaat aaatagaaat agtaaaagga cgctttaata cgaagcgtcc





3601
tatttaattt gaaggagccc tcaaacaggg aatcctt.









The coding regions for each of the lmuA and lmuB gene sequences within this embodiment of a Lamassu cassette (SEQ ID NO: 8) are as follows: nucleotides 877-1863 encode an embodiment of a LmuA polypeptide, and nucleotides 1868-3562 encode an embodiment of a LmuB polypeptide.


In some embodiments, a Defense System VIII comprising a LmuA polypeptide and a LmuB polypeptide is encoded by the nucleic acid sequence set forth in SEQ ID NO: 8. In some embodiments, a Defense System VIII comprising a LmuA polypeptide and a LmuB polypeptide, is encoded by a nucleic acid sequence having at least 80% homology to the sequence set forth in SEQ ID NO: 8. In some embodiments, a Defense System VIII comprising a LmuA polypeptide and a LmuB polypeptide, is encoded by a nucleic acid sequence having at least 85% homology, or 90% homology, or 95% homology, or 97% homology, or 98% homology, or 99% homology to the sequence set forth in SEQ ID NO: 8. In some embodiments, a Defense System VIII comprising a LmuA polypeptide and a LmuB polypeptide, is encoded by a nucleic acid sequence having at least 80% identity to the sequence set forth in SEQ ID NO: 8. In some embodiments, a Defense System VIII comprising a LmuA polypeptide and a LmuB polypeptide, is encoded by a nucleic acid sequence having at least 85% identity, or 90% identity, or 95% identity, or 97% identity, or 98% identity, or 99% identity to the sequence set forth in SEQ ID NO: 8.


In some embodiments, a construct comprising the Lamassu defense system encodes one component of the defense system, whereby multiple constructs, for example but not limited to, two constructs may be used to assemble the functional defense system. In some embodiments, the components of a Lamassu defense system comprise genes lmuA and lmuB. In some embodiments, the components of a Lamassu defense system consist of genes lmuA and lmuB. In some embodiments, the components of a Lamassu defense system comprise nucleic acid sequences encoding a LmuA polypeptide and a LmuB polypeptide. In some embodiments, the components of a Lamassu defense system consist of nucleic acid sequences encoding a LmuA polypeptide and a LmuB polypeptide.


In some embodiments, a construct comprising the Lamassu defense system encodes one component of the defense system, whereby a second construct may be used to assemble the functional defense system. In some embodiments, a construct comprising the Lamassu defense system encodes one component of the defense system, whereby additional constructs may be used to assemble the functional defense system. For example, in some embodiments each of LmuA and LmuB may be encoded by nucleic acid sequences comprised in different constructs, wherein expression of the combination of constructs produces a functional Lamassu defense system.


In some embodiments, the components making up a functional Lamassu anti-phage defense system comprise a LmuA polypeptide and a LmuB polypeptide, each encoded by a lmuA and a lmuB gene, respectively.


In some embodiments, a lmuB gene encodes a polypeptide comprising a RecF/RecN/SMC N-terminal domain. In some embodiments, a LmuB polypeptide comprises a RecF/RecN/SMC N-terminal domain.


In some embodiments, a Lamassu defense system having an anti-phage activity comprises a nucleic acid encoding a LmuA polypeptide. In some embodiments, a Lamassu defense system having an anti-phage activity comprises a nucleic acid encoding a LmuA polypeptide and a LmuB polypeptide. In some embodiments, a Lamassu defense system having an anti-phage activity comprises a nucleic acid encoding a LmuB polypeptide.


In some embodiments, a Lamassu defense system having an anti-phage activity comprises a nucleic acid comprising a lmuA gene. In some embodiments, a Lamassu defense system having an anti-phage activity comprises a nucleic acid comprising a lmuA gene and a lmuB gene. In some embodiments, a Lamassu defense system having an anti-phage activity comprises a nucleic acid comprising lmuB gene.


In some embodiments, a Lamassu defense system having an anti-phage activity comprises a nucleic acid construct comprising nucleic acids encoding polypeptides in a set order. In one embodiment, the 5′ to 3′ order of polypeptides encoded is LmuA and LmuB. In some embodiments the 5′ to 3′ order of polypeptides does not affect the anti-phage activity. In some embodiments the 5′ to 3′ order of polypeptides does affect the anti-phage activity.


In some embodiments, the 5′ to 3′ order of polypeptides is random, for example any order of nucleic acid sequences encoding LmuA and LmuB.


In some embodiments, a Lamassu defense system having an anti-phage activity comprises a nucleic acid construct comprising genes in a set order. In some embodiment, the 5′ to 3′ order of genes is lmuA and lmuB. In some embodiment, the 5′ to 3′ order of genes in a Lamassu defense system is not lmuA and lmuB. In some embodiments the 5′ to 3′ order of genes does not affect the anti-phage activity. In some embodiments the 5′ to 3′ order of genes does affect the anti-phage activity.


In some embodiments, the 5′ to 3′ order of genes is random, for example any order of lmuA and lmuB.


In some embodiments, the Lamassu system (Defense System VIII) composition and order is as shown in FIG. 3B.


In some embodiments, a Lamassu defense system having an anti-phage activity originates from a microbial genome, for example a bacterial or an archaeal genome (Table 16). A skilled artisan would appreciate that the Lamassu system is not present in the majority of bacteria and or archaea species.


In some embodiments, a functional Lamassu defense system comprises a construct comprising nucleic acid sequences encoding polypeptides, wherein the nucleic acid sequence encoding each polypeptide may originate from a different microbial species. For example, the source of the nucleic acid sequence encoding a LmuA polypeptide may be one microbial species, while the source of the nucleic acid sequence encoding a LmuB polypeptide may be a different microbial species. In some embodiments, a functional Lamassu defense system comprises a non-naturally occurring combination of polypeptide components. In some embodiments, a functional Lamassu defense system comprises a combination of at least two polypeptides that do not naturally occur together.


In some embodiments, a functional Lamassu defense system comprises a construct comprising nucleic acid sequences encoding polypeptides, wherein the nucleic acid sequence encoding each polypeptide may originate from a different bacterial species. For example, the source of the nucleic acid sequence encoding a LmuA polypeptide may be one bacterial species, while the source of the nucleic acid sequence encoding a LmuB polypeptide may be a different bacterial species.


In some embodiments, the source of the nucleic acid encoding a LmuA polypeptide and a LmuB polypeptide is the same. In some embodiments, the source of the nucleic acid encoding a LmuA polypeptide and a LmuB polypeptide is the not the same. In some embodiments, the source of the nucleic acid sequence of any of the components of a Lamassu defense system comprises any of the species listed in Table 16.


In some embodiments, a Lamassu defense system having an anti-phage activity comprises a nucleic acid construct comprising non-coding regions between the nucleic acid sequences encoding the polypeptides. In some embodiments, the non-coding regions between the nucleic acid sequences comprises nucleic acid sequence not naturally occurring in the microbial species of origin. In some embodiments, the non-coding regions between the nucleic acid sequences comprises nucleic acid sequence is the naturally occurring in the microbial species of origin.


In some embodiments, a Lamassu system disclosed herein comprises a multi-gene phage resistance system broadly distributed in microbial genomes, for example but not limited to bacteria and archaea. A skilled artisan would appreciate that the majority of bacteria and archaea do not comprise a Lamassu defense system.


According to some embodiments, the Lamassu defense system components are located in a gene cluster (a cassette of genes) in a microbial cell genome. According to some embodiments, the Lamassu system components are located in close proximity (e.g. positioned within 20 genes, 10 genes, 5 genes or less one from the other) in a genome of a prokaryotic cell. According to some embodiments the prokaryotic cell expresses an endogenous Lamassu defense system. According to some embodiments, the prokaryotic cell expresses an endogenous functional Lamassu defense system. According to some embodiments, the species of prokaryotic cell is selected from the group consisting of the species listed in Table 16.


According to some embodiments a prokaryotic cell expresses a non-endogenous Lamassu defense system. According to some embodiments, a prokaryotic cell expresses a non-endogenous functional Lamassu defense system. According to some embodiments, the species of prokaryotic cell expressing a non-endogenous functional Lamassu defense system is selected from the group consisting of the species listed in Table 16.


In some embodiments, Lamassu defense system components comprise LmuA and LmuB polypeptides. In some embodiments, Lamassu defense system components comprise functional portions of LmuA and LmuB polypeptides. In some embodiments, the Lamassu defense system functional components are encoded by lmuA and lmuB genes.


Non-limiting embodiments of endogenous Lamassu systems and the respective location of their components are provided in Table 16 herein.


In some embodiments, the components of a Lamassu system may be identified by the presence of similar domains present within each component. In some embodiments, domains comprise pfam domains and or clusters of orthologous groups (COG) domains.


In some embodiments, the term “LmuA” refers to the polynucleotide or expression product e.g., the polypeptide encoded by the lmuA gene. In some embodiments, the term “LmuA” refers to a LmuA polypeptide. In some embodiments, the lmuA gene encodes a polypeptide comprising a pfam14130 domain. In some embodiments, the lmuA gene encodes a polypeptide comprising a DUF4297 domain. In some embodiments, the lmuA gene encodes a polypeptide comprising a pfam14130 domain and a DUF4297 domain. In some embodiments, the LmuA polypeptide comprises a pfam14130 domain. In some embodiments, the LmuA polypeptide comprises a DUF4297 domain. In some embodiments, the LmuA polypeptide comprises a pfam14130 domain and a DUF4297 domain.


In some embodiments, LmuA polypeptide is encoded by a gene positioned within 5-60 genes of a gene encoding a LmuB polypeptide in a genome of a prokaryotic cell. In some embodiments, LmuA polypeptide is encoded by a gene positioned within 5 genes upstream (5′) or downstream (3′) to a gene encoding a LmuB polypeptide in a genome of a prokaryotic cell. In some embodiments, LmuA polypeptide is encoded by a gene positioned within 5 genes upstream (5′) and downstream (3′) to a gene encoding a LmuB polypeptide in a genome of a prokaryotic cell.


In some embodiments, LmuA and LmuB are encoded by genes positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, LmuA and LmuB are encoded by genes positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell.


In some embodiments, lmuA and lmuB genes are positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, lmuA and lmuB, genes are positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell.


As used herein, the term “LmuA” refers to the polynucleotide or expression product e.g., polypeptide encoded by the lmuA gene. In some embodiments, the term “LmuA” refers to a LmuA polypeptide. In some embodiments, the product of the lmuA gene comprises a pfam14130 domain. In some embodiments, the lmuA gene encodes a DUF4297 domain. In some embodiments, the product of the lmuA gene comprises a pfam14130 domain or a DUF4297 domain, or any combination thereof. In some embodiments, the product of the lmuA gene comprises a pfam14130 domain and a DUF4297 domain.


In some embodiments, LmuA polypeptide is encoded by a gene positioned within 5-60 genes of a gene encoding a LmuB polypeptide in a genome of a prokaryotic cell. In some embodiments, LmuA polypeptide is encoded by a gene positioned within 5 genes upstream (5′) or downstream (3′) to a gene encoding a LmuB polypeptide in a genome of a prokaryotic cell. In some embodiments, LmuA polypeptide is encoded by a gene positioned within 5 genes upstream (5′) and downstream (3′) to a gene encoding a LmuB polypeptide in a genome of a prokaryotic cell.


In some embodiments, a LmuA polypeptide is about 361 amino acids long (median gene size).


In some embodiments, the LmuA polypeptide comprises the amino acid sequence having at least 80% homology to a sequence selected from the group consisting of the polypeptides referenced in Table 16, rows 2-698, columns H and I. In some embodiments, the LmuA polypeptide comprises the amino acid sequence having at least 80% homology within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 16, rows 2-698, columns H and I. In some embodiments, the LmuA polypeptide comprises a homolog of a polypeptide having the amino acid sequences set forth in the polypeptides referenced in Table 16, rows 2-698, columns H and I.


In some embodiments, the LmuA polypeptide comprises the amino acid sequence having at least 80% identity to a sequence selected from the group consisting of the polypeptides referenced in Table 16, rows 2-698, columns H and I. In some embodiments, the LmuA polypeptide comprises the amino acid sequence having at least 80% identity within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 16, rows 2-698, columns H and I.


In some embodiments, the LmuA polypeptide comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polypeptides referenced in Table 16, rows 2-698, columns H and I. In some embodiments, the LmuA polypeptide comprises the amino acid sequence having at least 80%, 85%, 90%, 95% homology within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 16, rows 2-698, columns H and I. In some embodiments, the LmuA polypeptide comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polypeptides referenced in Table 16, rows 2-698, columns H and I. In some embodiments, the LmuA polypeptide comprises the amino acid sequence having at least 80%, 85%, 90%, 95% identity within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 16, rows 2-698, columns H and I. In some embodiments, the LmuA polypeptide comprises an amino acid sequence selected from the group consisting of the polypeptides referenced in Table 16, rows 2-698, columns H and I.


In some embodiments, the LmuA polypeptide comprises an amino acid sequence encoded by a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polynucleotides referenced in Table 16, rows 2-698, columns H and J. In some embodiments, the LmuA polypeptide comprises the amino acid sequence encoded by a nucleic acid sequence having at least 80%, 85%, 90%, 95% homology within similar domain regions within a sequence selected from the group consisting of the polynucleotides referenced in Table 16, rows 2-698, columns H and J. In some embodiments, the LmuA polypeptide comprises an amino acid sequence encoded by a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polynucleotides referenced in Table 16, rows 2-698, columns H and J. In some embodiments, the LmuA polypeptide comprises the amino acid sequence encoded by a nucleic acid sequence having at least 80%, 85%, 90%, 95% homology within similar domain regions within a sequence selected from the group consisting of the polynucleotides referenced in Table 16, rows 2-698, columns H and J. In some embodiments, the LmuA polypeptide comprises an amino acid sequence encoded from a nucleic acid sequence selected from the group consisting of the polynucleotides referenced in Table 16, rows 2-698, columns H and J.


In some embodiments, the nucleic acid sequence of a lmuA gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polynucleotides referenced in Table 16, rows 2-698, columns H and J. In some embodiments, the lmuA gene comprises a nucleic acid sequence having at least 80%, 85%, 90%, 95% homology within encoded similar domain regions in comparison with nucleotide sequence encoding these domain within a sequence selected from the group consisting of the polynucleotides referenced in Table 16, rows 2-698, columns H and J. In some embodiments, the nucleic acid sequence of a lmuA gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polynucleotides referenced in Table 16, rows 2-698, columns H and J. In some embodiments, the lmuA gene comprises a nucleic acid sequence having at least 80%, 85%, 90%, 95% identity within encoded similar domain regions in comparison with nucleotide sequence encoding these domain within a sequence selected from the group consisting of the polynucleotides referenced in Table 16, rows 2-698, columns H and J. In some embodiments, the nucleic acid sequence of a lmuA gene comprises a nucleic acid sequence selected from the group consisting of the polynucleotides referenced in Table 16, rows 2-698, columns H and J.


As used herein, the term “LmuB” refers to the polynucleotide or expression product e.g., polypeptide encoded by the lmuB gene. In some embodiments, the term “LmuB” refers to a LmuB polypeptide. In some embodiments, the product of the lmuB gene comprises a pfam02463 domain. In some embodiments, the lmuB gene encodes a RecF/RecN/SMC N-terminal domain.


In some embodiments, LmuB polypeptide is encoded by a gene positioned within 5-60 genes of a gene encoding a LmuA polypeptide in a genome of a prokaryotic cell. In some embodiments, LmuB polypeptide is encoded by a gene positioned within 5 genes upstream (5′) or downstream (3′) to a gene encoding a LmuA polypeptide in a genome of a prokaryotic cell. In some embodiments, LmuB polypeptide is encoded by a gene positioned within 5 genes upstream (5′) and downstream (3′) to a gene encoding a LmuA polypeptide in a genome of a prokaryotic cell.


In some embodiments, a LmuB polypeptide is about 559 amino acids long (median gene size).


In some embodiments, the LmuB polypeptide comprises an amino acid sequence having at least 80% homology to a sequence selected from the group consisting of the polypeptides referenced in Table 16, rows 2-698, columns L and M. In some embodiments, the LmuB polypeptide comprises the amino acid sequence having at least 80% homology within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 16, rows 2-698, columns L and M. In some embodiments, a homologue of the LmuB polypeptide comprises a RecF/RecN/SMC N-terminal domain. In some embodiments, the LmuB polypeptide comprises an amino acid sequence having at least 80% identity to a sequence selected from the group consisting of the polypeptides referenced in Table 16, rows 2-698, columns L and M.


In some embodiments, the LmuB polypeptide comprises the amino acid sequence having at least 80% identity to a sequence selected from the group consisting of the polypeptides referenced in Table 16, rows 2-698, columns L and M. In some embodiments, the LmuB polypeptide comprises the amino acid sequence having at least 80% identity within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 16, rows 2-698, columns L and M.


In some embodiments, the LmuB polypeptide comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polypeptides referenced in Table 16, rows 2-698, columns L and M. In some embodiments, the LmuB polypeptide comprises the amino acid sequence having at least 80%, 85%, 90%, 95% homology within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 16, rows 2-698, columns L and M. In some embodiments, the LmuB polypeptide comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polypeptides referenced in Table 16, rows 2-698, columns L and M. In some embodiments, the LmuB polypeptide comprises the amino acid sequence having at least 80%, 85%, 90%, 95% identity within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 16, rows 2-698, columns L and M. In some embodiments, the LmuB polypeptide comprises an amino acid sequence selected from the group consisting of the polypeptides referenced in Table 16, rows 2-698, columns L and M.


In some embodiments, the LmuB polypeptide comprises an amino acid sequence encoded by a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polynucleotides referenced in Table 16, rows 2-698, columns L and N. In some embodiments, the LmuB polypeptide comprises the amino acid sequence encoded by a nucleic acid sequence having at least 80%, 85%, 90%, 95% homology within similar domain regions within a sequence selected from the group consisting of the polynucleotides referenced in Table 16, rows 2-698, columns L and N. In some embodiments, the LmuB polypeptide comprises an amino acid sequence encoded by a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polynucleotides referenced in Table 16, rows 2-698, columns L and N. In some embodiments, the LmuB polypeptide comprises the amino acid sequence encoded by a nucleic acid sequence having at least 80%, 85%, 90%, 95% homology within similar domain regions within a sequence selected from the group consisting of the polynucleotides referenced in Table 16, rows 2-698, columns L and N. In some embodiments, the LmuB polypeptide comprises an amino acid sequence encoded from a nucleic acid sequence selected from the group consisting of the polynucleotides referenced in Table 16, rows 2-698, columns L and N.


In some embodiments, the nucleic acid sequence of a lmuB gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polynucleotides referenced in Table 16, rows 2-698, columns L and N. In some embodiments, the lmuB gene comprises a nucleic acid sequence having at least 80%, 85%, 90%, 95% homology within encoded similar domain regions in comparison with nucleotide sequence encoding these domain within a sequence selected from the group consisting of the polynucleotides referenced in Table 16, rows 2-698, columns L and N. In some embodiments, the nucleic acid sequence of a lmuB gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polynucleotides referenced in Table 16, rows 2-698, columns L and N. In some embodiments, the lmuB gene comprises a nucleic acid sequence having at least 80%, 85%, 90%, 95% identity within encoded similar domain regions in comparison with nucleotide sequence encoding these domain within a sequence selected from the group consisting of the polynucleotides referenced in Table 16, rows 2-698, columns L and N. In some embodiments, the lmuB gene homolog encodes a polypeptide comprising a RecF/RecN/SMC N-terminal domain. In some embodiments, the nucleic acid sequence of a lmuB gene comprises a nucleic acid sequence selected from the group consisting of the polynucleotides referenced in Table 16, rows 2-698, columns L and N.


A skilled artisan would appreciate that the terms a “functional portion of a Defense System VIII component” or “functional fragment of Defense System VIII component” or “functional portion of a Lamassu defense system component” or “functional fragment of Lamassu defense system component” refers to a functional portion of a Lamassu polynucleotide or polypeptide, as disclosed herein, which expression is sufficient to elicit an anti-phage activity alone or in combination with the at least one of the other Lamassu polynucleotides or polypeptides disclosed herein or functional portions thereof.


The terms “LmuA”, “LmuB”, “lmuA” and “lmuB”, also refer to functional LmuA, LmuB, lmuA and lmuB, homologs, which exhibit the desired activity (i.e., conferring phage resistance). Such homologs can be, for example, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical or homologous to the polypeptide sequences referenced in Table 16 rows 2-698 columns H and I and L and M, respectively, or 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical or homologous to the polynucleotide sequences referenced in Table 16 rows 2-698 columns H and J and L and N, respectively, respectively. In some embodiments, such homologs comprise at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% homology or identity within similar domain regions of the polypeptide sequences referenced in Table 16 rows 2-698 columns H and I and L and M, respectively, or 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity or homology within nucleotide sequences encoding similar domain regions to the polynucleotide sequences referenced in Table 16 rows 2-698 columns H and J and L and N, respectively.


Table 16 presents embodiments of components of Defense System VIII that may be found in a diverse array of bacteria and archaea genomes (referenced in Table 18). Table 16 presents embodiments of nucleic acid sequences encoding gene cassettes of Defense System VIII (referenced in Table 18).


The Kiwa Defense System


In some embodiments, a defense system disclosed herein comprises a Kiwa anti-phage defense system. (Table 17)


In some embodiments, a Kiwa defense system provides a host cell with resistance to entry of foreign nucleic acid invasion. In some embodiments, a host cell expressing a functional Kiwa defense system (Defense System IX) provides the host cell resistance foreign nucleic acid invasion.


In some embodiments, a Kiwa defense system provides a host cell with resistance to at least one phage.


In some embodiments, a microbial cell comprising a Kiwa defense system protects the microbial cell from phage infection. In some embodiments, a microbial cell expressing a Kiwa defense system protects the microbial cell from phage infection. In some embodiments, a microbial cell expressing a functional Kiwa defense system protects the microbial cell from phage infection. In some embodiments, a bacterial cell comprising a Kiwa defense system protects the bacterial cell from phage infection. In some embodiments, a bacterial cell expressing a Kiwa defense system protects the bacterial cell from phage infection. In some embodiments, a bacterial cell expressing a functional Kiwa defense system protects the bacterial cell from phage infection.


In some embodiments, a Kiwa defense system provides a host cell with resistance to a plasmid.


As used herein, the term “a Kiwa anti-phage defense system” may be used interchangeably with the term “a Defense System IX”, having all the same meanings and qualities. A skilled artisan would appreciate that the term “Kiwa system” may be used interchangeably in some embodiments with “Kiwa defense system”, and “Kiwa the defense system”, “Kiwa anti-phage system”, having all the same meanings and qualities.


In some embodiments, a microbial species does not comprise an endogenous Defense System IX. In some embodiments, a microbial species does not express an endogenous Defense System IX. In some embodiments, a microbial species does not express an endogenous functional Defense System IX.


In some embodiments, a bacterial species does not comprise an endogenous Defense System IX. In some embodiments, a bacterial species does not express an endogenous Defense System IX. In some embodiments, a bacterial species does not express an endogenous functional Defense System IX.


A Kiwa defense system comprises, in some embodiments, a nucleic acid construct comprising a nucleic acid sequence encoding a KwaA polypeptide and a KwaB polypeptide comprising a pfam16162 domain or a DUF4868 domain or a combination thereof. In some embodiments, a Kiwa defense system comprises, a nucleic acid construct comprising a nucleic acid sequence encoding a KwaA polypeptide and a KwaB polypeptide comprising a pfam16162 domain or a DUF4868 domain or a combination thereof, wherein said KwaA polypeptide is encoded by a gene positioned within 5 genes of a gene encoding a KwaB polypeptide in the genome of a prokaryotic cell. In some embodiments, a Kiwa defense system comprises a nucleic acid construct comprising a nucleic acid sequence comprising a kwaA gene and a kwaB gene.


In some embodiments, a Kiwa defense system comprises, a KwaA polypeptide and a KwaB polypeptide comprising a pfam16162 domain or a DUF4868 domain or a combination thereof. In some embodiments, a Kiwa defense system comprises, a KwaA polypeptide and a KwaB polypeptide comprising a pfam16162 domain or a DUF4868 domain or a combination thereof, wherein said KwaA polypeptide is encoded by a gene positioned within 5 genes of a gene encoding a KwaB polypeptide in the genome of a prokaryotic cell. In some embodiments, a Kiwa defense system comprises KwaA polypeptide and a KwaB polypeptide.


A Kiwa defense system comprises, in some embodiments, a nucleic acid construct comprising a nucleic acid sequence encoding a KwaA polypeptide and a KwaB polypeptide comprising a pfam16162 domain or DUF4868 domain or a combination thereof. In some embodiments, a Kiwa defense system comprises a nucleic acid construct comprising a nucleic acid sequence encoding a KwaA polypeptide and a KwaB polypeptide.


In some embodiments, a Defense System IX comprises a KwaA polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 17 rows 2-935 columns H and I; or a KwaB polypeptide comprising a pfam16162 domain or a DUF4868 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 17 rows 2-935 columns H and I; or a combination thereof.


In some embodiments, a Defense System IX comprises at least two different polypeptide components selected from a KwaA polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 17 rows 2-935 columns H and I; and a KwaB polypeptide comprising a pfam16162 domain or a DUF4868 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 17 rows 2-935 columns H and I.


In some embodiments, a Kiwa defense system having an anti-phage activity comprises a nucleic acid construct comprising a nucleic acid sequence encoding a KwaA polypeptide and a KwaB polypeptide. In some embodiments, a Kiwa defense system having an anti-phage activity comprises a nucleic acid construct comprising a nucleic acid sequence comprising a kwaA gene and a kwaB gene.


In some embodiments, the Kiwa anti-phage defense system comprises a nucleic acid construct comprising nucleic acid sequences encoding a cassette comprising kwaA and kwaB genes.


In some embodiments, a Kiwa (Defense System IX) gene cassette comprises the nucleic acid sequence:












(SEQ ID NO: 3; construct 2 in Table 4)
















1
taatggtctt ccttccattg gtatctcgtg agtatacaag caatatcgaa tcggcaaata





61
tactcattag tatactcaca agcctgttga tgtgggttgg ttcaggttga cttcagttga





121
ggagaaaagc tggaaaagcc ttgcgtggcg cggatttcag gcataaaaaa agacctcagt





181
tgaggtctat ttacatactt ttggtgcgaa ggccggactc gaacatcgca actatcctta





241
tgatcttaat ggattaaaaa ttaccatatt ggtcatgata ccatcattga taccatcaga





301
cccgattgat gataatcgaa cagtaataaa atatgactaa acaatttatg cttcaacata





361
agattgaatg ctttgatcta ccattttaat gcagtggaaa aatttttaac acaatactta





421
agaaaaataa tttcatataa aaactacatt tcatttcata tagttaacac accaaaaaca





481
actgtatata aacccagtaa aaaatggtag aatcactatt gtgttcaatt gttgaacatt





541
tataatacat ttgtcggata ggggggtgtt tatgcaaagg aacacataca acaaagtagg





601
tctatacatc ctatctttag ctatgctttt tgtttttatt attatcctga ctgccaaaat





661
ccccttttgc ttcacttcgg attgtagctt cataggtttg aagaaacttg tattaacaaa





721
tattgttcct attgtttgct ttgtattttt tctatttagt atttattttt ataatagatt





781
aaaaaacata acaaaataca atggacaaga tagcgttaaa ataacatcat gtcaaagcga





841
aagctatgaa agtttaacat tcttagcaac atacattgta ccttttatgg ggtttagttt





901
tgaagacatg caaaagaata tagcatatct tttgcttgta gtagtaatag gcattatttt





961
tattaaaaca gacaagtatt atgcgaatcc aactttagct ctgtttggct ttaaactata





1021
cagggtaaat atactacacc caggaagtgg agaaacaaaa aatctgatag ctatttcaaa





1081
tgatgtatta aaagtggacg ataatgttta ttatagtttc tttgacgaat ttgtttttat





1141
agcaaggaaa aaaatatgac tactcagcag ttaaaagaaa aaatttcaaa aataattgat





1201
aactttagcg gaatcagggt tgtatttact actactgcta atgaactaaa gctttccaga





1261
attgaaggga gtgcattaaa tagcatagct gaagggttta ttgacaaaat caaagaagac





1321
attataaata atgaagatct cacctcaccc ttgctgtcca attttgatga tagaaaaaat





1381
gccttgttta aatttgatta cgaacaatat cctgaagaat ttaacaaaat cactcaggcc





1441
atcgctatcc ctcctaactc acaagattat tataaccctt taaataaatt cacagatgtg





1501
aaaggaatta taattttaat aagtggagat aacaaatgcc tggctcttta taaaaacaaa





1561
actaaccttg cagtattgag aaatagcaga aaaatgttta atttagtccc tgaccctgat





1621
ggatacttga aacaactccc taatgagata ttacggttag atttcaatta tgatctattt





1681
tcaattggtg aggattttta cattaaaaat cacaagactc ttgaaactca aatgaaattt





1741
catcaagtga ttgaagccca agcagttatt gctttaaatt ctttacggga ttcactacta





1801
attgaagaca tatcaggttt agaaaagagt tcgagagaaa tttcattcgc tagaaagttg





1861
gcaaaaatct ccaaacattc tcctgttttg gggaaaatag atactaaaac aattattgat





1921
tatgtatccc aacataaata tttatctgca atacttcaga ttaatgaagc gggagataag





1981
ttattaatta aaaccaagac atcacagaag catttcatta aactcatgag cgatgattat





2041
ttacaatcag atctaaccaa aataatatac atgagcatag caaaagacag attagatgaa





2101
tagaacttta agtagaagtg acaaatatta taaaccattc ttgaaatata tttgtcacta





2161
ttactaat.









The coding regions for each of the kwaA and kwaB gene sequences within this embodiment of a Kiwa cassette (SEQ ID NO: 3) are as follows: nucleotides 572-1159 encode an embodiment of a KwaA polypeptide, and nucleotides 1156-2103 encode an embodiment of a KwaB polypeptide.


In some embodiments, a Defense System IX comprising a KwaA polypeptide and a KwaB polypeptide is encoded by the nucleic acid sequence set forth in SEQ ID NO: 3. In some embodiments, a Defense System IX comprising a KwaA polypeptide and a KwaB polypeptide, is encoded by a nucleic acid sequence having at least 80% homology to the sequence set forth in SEQ ID NO: 3. In some embodiments, a Defense System IX comprising a KwaA polypeptide and a KwaB polypeptide, is encoded by a nucleic acid sequence having at least 85% homology, or 90% homology, or 95% homology, or 97% homology, or 98% homology, or 99% homology to the sequence set forth in SEQ ID NO: 3. In some embodiments, a Defense System IX comprising a KwaA polypeptide and a KwaB polypeptide, is encoded by a nucleic acid sequence having at least 80% identity to the sequence set forth in SEQ ID NO: 3. In some embodiments, a Defense System IX comprising a KwaA polypeptide and a KwaB polypeptide, is encoded by a nucleic acid sequence having at least 85% identity, or 90% identity, or 95% identity, or 97% identity, or 98% identity, or 99% identity to the sequence set forth in SEQ ID NO: 3.


In some embodiments, a construct comprising the Kiwa defense system encodes one component of the defense system, whereby multiple constructs may be used to assemble the functional defense system. In some embodiments, the components of a Kiwa defense system comprise genes kwaA and kwaB. In some embodiments, the components of a Kiwa defense system consist of genes kwaA and kwaB. In some embodiments, the components of a Kiwa defense system comprise nucleic acid sequences encoding a KwaA polypeptide and a KwaB polypeptide. In some embodiments, the components of a Kiwa defense system consist of nucleic acid sequences encoding a KwaA polypeptide and a KwaB polypeptide.


In some embodiments, a construct comprising the Kiwa defense system encodes one component of the defense system, whereby a second construct may be used to assemble the functional defense system. In some embodiments, a construct comprising the Kiwa defense system encodes one component of the defense system, whereby additional constructs may be used to assemble the functional defense system. For example, in some embodiments each of KwaA and KwaB may be encoded by nucleic acid sequences comprised in different constructs, wherein expression of the combination of constructs produces a functional Kiwa defense system.


In some embodiments, the components making up a functional Kiwa anti-phage defense system comprise a KwaA polypeptide and a KwaB polypeptide, each encoded by a kwaA and a kwaB gene, respectively.


In some embodiments, a Kiwa defense system having an anti-phage activity comprise a nucleic acid encoding a KwaA polypeptide. In some embodiments, a Kiwa defense system having an anti-phage activity comprise a nucleic acid encoding a KwaA polypeptide and a KwaB polypeptide.


In some embodiments, a Kiwa defense system having an anti-phage activity comprise a nucleic acid comprising a kwaA gene. In some embodiments, a Kiwa defense system having an anti-phage activity comprise a nucleic acid comprising a kwaA gene and a kwaB gene.


In some embodiments, a Kiwa defense system having an anti-phage activity comprises a nucleic acid construct comprising nucleic acids encoding polypeptides in a set order. In one embodiment, the 5′ to 3′ order of polypeptides encoded is KwaA and KwaB. In some embodiments the 5′ to 3′ order of polypeptides does not affect the anti-phage activity. In some embodiments the 5′ to 3′ order of polypeptides does affect the anti-phage activity.


In some embodiments, the 5′ to 3′ order of polypeptides is random, for example any order of KwaA and KwaB.


In some embodiments, a Kiwa defense system having an anti-phage activity comprises a nucleic acid construct comprising genes in a set order. In some embodiment, the 5′ to 3′ order of genes is kwaA and kwaB. In some embodiment, the 5′ to 3′ order of genes in a Kiwa defense system is not kwaA and kwaB. In some embodiments the 5′ to 3′ order of genes does not affect the anti-phage activity. In some embodiments the 5′ to 3′ order of genes does affect the anti-phage activity.


In some embodiments, the 5′ to 3′ order of genes is random, for example any order of kwaA and kwaB.


In some embodiments, the Kiwa system (Defense System IX) composition and order is as shown in FIG. 3B.


In some embodiments, a Kiwa defense system having an anti-phage activity originates from a microbial genome, for example a bacterial or an archaeal genome (Table 17). A skilled artisan would appreciate that the Kiwa system is not present in the majority of bacteria and or archaea species.


In some embodiments, a functional Kiwa defense system comprises a construct comprising nucleic acid sequences encoding polypeptides, wherein the nucleic acid sequence encoding each polypeptide may originate from a different microbial species. For example, the source of the nucleic acid sequence encoding a KwaA polypeptide may be one microbial species, while the source of the nucleic acid sequence encoding a KwaB polypeptide may be a different microbial species. In some embodiments, a functional Kiwa defense system comprises a non-naturally occurring combination of polypeptide components. In some embodiments, a functional Kiwa defense system comprises a combination of at least two polypeptides that do not naturally occur together.


In some embodiments, a functional Kiwa defense system comprises a construct comprising nucleic acid sequences encoding polypeptides, wherein the nucleic acid sequence encoding each polypeptide may originate from a different bacterial species. For example, the source of the nucleic acid sequence encoding a KwaA polypeptide may be one bacterial species, while the source of the nucleic acid sequence encoding a KwaB polypeptide may be a different bacterial species.


In some embodiments, the source of the nucleic acid encoding a KwaA polypeptide and a KwaB polypeptide is the same. In some embodiments, the source of the nucleic acid encoding a KwaA polypeptide and a KwaB polypeptide is the not the same. In some embodiments, the source of the nucleic acid sequence of any of the components of a Kiwa defense system comprises any of the species listed in Table 17.


In some embodiments, a Kiwa defense system having an anti-phage activity comprises a nucleic acid construct comprising non-coding regions between the nucleic acid sequences encoding the polypeptides. In some embodiments, the non-coding regions between the nucleic acid sequences comprises nucleic acid sequence not naturally occurring in the microbial species of origin. In some embodiments, the non-coding regions between the nucleic acid sequences comprises nucleic acid sequence is the naturally occurring in the microbial species of origin.


In some embodiments, a Kiwa system disclosed herein comprises a multi-gene phage resistance system broadly distributed in microbial genomes, for example but not limited to bacteria and archaea. According to some embodiments, the Kiwa system components are located in a gene cluster (a cassette of genes) in a microbial cell genome. According to some embodiments, the Kiwa system components are located in close proximity (e.g. positioned within 20 genes, 10 genes, 5 genes or less one from the other) in a genome of a prokaryotic cell. According to some embodiments the prokaryotic cell expresses an endogenous Kiwa defense system. According to some embodiments, the prokaryotic cell expresses an endogenous functional Kiwa defense system. According to some embodiments, the species of prokaryotic cell is selected from the group consisting of the species listed in Table 17. According to some embodiments a prokaryotic cell expresses a non-endogenous Kiwa defense system. According to some embodiments, a prokaryotic cell expresses a non-endogenous functional Kiwa defense system. According to some embodiments, the species of prokaryotic cell expressing a non-endogenous functional Kiwa defense system is selected from the group consisting of the species listed in Table 17.


In some embodiments, Kiwa defense system components comprise KwaA and KwaB polypeptides. In some embodiments, a Kiwa defense system components comprise functional portions of KwaA and KwaB polypeptides. In some embodiments, the Kiwa defense system components are encoded by kwaA and kwaB genes.


Non-limiting embodiments of endogenous Kiwa systems and the respective location of their components are provided in Table 17 herein.


In some embodiments, the components of a Kiwa system may be identified by the presence of similar domains present within each component. In some embodiments, domains comprise pfam domains and or clusters of orthologous groups (COG) domains.


In some embodiments, a Defense System IX comprises a membrane associated complex.


In some embodiments, the term “KwaA” refers to the polynucleotide or expression product e.g., the polypeptide encoded by the kwaA gene. In some embodiments, the term “KwaA” refers to a KwaA polypeptide. In some embodiments, a KwaA polypeptide comprises transmembrane helices. In some embodiments, a kwaA gene encodes a polypeptide comprising transmembrane helices.


In some embodiments, KwaA polypeptide is encoded by a gene positioned within 5-60 genes of a gene encoding a KwaB polypeptide in a genome of a prokaryotic cell. In some embodiments, KwaA polypeptide is encoded by a gene positioned within 5 genes upstream (5′) or downstream (3′) to a gene encoding a KwaB polypeptide in a genome of a prokaryotic cell. In some embodiments, KwaA polypeptide is encoded by a gene positioned within 5 genes upstream (5′) and downstream (3′) to a gene encoding a KwaB polypeptide in a genome of a prokaryotic cell.


In some embodiments, KwaA and KwaB are encoded by genes positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, KwaA and KwaB are encoded by genes positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, nucleic acid encoding additional copies of KwaB is positions 3′ of the nucleic acid sequence first encoding a KwaB polypeptide.


In some embodiments, kwaA and kwaB genes are positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, kwaA and kwaB, genes are positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell.


In some embodiments, a KwaA polypeptide is about 194 amino acids long (median gene size).


In some embodiments, the KwaA polypeptide comprises the amino acid sequence having at least 80% homology to a sequence selected from the group consisting of the polypeptides referenced in Table 17, rows 2-935, columns H and I. In some embodiments, the KwaA polypeptide comprises the amino acid sequence having at least 80% homology within similar domain regions to a sequence selected from the group consisting of the polypeptides referenced in Table 17, rows 2-935, columns H and I. In some embodiments, a KwaA homolog comprises transmembrane helices. In some embodiments, the KwaA polypeptide comprises a homolog of a polypeptide having the amino acid sequences set forth in the polypeptides referenced in Table 17, rows 2-935, columns H and I.


In some embodiments, the KwaA polypeptide comprises the amino acid sequence having at least 80% identity to a sequence selected from the group consisting of the polypeptides referenced in Table 17, rows 2-935, columns H and I. In some embodiments, the KwaA polypeptide comprises the amino acid sequence having at least 80% identity within similar domain regions to a sequence selected from the group consisting of the polypeptides referenced in Table 17, rows 2-935, columns H and I.


In some embodiments, the KwaA polypeptide comprises the amino acid sequence having at least 80% identity to a sequence selected from the group consisting of the polypeptides referenced in Table 17, rows 2-935, columns H and I. In some embodiments, the KwaA polypeptide comprises the amino acid sequence having at least 80% identity within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 17, rows 2-935, columns H and I.


In some embodiments, the KwaA polypeptide comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polypeptides referenced in Table 17, rows 2-935, columns H and I. In some embodiments, the KwaA polypeptide comprises the amino acid sequence having at least 80%, 85%, 90%, 95% homology within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 17, rows 2-935, columns H and I. In some embodiments, the KwaA polypeptide comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polypeptides referenced in Table 17, rows 2-935, columns H and I. In some embodiments, the KwaA polypeptide comprises the amino acid sequence having at least 80%, 85%, 90%, 95% identity within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 17, rows 2-935, columns H and I. In some embodiments, the KwaA polypeptide comprises an amino acid sequence selected from the group consisting of the polypeptides referenced in Table 17, rows 2-935, columns H and I.


In some embodiments, the KwaA polypeptide comprises an amino acid sequence encoded by a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polynucleotides referenced in Table 17, rows 2-935, columns H and J. In some embodiments, the KwaA polypeptide comprises the amino acid sequence encoded by a nucleic acid sequence having at least 80%, 85%, 90%, 95% homology within similar domain regions within a sequence selected from the group consisting of the polynucleotides referenced in Table 17, rows 2-935, columns H and J. In some embodiments, the KwaA polypeptide comprises an amino acid sequence encoded by a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polynucleotides referenced in Table 17, rows 2-935, columns H and J. In some embodiments, the KwaA polypeptide comprises the amino acid sequence encoded by a nucleic acid sequence having at least 80%, 85%, 90%, 95% homology within similar domain regions within a sequence selected from the group consisting of the polynucleotides referenced in Table 17, rows 2-935, columns H and J. In some embodiments, the KwaA polypeptide comprises an amino acid sequence encoded from a nucleic acid sequence selected from the group consisting of the polynucleotides referenced in Table 17, rows 2-935, columns H and J.


In some embodiments, the nucleic acid sequence of a kwaA gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polynucleotides referenced in Table 17, rows 2-935, columns H and J. In some embodiments, the kwaA gene comprises a nucleic acid sequence having at least 80%, 85%, 90%, 95% homology within encoded similar domain regions in comparison with nucleotide sequence encoding these domain within a sequence selected from the group consisting of the polynucleotides referenced in Table 17, rows 2-935, columns H and J. In some embodiments, the nucleic acid sequence of a kwaA gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polynucleotides referenced in Table 17, rows 2-935, columns H and J. In some embodiments, the kwaA gene comprises a nucleic acid sequence having at least 80%, 85%, 90%, 95% identity within encoded similar domain regions in comparison with nucleotide sequence encoding these domain within a sequence selected from the group consisting of the polynucleotides referenced in Table 17, rows 2-935, columns H and J. In some embodiments, a kwaA gene homolog encodes a polypeptide comprising transmembrane helices. In some embodiments, the nucleic acid sequence of a kwaA gene comprises a nucleic acid sequence selected from the group consisting of the polynucleotides referenced in Table 17, rows 2-935, columns H and J.


As used herein, the term “KwaB” refers to the polynucleotide or expression product e.g., polypeptide encoded by the kwaB gene. In some embodiments, the term “KwaB” refers to a KwaB polypeptide. In some embodiments, the product of the kwaB gene comprises a pfam16162 domain. In some embodiments, the product of the kwaB gene comprises a DUF4868 domain.


In some embodiments, KwaB polypeptide is encoded by a gene positioned within 5-60 genes of a gene encoding a KwaA polypeptide in a genome of a prokaryotic cell. In some embodiments, KwaB polypeptide is encoded by a gene positioned within 5 genes upstream (5′) or downstream (3′) to a gene encoding a KwaA polypeptide in a genome of a prokaryotic cell. In some embodiments, KwaB polypeptide is encoded by a gene positioned within 5 genes upstream (5′) and downstream (3′) to a gene encoding a KwaA polypeptide in a genome of a prokaryotic cell.


In some embodiments, KwaA and KwaB are encoded by genes positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments KwaA and KwaB are encoded by genes positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell.


In some embodiments, a KwaB polypeptide is about 315 amino acids long (median gene size).


In some embodiments, the KwaB polypeptide comprises the amino acid sequence having at least 80% homology to a sequence selected from the group consisting of the polypeptides referenced in Table 17, rows 2-935, columns L and M. In some embodiments, the KwaB polypeptide comprises the amino acid sequence having at least 80% homology within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 17, rows 2-935, columns L and M. In some embodiments, the KwaB polypeptide comprises a homolog of a polypeptide having the amino acid sequences set forth in the polypeptides referenced in Table 17, rows 2-935, columns L and M.


In some embodiments, the KwaB polypeptide comprises the amino acid sequence having at least 80% identity to a sequence selected from the group consisting of the polypeptides referenced in Table 17, rows 2-935, columns L and M. In some embodiments, the KwaB polypeptide comprises the amino acid sequence having at least 80% identity within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 17, rows 2-935, columns L and M.


In some embodiments, the KwaB polypeptide comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polypeptides referenced in Table 17, rows 2-935, columns L and M. In some embodiments, the KwaB polypeptide comprises the amino acid sequence having at least 80%, 85%, 90%, 95% homology within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 17, rows 2-935, columns L and M. In some embodiments, the KwaB polypeptide comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polypeptides referenced in Table 17, rows 2-935, columns L and M. In some embodiments, the KwaB polypeptide comprises the amino acid sequence having at least 80%, 85%, 90%, 95% identity within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 17, rows 2-935, columns L and M. In some embodiments, the KwaB polypeptide comprises an amino acid sequence selected from the group consisting of the polypeptides referenced in Table 17, rows 2-935, columns L and M.


In some embodiments, the KwaB polypeptide comprises an amino acid sequence encoded by a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polynucleotides referenced in Table 17, rows 2-935, columns L and N. In some embodiments, the KwaB polypeptide comprises the amino acid sequence encoded by a nucleic acid sequence having at least 80%, 85%, 90%, 95% homology within similar domain regions within a sequence selected from the group consisting of the polynucleotides referenced in Table 17, rows 2-935, columns L and N. In some embodiments, the KwaB polypeptide comprises an amino acid sequence encoded by a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polynucleotides referenced in Table 17, rows 2-935, columns L and N. In some embodiments, the KwaB polypeptide comprises the amino acid sequence encoded by a nucleic acid sequence having at least 80%, 85%, 90%, 95% homology within similar domain regions within a sequence selected from the group consisting of the polynucleotides referenced in Table 17, rows 2-935, columns L and N. In some embodiments, the KwaB polypeptide comprises an amino acid sequence encoded from a nucleic acid sequence selected from the group consisting of the polynucleotides referenced in Table 17, rows 2-935, columns L and N.


In some embodiments, the nucleic acid sequence of a kwaB gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polynucleotides referenced in Table 17, rows 2-935, columns L and N. In some embodiments, the kwaB gene comprises a nucleic acid sequence having at least 80%, 85%, 90%, 95% homology within encoded similar domain regions in comparison with nucleotide sequence encoding these domain within a sequence selected from the group consisting of the polynucleotides referenced in Table 17, rows 2-935, columns L and N. In some embodiments, the nucleic acid sequence of a kwaB gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polynucleotides referenced in Table 17, rows 2-935, columns L and N. In some embodiments, the kwaB gene comprises a nucleic acid sequence having at least 80%, 85%, 90%, 95% identity within encoded similar domain regions in comparison with nucleotide sequence encoding these domain within a sequence selected from the group consisting of the polynucleotides referenced in Table 17, rows 2-935, columns L and N. In some embodiments, the nucleic acid sequence of a kwaB gene comprises a nucleic acid sequence selected from the group consisting of the polynucleotides referenced in Table 17, rows 2-935, columns L and N.


A skilled artisan would appreciate that the terms a “functional portion of a Defense System IX component” or “functional fragment of Defense System IX component” or “functional portion of a Kiwa defense system component” or “functional fragment of Kiwa defense system component” refers to a functional portion of a Kiwa polynucleotide or polypeptide, as disclosed herein, which expression is sufficient to elicit an anti-phage activity alone or in combination with the at least one of the other Kiwa polynucleotides or polypeptides disclosed herein or functional portions thereof.


The terms “KwaA”, “KwaB”, “kwaA” and “kwaB”, also refer to functional KwaA, KwaB, kwaA and kwaB homologs, which exhibit the desired activity (i.e., conferring phage resistance). Such homologs can be, for example, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical or homologous to the polypeptide sequences referenced in Table 17 rows 2-935 columns H and I and L and M, respectively, or 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical or homologous to the polynucleotide sequences referenced in Table 17 rows 2-935 columns H and J and L and N, respectively, respectively. In some embodiments, such homologs comprise at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% homology or identity within similar domain regions of the polypeptide sequences referenced in Table 17 rows 2-935 columns H and I and L and M, respectively, or 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity or homology within nucleotide sequences encoding similar domain regions to the polynucleotide sequences referenced in Table 17 rows 2-935 columns H and J and L and N, respectively.


Table 17 presents embodiments of components of Defense System IX that may be found in a diverse array of bacteria and archaea genomes (referenced in Table 18). Table 17 presents embodiments of nucleic acid sequences encoding gene cassettes of Defense System IX (referenced in Table 18).


The Wadjet Defense System


In some embodiments, a defense system disclosed herein comprises a Wadjet anti-plasmid defense system. (Table 11)


In some embodiments, a Wadjet defense system provides a host cell with resistance to entry of foreign nucleic acid invasion. In some embodiments, a host cell expressing a functional Wadjet defense system (Defense System Xa; Defense System Xb; or Defense System Xc) provides the host cell resistance foreign nucleic acid invasion.


In some embodiments, a Wadjet defense system provides a host cell with reduced efficiency of transformation of plasmids. In some embodiments, a Wadjet defense system provides a host cell with protective activity against plasmids.


In some embodiments, a Type I Wadjet defense system provides a host cell with reduced efficiency of transformation of plasmids. In some embodiments, a Wadjet Type I defense system provides a host cell with protective activity against plasmids. In some embodiments, a Type II Wadjet defense system provides a host cell with reduced efficiency of transformation of plasmids. In some embodiments, a Wadjet Type II defense system provides a host cell with protective activity against plasmids. In some embodiments, a Type III Wadjet defense system provides a host cell with reduced efficiency of transformation of plasmids. In some embodiments, a Wadjet Type III defense system provides a host cell with protective activity against plasmids.


In some embodiments, expression of a Wadjet Type I defense system in microbial cells protects the microbial cell from plasmid entry, reducing or eliminating plasmid transformation. In some embodiments, expression of a Wadjet Type II defense system in a microbial cell protects the microbial cell from plasmid entry, reducing or eliminating plasmid transformation. In some embodiments, expression of a Wadjet Type III defense system in a microbial cell protects the microbial cell from plasmid entry, reducing or eliminating plasmid transformation.


In some embodiments, expression of a Wadjet Type I defense system in bacterial cell protects the bacterial cell from plasmid entry, reducing or eliminating plasmid transformation. In some embodiments, expression of a Wadjet Type II defense system in bacteria protects the bacterial cell from plasmid entry, reducing or eliminating plasmid transformation. In some embodiments, expression of a Wadjet Type III defense system in bacteria protects the bacterial cell from plasmid entry, reducing or eliminating plasmid transformation.


In some embodiments, a microbial cell comprising a Wadjet Type I defense system protects the microbial cell from plasmid entry, reducing or eliminating plasmid transformation. In some embodiments, a microbial cell expressing a Wadjet Type I defense system protects the microbial cell from plasmid entry, reducing or eliminating plasmid transformation. In some embodiments, a microbial cell expressing a functional Wadjet Type I defense system protects the microbial cell from plasmid entry, reducing or eliminating plasmid transformation.


In some embodiments, a bacterial cell comprising a Wadjet Type I defense system protects the bacterial cell from plasmid entry, reducing or eliminating plasmid transformation. In some embodiments, a bacterial cell expressing a Wadjet Type I defense system protects the bacterial cell from plasmid entry, reducing or eliminating plasmid transformation. In some embodiments, a bacterial cell expressing a functional Wadjet Type I defense system protects the bacterial cell from plasmid entry, reducing or eliminating plasmid transformation.


In some embodiments, a microbial cell comprising a Wadjet Type II defense system protects the microbial cell from plasmid entry, reducing or eliminating plasmid transformation. In some embodiments, a microbial cell expressing a Wadjet Type II defense system protects the microbial cell from plasmid entry, reducing or eliminating plasmid transformation. In some embodiments, a microbial cell expressing a functional Wadjet Type II defense system protects the microbial cell from plasmid entry, reducing or eliminating plasmid transformation.


In some embodiments, a bacterial cell comprising a Wadjet Type II defense system protects the bacterial cell from plasmid entry, reducing or eliminating plasmid transformation. In some embodiments, a bacterial cell expressing a Wadjet Type II defense system protects the bacterial cell from plasmid entry, reducing or eliminating plasmid transformation. In some embodiments, a bacterial cell expressing a functional Wadjet Type II defense system protects the bacterial cell from plasmid entry, reducing or eliminating plasmid transformation.


In some embodiments, a microbial cell comprising a Wadjet Type III defense system protects the microbial cell from plasmid entry, reducing or eliminating plasmid transformation. In some embodiments, a microbial cell expressing a Wadjet Type III defense system protects the microbial cell from plasmid entry, reducing or eliminating plasmid transformation. In some embodiments, a microbial cell expressing a functional Wadjet Type III defense system protects the microbial cell from plasmid entry, reducing or eliminating plasmid transformation.


In some embodiments, a bacterial cell comprising a Wadjet Type III defense system protects the bacterial cell from plasmid entry, reducing or eliminating plasmid transformation. In some embodiments, a bacterial cell expressing a Wadjet Type III defense system protects the bacterial cell from plasmid entry, reducing or eliminating plasmid transformation. In some embodiments, a bacterial cell expressing a functional Wadjet Type III defense system protects the bacterial cell from plasmid entry, reducing or eliminating plasmid transformation.


In some embodiments, a Wadjet defense system provides a host cell with resistance to at least one phage. In some embodiments, a Wadjet Type I defense system provides a host cell with resistance to at least one phage. In some embodiments, a Wadjet Type II defense system provides a host cell with resistance to at least one phage. In some embodiments, a Wadjet Type III defense system provides a host cell with resistance to at least one phage.


In some embodiments, a Wadjet defense system (Defense system Xa, Xb, or Xc) provides a host cell with resistance to entry of conjugative elements. In some embodiments, a host cell expressing a function Wadjet defense system (Defense System Xa, Xb, or Xc) provides the host cell resistance from entry of conjugative elements.


As used herein, the term “a Wadjet anti-plasmid defense system” may be used interchangeably with the term “a Defense System X”, having all the same meanings and qualities. Further, in some embodiments, the term “a Wadjet Type I defense system” may be used interchangeably with the term “a Defense System Xa”, having all the same meanings and qualities, and in some embodiments, the term “a Wadjet Type II defense system” may be used interchangeably with the term “a Defense System Xb”, having all the same meanings and qualities, and in some embodiments, the term “a Wadjet Type III defense system” may be used interchangeably with the term “a Defense System Xc”, having all the same meanings and qualities.


A skilled artisan would appreciate that the term “Wadjet system” may be used interchangeably in some embodiments with “Wadjet defense system”, “Wadjet the defense system”, “Wadjet defense system”, “Wadjet anti-plasmid system”, “Wadjet Type I defense system”, “Wadjet Type II defense system”, “Wadjet Type III defense system”, “Defense System Xa”, “Defense System Xb”, and “Defense System Xc”.


In some embodiments, a microbial species does not comprise an endogenous Defense System X. In some embodiments, a microbial species does not express an endogenous Defense System X. In some embodiments, a microbial species does not express an endogenous functional Defense System X.


In some embodiments, a bacterial species does not comprise an endogenous Defense System X. In some embodiments, a bacterial species does not express an endogenous Defense System X. In some embodiments, a bacterial species does not express an endogenous functional Defense System X.


In some embodiments, a microbial species does not comprise an endogenous Defense System Xa. In some embodiments, a microbial species does not express an endogenous Defense System Xa. In some embodiments, a microbial species does not express an endogenous functional Defense System Xa.


In some embodiments, a bacterial species does not comprise an endogenous Defense System Xa. In some embodiments, a bacterial species does not express an endogenous Defense System Xa. In some embodiments, a bacterial species does not express an endogenous functional Defense System Xa.


In some embodiments, a microbial species does not comprise an endogenous Defense System Xb. In some embodiments, a microbial species does not express an endogenous Defense System Xb. In some embodiments, a microbial species does not express an endogenous functional Defense System Xb.


In some embodiments, a bacterial species does not comprise an endogenous Defense System Xb. In some embodiments, a bacterial species does not express an endogenous Defense System Xb. In some embodiments, a bacterial species does not express an endogenous functional Defense System Xb.


In some embodiments, a microbial species does not comprise an endogenous Defense System Xc. In some embodiments, a microbial species does not express an endogenous Defense System Xc. In some embodiments, a microbial species does not express an endogenous functional Defense System Xc.


In some embodiments, a bacterial species does not comprise an endogenous Defense System Xc. In some embodiments, a bacterial species does not express an endogenous Defense System Xc. In some embodiments, a bacterial species does not express an endogenous functional Defense System Xc.


A Wadjet defense system (Defense System X) comprises, in some embodiments, a nucleic acid construct comprising a nucleic acid construct comprising a nucleic acid sequence encoding a JetA polypeptide comprising a pfam11855 domain or a DUF3375 domain or a pfam09660 domain or a DUF2397 domain or no known domain, or any combination thereof; a JetB polypeptide comprising a pfam13835 domain or a DUF4194 domain or a pfam09661 domain or a DUF2398 domain or no known domain, or any combination thereof; a JetC polypeptide comprising a pfam13555 domain or a pfam13558 domain or a COG4913 domain or a COG1196 domain, or a combination thereof; and a JetD polypeptide comprising a pfam11795 domain or a DUF3322 domain or a pfam09983 domain or a DUF2220 domain or a pfam11796 domain or a DUF3323 domain or a pfam09664 domain or a DUF2399 domain or a COG4924 domain, or any combination thereof.


A Wadjet defense system (Defense System X) comprises, in some embodiments, a JetA polypeptide comprising a pfam11855 domain or a DUF3375 domain or a pfam09660 domain or a DUF2397 domain or no known domain, or any combination thereof; a JetB polypeptide comprising a pfam13835 domain or a DUF4194 domain or a pfam09661 domain or a DUF2398 domain or no known domain, or any combination thereof; a JetC polypeptide comprising a pfam13555 domain or a pfam13558 domain or a COG4913 domain or a COG1196 domain, or a combination thereof; and a JetD polypeptide comprising a pfam11795 domain or a DUF3322 domain or a pfam09983 domain or a DUF2220 domain or a pfam11796 domain or a DUF3323 domain or a pfam09664 domain or a DUF2399 domain or a COG4924 domain, or any combination thereof.


In some embodiments, a Wadjet Type I defense system (Defense System Xa) comprises a nucleic acid construct comprising a nucleic acid construct comprising a nucleic acid sequence encoding a JetA polypeptide comprising a pfam11855 domain or a DUF3375 domain, or any combination thereof; a JetB polypeptide comprising a pfam13835 domain or a DUF4194 domain, or any combination thereof; a JetC polypeptide comprising a pfam13555 domain or a pfam13558 domain or a COG4913 domain, or a combination thereof; and a JetD polypeptide comprising a pfam11795 domain or a DUF3322 domain or a pfam09983 domain or a DUF2220 domain or a COG4924 domain, or any combination thereof. In some embodiments, a Wadjet Type I defense system comprises a nucleic acid construct comprising a nucleic acid sequence comprising a jetA, jetB, jetC, jetD gene.


In some embodiments, a Wadjet Type I defense system (Defense System Xa) comprises a JetA polypeptide comprising a pfam11855 domain or a DUF3375 domain, or any combination thereof; a JetB polypeptide comprising a pfam13835 domain or a DUF4194 domain, or any combination thereof; a JetC polypeptide comprising a pfam13555 domain or a pfam13558 domain or a COG4913 domain, or a combination thereof; and a JetD polypeptide comprising a pfam11795 domain or a DUF3322 domain or a pfam09983 domain or a DUF2220 domain or a COG4924 domain, or any combination thereof. In some embodiments, a Wadjet Type I defense system comprises a JetA polypeptide, a JetB polypeptide, a JetC polypeptide, and a JetD polypeptide.


In some embodiments, a Defense System Xa comprises a JetA polypeptide comprising a pfam11855 domain or a DUF3375 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2-2322 columns J and K; or a JetB polypeptide comprising a pfam13835 domain or a DUF4194 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2-2322 columns N and O; or a JetC polypeptide comprising a pfam13555 domain or a pfam13558 domain or a COG4913 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2-2322 columns R and S; or a JetD polypeptide comprising a pfam11795 domain or a DUF3322 domain or a pfam09983 domain or a DUF2220 domain or a COG4924 domain or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2-2322 columns V and W; or any combination thereof.


In some embodiments, a Defense System Xa comprises at least two different polypeptide components selected from a JetA polypeptide comprising a pfam11855 domain or a DUF3375 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2-2322 columns J and K; a JetB polypeptide comprising a pfam13835 domain or a DUF4194 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2-2322 columns N and O; a JetC polypeptide comprising a pfam13555 domain or a pfam13558 domain or a COG4913 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2-2322 columns R and S; and a JetD polypeptide comprising a pfam11795 domain or a DUF3322 domain or a pfam09983 domain or a DUF2220 domain or a COG4924 domain or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2-2322 columns V and W. In some embodiments, a Defense System Xa comprises at least three different polypeptide components selected from a JetA polypeptide comprising a pfam11855 domain or a DUF3375 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2-2322 columns J and K; a JetB polypeptide comprising a pfam13835 domain or a DUF4194 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2-2322 columns N and O; a JetC polypeptide comprising a pfam13555 domain or a pfam13558 domain or a COG4913 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2-2322 columns R and S; and a JetD polypeptide comprising a pfam11795 domain or a DUF3322 domain or a pfam09983 domain or a DUF2220 domain or a COG4924 domain or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2-2322 columns V and W. In some embodiments, a Defense System Xa comprises four different polypeptide components selected from a JetA polypeptide comprising a pfam11855 domain or a DUF3375 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2-2322 columns J and K; a JetB polypeptide comprising a pfam13835 domain or a DUF4194 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2-2322 columns N and O; a JetC polypeptide comprising a pfam13555 domain or a pfam13558 domain or a COG4913 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2-2322 columns R and S; and a JetD polypeptide comprising a pfam11795 domain or a DUF3322 domain or a pfam09983 domain or a DUF2220 domain or a COG4924 domain or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2-2322 columns V and W.


In some embodiments, a Wadjet Type II defense system (Defense System Xb) comprises a nucleic acid construct comprising a nucleic acid construct comprising a nucleic acid sequence encoding a JetAii polypeptide comprising a pfam09660 domain or a DUF2397 domain, or any combination thereof; a JetBii polypeptide comprising a pfam09661 domain or a DUF2398 domain, or any combination thereof; a JetCii polypeptide comprising a pfam13558 domain; and a JetDii polypeptide comprising a pfam11796 domain or a DUF3323 domain or a pfam09664 domain or a DUF2399 domain, or any combination thereof. In some embodiments, a Wadjet Type II defense system comprises a nucleic acid construct comprising a nucleic acid sequence comprising a jetAii, jetBii, jetCii, jetDii gene.


In some embodiments, a Wadjet Type II defense system (Defense System Xb) comprises a JetAii polypeptide comprising a pfam09660 domain or a DUF2397 domain, or any combination thereof; a JetBii polypeptide comprising a pfam09661 domain or a DUF2398 domain, or any combination thereof; a JetCii polypeptide comprising a pfam13558 domain; and a JetDii polypeptide comprising a pfam11796 domain or a DUF3323 domain or a pfam09664 domain or a DUF2399 domain, or any combination thereof. In some embodiments, a Wadjet Type II defense system comprises a JetAii polypeptide, a JetBii polypeptides, a JetCii polypeptide, and a JetDii polypeptide.


In some embodiments, a Defense System Xb comprises a JetAii polypeptide comprising a pfam09660 domain or a DUF2397 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2323-2844 columns J and K; or a JetBii polypeptide comprising a pfam09661 domain or a DUF2398 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2323-2844 columns N and O; or a JetCii polypeptide comprising a pfam13558 domain or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2323-2844 columns R and S; or a JetDii polypeptide comprising a pfam11796 domain or a DUF3323 domain or a pfam09664 domain or a DUF2399 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2323-2844 columns V and W; or any combination thereof.


In some embodiments, a Defense System Xb comprises at least two different polypeptide components selected from a JetAii polypeptide comprising a pfam09660 domain or a DUF2397 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2323-2844 columns J and K; a JetBii polypeptide comprising a pfam09661 domain or a DUF2398 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2323-2844 columns N and O; a JetCii polypeptide comprising a pfam13558 domain or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2323-2844 columns R and S; and a JetDii polypeptide comprising a pfam11796 domain or a DUF3323 domain or a pfam09664 domain or a DUF2399 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2323-2844 columns V and W. In some embodiments, a Defense System Xb comprises at least three different polypeptide components selected from a JetAii polypeptide comprising a pfam09660 domain or a DUF2397 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2323-2844 columns J and K; a JetBii polypeptide comprising a pfam09661 domain or a DUF2398 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2323-2844 columns N and O; a JetCii polypeptide comprising a pfam13558 domain or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2323-2844 columns R and S; and a JetDii polypeptide comprising a pfam11796 domain or a DUF3323 domain or a pfam09664 domain or a DUF2399 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2323-2844 columns V and W. In some embodiments, a Defense System Xb comprises four different polypeptide components selected from a JetAii polypeptide comprising a pfam09660 domain or a DUF2397 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2323-2844 columns J and K; a JetBii polypeptide comprising a pfam09661 domain or a DUF2398 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2323-2844 columns N and O; a JetCii polypeptide comprising a pfam13558 domain or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2323-2844 columns R and S; and a JetDii polypeptide comprising a pfam11796 domain or a DUF3323 domain or a pfam09664 domain or a DUF2399 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2323-2844 columns V and W.


In some embodiments, a Wadjet Type III defense system (Defense System Xc) comprises a nucleic acid construct comprising a nucleic acid construct comprising a nucleic acid sequence encoding a JetDiii polypeptide comprising a pfam09664 domain or a DUF2399 domain or a pfam09983 domain or a DUF2220 domain, or any combination thereof; a JetAiii polypeptide comprising no known domain; a JetBiii polypeptide comprising no known domain; and a JetCiii polypeptide comprising a COG1196 domain. In some embodiments, a Wadjet Type III defense system (Defense System Xc) comprises a nucleic acid construct comprising a nucleic acid construct comprising a nucleic acid sequence encoding a JetDiii polypeptide comprising a pfam09664 domain or a DUF2399 domain or a pfam09983 domain or a DUF2220 domain, or any combination thereof; a JetAiii polypeptide; a JetBiii polypeptide; and a JetCiii polypeptide comprising a COG1196 domain, said JetAiii polypeptide being encoded by a gene positioned within 5 genes of a gene encoding JetDiii and or JetCiii in a genome of a prokaryote, and said JetBiii polypeptide being encoded by a gene positioned within 5 genes of a gene encoding JetDiii and or JetCiii in the genome of the prokaryote. In some embodiments, a Wadjet Type III defense system comprises a nucleic acid construct comprising a nucleic acid sequence comprising a jetDiii, jetAiii, jetBiii, and a jetCiii gene.


In some embodiments, a Wadjet Type III defense system (Defense System Xc) comprises a JetDiii polypeptide comprising a pfam09664 domain or a DUF2399 domain or a pfam09983 domain or a DUF2220 domain, or any combination thereof; a JetAiii polypeptide; a JetBiii polypeptide; and a JetCiii polypeptide comprising a COG1196 domain. In some embodiments, a Wadjet Type III defense system (Defense System Xc) comprises a JetDiii polypeptide comprising a pfam09664 domain or a DUF2399 domain or a pfam09983 domain or a DUF2220 domain, or any combination thereof; a JetAiii polypeptide; a JetBiii polypeptide; and a JetCiii polypeptide comprising a COG1196 domain, said JetAiii polypeptide being encoded by a gene positioned within 5 genes of a gene encoding JetDiii and or JetCiii in a genome of a prokaryote, and said JetBiii polypeptide being encoded by a gene positioned within 5 genes of a gene encoding JetDiii and or JetCiii in the genome of the prokaryote. In some embodiments, a Wadjet Type III defense system comprises a JetDiii polypeptide, a JetAiii polypeptide, a JetBiii polypeptide, and a JetCiii polypeptide.


In some embodiments, a Defense System Xc comprises a JetAiii polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2845-3174 columns J and K; or a JetBiii polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2845-3174 columns N and O; or a JetCiii polypeptide comprising a COG1196 domain or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2845-3174 columns R and S; or a JetDiii polypeptide comprising a pfam09983 domain or a pfam09664 domain or a DUF2220 or a DUF2399 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2845-3174 columns V and W; or any combination thereof.


In some embodiments, a Defense System Xc comprises at least two different polypeptide components selected from a JetAiii polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2845-3174 columns J and K; a JetBiii polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2845-3174 columns N and O; a JetCiii polypeptide comprising a COG1196 domain or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2845-3174 columns R and S; and a JetDiii polypeptide comprising a pfam09983 domain or a pfam09664 domain or a DUF2220 or a DUF2399 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2845-3174 columns V and W. In some embodiments, a Defense System Xc comprises at least three different polypeptide components selected from a JetAiii polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2845-3174 columns J and K; a JetBiii polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2845-3174 columns N and O; a JetCiii polypeptide comprising a COG1196 domain or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2845-3174 columns R and S; and a JetDiii polypeptide comprising a pfam09983 domain or a pfam09664 domain or a DUF2220 or a DUF2399 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2845-3174 columns V and W. In some embodiments, a Defense System Xc comprises four different polypeptide components selected from a JetAiii polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2845-3174 columns J and K; a JetBiii polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2845-3174 columns N and O; a JetCiii polypeptide comprising a COG1196 domain or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2845-3174 columns R and S; and a JetDiii polypeptide comprising a pfam09983 domain or a pfam09664 domain or a DUF2220 or a DUF2399 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2845-3174 columns V and W.


In some embodiments, a JetAiii polypeptide comprises identical domains as are present in JetA and JetAii. In some embodiments, a JetAiii polypeptide comprises homologous domains with domains present in JetA and JetAii, wherein the amino acid sequences comprise at least 80% homology. In some embodiments, a JetBiii polypeptide comprises identical domains as are present in JetB and JetBii. In some embodiments, a JetBiii polypeptide comprises homologous domains with domains present in JetB and JetBii, wherein the amino acid sequences comprise at least 80% homology.


In some embodiments, a Wadjet Type I defense system having an anti-plasmid activity comprises a nucleic acid construct comprising a nucleic acid sequence encoding a JetA polypeptide, a JetB polypeptide, a JetC polypeptide, and a JetD polypeptide. In some embodiments, a Wadjet Type I defense system having an anti-plasmid activity comprises a nucleic acid construct comprising a nucleic acid sequence comprising a jetA gene, a jetB gene, a jetC gene, and a jetD gene.


In some embodiments, a Wadjet Type II defense system having an anti-plasmid activity comprises a nucleic acid construct comprising a nucleic acid sequence encoding a JetAii polypeptide, a JetBii polypeptide, a JetCii polypeptide, and a JetDii polypeptide. In some embodiments, a Wadjet Type II defense system having an anti-plasmid activity comprises a nucleic acid construct comprising a nucleic acid sequence comprising a jetAii gene, a jetBii gene, a jetCii gene, and a jetDii gene.


In some embodiments, a Wadjet Type III defense system having an anti-plasmid activity comprises a nucleic acid construct comprising a nucleic acid sequence encoding a JetAiii polypeptide, a JetBiii polypeptide, a JetCiii polypeptide, and a JetDiii polypeptide. In some embodiments, a Wadjet Type III defense system having an anti-plasmid activity comprises a nucleic acid construct comprising a nucleic acid sequence comprising a jetAiii gene, a jetBiii gene, a jetCiii gene, and a jetDiii gene.


In some embodiments, the Wadjet Type I anti-plasmid defense system comprises a nucleic acid construct comprising nucleic acid sequences encoding a cassette comprising jetA, jetB, jetC, and jetD genes. In some embodiments, a construct comprising the Wadjet Type I defense system encodes one component of the defense system, whereby multiple constructs may be used to assemble the functional defense system.


In some embodiments, a Wadjet Type I (Defense System Xa) gene cassette comprises the nucleic acid sequence:












(SEQ ID NO: 17; construct 59 of Table 4)
















1
gttgatcaag aaacaactta tagcgtgtag tttttgttgg ataaaatttt aaaagttatg





61
taatttgatg caggggaatt gaaacgtaat atagaaattt ataattataa ttatagagtt





121
aaatgatggt gcttaatgga agacgatgat agcgaaaaag gaggctgaaa tgaaaaaact





181
atttgaatgc attccggaaa attatttcaa tttgtttgct gggaaaaatc gggggtttta





241
tgctgaagtt gcttttttac tatatgaaca attccatatc aatcgagctg gtattttata





301
cagtttgatg aaagatgagg ttcaagaatt aatagaaacg aaagaagagt taggagaatg





361
tattgatata gaagatgaaa tagaagaaaa agagcaagac agtgctggga gagcaaatga





421
ggtgcttcga cgtttaaaga aacttaaatg gattgatgta gaagtacgtg atcaatttga





481
agagtttata gtgcttccag tgtattctag ccgtattttg gctgtgctaa aggaaatttg





541
tgaaaataga acaattgaat atcaaagata ttgttttacg acatatcaat tattaacagg





601
agtggaggcg gaggagcgcc cagcttcagc tattttggag tctgaaaaat atagtgagca





661
actttatgat gaattaacaa ttttactgca caatatgaaa aatcatatgg aaacaattgc





721
agctaaagat gatatacaac aagtgttaga gcatcatttt ggagaatata aaaaagatat





781
aattgataaa agttaccatc gtttaaggac atcggatcat gtgtcgagat atcgaaataa





841
aatattggag cgtatacaga cttggttttt agatgataaa ttcatgaaac gtgctgccga





901
agatgctgta gaaagtggat attctgctaa ctgggaagaa gcaatggatg gattaagtaa





961
gaaaatgtat agggttgaag aaatttatag taatttagat gaaatttgta atcaaattga





1021
tgcacgccat tatcaatatt tacgagcagt tttagatcgt tctagatatt taagtactta





1081
taatgacagt atcaattaca aaatatctta tattttagaa catatagggc aaatggacga





1141
gaatatactc gattcttctc tgtttcgttt agtacagttg cggcaacttc aagaagcgtc





1201
actgttatcc ccacgtaaga aaaaaggtgt atatgaacca gaacagcatg aggttaatga





1261
aattagtgat gagatgcgag aggagctaaa ggctgaaaat ataagacgta tggaaaaggt





1321
tatgaatcga aagaaaatcc aaaaatttgt gttagaagca atgaaggggc gtcaagagat





1381
agagatgagt gaattgaatt tgcaaaatga ggatgacgct ttgtatttaa tttacgttta





1441
tttgtatggt tatagtaagg gaactggata caagcttagt gaagagccac ctgaatttat





1501
tacacaaaag gggtatacat tttctaatcg tacgataaaa cgagaaaatt agggggaagt





1561
tatgcaaaat gtatcggaaa gagaaagaga agagatgggg attgttgtta attatttatt





1621
ctcccataat tttttattga aagaatttga acgtgagaag tatcacctgg cagtacggaa





1681
taaagatatt attaagcaat atttacaggt aattggttgg gattttattg tggatgaaaa





1741
gcatgggtgt attgttattg tttcgccaca ttacgagcat cgtttgaaat tgaagaaaga





1801
cgaaacgatt tggttgttag tattaagact tatttatgag gaaaagcgta gcgctctatc





1861
tattagtcaa tatcccttta ccactcttca agaaatcaag gggaaatatg agacgtttcg





1921
attaccgttt gtatcaaaaa caaaattacg tgaacttgtg cagattggaa agcaaaatca





1981
acttttgaga ccaattgata atgacataga gtcggatgat tgtcgttttc agcttttcca





2041
ttcatgcatt catgtgctgc aacaaggaga tttaaatgta ttgtatgaaa aaataaaatc





2101
ttatagtgag ggtggggatc acagtgaaat ggatgaagaa actacgatta attaattggc





2161
attattatag tgatgaaaca attttatttg gaaaacaaac agtgatatct ggacatacag





2221
gagcagggaa atcgactgtt attgatgctt tacaagtcct atttatttcc gatgagcgga





2281
agattaaatt taattcagca gcatatgagg aggccaatcg tactttaatt aattatttgc





2341
gggggaagat aggtacagaa gaaaaacctt ttgtaagaga agggtatttt acaacatata





2401
ttgttgctga gttttatgat gagaaggcag gagagagttt tgtaattggt atttcaattg





2461
atgtatttaa agatgatgaa aaagtaaaag agtattttat tataccgaaa tctgagatta





2521
atatgatttc gttttttagt acaaaagacg agaaacgtta tgtggaaaag caagcagact





2581
tttgtaaaaa aataagagaa caatttccag aggctataat tgaaaaaagt tcaaatcaat





2641
atcaaaaggc tttattacaa cgttttggtg gattacatga aagatttgtt aaaacgtttg





2701
caagagcatt atcgtttaaa ccaatcgata acatgaaaga ttttgtatat aaaaatatat





2761
tggacgaaaa agaattaaaa atcgacgtta tgaggaatat ttttcaaaca catgaagaat





2821
tgcaaagaga attagaagaa ttaaaagaac gaaaggaaga gctggagcga atagataata





2881
tttatttgga atgtgtaaag ctggaagcgg atatttccat acaagaatat gttcttagag





2941
ggctagagta tttattaata caagaagaaa agagcatgtg taaaaaaagt attgaacaga





3001
gagaaaaaga attaagaaaa tgtgaatcag atcaaaaaaa gacagcggaa caaaaagagc





3061
atgctagaaa aaaagagact gagtatgaaa ttaagattaa ggatagtgct gaacaaaaaa





3121
gacaaaaaca attacaagaa caaatagctc aagcgaaaaa agaatgtggt gatttagagt





3181
gtaccaaaaa catatatgtt catagtttag caagagaaga aaaggatgtt tctagtcttt





3241
taaattatca aggtaatgaa tatttctctt taagcaagga cgagaagcat gcattggaaa





3301
taggaagaga ttgtctagcc ttcttgtcac ataatgatgg tactggaggg aatagggaag





3361
agcaaacatt aaataaactt ggagagagtt taaaaagaat tagtgggcgt ttttataaga





3421
gtacagcaga attggaacac agatctgctg aattgaaaac agaagagaaa gaattacttt





3481
ctgatataga gaatttaaaa agaaggaagc gtccttatcc catgtctgtt gaaaagttga





3541
agggattact agaaaaacat ttagaggatc aatcgaaggt atggattctt tgtgaagagt





3601
tagaaataaa aaatgataaa tggcgaaatg ccctagaagg gtatttgaat actcaaagat





3661
ttgatatttt ggtagaacca catatgtttg cgactgcact gtctatctac gaaaaggaaa





3721
agtggaatct tggtcttgaa ggtgttggac ttgttgatac tgaaaaagaa caaacatatt





3781
tagggaaagt tgagaagggt tctttagctg aagagatagt aggtggtaac ccaatagtac





3841
aggctcgaat tcatcattta ttaggtaggg ttataaaggc agacaatgaa caagaattac





3901
gaaagtataa aacagctgtt actgcgacat gtatgagtta tcaacgtctt gtagcacgcc





3961
aaattcctag aaaagtatat gaaaccccat atataggtgc acatgctatt caaaagcaat





4021
tagaaattaa agaagaaaac ttaaaggaaa ttcaaacaga actgcaaata gtaggatact





4081
atattaaaga ctttaagaaa tggattgaaa ttttagaaga taagcaatcg gattataaga





4141
attatatatt aaatttctca ttaaacgata gtatcttgga gtttaataag aacataaata





4201
aatggaagag tgaactaaat actcttgatt tgtcacgttt agaaagttta cgccaaaagt





4261
tgaaagagtg gaatggaaaa tataatcaat ttaatggaga agaaggtaga ctgtttgaac





4321
aaattgggaa ggtgaaggaa gaacttcaaa gagtgaatgc tgagttatgg aaaaaggaaa





4381
aggccgcaac agagatttta gagaagtgga aaaattggaa gtttgaatat agaatcgaat





4441
tattacaaga ggctgagcaa aggtacgagc aagctatttc tacaaataaa gcttatggtg





4501
ctataaaaaa taaatacgaa aataataaaa aagaaaatca aaataaatac gaagaaaaaa





4561
ggggttttct agaaagtgaa cgtaagtctt ataatgaagc gcgaactttc caaggaatta





4621
tacaggctaa agataataag cagtacgaag aagcgctccg gaaaattgca aacctcgata





4681
tcccaaagtt tgaacaagag atcaaggaaa cgttgcagca agctgaagag gaatttcagt





4741
ctcactttat ttacaagatg cgtgaggcta ttcaagcggc gcgtagagaa tttaatcaat





4801
tgaaccatgc gttaggaaga tttaaattcc gaaatgacac gtatcgattt gtaataaagc





4861
caagtgaaca atataaaaaa ttttatgatg taattatgga tgaaagagta cagccggaga





4921
tatctctatt tgattttggt gatgaagata gggcggagat tttaaaggac ttatttggta





4981
gattagtggt gggcgagtat ggtgaaaacg aagagtttgt ggactatcgt aattatctcg





5041
attttgattt aagcattaat aatgaaaatg gaacaagatt tatgtctaac ttattacgtg





5101
agcaatctgg tggagagacg caaacacctt tttatattgc catcctagca tcatttcaac





5161
acctttatcg aaataaaaat accattcgtt tagtagtgtt tgatgaggct tttaataaaa





5221
tggatgaaga gcggattcaa attagtttac gtcttattaa acagttggac ttgcaattaa





5281
ttgcagctgt gccagatgag aaaatggctc atatggcagc tgaggcagat acagctataa





5341
taattaaccg aatagggcat tcatgtttta ctgacatatt atcttatcca agggaggacg





5401
aggcaattgg attacaagag caagattctt tcagtcttat tgaataaata tgaaaatagt





5461
aaaactgctc atacaggtga gagaagtgct cagcgccctc aattttcatt tcggcaaaaa





5521
catgaacttt ctaaagcata taatgatgaa atggattata cgaaccgatt agaaattaat





5581
actgcattaa aggacttaat tcgtaaaaaa attattgaag tgaaatggga aaagtgggaa





5641
gagaatcgaa ttgctgaaaa ggtttattta cagtatgatt ttattccaca agcttataga





5701
gaagctggta tagaaccaaa aattgaaaag atgaatagga ttttaaaagt gttagaacca





5761
cttgctgttc attcatggga gtgggttcga caatggtata aagaagtaca acagtcgttt





5821
caaaataata aaacggcacg aattaattta aacgatgtta aaggatatga actacttgta





5881
aaagcacttt ctagattaga aggtttggaa gatagtatac cgaaaaggac ctttagccaa





5941
ttagtattcg gggatacaaa actttttgaa actacgatac aaaaccgatt attaataata





6001
tataaaaggt acggagatat agaatatgaa agtgataaag aatatttaga gagtattggg





6061
attttagaga atatccaacc tgtctatata aaaggaaatg ttgatattcg tgttagagga





6121
gagaagattg ctctcggttc ctttcctggt gggttcggtt taatggatga aacaataaaa





6181
gaactagaaa ttcagtatgt acacgatgaa agtataatgc ttattgaaaa catgaccaca





6241
tactatgaac aaattaaaaa aaataataat attttattta tctatacagg tgggtttcct





6301
aagaagaatg tacagcaatt gttaaaaaag ttgaatatat atttggaaaa tcatccagtt





6361
ccagtatatc actatggaga tctggactac ggaggaatcc aaatatttga gtacattaag





6421
cgttcgtttt tttcagggct tgagccgtat atgatggatg tagctaccta caggcaattt





6481
gtaaagtacg ggatggaatt tggtgaaggg tatgaagaaa aattactgaa gatgttagag





6541
aatgagcagt attctttatg gcatgagtta attaaagaaa tgcttaaaga aaagaagcgt





6601
gttgagcagg aagtgatagt tagaaacgta atttagtgta tttatataaa tttaaaaagg





6661
atgtctatag accaggataa cggtttatgg gcatttttta ttaggttttg tataaaagag





6721
atttagttag aggaaatgag atttaatatg ttttgtaaac gccataatat taacgcctga





6781
atttttttag gagaggaaag tagagtgttg gctttgtttt tcgtaattaa ctaagtaatg





6841
tgagaagttt tttatatggg gttatttata taattattaa gtgctagata atgaattgtt





6901
agtccatcct tattttggag gcatgttcta attaaataaa ctggttggat gtaataagtg





6961
aattcctggt aatttatcgt tggaaaaaaa tatatattat gtataattag tgtataaata





7021
aaattctctg aaatttgaaa ggtgataaaa.









The coding regions for each of the jetA, jetB, jetC, and jetD gene sequences within this embodiment of a Wadjet Type I cassette (SEQ ID NO: 17) are as follows: nucleotides 146-1552 encode an embodiment of a JetA polypeptide, nucleotides 1562-2155 encode an embodiment of a JetB polypeptide, nucleotides 2133-5447 encode an embodiment of a JetC polypeptide, and nucleotides 5551-6636 encode an embodiment of a JetD polypeptide.


In some embodiments, a Defense System Xa comprising a JetA polypeptide, a JetB polypeptide, a JetC polypeptide, and a JetD polypeptide is encoded by the nucleic acid sequence set forth in SEQ ID NO: 17. In some embodiments, a Defense System Xa comprising a JetA polypeptide, a JetB polypeptide, a JetC polypeptide, and a JetD polypeptide, is encoded by a nucleic acid sequence having at least 80% homology to the sequence set forth in SEQ ID NO: 17. In some embodiments, a Defense System Xa comprising a JetA polypeptide, a JetB polypeptide, a JetC polypeptide, and a JetD polypeptide, is encoded by a nucleic acid sequence having at least 85% homology, or 90% homology, or 95% homology, or 97% homology, or 98% homology, or 99% homology to the sequence set forth in SEQ ID NO: 17. In some embodiments, a Defense System Xa comprising a JetA polypeptide, a JetB polypeptide, a JetC polypeptide, and a JetD polypeptide, is encoded by a nucleic acid sequence having at least 80% identity to the sequence set forth in SEQ ID NO: 17. In some embodiments, a Defense System Xa comprising a JetA polypeptide, a JetB polypeptide, a JetC polypeptide, and a JetD polypeptide, is encoded by a nucleic acid sequence having at least 85% identity, or 90% identity, or 95% identity, or 97% identity, or 98% identity, or 99% identity to the sequence set forth in SEQ ID NO: 17.


In some embodiments, the Wadjet Type II anti-plasmid defense system comprises a nucleic acid construct comprising nucleic acid sequences encoding a cassette comprising jetAii, jetBii, jetiiC, and jetiiD genes. In some embodiments, a construct comprising the Wadjet Type II defense system encodes one component of the defense system, whereby multiple constructs may be used to assemble the functional defense system.


In some embodiments, a Wadjet Type II (Defense System Xb) gene cassette comprises the nucleic acid sequence:












(SEQ ID NO: 18; construct 60 of Table 4)
















1
tctttgggtt cctttacttt ttgtaaaaaa tttaattctt tgcctgaagt atttcgaaaa





61
actgaaagcc tttaaaaaga atttcaccaa tcagtttaat tacagaccaa gattacaata





121
aatttaaaac cattcgatgt caatgtttaa atggaaaaac gtaagtatag gaatccttag





181
ttcaatatta tacaatggga ataatagaca aaaaatagga tgatgatcca tggattcaac





241
aatgaaaaaa ataatagagg ccagttattt aacagccgac tccgcggcac actatcgaac





301
gattcttcgc tatttttatc accagcacga aagaatgaga gattttattg caccggaaga





361
gttattggaa catatgcgtt cgatacctgc cttcgcggac tttcaagagg accagctcca





421
ccagcaatta gcgcagcttg taaaatggaa taatttaatt gccaggcagg atatgacaaa





481
cgcaaaaaca attgaagaat ataaaaagaa acggttccgt tatcaatgta caccctacac





541
ggttgagatt gagagaatga ttgtgcaact agaaaaatta ggagatacgt tccaagggtc





601
gttagaacgc tcccaatttg atcgcctttt ccaagcaata accagccttc aaaatgaact





661
agagaatgac ctaaacaaat cggcagaaga atatatgcgg atttgggagg acgtatttcg





721
ctattttcaa acgattcgta ccagcactgc tgattatatt gcttatatta atagtgaaca





781
aaccgatcaa cgaatgcaaa cagaggcatt tctagtctat aaaaatcagt ttacaacata





841
tttgcgagat tttattgtat ccttgcaaaa aacatcgctg caaatccagc attcattatc





901
agaattaacc ttggaacggt tacagcattt ttttcaaaaa ttaatcgagc atcgcggggc





961
aattccccgt cttgaggatg tttcgtcatc tacaaacgat tggcttactg aatatgagga





1021
atattggttt tcattacggc agtggttttt agggtcggct gttcagcaaa gtgaactaga





1081
tatccttcag tggcagacca atgaaatgat tcgccggatg acaagatacg ttcagcgcat





1141
cggtgaaagg cagcagcatt ttcgcagccg aaaaaaggac tatctgcaat tatcaaaatg





1201
gtttgttgaa tgcagggata gtgaggaagc tcataaactt tcagcagttg tattcggctc





1261
gatgacgatt caacatctcc agcttgagga agcgaccact gaaaaccttc atgtcgatac





1321
atgggatgag gcaccgactg aattaacgat aaaaccgaga acggtccgct accgtgaaaa





1381
aacaaaaccg ggatcgttta actcgaatga acagaagaaa aaagagcagc gagaactcta





1441
tttaaaggaa agagaacaag agaaaaagtt aatcgaaaaa tatatgaccc aaggtaaaat





1501
tacgctttca gcactctcga cagttgaacc attcatccgc aaggttttgt taagctggat





1561
tgggaaatca atggcggcca aaaatcgcat ggtcaagact gattacgggc ttcacgtaaa





1621
ggtaatgctt gattatgaga aaactattac cttacaagct gaggatggca atttactaat





1681
gcctgatgcg acattcttgt ttgaggagac taggtgatga taatggaaca aacgcaatta





1741
ttcgatgaaa aggcaatcca aggaatggac atcttgtttc atcattactg gatcttacgt





1801
gccgaacaac ctgaatggta tcagctgatt cgtgagcggg agaaggtatt gcgccgctat





1861
cttgatgaaa agttcggcct gcggctaatt gttcatcaac attttattaa actggaaaaa





1921
attcctgttg aaccggaagg ctggatgggc atccaagatt tccaagagcc aatggactat





1981
gcgatttttt gctgcgcact tgccttttta gaggggaaag cagtggatga acagtttttg





2041
ctttccgaac tatgtcaaga gattcaagcc gattatcctg gagattttcc gcttgattgg





2101
acgctctata cccaccggaa atcattgata agagctgtaa aagttttgat ggaatttcag





2161
ctcatacgaa ccattgatgg ggatatcggc cgcttcgatc aaaatgaaga gcaggaagtt





2221
ttatatgaag ctagcaccta tagtcgatat ttcatgagaa catatccaga tgatttttcg





2281
agctatcagc actggagcga gttactaaaa gaagattgga aattgaacca agaggatgaa





2341
cgtaggaagc gggtgtaccg caagctgttc ttttcacctg gtttgcatcg gctagatcaa





2401
caggatcctg attttctcta tatccggaac tatcgtaacc gcttagcaga agatattgaa





2461
aagcacagtg agtataaact ccatgtctat aaaaatacgg catttttatc gattgcggag





2521
ccaaggcaat atcaacaggt ttttcctaat tccaaggcat ccactgacat tatccttcag





2581
ttgtcaaagt acattcatgg ggagcctgag cgcttcaaag caaacgaaaa tggtgaaata





2641
ctgatgacgg aaggtgagtt tgaacaagtt gtggatgatt tacggcagca atttggaaca





2701
ggctgggcaa agtattttcg cgatatgagt acaaaaggaa ttcgaacgga actgcttcgt





2761
gccatgaagg attggatgat ggcggaagtg gattcagaaa cttctcttat tcggattaag





2821
tcattaacag gggtcatgac gggggaatat ccgagtgatt ttcaaacagg aggaacagaa





2881
tgatgacaga ggcaaaatgg gtgatgaacc gtgcggggtt attgaatttt tggtattacg





2941
atgatgaaat ttttcctttc tcggatggaa agctactgct taggggaacg aacggctccg





3001
ggaaatctgt aaccatgcaa agcttcctgc ctgttttgtt agacgggaaa aaatcacctg





3061
accgactcga tccatttgga tctaaagccc gcagaatgga agattattta ctcggggaaa





3121
aagaggtggt cgatcgtgat gagcgtacag ggtatctttt tatcgaatat aaaaaggccg





3181
gcgtagagcg atacattaca actgggatcg ggatgcaagc caagcggcat aaaggaatta





3241
agtcttggta ttttgtgatt accgataatc gcagaattgg atatgatttt gaacttgcac





3301
attcgcaact aggagaccga gttccttttt ccgcaaagga actggaaaat cggatcggag





3361
agggcggcta tgttgttcat acccagcgcg aatatatgga gctggtgaat aaatatattt





3421
ttggtttcca atcaaatgaa gcttatgaag acttgatcaa gcttttaatc caattacgaa





3481
gtcctaaact ttcgaaggat tttaaaccga cagtgattta tgaaatatta gagtcggcct





3541
tgcctccttt gaccgatgat gagttaaggc atctatctga taccattgaa agtatggatc





3601
aaacccagca gcagctcgaa cagttggaac gggaatttgc ctctagcagc aggctggtta





3661
accagtatca ttcctataat caatatattt tggccgaacg ggcagggaag tggcaggatg





3721
ccttaaaaag gtacactgtt gctgaggaac atgtaaaagg tttaacagcc caagacgaag





3781
aattgactca agaaattaaa caagaagagg aacagaagca gcaatttgcc cagcagcaag





3841
aaattgcctt agaagaaaaa aagcggttgg agcgccatga ggtttggaat ctggaagagg





3901
ataagcgtaa gaaaatagaa aatacaaaat ctttaagtag tgaaataaat tccttacaaa





3961
agaaatggga ccacaaaaac agtcagtaca atcgtctatg gcaggagcgg gagcagagtc





4021
aaaaccagat aaggcagcat gaaagcggca tggaagattt attaggggag ctgcaatttg





4081
atgcggaaga ggctgctttt tcagagcatg aggttaacgt ccatgatttc gaacgtcatc





4141
aggaggagga gtttgatttt tccatctgga ttggtgagat tggcagtcat gaacaattac





4201
ttgcgaattt aaatcaatta gctgatgagg aaaatcgtct gtcagaagag cataaccggc





4261
tccaacggca atcctctgag aaaaagaaag aggtagatgc aatccgcaag aatctcgatc





4321
atttagccga ttggtttacg gaagagaagc aaaggttgga gcatcaggta tttacttgga





4381
ttgagcagca tccaaagctt attttttcaa atgaaagacg ccaagaaatc gcccgatcaa





4441
tcgaaggttt atatgaagaa aatcggtacg agcaagtgag ggaaaaactc cttgctgtgg





4501
ttaatgatta tattaccgat atcagtacga agaaaaagct catggagaca aaaatagaag





4561
ataaaaagca cgaattggaa gcagcacgag cagaattgca tcactggaag acattaaaaa





4621
tgccaaaccc ggatcgtgct aaggatacag aggcatttcg cttgcagctg ctagaagacg





4681
ggcaggcatt tattccgttt tatgcggccg ttgagttcca agatgatgtg accgaagaac





4741
agaaagagcg gattgaatct gcgttaaaac aaacgggcat attggacagc ttgatcactg





4801
aaaatgccct tgccccaacc catgatcggg taattcgtcc tgagccgcaa ttactcggat





4861
atacgttagc agattatttg cgtccggatt tagaggcaga cagtcttatt tcaaacaaac





4921
ttgttgatga aatattacgg agcatctccc ttgaacagga aggggcaggt tttcatgtgg





4981
atgtcgatgg atcatattca cttggttgtt tagtggggca tgcaccaaat gaagggccgt





5041
ctaaatatat cggccgctca tcccgcaaac gataccagca agagaaaatc aaagaatgtc





5101
aggaaaccat tgagcaactc caattagagt tagaggagct aaaggtgcaa ctcagtcaat





5161
acgaagagaa tctcctccaa gcagcacaat ggaagcagac catgccaaca gatcaggaac





5221
ttaatgactt gaatgttcag attgaaaaga ccggccatca attggaggag caaaaaaagg





5281
ttctttttca gctggatgaa cagtggaagc aagtacacgg tcacctccaa gtgattaaaa





5341
tacagctcca tcaagaaggc cgccagctaa atctttcttt aactaaagaa gtcttagggc





5401
aagcattaat ctcagctaaa aactatcgtg atcaactcta tagctttaaa gatctttttc





5461
aaaaatgttt atttgcccgg aaaagaatag aggatttaac tcatcgctta tttgaaatgg





5521
aaacggaact ggacgatctt aaaggggatc aaaatgtcaa ggaatcacag ttgcggaaag





5581
aaaaggctga aattgagtca attgagcaac agctgaagct aaaagggatc gaggaagtaa





5641
gacttcggat tcaacaagtg cagcaggagc taagggaagc aacagaaggc atcaatcatc





5701
tacttgaaac cattcctcag aagaaagcaa aacaagaaac ctgtcaaaat gaattagcag





5761
cagctaaaac aagtgcggaa ttctggtcaa atatggcgga cgaatgggaa cagatggtga





5821
gagcggatat cgcccgtggt tttgtagaag ttgttgaaat ggatcctgtt aaaatcgtta





5881
aacagctgga atccatttta ggaaaatatg accgttcgaa gctaaatgaa cagctaacaa





5941
agacgttcat caatgaacag atatttttaa cggagtacag gatgtttgaa tacccggaag





6001
agaccgagcg tccagagtgg ttttcgaagg aatggggcga atactatgaa ccatttatga





6061 
atgaatggaa tcagcttcaa agccgccgtt taattctaat ggaatataaa ggccagcgtg





6121
tcagtccgta ttttgtgttc acatcactgg aaaaagagtt agaagaccaa aaaggttggc





6181
ttgatgaaca agaccgccaa ctctatgagg atattatcgt caatacagtt ggagtaatct





6241
tacgaaatcg aatcaaacgt gccgaaaaat gggtgagtga gatggacaaa atcatggaaa





6301
gccgtgataa ttcatctgga ttaacgttct cgattgcatg gaaaccatta acggccgaat





6361
cggaacaaga attggataca aaagacttgg ttaagctttt gcagcggaat agtaagtttt





6421
tgaacgagga tgatttaaat cggattacaa aacacttcca atcgagaata ggaaaagcga





6481
aggaattaat tcagttacgg aatgaaggat cgacgcttca tcaagtgtta aaagaagtgt





6541
tggattatcg gaagtggttc acttttgttc tttcatttaa acgtgtaaat gaaccgaaac





6601
gagaattgac gaacaatgcc ttctttaaat ttagcggcgg cgagaaggca atggcgatgt





6661
atattccgtt gtttacggcg gcctattcaa gatataaaga agcaggagag atggcgccgt





6721
atatcatttc actcgatgag gcctttgccg gggtcgatga gaataatatc cgtgacatgt





6781
ttgaagtggt ggaacagctt ggctttaact atataatgaa ctcacaagcc ttatggggag





6841
attatgacac catttcaagt ctatcaattt gcgagttagt acggccaaag aatgccgact





6901
ttgttactgt gattcgctat caatgggacg ggaaacagcg cacctttgtg gtggacgatg





6961
agcacgttga ggagctagtg acacatgatt gacaaagtac aggtgtttag ggacgaacca





7021
ggttttgtta aattgtttac cctatttaaa gaaaaatacc gttcaatcgg gagaatcggc





7081
ggcatggtga gtttggatgg cttttcctat gatgaggtgg aatcaattgc cggctttttg





7141
ggacagtctg ttgaagcgct ccttgaaaaa gggaaggttt cattactttc ttttgaaaaa





7201
gaattaccgt tgaccggttt tgcagagtat tcccttattg aattgcttga agaagtgctc





7261
ggggagtcga tacttactaa acatgaggaa agtggcattg aagaagagaa agaaaagagg





7321
tttttacaag agttatcttt tatatgtcct gagggaagtt ggtggtggga ctggattgag





7381
tcgaaaccgc cggattcccg gtggatttgg tcgctttata agcaggatgc ggttggttta





7441
atggaaaaat tcatcaccgt ttttaaagca tatcaagatc ttccctgtaa ggagaataag





7501
tatgaaagac tgccgctgtt tgcccaacga acaacgggaa atccacatat tttcgataat





7561
aatcaactaa ctgggaaatt gctcgtcaat tgcctgcagg tagatcaaca gcttaagggg





7621
cgacgcgtac cgggaatgcc gaaaacaaca gaggatctaa atgatttgct aggtttgtat





7681
ggtttgatga gggatgattt gtggagtttt gtttcctgcc gcggattact tgcggaaggt





7741
gaaatgggga ttcatcctgt ttggaaagcc gcagctgaaa ctgacacagt tctaaacgtt





7801
ccgcttaagg aattactgaa aataaaaaga atctggcccg ctgcaggaaa aaaggtttgg





7861
attgttgaaa attcaagtgt ttgttcgacg attgttgatg aggttgctga tgctcctgta





7921
atctgcaccc acgggcaatt tcgggctgcg agctggatat tgttggagtt attagtggaa





7981
gcgggctgtc acctttacta ttcgggtgac ctagatccgg aaggggtatc gatggcacag





8041
cggcttttcg atcgttatca gggtcatgta acttgttgga ggatggatgt tgaatcctat





8101
gataaaacca tttcagatga ggatatttct ggcaggcttt ctaaattgga gtcaataact





8161
gcacctgaac ttcttgaagt agtgaatgtc cttaaaatgc ggcaaaaagc gggctatcaa





8221
gaaggtttag ttgagcaact tgttcaggat attaaaaacg agtttaatgt gttactttag





8281
gttgaatcaa atatagtagg aatccagttg gatccccacc acaaaaagcg ctat. 









The coding regions for each of the jetAii, jetBii, jetCii, and jetDii gene sequences within this embodiment of a Wadjet Type II cassette (SEQ ID NO: 18) are as follows: nucleotides 230-1717 encode an embodiment of a JetAii polypeptide, nucleotides 1717-2883 encode an embodiment of a JetBii polypeptide, nucleotides 2883-6992 encode an embodiment of a JetCii polypeptide, and nucleotides 6985-8280 encode an embodiment of a JetDii polypeptide.


In some embodiments, a Defense System Xb comprising a JetAii polypeptide, a JetBii polypeptide, a JetCii polypeptide, and a JetDii polypeptide is encoded by the nucleic acid sequence set forth in SEQ ID NO: 18. In some embodiments, a Defense System Xb comprising a JetAii polypeptide, a JetBii polypeptide, a JetCii polypeptide, and a JetDii polypeptide, is encoded by a nucleic acid sequence having at least 80% homology to the sequence set forth in SEQ ID NO: 18. In some embodiments, a Defense System Xb comprising a JetAii polypeptide, a JetBii polypeptide, a JetCii polypeptide, and a JetDii polypeptide, is encoded by a nucleic acid sequence having at least 85% homology, or 90% homology, or 95% homology, or 97% homology, or 98% homology, or 99% homology to the sequence set forth in SEQ ID NO: 18. In some embodiments, a Defense System Xb comprising a JetAii polypeptide, a JetBii polypeptide, a JetCii polypeptide, and a JetDii polypeptide, is encoded by a nucleic acid sequence having at least 80% identity to the sequence set forth in SEQ ID NO: 18. In some embodiments, a Defense System Xb comprising a JetAii polypeptide, a JetBii polypeptide, a JetCii polypeptide, and a JetDii polypeptide, is encoded by a nucleic acid sequence having at least 85% identity, or 90% identity, or 95% identity, or 97% identity, or 98% identity, or 99% identity to the sequence set forth in SEQ ID NO: 18.


In some embodiments, the Wadjet Type III anti-plasmid defense system comprises a nucleic acid construct comprising nucleic acid sequences encoding a cassette comprising jetAiii jetBiii, jetCiii, and jetDiii genes. In some embodiments, a construct comprising the Wadjet Type III defense system encodes one component of the defense system, whereby multiple constructs may be used to assemble the functional defense system.


In some embodiments, a Wadjet Type III (Defense System Xc) gene cassette comprises the nucleic acid sequence:












(SEQ ID NO: 19; construct 61 of Table 4)
















1
ttccgatact ctttagccat aaagcgatga attctgctgt tccgccgaat atcgcaacgg





61
ttagtgcata tggtaaacct acgcctagtg cacggatttc agttggaaag agttctgctt





121
ttacattgcg ttaatcgatg tgtaaccagt aacgatgatg aggccgacca tcatgagtga





181
aaatgctacc atgggttcta tatccatcat ttttaaaact tggtggatat ggagggacct





241
ggtactgttt tggttttgtg atgtctgtgg gatttcttgc tagcttctgc atgatttgtc





301
ggtaagtcga tatattcgga gttgcggtcg atataattgg ataatcgttg atatattttt





361
taaaggtatg gcattcattg gtagaaagag tgatgcgagc ttatgttaca atggaaatag





421
cttgtaagta aggaagtgac agtatgaatg gtatacaatt tgttcaattg tatgtaatga





481
aaagtgctga aaagattgat gagttgtata taaaaaaaga acaaggtatc acaactctcc





541
ccattataaa gcagaccccg cgtaagatta taaaaacagc ggaacttctt tttagtgaag





601
aagaggtttc ggatgtttct actactatta caaaaaactt ttattcacct aatgtaagga





661
aaagagaaag tgatgtttta aagtggttaa cgatacatga aatgatagat tgtatagaac





721
gagggatttt aattaaggaa gttcgttttg agaaggatgg gaaaactgtg cattccattt





781
tctatcgaat ggggtacggt ttgtttacat atatggaaaa gaaacaacag ctagaaaagg





841
taagagagga agaggcttta cagcaatgga tgaagcgcaa gcagtctatg ccgaagtaca





901
taaatgagta tacggaaaga ttgtggcatg ttttgtgcaa tattgaaagt gatttgtctt





961
ctatagatga aaaacgttgg tcgtttcaga agacgttttt atttttagag tttttacttg





1021
ctacatataa aatgagttgt gaaaagcgta cgtttgattg gaaagagatt ggtgcggcgt





1081
attatgaagt gattggtggt tctaaaaagt ttgatcaaca taaaaaagag tttcttaata





1141
agctggaaga tttgttagat gctccgccgc attgtttagg tttagtgagc ttagggacag





1201
tgacgcctat ctttttttgc gggaatttat atgaaggtaa tacgcgttat gagtgtgaca





1261
cagtgcgttc tttaacggat ttagttgtat ttcgtcatgc gtataaaacg gatgcgaagg





1321
tgttatggct cgttgaaaat agagcggtat taacgaggat tgccgcagag gatgatttta





1381
tttcaagtac aggtagtctc gttatcggag tggatgggca attacgtagt gggcataaaa





1441
ggttgattca aagcgtattg gaccactcaa aatctattac gaaaattatt atttggacgg





1501
attatgatgg ggcaggagag attattagtg ataagttatt cgaactagtt gctccatatg





1561
aacagtatac aagatggatt tcttcagaag gtaaggcgtt aaataaagat gaatttgagc





1621
aatccgttcg tttacgcgaa agtgaacaag aagagagttt aggaggtgtg gatgcttgga





1681
aggaatggat cagtcagtaa tttcgatttt gcaaacagat ccgtcgcata tgggagtacg





1741
aaatgcgatg aaagatttaa ataaattatc aggtgttatt tcagagcttg gagagagtga





1801
gtattttaat gatccattga aaacgtatga gtttctacta ttattaaata ttttaaatga





1861
agaagcgctt ggattgacgt cttctattga agatgtgcgt acgttgaaat tccgttaccg





1921
taatatgtac ggcggggatc cgtcaattcg tttagagcat ttcattaata ttttagataa





1981
atatggatgg atctcaaaag ggaaaagcaa gattacgatg atggacgttg ggaagcgaat





2041
gattgatgtg ttaattcgcc tagcaaacga ttcgttagcg tattacatgc aagatgaaat





2101
aacgaggtct ttatatcaag caaaccgtga tgcggattta agtgaagcgt atgatgataa





2161
aggtgtatcg ggcggaaata aattagcgag tatgataaaa aatgtagaag aagcggtaga





2221
aagactgaaa gagagagaac tcgaatattt agcggaccgc tatgcgttgc cgcaagtgca





2281
gattattcat cgtttaatga atgaattaaa tgttcgtttt gaagaaaggt tccaaaagtt





2341
tcaaacgttt gaagaaagtc ttgtgttaga gcctcttgtg aaaagaggaa cgagcgttat





2401
gtttgaaggt tcacaggtta gtcttggaac gattaagaag attttacatt ttacacatat





2461
tcagcagtct acagtcggag cgaatattcg tcatgatgcg cttcgtcgtt ttattgaaaa





2521
ttgttttacg aagcaaaata tggaattgcc agatgcacat gaaattttaa gttttatgga





2581
gcaagaccgt agagaaggcg agagacaaga tgggttatgg atgccagtac agtttgcggc





2641
gccgttatca agtgctgcga tttctagtgg tattcagttt ttagaagagt acgagccata





2701
tacggatcat atagaagaag ttgtgcagga agaatatgaa gagatagaag aaatgtcaga





2761
agcagaagtg aagaagctaa tggcagatca gcagtggagt atgacgaaag agcaaattca





2821
aacggaacga ttagaagagt ttcttatgga acaagaagaa gtcgatatgg aagagcttgt





2881
gcttgaagcc ggttctaata cgtggggaga tgcggtaaat gcattaatcg cactgtcagc





2941
tttaaccgct aataataagg cggatattat cgataatcaa aatgtaaaag aaagaaacat





3001
agaaaaagaa tgggaatggg gcagtgacga tgataaaaga aaacgagttc gaagccgaga





3061
aaggaattaa tccgctcgcg aaattaggag aacttcggta catattgtct cgtgatgaag





3121
agcatacgtt tatgcaactt ttattttcat cttcagcgcg tatgagagca acaaattttg





3181
gattgcgccg caaagaagta atgaaaatgc ttgggttaaa tagtgaggat atagaagggt





3241
ttgagtcatt tgtaatgcga ataaatggtg cgctaagtgg ctattttcag tgtgtatatg





3301
atgagagacg tgatcaagtc attgtgatga tgcgagtacc agcaaaacaa gcgagagaag





3361
tattatcttc agaaagttta ggattactta tgtttatttt ctaccatcaa gaagtgttgc





3421
aaaatgaatt tacattattt aatcaattac ttagtgcgct tggacatgaa acgttgcaag





3481
cacgtagaaa agtacaaaca aatttagatc cacttttaaa aattggggct attacgaaat





3541
atgattctcc gtcccaagaa gaagcatatg cgttaactgc cattggaagt agaatgtttt





3601
cagattcgtt cttacatagg gcggctgagt ttagtcagtc acaacaactt catatggatg





3661
atgttttaaa attctttaag cgttataacg taggaggtgg agagacgata tgattccata





3721
ccgtatttct ttttctggta tacgtgatta taagccgaga acgatttctt taatggggaa





3781
gcgtgatcac attttaattt caggtgcaaa tggtgccggg aaatcgacgc tgacattttg





3841
ctggggcgct gttatggcgt ctacgaaagt aaatgtggaa gggcttcgtt cgaaaaatct





3901
tccagacaat agagtatggc gagcgaaaat tgaacttata tatgaaaatg atggatttgt





3961
agatgcagca agatttgtga gatttacgct tgatttagaa caagagccag gtcatccatt





4021
gaaaaaagaa tattatattg cagaaggcga tcgggtagat gagtgggagc aagaaacgcg





4081
tttctcatct tcagataagc attttaactt tagagagtat aaaagaatgc ttcttcaaaa





4141
atataaaatt gatccagatg cgttctattt aatttggtac caacaagatg taaatcaatt





4201
tgcagtgatg aagcctgaag agaggttccg tatttttagc gagatgacag gaattgaaag





4261
tattcaaaag tcttgggagt ctttcaaaga acaagaacgt gataaggaag cgattttgca





4321
aacggctcgt aataaccaaa ttcaatataa gttcgaactt gagcgttggg agaaagagaa





4381
aaatcgttat gaagatcaac aaagccgtat aaaacgaggg attctgcaat ataaaacagc





4441
gttatgtaca ctagaagatc attattatac agaacgtatg aagtataagg atgagctaga





4501
agatgtgaaa gagaatcttg atgagaagta tgaagaagct cagcaaggag aaaaacagtt





4561
tgcacaatta gaggcggagt tactagcgaa acaagctgag tttcaaagtg cagaaaaaga





4621
gcgtgaaatt gccgaggaac gacaactaca gtgcaaaaag gaaagtaaag ataaagagcg





4681
agaatggaat gcaatgaaag aagagataaa agacgtaaca gatcgcgtga aaaatatagg





4741
aattagtgaa gatgttgtaa gagcagaaaa gagtagtaaa gagcagcaat tgcaagaagc





4801
tgaaaaggaa aaggtatata cagagcagct tattagtgag acaagttata atttaaatga





4861
attaaggtca gaagttgcga agctagaagt gcaagtagat aatgatgaag cagctgtcgt





4921
ttctgcaaag aattacatag tgcaatataa gtctagtttc tatatggaag aaaagcatac





4981
aaaagtagaa agtatgatga gacagacgaa agatcttgtt gaaacggtga agaaagatct





5041
tcagcaaaaa tacgaagaga aaaagcagct agagctaaat cgttacgtca gtccgaggca





5101
agaagaagga cttagatact taagaaggga agggttacaa gcttatccgc ttcgagactt





5161
aatagaatta gaaggcgacg cagaatttcg tcatgaagat attttaaata caattaaata





5221
tgcgatcttc gtagaatcaa aagaattcag accaccgaat gatttgtatt acgtaccgtt





5281
gccactcatt gttccaactg aaagtgttat ttccttaccg cagtataagc tgagaattaa





5341
agaaggagac aacgaaaaac ttgtttctgt agcaatgaaa gctttatggt gggtaaaaca





5401
attctttaca ggtgagcagc catgtattca aaagaatagt ttaattgata taagaggatt





5461
ccgtggggaa caagaaaaaa cggaatacat tttaagtgaa aaagcaatta tgcaacgttt





5521
agaagagaca ggaaaatgga ttgaagaaca tgaaaaacag ctcatccaat atgagcgtga





5581
tattcaaaca ctggaagaaa aagaaagaaa acttcacgac attgtatata aactaagaga





5641
tgcagaagcc gttttacaaa aagctgccga acgcacattt agaatcgaac agttagggcg





5701
aaaaacggaa gagaaacaaa ggctagaaca ggaaatacaa aggctatatg caattaacca





5761
agaattgcat acgcgcatat ctcgcttaag agagcgtctt gaaacgttag aacagtacga





5821
aatgatatat gaagaactgc ataaggaaaa agaaaaaatt gcacatatgc aaaagcttga





5881
acaaattcat agagagttat tggatgagct caagagagta gtagagcaaa gagatatact





5941
ggatgagact tgtaatagat tggaaattga atgtaataaa gcgagtcaaa aaacgaaaca





6001
acaaaaacaa gaagtagaag aactacgcgc gtatattcag cgtttagaaa agaaaaaaca





6061
agatgttcaa gagcatttca taacgacaga agaaaaacta attagcatac aaagagaaaa





6121
ccaggatgcg aatgacacgt atggaaaatt attagagcaa ctaggttggg aaaaacaaat





6181
agaagagtgg tctgaagcga aagcactttc tcaaaaacaa agcgcagaga ttacactaga





6241
aggagcactc ggtgaaacag ttgatccact agcgccagaa aattacgcga agatgaaaga





6301
agaaaatgaa aaaagtaatg cagaactgca taacgcagaa caaattttga acgaacttcg





6361
cgaaaatata gcacttatga gagaacgtct cgaaacgacg atccaaatga atgctcataa





6421
aatccataaa aagtttgaac agtacatgga acaattccac ttcgaaggaa aagtagaatg





6481
gaacatggac acaaacaaac acggtgacat gcgttactat ctctacataa aagcgcgtaa





6541
aaaaggtcac cgtggcaaaa tggaagacat tagcgccaaa ggacgcggag gcaaagtagg





6601
aagcggcgta tcaggaggag aagaatccct ttcatctcta ctattcgcac tagccttact





6661
acaaacaatc gaagcatccc caggctacat catcctagac gaatacgaca gcgccctaga





6721
cgacagccga aaagaaaaag tcttcaccct attcgaagag gaactaaatc ggaaaatgat





6781
catcgtctca ccaaaaagtc atgatccaaa ctacttacaa cacttctcgc aagcattaac





6841
agttatgcac gatgcgagtg tgccggttag tcgaattttg cagattaaga gggcggtaga





6901
agaaactgaa actgtaatca aggataacta atttaaaacg tccatatcaa attttgatat





6961
ggacgtttta ttgctgttta atatggagat aaagaaaata aggatgtgat tgtaaa.









The coding regions for each of the jetAiii, jetBiii, jetCiii, and jetDiii gene sequences within this embodiment of a Wadjet Type III cassette (SEQ ID NO: 19) are as follows: nucleotides 444-1700 encode an embodiment of a JetDiii polypeptide, nucleotides 1676-3070 encode an embodiment of a JetAiii polypeptide, nucleotides 3030-3713 encode an embodiment of a JetBiii polypeptide, and nucleotides 3710-6931 encode an embodiment of a JetCiii polypeptide.


In some embodiments, a Defense System Xc comprising a JetAiii polypeptide, a JetBiii polypeptide, a JetCiii polypeptide, and a JetDiii polypeptide is encoded by the nucleic acid sequence set forth in SEQ ID NO: 19. In some embodiments, a Defense System Xc comprising a JetAiii polypeptide, a JetBiii polypeptide, a JetCiii polypeptide, and a JetDiii polypeptide, is encoded by a nucleic acid sequence having at least 80% homology to the sequence set forth in SEQ ID NO: 19. In some embodiments, a Defense System Xc comprising a JetAiii polypeptide, a JetBiii polypeptide, a JetCiii polypeptide, and a JetDiii polypeptide, is encoded by a nucleic acid sequence having at least 85% homology, or 90% homology, or 95% homology, or 97% homology, or 98% homology, or 99% homology to the sequence set forth in SEQ ID NO: 19. In some embodiments, a Defense System Xc comprising a JetAiii polypeptide, a JetBiii polypeptide, a JetCiii polypeptide, and a JetDiii polypeptide, is encoded by a nucleic acid sequence having at least 80% identity to the sequence set forth in SEQ ID NO: 19. In some embodiments, a Defense System Xc comprising a JetAiii polypeptide, a JetBiii polypeptide, a JetCiii polypeptide, and a JetDiii polypeptide, is encoded by a nucleic acid sequence having at least 85% identity, or 90% identity, or 95% identity, or 97% identity, or 98% identity, or 99% identity to the sequence set forth in SEQ ID NO: 19.


In some embodiments, the components of a Wadjet Type I defense system (Defense System Xa) comprise genes jetA, jetB, jetC, and jetD. In some embodiments, the components of a Wadjet Type I defense system consist of genes jetA, jetB, jetC, and jetD. In some embodiments, the components of a Wadjet Type I defense system comprise nucleic acid sequences encoding a JetA polypeptide, a JetB polypeptide, a JetC polypeptide, and a JetD polypeptide. In some embodiments, the components of a Wadjet Type I defense system consist of nucleic acid sequences encoding a JetA polypeptide, a JetB polypeptide, a JetC polypeptide, and a JetD polypeptide. In some embodiments, the components of a Wadjet Type I defense system comprise a jetB gene, a jetC gene, and a jetD gene. In some embodiments, the components of a Wadjet Type I defense system consist of a jetB gene, a jetC gene, and a jetD gene. In some embodiments, the components of a Wadjet Type I defense system comprise nucleic acid sequences encoding a JetB polypeptide, and a JetC polypeptide, and an MKsG polypeptide. In some embodiments, the components of a Wadjet Type I defense system consist of nucleic acid sequences encoding a JetB polypeptide, and a JetC polypeptide, and an MKsG polypeptide.


In some embodiments, the components of a Wadjet Type I defense system (Defense System Xa) comprise JetA, JetB, JetC, and JetD polypeptides. In some embodiments, the components of a Wadjet Type I defense system (Defense System Xa) consist of JetA, JetB, JetC, and JetD polypeptides. In some embodiments, the components of a Wadjet Type I defense system (Defense System Xa) comprise JetB, JetC, and JetD polypeptides. In some embodiments, the components of a Wadjet Type I defense system (Defense System Xa) consist of JetB, JetC, and JetD polypeptides. In some embodiments, the components of a Wadjet Type I defense system (Defense System Xa) comprise JetC, and JetD polypeptides. In some embodiments, the components of a Wadjet Type I defense system (Defense System Xa) consist of, and JetD polypeptides. In some embodiments, the components of a Wadjet Type I defense system (Defense System Xa) comprise a JetD polypeptide. In some embodiments, the components of a Wadjet Type I defense system (Defense System Xa) consist of a JetD polypeptide. In some embodiments, the components of a Wadjet Type I defense system (Defense System Xa) comprise JetA, JetC, and JetD polypeptides. In some embodiments, the components of a Wadjet Type I defense system (Defense System Xa) consist of JetA, JetC, and JetD polypeptides. In some embodiments, the components of a Wadjet Type I defense system (Defense System Xa) comprise JetA and JetD polypeptides. In some embodiments, the components of a Wadjet Type I defense system (Defense System Xa) consist of JetA and JetD polypeptides. In some embodiments, the components of a Wadjet Type I defense system (Defense System Xa) comprise JetA and JetC polypeptides. In some embodiments, the components of a Wadjet Type I defense system (Defense System Xa) consist of JetA and JetC polypeptides. In some embodiments, the components of a Wadjet Type I defense system (Defense System Xa) comprise JetB and JetC polypeptides. In some embodiments, the components of a Wadjet Type I defense system (Defense System Xa) consist of JetB and JetC polypeptides. In some embodiments, the components of a Wadjet Type I defense system (Defense System Xa) comprise JetB and JetD polypeptides. In some embodiments, the components of a Wadjet Type I defense system (Defense System Xa) consist of JetB and JetD polypeptides. In some embodiments, the components of a Wadjet Type I defense system (Defense System Xa) comprise JetB and JetC polypeptides. In some embodiments, the components of a Wadjet Type I defense system (Defense System Xa) consist of JetC and JetD polypeptides.


In some embodiments, the components of a Wadjet Type II defense system (Defense System Xb) comprise JetAii, JetBii, JetCii, and JetDii polypeptides. In some embodiments, the components of a Wadjet Type II defense system (Defense System Xb) consist of JetAii, JetBii, JetCii, and JetDii polypeptides. In some embodiments, the components of a Wadjet Type II defense system (Defense System Xb) comprise JetBii, JetCii, and JetDii polypeptides. In some embodiments, the components of a Wadjet Type II defense system (Defense System Xb) consist of JetBii, JetCii, and JetDii polypeptides. In some embodiments, the components of a Wadjet Type II defense system (Defense System Xb) comprise JetCii, and JetDii polypeptides. In some embodiments, the components of a Wadjet Type II defense system (Defense System Xb) consist of, and JetDii polypeptides. In some embodiments, the components of a Wadjet Type II defense system (Defense System Xb) comprise a JetDii polypeptide. In some embodiments, the components of a Wadjet Type II defense system (Defense System Xb) consist of a JetDii polypeptide. In some embodiments, the components of a Wadjet Type II defense system (Defense System Xb) comprise JetAii, JetCii, and JetDii polypeptides. In some embodiments, the components of a Wadjet Type II defense system (Defense System Xb) consist of JetAii, JetCii, and JetDii polypeptides. In some embodiments, the components of a Wadjet Type II defense system (Defense System Xb) comprise JetAii and JetDii polypeptides. In some embodiments, the components of a Wadjet Type II defense system (Defense System Xb) consist of JetAii and JetDii polypeptides. In some embodiments, the components of a Wadjet Type II defense system (Defense System Xb) comprise JetAii and JetCii polypeptides. In some embodiments, the components of a Wadjet Type II defense system (Defense System Xb) consist of JetAii and JetCii polypeptides. In some embodiments, the components of a Wadjet Type II defense system (Defense System Xb) comprise JetBii and JetCii polypeptides. In some embodiments, the components of a Wadjet Type II defense system (Defense System Xb) consist of JetBii and JetCii polypeptides. In some embodiments, the components of a Wadjet Type II defense system (Defense System Xb) comprise JetBii and JetDii polypeptides. In some embodiments, the components of a Wadjet Type II defense system (Defense System Xb) consist of JetBii and JetDii polypeptides. In some embodiments, the components of a Wadjet Type II defense system (Defense System Xb) comprise JetBii and JetCii polypeptides. In some embodiments, the components of a Wadjet Type II defense system (Defense System Xb) consist of JetCii and JetDii polypeptides.


In some embodiments, the components of a Wadjet Type III defense system (Defense System Xc) comprise JetAiii, JetBiii, JetCiii, and JetDiii polypeptides. In some embodiments, the components of a Wadjet Type III defense system (Defense System Xc) consist of JetAiii, JetBiii, JetCiii, and JetDiii polypeptides. In some embodiments, the components of a Wadjet Type III defense system (Defense System Xc) comprise JetBiii, JetCiii, and JetDiii polypeptides. In some embodiments, the components of a Wadjet Type III defense system (Defense System Xc) consist of JetBiii, JetCiii, and JetDiii polypeptides. In some embodiments, the components of a Wadjet Type III defense system (Defense System Xc) comprise JetCiii, and JetDiii polypeptides. In some embodiments, the components of a Wadjet Type III defense system (Defense System Xc) consist of, and JetDiii polypeptides. In some embodiments, the components of a Wadjet Type III defense system (Defense System Xc) comprise a JetDiii polypeptide. In some embodiments, the components of a Wadjet Type III defense system (Defense System Xc) consist of a JetDiii polypeptide. In some embodiments, the components of a Wadjet Type III defense system (Defense System Xc) comprise JetAiii, JetCiii, and JetDiii polypeptides. In some embodiments, the components of a Wadjet Type III defense system (Defense System Xc) consist of JetAiii, JetCiii, and JetDiii polypeptides. In some embodiments, the components of a Wadjet Type III defense system (Defense System Xc) comprise JetAiii and JetDiii polypeptides. In some embodiments, the components of a Wadjet Type III defense system (Defense System Xc) consist of JetAiii and JetDiii polypeptides. In some embodiments, the components of a Wadjet Type III defense system (Defense System Xc) comprise JetA11i and JetCiii polypeptides. In some embodiments, the components of a Wadjet Type III defense system (Defense System Xc) consist of JetAiii and JetCiii polypeptides. In some embodiments, the components of a Wadjet Type III defense system (Defense System Xc) comprise JetBiii and JetCiii polypeptides. In some embodiments, the components of a Wadjet Type III defense system (Defense System Xc) consist of JetBiii and JetCiii polypeptides. In some embodiments, the components of a Wadjet Type III defense system (Defense System Xc) comprise JetBiii and JetDiii polypeptides. In some embodiments, the components of a Wadjet Type III defense system (Defense System Xc) consist of JetBiii and JetDiii polypeptides. In some embodiments, the components of a Wadjet Type III defense system (Defense System Xc) comprise JetBiii and JetCiii polypeptides. In some embodiments, the components of a Wadjet Type III defense system (Defense System Xc) consist of JetCiii and JetDiii polypeptides.


In some embodiments, a Wadjet system Type I, Type II, or Type III, comprising a non-functional JetA/JetAii/JetAiii polypeptide or lacking a JetA/JetAii/JetAiii polypeptide has increased transformation efficiency. In some embodiments, a Wadjet system Type I, Type II, or Type III, comprising a non-functional JetC/JetCii/JetCiii polypeptide or lacking a JetC/JetCii/JetCiii polypeptide has increased transformation efficiency. In some embodiments, a Wadjet system Type I, Type II, or Type III, comprising a non-functional JetD/JetDii/JetDiii polypeptide or lacking a JetD/JetDii/JetDiii polypeptide has increased transformation efficiency.


In some embodiments, a construct comprising the Wadjet defense system encodes more than one component of the defense system but less than all of the components required for a functionally active defense system, whereby multiple constructs may be used to assemble the functional defense system. For example, in some embodiments each of jetA, jetB, jetC, and jetD may be encoded by nucleic acid sequences comprised in different constructs, wherein expression of the combination of constructs produces a functional a Wadjet Type I defense system. In some embodiments each of jetAii, jetBii, jetCii, and jetDii may be encoded by nucleic acid sequences comprised in different constructs, wherein expression of the combination of constructs produces a functional a Type II Wadjet defense system. In some embodiments each of jetAiii, jetBiii, jetCiii, and jetDiii may be encoded by nucleic acid sequences comprised in different constructs, wherein expression of the combination of constructs produces a functional a Type III Wadjet defense system.


In some embodiments, components of a Wadjet Type I defense system (Defense Systems Xa) may be encoded by a nucleic acid encoding 1, 2, 3, or 4 components of the Wadjet defense system as described herein. For example, in some embodiments, a construct comprises a nucleic acid comprising a jetA gene. In some embodiments, a construct comprises a nucleic acid comprising a jetA gene and a jetB gene. In some embodiments, a construct comprises a nucleic acid comprising a jetA gene and a jetC gene. In some embodiments, a construct comprises a nucleic acid comprising a jetA gene and a jetD gene. In some embodiments, a construct comprises a nucleic acid comprising a jetB gene. In some embodiments, a construct comprises a nucleic acid comprising a jetB gene and a jetC gene. In some embodiments, a construct comprises a nucleic acid comprising a jetB gene and a jetD gene. In some embodiments, a construct comprises a nucleic acid comprising a jetC gene. In some embodiments, a construct comprises a nucleic acid comprising a jetC gene and a jetD gene. In some embodiments, a construct comprises a nucleic acid comprising a jetD gene. In some embodiments, a construct comprises a nucleic acid comprising a jetA gene, a jetB gene, and a jetC gene. In some embodiments, a construct comprises a nucleic acid comprising a jetA gene, a jetB gene, and a jetD gene. In some embodiments, a construct comprises a nucleic acid comprising a jetA gene, a jetC gene, and a jetD gene. In some embodiments, a construct comprises a nucleic acid comprising a jetD gene, a jetB gene, and a jetC gene. In some embodiments, a construct comprises a nucleic acid comprising a jetD gene, a jetB gene, a jetC gene, and a jetA gene.


In some embodiments, components of a Wadjet Type II defense system (Defense Systems Xb) may be encoded by a nucleic acid encoding 1, 2, 3, or 4 components of the Wadjet defense system as described herein. For example, in some embodiments, a construct comprises a nucleic acid comprising a jetAii gene. In some embodiments, a construct comprises a nucleic acid comprising a jetAii gene and a jetBii gene. In some embodiments, a construct comprises a nucleic acid comprising a jetAii gene and a jetDii gene. In some embodiments, a construct comprises a nucleic acid comprising a jetBii gene. In some embodiments, a construct comprises a nucleic acid comprising a jetBii gene and a jetCii gene. In some embodiments, a construct comprises a nucleic acid comprising a jetBii gene and a jetDii gene. In some embodiments, a construct comprises a nucleic acid comprising a jetCii gene. In some embodiments, a construct comprises a nucleic acid comprising a jetCii gene and a jetDii gene. In some embodiments, a construct comprises a nucleic acid comprising a jetDii gene. In some embodiments, a construct comprises a nucleic acid comprising a jetAii gene, a jetBii gene, and a jetCii gene. In some embodiments, a construct comprises a nucleic acid comprising a jetAii gene, a jetBii gene, and a jetDii gene. In some embodiments, a construct comprises a nucleic acid comprising a jetAii gene, a jetCii gene, and a jetDii gene. In some embodiments, a construct comprises a nucleic acid comprising a jetDii gene, a jetBii gene, and a jetCii gene. In some embodiments, a construct comprises a nucleic acid comprising a jetDii gene, a jetBii gene, a jetCii gene, and a jetAii gene.


In some embodiments, components of a Wadjet Type III defense system (Defense Systems Xc) may be encoded by a nucleic acid encoding 1, 2, 3, or 4 components of the Wadjet defense system as described herein. For example, in some embodiments, a construct comprises a nucleic acid comprising a jetAiii gene. In some embodiments, a construct comprises a nucleic acid comprising a jetAiii gene and a jetBiii gene. In some embodiments, a construct comprises a nucleic acid comprising a jetAiii gene and a jetCiii gene. In some embodiments, a construct comprises a nucleic acid comprising a jetAiii gene and a jetDiii gene. In some embodiments, a construct comprises a nucleic acid comprising a jetBiii gene. In some embodiments, a construct comprises a nucleic acid comprising a jetBiii gene and a jetCiii gene. In some embodiments, a construct comprises a nucleic acid comprising a jetBiii gene and a jetDiii gene. In some embodiments, a construct comprises a nucleic acid comprising a jetDiii gene. In some embodiments, a construct comprises a nucleic acid comprising a jetCiii gene and a jetDiii gene. In some embodiments, a construct comprises a nucleic acid comprising a jetDiii gene. In some embodiments, a construct comprises a nucleic acid comprising a jetAiii gene, a jetiiiB gene, and a jetCiii gene. In some embodiments, a construct comprises a nucleic acid comprising a jetAiii gene, a jetBiii gene, and a jetDiii gene. In some embodiments, a construct comprises a nucleic acid comprising a jetAiii gene, a jetCiii gene, and a jetDiii gene. In some embodiments, a construct comprises a nucleic acid comprising a jetDiii gene, a jetBiii gene, and a jetCiii gene. In some embodiments, a construct comprises a nucleic acid comprising a jetDiii gene, a jetBiii gene, a jetCiii gene, and a jetAiii gene.


In some embodiments, components of a Wadjet defense system (Defense System Xa, Xb, or Xc) may comprise a nucleic acid encoding 1, 2, 3, or 4 polypeptide components of the Wadjet defense system. For example, in some embodiments, a construct comprises a nucleic acid encoding a JetA or a JetAii or a JetAiii polypeptide, respectively. In some embodiments, a construct comprises a nucleic acid encoding a JetA or a JetAii or a JetAiii polypeptide, respectively and a JetB or a JetBii or a JetBiii polypeptide, respectively. In some embodiments, a construct comprises a nucleic acid encoding a JetA or a JetAii or a JetAiii polypeptide, respectively and a JetC or a JetCii or a JetCiii polypeptide, respectively. In some embodiments, a construct comprises a nucleic acid encoding a JetA or a JetAii or a JetAiii polypeptide, respectively and a JetD or a JetDii or a JetDiii polypeptide, respectively. In some embodiments, a construct comprises a nucleic acid encoding a JetB or a JetBii or a JetBiii polypeptide, respectively. In some embodiments, a construct comprises a nucleic acid encoding a JetB or a JetBii or a JetBiii polypeptide, respectively and a JetC or a JetCii or a JetCiii polypeptide, respectively. In some embodiments, a construct comprises a nucleic acid encoding a JetB or a JetBii or a JetBiii polypeptide, respectively and a JetD or a JetDii or a JetDiii polypeptide, respectively. In some embodiments, a construct comprises a nucleic acid encoding a JetC or a JetCii or a JetCiii polypeptide, respectively. In some embodiments, a construct comprises a nucleic acid encoding a JetC or a JetCii or a JetCiii polypeptide, respectively and a JetD or a JetDii or a JetDiii polypeptide, respectively. In some embodiments, a construct comprises a nucleic acid encoding a JetD or a JetDii or a JetDiii polypeptide, respectively. In some embodiments, a construct comprises a nucleic acid encoding a JetA or a JetAii or a JetAiii polypeptide, respectively, a JetB or a JetBii or a JetBiii polypeptide, respectively, and a JetC or a JetCii or a JetCiii polypeptide, respectively. In some embodiments, a construct comprises a nucleic acid encoding a JetA or a JetAii or a JetAiii polypeptide, a JetB or a JetBii or a JetBiii polypeptide, respectively, and a JetD or a JetDii or a JetDiii polypeptide, respectively. In some embodiments, a construct comprises a nucleic acid encoding a JetA or a JetAii or a JetAiii polypeptide, a JetC polypeptide, and a JetD or a JetDii or a JetDiii polypeptide, respectively. In some embodiments, a construct comprises a nucleic acid encoding a JetD or a JetDii or a JetDiii polypeptide, respectively, a JetB or a JetBii or a JetBiii polypeptide, respectively, and a JetC or a JetCii or a JetCiii polypeptide, respectively.


In some embodiments, the components making up a functional Wadjet Type I anti-plasmid defense system comprise a JetA polypeptide, a JetB polypeptide, a JetC polypeptide, and a JetD polypeptide, each encoded by a jetA, a jetB, a jetC, and a jetD gene, respectively.


In some embodiments, the components making up a functional Wadjet Type II anti-plasmid defense system comprise a JetAii polypeptide, a JetBii polypeptide, a JetCii polypeptide, and a JetDii polypeptide, each encoded by a jetAii, a jetBii, a jetCii, and a jetDii gene, respectively


In some embodiments, the components making up a functional Wadjet Type III anti-plasmid defense system comprise a JetAiii polypeptide, a JetBiii polypeptide, a JetCiii polypeptide, and a JetDiii polypeptide, each encoded by a jetAiii, a jetBiii, a jetCiii, and a jetDiii gene, respectively


In some embodiments, a Wadjet defense system having an anti-plasmid activity (Defense System Xa, Xb, or Xc) comprises a nucleic acid encoding a JetA or a JetAii or a JetAiii polypeptide, respectively. In some embodiments, a Wadjet defense system having an anti-plasmid activity (Defense System Xa, Xb, or Xc) comprise a nucleic acid encoding a JetA or a JetAii or a JetAiii polypeptide, respectively and a JetB or a JetBii or a JetBiii polypeptide, respectively. In some embodiments, a Wadjet defense system having an anti-plasmid activity (Defense System Xa, Xb, or Xc) comprise a nucleic acid encoding a JetA or a JetAii or a JetAiii polypeptide, respectively and a JetC or a JetCii or a JetCiii polypeptide, respectively. In some embodiments, a Wadjet defense system having an anti-plasmid activity (Defense System Xa, Xb, or Xc) comprise a nucleic acid encoding a JetA or a JetAii or a JetAiii polypeptide, respectively and a JetD or a JetDii or a JetDiii polypeptide, respectively. In some embodiments, a Wadjet defense system having an anti-plasmid activity (Defense System Xa, Xb, or Xc) comprise a nucleic acid encoding a JetA or a JetAii or a JetAiii polypeptide, respectively, a JetB or a JetBii or a JetBiii polypeptide, respectively, and a JetC or a JetCii or a JetCiii polypeptide, respectively. In some embodiments, a Wadjet defense system having an anti-plasmid activity (Defense System Xa, Xb, or Xc) comprise a nucleic acid encoding a JetA or a JetAii or a JetAiii polypeptide, respectively, a JetB or a JetBii or a JetBiii polypeptide, respectively, and a JetD or a JetDii or a JetDiii polypeptide, respectively. In some embodiments, a Wadjet defense system having an anti-plasmid activity (Defense System Xa, Xb, or Xc) comprise a nucleic acid encoding a JetA or a JetAii or a JetAiii polypeptide, respectively, a JetC or a JetCii or a JetCiii polypeptide, respectively, and a JetD or a JetDii or a JetDiii polypeptide, respectively. In some embodiments, a Wadjet defense system having an anti-plasmid activity (Defense System Xa, Xb, or Xc) comprise a nucleic acid encoding a JetB or a JetBii or a JetBiii polypeptide, respectively. In some embodiments, a Wadjet defense system having an anti-plasmid activity (Defense System Xa, Xb, or Xc) comprise a nucleic acid encoding a JetB or a JetBii or a JetBiii polypeptide, respectively and a JetC or a JetCii or a JetCiii polypeptide, respectively. In some embodiments, a Wadjet defense system having an anti-plasmid activity (Defense System Xa, Xb, or Xc) comprise a nucleic acid encoding a JetB or a JetBii or a JetBiii polypeptide, respectively and a JetD or a JetDii or a JetDiii polypeptide, respectively. In some embodiments, a Wadjet defense system having an anti-plasmid activity (Defense System Xa, Xb, or Xc) comprise a nucleic acid encoding a JetC or a JetCii or a JetCiii polypeptide, respectively. In some embodiments, a Wadjet defense system having an anti-plasmid activity (Defense System Xa, Xb, or Xc) comprise a nucleic acid encoding a JetC or a JetCii or a JetCiii polypeptide, respectively and a JetD or a JetDii or a JetDiii polypeptide, respectively.


In some embodiments, a Wadjet defense system having an anti-plasmid activity (Defense System Xa, Xb, or Xc) comprises a nucleic acid comprising a jetA, jetAii, or jetAiii gene, respectively. In some embodiments, a Wadjet defense system having an anti-plasmid activity (Defense System Xa, Xb, or Xc) comprises a nucleic acid comprising a jetA, jetAii, or jetAiii gene, respectively and a jetB, jetBii, or jetBiii gene, respectively. In some embodiments, a Wadjet defense system having an anti-plasmid activity (Defense System Xa, Xb, or Xc) comprises a nucleic acid comprising a jetA, jetAii, or jetAiii gene, respectively and a jetC, jetCii, or jetCiii gene, respectively. In some embodiments, a Wadjet defense system having an anti-plasmid activity (Defense System Xa, Xb, or Xc) comprises a nucleic acid comprising a jetA, jetAii, or jetAiii gene, respectively and a jetD, jetDii, or jetDiii gene, respectively. In some embodiments, a Wadjet defense system having an anti-plasmid activity (Defense System Xa, Xb, or Xc) comprises a nucleic acid comprising a jetA, jetAii, or jetAiii gene, respectively, a jetB, jetBii, or jetBiii gene, respectively, and a jetC, jetCii, or jetCiii gene, respectively. In some embodiments, a Wadjet defense system having an anti-plasmid activity (Defense System Xa, Xb, or Xc) comprises a nucleic acid comprising a jetA, jetAii, or jetAiii gene, respectively, a jetB, jetBii, or jetBiii gene, respectively, and a jetD, jetDii, or jetDiii gene, respectively gene. In some embodiments, a Wadjet defense system having an anti-plasmid activity comprise a nucleic acid comprising a jetA, jetAii, or jetAiii gene, respectively, a jetC, jetCii, or jetCiii gene, respectively, and a jetD gene. In some embodiments, a Wadjet defense system having an anti-plasmid activity (Defense System Xa, Xb, or Xc) comprises a nucleic acid comprising a jetB, jetBii, or jetBiii gene, respectively. In some embodiments, a Wadjet defense system having an anti-plasmid activity (Defense System Xa, Xb, or Xc) comprises a nucleic acid comprising a jetB, jetBii, or jetBiii gene, respectively and a jetC, jetCii, or jetCiii gene, respectively. In some embodiments, a Wadjet defense system having an anti-plasmid activity comprise a nucleic acid comprising a jetB, jetBii, or jetBiii gene, respectively and a jetD, jetDii, or jetDiii gene, respectively. In some embodiments, a Wadjet defense system having an anti-plasmid activity (Defense System Xa, Xb, or Xc) comprises a nucleic acid comprising a jetB, jetBii, or jetBiii gene, respectively, a jetD, jetDii, or jetDiii gene, respectively, and a jetC, jetCii, or jetCiii gene, respectively. In some embodiments, a Wadjet defense system having an anti-plasmid activity (Defense System Xa, Xb, or Xc) comprises a nucleic acid comprising a jetC, jetCii, or jetCiii gene, respectively. In some embodiments, a Wadjet defense system having an anti-plasmid activity (Defense System Xa, Xb, or Xc) comprises a nucleic acid comprising a jetC, jetCii, or jetCiii gene, respectively and a jetD, jetDii, or jetDiii gene, respectively. In some embodiments, a Wadjet defense system having an anti-plasmid activity (Defense System Xa, Xb, or Xc) comprises a nucleic acid comprising a jetD, jetDii, or jetDiii gene, respectively.


In some embodiments, a Wadjet Type I defense system having an anti-plasmid activity comprises a nucleic acid construct comprising nucleic acids encoding polypeptides in a set order. In one embodiment, the 5′ to 3′ order of polypeptides encoded is JetA, JetB, JetC, and JetD. In some embodiments the 5′ to 3′ order of polypeptides does not affect the anti-plasmid activity. In some embodiments the 5′ to 3′ order of polypeptides does affect the anti-plasmid activity.


In some embodiments, the 5′ to 3′ order of polypeptides is random comprising any order of JetA, JetB, JetC, and JetD. In some embodiments, for example but not limited to, the order is JetB, JetC, JetD, and JetA; or JetC, JetD, JetA, and JetB; or JetD, JetA, JetB, and JetC.


In some embodiments, a Wadjet Type I defense system having an anti-plasmid activity comprises a nucleic acid construct comprising genes in a set order. In some embodiment, the 5′ to 3′ order of genes is jetA, jetB, jetC, and jetD. In some embodiment, the 5′ to 3′ order of genes in a Wadjet defense system is not jetA, jetB, jetC, and jetD. In some embodiments the 5′ to 3′ order of genes does not affect the anti-plasmid activity. In some embodiments the 5′ to 3′ order of genes does affect the anti-plasmid activity.


In some embodiments, the 5′ to 3′ order of genes is random, for example any order of jetA, jetB, jetC, and jetD. In some embodiments, for example but not limited to, the order is jetB, jetC, jetD, and jetA; or jetC, jetD, jetA, and jetB; or jetD, jetA, jetB, and jetC.


In some embodiments, a Wadjet Type II defense system having an anti-plasmid activity comprises a nucleic acid construct comprising nucleic acids encoding polypeptides in a set order. In one embodiment, the 5′ to 3′ order of polypeptides encoded is JetAii, JetBii, JetCii, and JetDii. In some embodiments the 5′ to 3′ order of polypeptides does not affect the anti-plasmid activity. In some embodiments the 5′ to 3′ order of polypeptides does affect the anti-plasmid activity.


In some embodiments, the 5′ to 3′ order of polypeptides is random comprising any order of JetAii, JetBii, JetCii, and JetDii. In some embodiments, for example but not limited to, the order is JetBii, JetCii, JetDii, and JetAii; or JetCii, JetDii, JetAii, and JetBii; or JetDii, JetAii, JetBii, and JetCii.


In some embodiments, a Wadjet Type II defense system having an anti-plasmid activity comprises a nucleic acid construct comprising genes in a set order. In some embodiment, the 5′ to 3′ order of genes is jetAii, jetBii, jetCii, and jetDii. In some embodiment, the 5′ to 3′ order of genes in a Wadjet defense system is not jetAii, jetBii, jetCii, and jetDii. In some embodiments the 5′ to 3′ order of genes does not affect the anti-plasmid activity. In some embodiments the 5′ to 3′ order of genes does affect the anti-plasmid activity.


In some embodiments, the 5′ to 3′ order of genes is random, for example any order of jetAii, jetBii, jetCii, and jetDii. In some embodiments, for example but not limited to, the order is jetBii, jetCii, jetDii, and jetAii; or jetCii, jetDii, jetAii, and jetBii; or jetDii, jetAii, jetBii, and jetCii.


In some embodiments, a Wadjet Type III defense system having an anti-plasmid activity comprises a nucleic acid construct comprising nucleic acids encoding polypeptides in a set order. In one embodiment, the 5′ to 3′ order of polypeptides encoded is JetAiii, JetBiii, JetCiii, and JetDiii. In some embodiments the 5′ to 3′ order of polypeptides does not affect the anti-plasmid activity. In some embodiments the 5′ to 3′ order of polypeptides does affect the anti-plasmid activity.


In some embodiments, the 5′ to 3′ order of polypeptides is random comprising any order of JetAiii, JetBiii, JetCiii, and JetDiii. In some embodiments, for example but not limited to, the order is JetBiii, JetCiii, JetDiii, and JetAiii; or JetCiii, JetDiii, JetAiii, and JetBiii; or JetDiii, JetAiii, JetBiii, and JetCiii.


In some embodiments, a Wadjet Type I defense system having an anti-plasmid activity comprises a nucleic acid construct comprising genes in a set order. In some embodiment, the 5′ to 3′ order of genes is jetAiii, jetBiii, jetCiii, and jetDiii. In some embodiment, the 5′ to 3′ order of genes in a Wadjet defense system is not jetAiii, jetBiii, jetCiii, and jetDiii. In some embodiments the 5′ to 3′ order of genes does not affect the anti-plasmid activity. In some embodiments the 5′ to 3′ order of genes does affect the anti-plasmid activity.


In some embodiments, the 5′ to 3′ order of genes is random, for example any order of jetAiii, jetBiii, jetCiii, and jetDiii. In some embodiments, for example but not limited to, the order is jetBiii, jetCiii, jetDiii, and jetAiii; or jetCiii, jetDiii, jetAiii, and jetBiii; or jetDiii, jetAiii, jetBiii, and jetCiii.


In some embodiments, the Wadjet Type I system (Defense System Xa) composition and order is as shown in FIG. 7B. In some embodiments, the Wadjet Type II system (Defense System Xb) composition and order is as shown in FIG. 7B. In some embodiments, the Wadjet Type III system (Defense System Xc) composition and order is as shown in FIG. 7B.


In some embodiments, a Wadjet Type I defense system having an anti-plasmid activity originates from a microbial genome, for example a bacterial or an archaeal genome (Table 11). In some embodiments, a Wadjet Type II defense system having an anti-plasmid activity originates from a microbial genome, for example a bacterial or an archaeal genome (Table 11). In some embodiments, a Wadjet Type III defense system having an anti-plasmid activity originates from a microbial genome, for example a bacterial or an archaeal genome (Table 11).


A skilled artisan would appreciate that a Wadjet system (Defense Xa, Xb, Xc) is not present in the majority of bacteria and or archaea species.


In some embodiments, a functional Wadjet defense system (Defense System Xa, Xb, or Xc) comprises a construct comprising nucleic acid sequences encoding polypeptides, wherein the nucleic acid sequence encoding each polypeptide may originate from a different microbial species. For example, the source of the nucleic acid sequence encoding a JetA, a JetAii, or a JetAiii polypeptides, respectively polypeptide may be one microbial species, the source of the nucleic acid sequence encoding a JetB, a JetBii, or a JetBiii polypeptides, respectively may be a different microbial species, the source of the nucleic acid sequence encoding a JetC, a JetCii, or a JetCiii polypeptides, respectively may be yet a different microbial species, and the source of the nucleic acid sequence encoding a JetD, a JetDii, or a JetDiii polypeptides, respectively may be still a different microbial species. In some embodiments, a functional Wadjet defense system (Defense System Xa, Xb, or Xc) comprises a non-naturally occurring combination of polypeptide components. In some embodiments, a functional Wadjet defense system (Defense System Xa, Xb, or Xc) comprises a combination of at least two polypeptides that do not naturally occur together. In some embodiments, a functional Wadjet defense system (Defense System Xa, Xb, or Xc) comprises a combination of at least three polypeptides that do not naturally occur together. In some embodiments, a functional Wadjet defense system (Defense System Xa, Xb, or Xc) comprises a combination of four polypeptides that do not naturally occur together.


In some embodiments, a functional Wadjet defense system (Defense System Xa, Xb, or Xc) comprises a construct comprising nucleic acid sequences encoding polypeptides, wherein the nucleic acid sequence encoding each polypeptide may originate from a different bacterial species. For example, the source of the nucleic acid sequence encoding a JetA, a JetAii, or a JetAiii polypeptides, respectively may be one bacterial species, the source of the nucleic acid sequence encoding a JetB, a JetBii, or a JetBiii polypeptides, respectively may be a different bacterial species, the source of the nucleic acid sequence encoding a JetC, a JetCii, or a JetCiii polypeptides, respectively may be yet a different bacterial species, and the source of the nucleic acid sequence encoding a JetD, a JetDii, or a JetDiii polypeptides, respectively may be still a different bacterial species.


In some embodiments, the source of the nucleic acid encoding a JetA, a JetAii, or a JetAiii polypeptides, respectively, a JetB, a JetBii, or a JetBiii polypeptides, respectively, a JetC, a JetCii, or a JetCiii polypeptides, respectively, and a JetD, a JetDii, or a JetDiii polypeptides, respectively is the same. In some embodiments, the source of the nucleic acid encoding a JetA, a JetAii, or a JetAiii polypeptides, respectively, a JetB, a JetBii, or a JetBiii polypeptides, respectively, a JetC, a JetCii, or a JetCiii polypeptides, respectively, and a JetD, a JetDii, or a JetDiii polypeptides, respectively is the not the same. In some embodiments, the source of some of the components is the same, while the source of other components is not the same. In some embodiments, the source of the nucleic acid sequence of some of the components is same and the source of other of the components is different. For example, but not limited to the source of any of the nucleic acid sequences encoding JetA, a JetAii, or a JetAiii polypeptides, respectively; JetB, a JetBii, or a JetBiii polypeptides, respectively; JetC, a JetCii, or a JetCiii polypeptides, respectively; and a JetD, a JetDii, or a JetDiii polypeptides, respectively may be the same or different, having any combination thereof. In some embodiments, the source of the nucleic acid sequence of any of the components of a Wadjet defense system (Defense Systems Xa, Xb, or Xc) comprises any of the species listed in Table 11.


In some embodiments, a Wadjet defense system (Defense Systems Xa, Xb, or Xc) having an anti-plasmid activity comprises a nucleic acid construct comprising non-coding regions between the nucleic acid sequences encoding the polypeptides. In some embodiments, the non-coding regions between the nucleic acid sequences comprises nucleic acid sequence not naturally occurring in the microbial species of origin. In some embodiments, the non-coding regions between the nucleic acid sequences comprises nucleic acid sequence is the naturally occurring in the microbial species of origin.


In some embodiments, a Wadjet system disclosed herein (Defense Systems Xa, Xb, or Xc) comprises a multi-gene phage resistance system broadly distributed in microbial genomes. According to some embodiments, the Wadjet system (Defense Systems Xa, Xb, or Xc) components are located in a gene cluster in a microbial cell genome. According to some embodiments, the Wadjet system (Defense Systems Xa, Xb, or Xc) components are located in close proximity (e.g. positioned within 20 genes, 10 genes, 5 genes or less one from the other) in a genome of a prokaryotic cell. According to some embodiments the prokaryotic cell expresses an endogenous Wadjet defense system (Defense Systems Xa, Xb, or Xc). According to some embodiments, the prokaryotic cell expresses an endogenous functional Wadjet defense system (Defense Systems Xa, Xb, or Xc). According to some embodiments, the species of prokaryotic cell is selected from the group consisting of the species listed in Table 11. According to some embodiments, a prokaryotic cell expresses a non-endogenous Wadjet defense system (Defense Systems Xa, Xb, or Xc). According to some embodiments, a prokaryotic cell expresses a non-endogenous functional Wadjet defense system (Defense Systems Xa, Xb, or Xc). According to some embodiments, the species of prokaryotic cell expressing a non-endogenous functional Wadjet defense system (Defense Systems Xa, Xb, or Xc) is selected from the group consisting of the species listed in Table 11.


In some embodiments, Wadjet Type I defense system components comprise JetA, JetB, JetC and JetD polypeptides. In some embodiments, Wadjet Type I defense system components comprise functional portions of JetA, JetB, JetC and JetD polypeptides. In some embodiments, the Wadjet Type I defense system components are encoded by jetA, jetB, jetC and jetD genes. In some embodiments, Wadjet Type I defense system components comprise JetB, JetC and JetD polypeptides.


In some embodiments, Wadjet Type II defense system components comprise JetAii, JetBii, JetCii and JetDii polypeptides. In some embodiments, Wadjet Type II defense system components comprise functional portions of JetAii, JetBii, JetCii and JetDii polypeptides. In some embodiments, the Wadjet Type II defense system components are encoded by jetAii, jetBii, jetCii and jetDii genes.


In some embodiments, Wadjet Type III defense system components comprise JetAiii, JetBiii, JetCiii and JetDiii polypeptides. In some embodiments, Wadjet Type III defense system components comprise functional portions of JetAiii, JetBiii, JetCiii and JetDiii polypeptides. In some embodiments, the Wadjet Type III defense system components are encoded by jetAiii, jetBiii, jetCiii and jetDiii genes.


Non-limiting embodiments of endogenous Wadjet systems (Defense Systems Xa, Xb, and Xc) and the respective location of their components are provided in Table 11 herein.


In some embodiments, the components of a Wadjet system may be identified by the presence of similar domains present within each component. In some embodiments, domains comprise pfam domains and or clusters of orthologous groups (COG) domains.


In some embodiments, the term “JetA” refers to the polynucleotide or expression product e.g., the polypeptide encoded by the jetA gene, comprising variants jetA, jetAii and jetAiii, associated with Defense Systems Xa, Xb, and Xc, respectively. In some embodiments, the terms “jetA”, “jetAii” and “jetAiii”, may be used interchangeably. In some embodiments, the term “JetA” refers to a JetA polypeptide or a JetAii polypeptide or a JetAiii polypeptide (FIG. 7B). In some embodiments, the terms JetA, JetAii, and JetAiii may be used interchangeably.


A skilled artisan would recognize that each Defense System X (Xa, Xb, and Xc) comprises a JetA polypeptide (A), a JetB polypeptide (B), a Jet C polypeptide (C), and a JetD polypeptide (C), wherein the polypeptides are encoded by a jetA gene, a jetB gene, a jetC gene, or a jetD gene, and variants thereof.


In some embodiments, the jetA gene encodes a polypeptide comprising a pfam11855 domain. In some embodiments, the jetA gene encodes a polypeptide comprising a DUF3375 domain. In some embodiments, the jetA gene encodes a polypeptide comprising a pfam09660 domain. In some embodiments, the jetA gene encodes a polypeptide comprising a DUF2397 domain. In some embodiments, the jetA gene encodes a polypeptide comprising no known domain. In some embodiments, the jetA gene encodes a polypeptide comprising a pfam11855 domain, or a DUF3375 domain, or a pfam09660 domain, or a DUF2397 domain, or any combination thereof. In some embodiments, the jetA gene encodes a polypeptide comprising a pfam11855 domain and a DUF3375 domain. In some embodiments, a jetA gene encodes a polypeptide comprising a pfam09660 domain and a DUF2397 domain.


In some embodiments, the jetA gene encodes a polypeptide comprising a member of the MukF-like family. MukF appears to play a role in chromosome partitioning during cell division. MukF has been described as a member of the kleisin family, which includes proteins that commonly mediate the interaction between SMCs and other accessory proteins.


In some embodiments, JetA polypeptide is encoded by a gene positioned within 5-60 genes of a gene encoding a JetB, JetC, and or JetD polypeptide in a genome of a prokaryotic cell. In some embodiments, JetA polypeptide is encoded by a gene positioned within 5 genes upstream (5′) or downstream (3′) to a gene encoding a JetB, JetC, and or JetD polypeptide in a genome of a prokaryotic cell. In some embodiments, JetA polypeptide is encoded by a gene positioned within 5 genes upstream (5′) and downstream (3′) to a gene encoding a JetB, JetC, and or JetD polypeptide, or any combination thereof, in a genome of a prokaryotic cell.


In some embodiments, JetA and JetB are encoded by genes positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, JetA and JetB are encoded by genes positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, JetA, JetB, and JetC are encoded by genes positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, JetA, JetB, and JetC are encoded by genes positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, JetA, JetB, JetC, and JetD are encoded by genes positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, JetA, JetB, JetC, and JetD are encoded by genes positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, JetD, JetA JetB, and JetC are encoded by genes positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, JetD, JetA, JetB, and JetC are encoded by genes positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell.


In some embodiments, jetA and jetB genes are positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, jetA, and jetB, genes are positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, jetA, jetB, and jetC genes are positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, jetA, jetB, and jetC genes are positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, jetA, jetB, jetC, and jetD genes are positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, jetA, jetB, jetC, and jetD genes are positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, jetD, jetA, jetB, and jetC genes are positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, jetD, jetD, jetB, and jetC genes are positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell.


In some embodiments, a JetA polypeptide is about 488 amino acids long (median gene size).


In some embodiments, the JetA polypeptide comprises the amino acid sequence having at least 80% homology to a sequence selected from the group consisting of the polypeptides referenced in Table 11, rows 2-3174, columns J and K. In some embodiments, the JetA polypeptide comprises the amino acid sequence having at least 80% homology to similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 11, rows 2-3174, columns J and K. In some embodiments, the JetA polypeptide comprises a homolog of a polypeptide having the amino acid sequences set forth in the polypeptides referenced in Table 11, rows 2-3174, columns J and K. In some embodiments, a homolog of a JetA polypeptide comprises a member of the MukF-like family. In some embodiments, the JetA polypeptide comprises the amino acid sequence having at least 80% identity to a sequence selected from the group consisting of the polypeptides referenced in Table 11, rows 2-3174, columns J and K. In some embodiments, the JetA polypeptide comprises the amino acid sequence having at least 80% identity to similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 11, rows 2-3174, columns J and K. In some embodiments, the JetA polypeptide comprises a homolog of a polypeptide having the amino acid sequences set forth in the polypeptides referenced in Table 11, rows 2-3174, columns J and K.


In some embodiments, the JetA polypeptide comprises the amino acid sequence having at least 80% identity to a sequence selected from the group consisting of the polypeptides referenced in Table 11, rows 2-3174, columns J and K. In some embodiments, the JetA polypeptide comprises the amino acid sequence having at least 80% identity within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 11, rows 2-3174, columns J and K.


In some embodiments, an JetA polypeptide comprises a MukF-like domain. In some embodiments, an JetA polypeptide comprises a MukF-like activity.


In some embodiments, the JetA polypeptide comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polypeptides referenced in Table 11, rows 2-3174, column J and K. In some embodiments, the JetA polypeptide comprises the amino acid sequence having at least 80%, 85%, 90%, 95% homology within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 11, rows 2-3174, columns J and K. In some embodiments, the JetA polypeptide comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polypeptides referenced in Table 11, rows 2-3174, columns J and K. In some embodiments, the JetA polypeptide comprises the amino acid sequence having at least 80%, 85%, 90%, 95% identity within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 11, rows 2-3174, columns J and K. In some embodiments, the JetA polypeptide comprises an amino acid sequence selected from the group consisting of the polypeptides referenced in Table 11, rows 2-3174, columns J and K.


In some embodiments, the JetA polypeptide comprises an amino acid sequence encoded by a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polynucleotides referenced in Table 11, rows 2-3174, columns J and L. In some embodiments, the JetA polypeptide comprises the amino acid sequence encoded by a nucleic acid sequence having at least 80%, 85%, 90%, 95% homology within similar domain regions within a sequence selected from the group consisting of the polynucleotides referenced in Table 11, rows 2-3174, columns J. and L In some embodiments, the JetA polypeptide comprises an amino acid sequence encoded by a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polynucleotides referenced in Table 11, rows 2-3174, columns J and L. In some embodiments, the JetA polypeptide comprises the amino acid sequence encoded by a nucleic acid sequence having at least 80%, 85%, 90%, 95% homology within similar domain regions within a sequence selected from the group consisting of the polynucleotides referenced in Table 11, rows 2-3174, columns J and L. In some embodiments, the JetA polypeptide comprises an amino acid sequence encoded from a nucleic acid sequence selected from the group consisting of the polynucleotides referenced in Table 11, rows 2-3174, columns J and L.


In some embodiments, the nucleic acid sequence of a jetA gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polynucleotides referenced in Table 11, rows 2-3174, columns J and L. In some embodiments, the jetA gene comprises a nucleic acid sequence having at least 80%, 85%, 90%, 95% homology within encoded similar domain regions in comparison with nucleotide sequence encoding these domain within a sequence selected from the group consisting of the polynucleotides referenced in Table 11, rows 2-3174, columns J and L. In some embodiments, the nucleic acid sequence of a jetA gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polynucleotides referenced in Table 11, rows 2-3174, columns J and L. In some embodiments, the jetA gene comprises a nucleic acid sequence having at least 80%, 85%, 90%, 95% identity within encoded similar domain regions in comparison with nucleotide sequence encoding these domain within a sequence selected from the group consisting of the polynucleotides referenced in Table 11, rows 2-3174, columns J and L. In some embodiments, the nucleic acid sequence of a jetA gene comprises a nucleic acid sequence selected from the group consisting of the polynucleotides referenced in Table 11, rows 2-3174, columns J and L.


In some embodiments, the term “JetB” refers to the polynucleotide or expression product e.g., the polypeptide encoded by the jetB gene, comprising variants jetB, jetBii and jetBiii, associated with Defense Systems Xa, Xb, and Xc, respectively. In some embodiments, the terms “jetB”, “jetBii” and “jetBiii”, may be used interchangeably. In some embodiments, the term “JetB” refers to a JetB polypeptide or a JetBii polypeptide or a JetBiii polypeptide (FIG. 7B). In some embodiments, the terms JetB, JetBii, and JetBiii may be used interchangeably.


In some embodiments, the product of the jetB gene comprises a pfam13835 domain. In some embodiments, the product of the jetB gene comprises a DUF4194 domain. In some embodiments, the product of the jetB gene comprises a pfam09661 domain. In some embodiments, the product of the jetB gene comprises a DUF2398 domain. In some embodiments, the product of the jetB gene comprises a pfam13835 domain and a DUF4194 domain. In some embodiments, the product of the jetB gene comprises a pfam09661 domain and a DUF2398 domain. In some embodiments, the product of the jetB gene comprises a pfam13835 domain, or a DUF4194 domain, or pfam09661 domain, or a DUF2398 domain, or any combination thereof. In some embodiments, the product of the jetB gene comprises a pfam13835 domain, a DUF4194 domain, a pfam09661 domain, and a DUF2398 domain. In some embodiments, the jetB gene encodes a member of MukE-like family.


In some embodiments, JetB polypeptide is encoded by a gene positioned within 5-60 genes of a gene encoding a JetA, a JetC, and or a JetD polypeptide in a genome of a prokaryotic cell. In some embodiments, JetB polypeptide is encoded by a gene positioned within 5 genes upstream (5′) or downstream (3′) to a gene encoding a JetA, JetC, and or a JetD polypeptide in a genome of a prokaryotic cell.


In some embodiments, JetB and JetC are encoded by genes positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments JetB and JetC are encoded by genes positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, JetB and JetD are encoded by genes positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments JetB and JetD are encoded by genes positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, JetB and JetA are encoded by genes positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments JetB and JetA are encoded by genes positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, JetB, JetC, and JetD are encoded by genes positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, JetB, JetC, and JetD are encoded by genes positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell.


In some embodiments, JetB polypeptide is encoded by a gene positioned within 5 genes upstream or downstream to a gene encoding jetA, jetC, and or jetD, in a genome of a prokaryotic cell. In some embodiments, JetB polypeptide is encoded by a gene positioned within 5 genes upstream or downstream to a gene encoding jetA in a genome of a prokaryotic cell. In some embodiments, JetB polypeptide is encoded by a gene positioned within 5 genes upstream or downstream to a gene encoding jetD in a genome of a prokaryotic cell. In some embodiments, JetB polypeptide is encoded by a gene positioned within 5 genes upstream or downstream to a gene encoding jetC in a genome of a prokaryotic cell.


In some embodiments, a JetB polypeptide is about 247 amino acids long (median gene size).


In some embodiments, the JetB polypeptide comprises an amino acid sequence having at least 80% homology to a sequence selected from the group consisting of the polypeptides referenced in Table 11, rows 2-3174, columns N and O. In some embodiments, the JetB polypeptide comprises an amino acid sequence having at least 80% homology to similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 11, rows 2-3174, columns N and O. In some embodiments, a homolog of the JetB polypeptide comprises a MukE-like family member. In some embodiments, the JetB polypeptide comprises an amino acid sequence having at least 80% identity to a sequence selected from the group consisting of the polypeptides referenced in Table 11, rows 2-3174, columns N and O. In some embodiments, the JetB polypeptide comprises an amino acid sequence having at least 80% identity to similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 11, rows 2-3174, columns N and O. In some embodiments, a JetB homolog comprises an amino acid sequence having at least 80% identity to a sequence selected from the group consisting of the polypeptides referenced in Table 11, rows 2-3174, columns N and O.


In some embodiments, a JetB polypeptide homolog comprises a MukE-like domain. In some embodiments, a JetB polypeptide homolog comprises a MukE-like activity.


In some embodiments, the JetB polypeptide comprises the amino acid sequence having at least 80% identity to a sequence selected from the group consisting of the polypeptides referenced in Table 11, rows 2-3174, columns N and O. In some embodiments, the JetB polypeptide comprises the amino acid sequence having at least 80% identity within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 11, rows 2-3174, columns N and O.


In some embodiments, the JetB polypeptide comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polypeptides referenced in Table 11, rows 2-3174, columns N and O. In some embodiments, the JetB polypeptide comprises the amino acid sequence having at least 80%, 85%, 90%, 95% homology within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 11, rows 2-3174, columns N and O. In some embodiments, the JetB polypeptide comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polypeptides referenced in Table 11, rows 2-3174, columns N and O. In some embodiments, the JetB polypeptide comprises the amino acid sequence having at least 80%, 85%, 90%, 95% identity within similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 11, rows 2-3174, columns N and O. In some embodiments, the JetB polypeptide comprises an amino acid sequence selected from the group consisting of the polypeptides referenced in Table 11, rows 2-3174, columns N and O.


In some embodiments, the JetB polypeptide comprises an amino acid sequence encoded by a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polynucleotides referenced in Table 11, rows 2-3174, columns N and P. In some embodiments, the JetB polypeptide comprises the amino acid sequence encoded by a nucleic acid sequence having at least 80%, 85%, 90%, 95% homology within similar domain regions within a sequence selected from the group consisting of the polynucleotides referenced in Table 11, rows 2-3174, columns N and P. In some embodiments, the JetB polypeptide comprises an amino acid sequence encoded by a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polynucleotides referenced in Table 11, rows 2-3174, columns N and P. In some embodiments, the JetB polypeptide comprises the amino acid sequence encoded by a nucleic acid sequence having at least 80%, 85%, 90%, 95% homology within similar domain regions within a sequence selected from the group consisting of the polynucleotides referenced in Table 11, rows 2-3174, columns N and P. In some embodiments, the JetB polypeptide comprises an amino acid sequence encoded from a nucleic acid sequence selected from the group consisting of the polynucleotides referenced in Table 11, rows 2-3174, columns N and P.


In some embodiments, the nucleic acid sequence of a jetB gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polynucleotides referenced in Table 11, rows 2-3174, columns N and P. In some embodiments, the jetB gene comprises a nucleic acid sequence having at least 80%, 85%, 90%, 95% homology within encoded similar domain regions in comparison with nucleotide sequence encoding these domain within a sequence selected from the group consisting of the polynucleotides referenced in Table 11, rows 2-3174, columns N and P. In some embodiments, the nucleic acid sequence of a jetB gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polynucleotides referenced in Table 11, rows 2-3174, columns N and P. In some embodiments, the jetB gene comprises a nucleic acid sequence having at least 80%, 85%, 90%, 95% identity within encoded similar domain regions in comparison with nucleotide sequence encoding these domain within a sequence selected from the group consisting of the polynucleotides referenced in Table 11, rows 2-3174, columns N and P. In some embodiments, the nucleic acid sequence of a jetB gene comprises a nucleic acid sequence selected from the group consisting of the polynucleotides referenced in Table 11, rows 2-3174, columns N and P.


In some embodiments, the term “JetC” refers to the polynucleotide or expression product e.g., the polypeptide encoded by the jetC gene, comprising variants jetC, jetCii and jetCiii, associated with Defense Systems Xa, Xb, and Xc, respectively. In some embodiments, the terms “jetC”, “jetCii” and “jetCiii”, may be used interchangeably. In some embodiments, the term “JetC” refers to a JetC polypeptide or a JetCii polypeptide or a JetCiii polypeptide (FIG. 7B). In some embodiments, the terms JetC, JetCii, and JetCiii may be used interchangeably.


In some embodiments, the product of a jetC gene comprises a pfam13555 domain. In some embodiments, the product of a jetC gene comprises a pfam13558 domain. In some embodiments, the product of a jetC gene comprises a COG4913 domain. In some embodiments, the product of a jetC gene comprises a COG1196 domain. In some embodiments, the product of a jetC gene comprises a pfam1555 domain or a pfam13558 domain or a COG4913 domain, or a COG1196 domain, or a combination thereof. In some embodiments, the product of a jetC gene comprises a pfam1555 domain and a pfam13558 domain. In some embodiments, the product of a jetC gene comprises a pfam1555 domain, a pfam13558 domain, and a COG4913 domain. In some embodiments, the product of a jetC gene comprises a pfam1555 domain and a COG4913 domain. In some embodiments, the product of a jetC gene comprises a pfam13558 domain and a COG4913 domain. In some embodiments, the product of a jetC gene comprises a MukB-like family member. MukB appears to be functionally related to the structural maintenance of chromosomes (SMC) proteins. MukB is also known as the E. coli condesin, a structural maintenance of chromosomes (SMC)-like protein, which forms a complex with MukE and the kleisin MukF. MukB is known to be able to mediate knotting of a DNA ring, an intramolecular reaction. In some embodiments, the product of a jetC gene comprises an ATP binding domain. In some embodiments, the product of a jetC gene comprises an exonuclease SbcC domain. In some embodiments, the product of a jetC gene comprises a MukB-like family member, or an ATP binding domain or an exonuclease SbcC domain, or a combination thereof. In some embodiments, the product of a jetC gene comprises a MukB-like family member and an ATP binding domain. In some embodiments, the product of a jetC gene comprises a MukB-like family member and an exonuclease SbcC domain. In some embodiments, the product of a jetC gene comprises an ATP binding domain and an exonuclease SbcC domain. In some embodiments, the product of a jetC gene comprises a MukB-like family member, an ATP binding domain and an exonuclease SbcC domain.


In some embodiments, JetC polypeptide is encoded by a gene positioned within 5-60 genes of a gene encoding JetA, and/or JetB and/or JetD in a genome of a prokaryotic cell. In some embodiments, JetC polypeptide is encoded by a gene positioned within 5 genes upstream (5′) or downstream (3′) to a gene encoding JetA, and/or JetB and/or JetD in a genome of a prokaryotic cell. In some embodiments, JetC polypeptide is encoded by a gene positioned within 5 genes upstream and downstream to a gene encoding JetA, and/or JetB and/or JetD in a genome of a prokaryotic cell.


In some embodiments, JetC and JetD are encoded by genes positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, JetC and JetD are encoded by genes positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell.


In some embodiments, jetC and jetD genes are positioned sequentially 5′ to 3′ in a genome of a prokaryotic cell. In some embodiments, jetC and jetD genes are positioned contiguously 5′ to 3′ in a genome of a prokaryotic cell.


In some embodiments, a JetC polypeptide is about 1476 amino acids long (median gene size).


In some embodiments, the JetC polypeptide comprises an amino acid sequence having at least 80% homology to a sequence selected from the group consisting of the polypeptides referenced in Table 11, rows 2-3174, columns R and S. In some embodiments, the JetC polypeptide comprises an amino acid sequence having at least 80% identity to a sequence selected from the group consisting of the polypeptides referenced in Table 11, rows 2-3174, columns R and S. In some embodiments, the JetC polypeptide comprises an amino acid sequence having at least 80% homology to similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 11, rows 2-3174, columns R and S. In some embodiments, the JetC polypeptide comprises an amino acid sequence having at least 80% identity to similar domain regions a sequence selected from the group consisting of the polypeptides referenced in Table 11, rows 2-3174, columns R and S. In some embodiments, an JetC homolog comprises an amino acid sequence having at least 80% homology to a sequence selected from the group consisting of the polypeptides referenced in Table 11, rows 2-3174, columns R and S.


In some embodiments, an JetC polypeptide homolog comprises an ATP binding domain. In some embodiments, an JetC polypeptide homolog comprises an exonuclease SbcC activity. In some embodiments, an JetC polypeptide homolog comprises an MukB like activity.


In some embodiments, the JetC polypeptide comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of SEQ ID NOs: In some embodiments, the JetC polypeptide comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 11, rows 2-3174, columns R and S. In some embodiments, a JetC homolog comprises an ATP binding domain. In some embodiments, a JetC homolog comprises an exonuclease SbcC activity. In some embodiments, a JetC homolog comprises a member of the MukB-like family. In some embodiments, a JetC homolog comprises an ATP binding domain, or an exonuclease SbcC activity, or a member of the MukB-like family, or any combination thereof. In some embodiments, a JetC homolog comprises an ATP binding domain and an exonuclease SbcC activity. In some embodiments, a JetC homolog comprises an ATP binding domain and a member of the MukB-like family. In some embodiments, a JetC homolog comprises an exonuclease SbcC activity and a member of the MukB-like family. In some embodiments, a JetC homolog comprises an ATP binding domain, and an exonuclease SbcC activity, and a member of the MukB-like family.


In some embodiments, the JetC polypeptide comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polypeptides referenced in Table 11, rows 2-3174, columns R and S. In some embodiments, the JetC polypeptide comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 11, rows 2-3174, columns R and S. In some embodiments, the JetC polypeptide comprises an amino acid sequence selected from the group consisting of the polypeptides referenced in Table 11, rows 2-3174, columns R and S.


In some embodiments, the JetC polypeptide comprises an amino acid sequence encoded by a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polynucleotides referenced in Table 11, rows 2-3174, columns R and T. In some embodiments, the JetC polypeptide comprises the amino acid sequence encoded by a nucleic acid sequence having at least 80%, 85%, 90%, 95% homology within similar domain regions within a sequence selected from the group consisting of the polynucleotides referenced in Table 11, rows 2-3174, columns R and T. In some embodiments, the JetC polypeptide comprises an amino acid sequence encoded by a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polynucleotides referenced in Table 11, rows 2-3174, columns R and T. In some embodiments, the JetC polypeptide comprises the amino acid sequence encoded by a nucleic acid sequence having at least 80%, 85%, 90%, 95% homology within similar domain regions within a sequence selected from the group consisting of the polynucleotides referenced in Table 11, rows 2-3174, columns R and T. In some embodiments, the JetC polypeptide comprises an amino acid sequence encoded from a nucleic acid sequence selected from the group consisting of the polynucleotides referenced in Table 11, rows 2-3174, columns R and T.


In some embodiments, the nucleic acid sequence of a jetC gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polynucleotides referenced in Table 11, rows 2-3174, column N. In some embodiments, the jetC gene comprises a nucleic acid sequence having at least 80%, 85%, 90%, 95% homology within encoded similar domain regions in comparison with nucleotide sequence encoding these domain within a sequence selected from the group consisting of the polynucleotides referenced in Table 11, rows 2-3174, columns R and T. In some embodiments, the nucleic acid sequence of a jetC gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polynucleotides referenced in Table 11, rows 2-3174, columns R and T. In some embodiments, the jetC gene comprises a nucleic acid sequence having at least 80%, 85%, 90%, 95% identity within encoded similar domain regions in comparison with nucleotide sequence encoding these domain within a sequence selected from the group consisting of the polynucleotides referenced in Table 11, rows 2-3174, columns R and T. In some embodiments, the nucleic acid sequence of a jetC gene comprises a nucleic acid sequence selected from the group consisting of the polynucleotides referenced in Table 11, rows 2-3174, columns R and T.


In some embodiments, the jetC gene homolog encodes a polypeptide comprising an ATP binding domain. In some embodiments, a jetC gene homolog encodes a polypeptide comprising an exonuclease SbcC activity. In some embodiments, a jetC gene homolog encodes a polypeptide comprising a member of the MukB-like family. In some embodiments, a JetC homolog jetC gene homolog encodes a polypeptide comprising ATP binding domain, or an exonuclease SbcC activity, or a member of the MukB-like family, or any combination thereof. In some embodiments, a jetC gene homolog encodes a polypeptide comprising an ATP binding domain and an exonuclease SbcC activity. In some embodiments, a jetC gene homolog encodes a polypeptide comprising an ATP binding domain and a member of the MukB-like family. In some embodiments, a jetC gene homolog encodes a polypeptide comprising an exonuclease SbcC activity and a member of the MukB-like family. In some embodiments, a jetC gene homolog encodes a polypeptide comprising an ATP binding domain, and an exonuclease SbcC activity, and a member of the MukB-like family.


In some embodiments, the term “JetD” refers to the polynucleotide or expression product e.g., the polypeptide encoded by the jetD gene, comprising variants jetD, jetDii and jetDiii, associated with Defense Systems Xa, Xb, and Xc, respectively. In some embodiments, the terms “jetD”, “jetDii” and “jetDiii”, may be used interchangeably. In some embodiments, the term “JetD” refers to a JetD polypeptide or a JetDii polypeptide or a JetDiii polypeptide (FIG. 7B). In some embodiments, the terms JetD, JetDii, and JetDiii may be used interchangeably.


In some embodiments, the product of the jetD gene comprises a pfam11795 domain. In some embodiments, the product of the jetD gene comprises a DUF3322 domain. In some embodiments, the product of the jetD gene comprises a pfam09983 domain. In some embodiments, the product of the jetD gene comprises a DUF2220 domain. In some embodiments, the product of the jetD gene comprises a pfam11796 domain. In some embodiments, the product of the jetD gene comprises a DUF3323 domain. In some embodiments, the product of the jetD gene comprises a pfam09664 domain. In some embodiments, the product of the jetD gene comprises a DUF2399 domain. In some embodiments, the product of the jetD gene comprises a COG4924 domain. In some embodiments, the product of the jetD gene comprises a pfam11795 domain, or a DUF3322 domain, or a pfam09983 domain, or a DUF2220 domain, or a pfam11796 domain, or a DUF3323 domain, or a pfam09664 domain, or DUF2399 domain, or a COG4924 domain, or any combination thereof. In some embodiments, the product of the jetD gene comprises a pfam11795 domain and a DUF3322 domain. In some embodiments, the product of the jetD gene comprises a pfam09983 and a DUF2220 domain. In some embodiments, the product of the jetD gene comprises a pfam11796 domain and a DUF3323 domain. In some embodiments, the product of the jetD gene comprises a pfam09664 domain and DUF2399 domain. In some embodiments, the product of the jetD gene comprises a pfam11796 domain and a DUF3323 domain, and a pfam09664 domain, and a DUF2399 domain. In some embodiments, the product of the jetD gene comprises a pfam11795 domain and a DUF3322 domain, and a pfam09983 domain, and a DUF2220 domain. In some embodiments, the product of the jetD gene comprises a pfam11795 domain and a DUF3322 domain, and a pfam09983 domain, and a DUF2220 domain, and a COG4924 domain.


In some embodiments, a JetD polypeptide comprises a pfam11795 domain. In some embodiments, a JetD polypeptide comprises a DUF3322 domain. In some embodiments, a JetD polypeptide comprises a pfam09983 domain. In some embodiments, a JetD polypeptide comprises a DUF2220 domain. In some embodiments, a JetD polypeptide comprises a pfam11796 domain. In some embodiments, a JetD polypeptide comprises a DUF3323 domain. In some embodiments, a JetD polypeptide comprises a pfam09664 domain. In some embodiments, a JetD polypeptide comprises a DUF2399 domain. In some embodiments, a JetD polypeptide comprises a COG4924 domain. In some embodiments, a JetD polypeptide comprises a pfam11795 domain, or a DUF3322 domain, or a pfam09983 domain, or a DUF2220 domain, or a pfam11796 domain, or a DUF3323 domain, or a pfam09664 domain, or DUF2399 domain, or a COG4924 domain, or any combination thereof. In some embodiments, a JetD polypeptide comprises a pfam11795 domain and a DUF3322 domain. In some embodiments, a JetD polypeptide comprises a pfam09983 and a DUF2220 domain. In some embodiments, a JetD polypeptide comprises a pfam11796 domain and a DUF3323 domain. In some embodiments, a JetD polypeptide comprises a pfam09664 domain and DUF2399 domain. In some embodiments, a JetD polypeptide comprises a pfam11796 domain and a DUF3323 domain, and a pfam09664 domain, and a DUF2399 domain. In some embodiments, a JetD polypeptide comprises a pfam11795 domain and a DUF3322 domain, and a pfam09983 domain, and a DUF2220 domain. In some embodiments, a JetD polypeptide comprises a pfam11795 domain and a DUF3322 domain, and a pfam09983 domain, and a DUF2220 domain, and a COG4924 domain.


In some embodiments, a JetD polypeptide is encoded by a gene positioned within 5-60 genes of a gene encoding JetA, and/or JetB and/or JetC in a genome of a prokaryotic cell. In some embodiments, a JetD polypeptide is encoded by a gene positioned within 5 genes upstream (5′) or downstream (3′) to a gene encoding JetA, and/or JetB and/or JetC in a genome of a prokaryotic cell. In some embodiments, JetD polypeptide is encoded by a gene positioned within 5 genes upstream or downstream to a gene encoding JetA, and/or JetB and JetC in a genome of a prokaryotic cell.


In some embodiments, a JetD polypeptide is about 347 amino acids long (median gene size).


In some embodiments, the JetD polypeptide comprises an amino acid sequence having at least 80% homology to a sequence selected from the group consisting of the polypeptides referenced in Table 11, rows 2-3174, columns V and W. In some embodiments, the JetD polypeptide comprises an amino acid sequence having at least 80% homology to similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 11, rows 2-3174, columns V and W. In some embodiments, a JetD polypeptide homologue comprises a topoisomerase IV/VI activity. In some embodiments, the JetD polypeptide comprises an amino acid sequence having at least 80% identity to a sequence selected from the group consisting of the polypeptides referenced in Table 11, rows 2-3174, columns V and W. In some embodiments, the JetD polypeptide comprises an amino acid sequence having at least 80% identity to similar domain regions within a sequence selected from the group consisting of the polypeptides referenced in Table 11, rows 2-3174, columns V and W. In some embodiments, an JetD homolog comprises an amino acid sequence having at least 80% identity to a sequence selected from the group consisting of the polypeptides referenced in Table 11, rows 2-3174, columns V and W.


In some embodiments, a JetD polypeptide homolog comprises a topoisomerase IV/VI domain. In some embodiments, a JetD polypeptide homolog comprises a topoisomerase IV/VI structural domain. In some embodiments, a JetD polypeptide homolog comprises a topoisomerase IV/VI activity.


In some embodiments, the JetD polypeptide comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95% homology to a sequence selected from the group consisting of the polypeptides referenced in Table 11, rows 2-3174, columns V and W. In some embodiments, the JetD polypeptide comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95% identity to a sequence selected from the group consisting of the polypeptides referenced in Table 11, rows 2-3174, columns V and W. In some embodiments, the JetD polypeptide comprises an amino acid sequence selected from the group consisting of the polypeptides referenced in Table 11, rows 2-3174, columns V and W.


In some embodiments, the JetD polypeptide comprises an amino acid sequence encoded from a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polynucleotides referenced in Table 11, rows 2-3174, columns V and X. In some embodiments, the JetD polypeptide comprises an amino acid sequence encoded from a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polynucleotides referenced in Table 11, rows 2-3174, columns V and X. In some embodiments, the JetD polypeptide comprises an amino acid sequence encoded from a nucleic acid sequence selected from the group consisting of the polynucleotides referenced in Table 11, rows 2-3174, columns V and X.


In some embodiments, the jetD gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% homology to a sequence selected from the group consisting of the polynucleotides referenced in Table 11, rows 2-3174, columns V and X. In some embodiments, a mksG gene homolog encodes a polypeptide comprising a topoisomerase IV/VI activity. In some embodiments, the jetD gene comprises a nucleic acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity to a sequence selected from the group consisting of the polynucleotides referenced in Table 11, rows 2-3174, columns V and X. In some embodiments, the nucleic acid sequence of the jetD gene is selected from the group consisting of the polynucleotides referenced in Table 11, rows 2-3174, columns V and X.


A skilled artisan would appreciate that the terms a “functional portion of a Defense System X component” or “functional fragment of Defense System X component” or “functional portion of a Wadjet defense system component” or “functional fragment of Wadjet defense system component” refers to a functional portion of a Wadjet polynucleotide or polypeptide, as disclosed herein, which expression is sufficient to elicit an anti-plasmid transformation efficiency activity alone or in combination with the at least one of the other Wadjet polynucleotides or polypeptides disclosed herein or functional portions thereof.


The terms “JetA”, “JetB”, “JetC”, “JetD”, “JetAii”, “JetBii”, “JetCii”, “JetDii”, jetAiii”, “jetBiii”, “jetCiii” and “jetDiii’ also refer to functional homologs, which exhibit the desired activity (i.e., conferring decreased efficiency of plasmid transformation). Such homologs can be, for example, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical or homologous to the polypeptide sequences referenced in Table 11 rows 2-3174 columns J and K, N and O, R and S and V and W, respectively, or 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical or homologous to the polynucleotide sequences referenced in Table 11 rows 2-3174 columns J and L, N and P, R and T and V and X. In some embodiments, such homologs comprise at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% homology or identity within similar domain regions of the polypeptide sequences referenced in Table 11 rows 2-3174 columns J and K, N and O, R and S and V and W, or 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity or homology within nucleotide sequences encoding similar domain regions to the polynucleotide sequences referenced in Table 11 rows 2-3174 columns J and L, N and P, R and T and V and X.


Table 11 presents embodiments of components of Defense System X (Xa, Xb, and Xc) that may be found in a diverse array of bacteria and archaea genomes (referenced in Table 18). Table 11 presents embodiments of nucleic acid sequences encoding gene cassettes of Defense System X (Xa, Xb, and Xc; referenced in Table 18).


Defense System Components, Nucleic Acid Sequences Thereof, and Amino Acid Sequences Thereof


Defense System components, nucleic acid sequences thereof, amino acid sequences thereof, and gene cassette nucleotide sequences thereof are presented below in Table 18.









TABLE 18







Defense Systems: Components and Gene Cassettes-


polypeptide and nucleotide sequences thereof











Com-




Defense System
ponent
Composition
Table References





Defense System Ia
ZorA
polypeptides
Table 8; Rows 2-1174;


ZORYA Type I


Column J “ZorA





protein_accession” and





Column K “PRT SEQ ID





NO:”


Defense System Ia
ZorB
polypeptides
Table 8; Rows 2-1174;


ZORYA Type I


Column N “ZorB





protein_accession” and





Column O “PRT SEQ ID





NO:”


Defense System Ia
ZorC
polypeptides
Table 8; Rows 2-1174;


ZORYA Type I


Column R “ZorC





protein_accession” and





Column S “PRT SEQ ID





NO:”


Defense System Ia
ZorD
polypeptides
Table 8; Rows 2-1174;


ZORYA Type I


Column V “ZorD





protein_accession” and





Column W “PRT SEQ ID





NO:”


Defense System Ia
zorA
poly-
Table 8; Rows 2-1174;


ZORYA Type I

nucleotides
Column J “ZorA





protein_accession” and





Column L “DNA SEQ ID





NO:”


Defense System Ia
zorB
poly-
Table 8; Rows 2-1174;


ZORYA Type I

nucleotides
ColumnN “ZorB





protein_accession” and





Column P “DNA SEQ ID





NO:”


Defense System Ia
zorC
poly-
Table 8; Rows 2-1174;


ZORYA Type I

nucleotides
ColumnR “ZorC





protein_accession” and





Column T “DNA SEQ ID





NO:”


Defense System Ia
zorD
poly-
Table 8; Rows 2-1174;


ZORYA Type I

nucleotides
ColumnV “ZorD





protein_accession” and





Column X “DNA SEQ ID





NO:”


Defense System Ia
Gene
poly-
Table 8; Rows 2-1174;


ZORYA Type I
Cassette
nucleotides
Column G





“genomic_accession” with





Start in Column AD





“Genomic Start Point” and





End in Column AE





“Genomic End Point”


Defense System Ib
ZorA
polypeptides
Table 8; Rows 1175-1830;


ZORYA Type II


Column J “ZorA





protein_accession” and





Column K “PRT SEQ ID





NO:”


Defense System Ib
ZorB
polypeptides
Table 8; Rows 1175-1830;


ZORYA Type I


ColumnN “ZorB





protein_accession” and





Column O “PRT SEQ ID





NO:”


Defense System Ib
ZorE
polypeptides
Table 8; Rows 1175-1830;


ZORYA Type I


Column Z “ZorE





protein_accession” and





Column AA “PRT SEQ ID





NO:”


Defense System Ib
zorA
poly-
Table 8; Rows 1175-1830;


ZORYA Type I

nucleotides
Column J “ZorA





protein_accession” and





Column L “DNA SEQ ID





NO:”


Defense System Ib
zorB
poly-
Table 8; Rows 1175-1830;


ZORYA Type I

nucleotides
Column N “ZorB





protein_accession” and





Column P “DNA SEQ ID





NO:”


Defense System Ib
zorE
poly-
Table 8; Rows 1175-1830;


ZORYA Type I

nucleotides
ColumnZ “ZorE





protein_accession” and





Column AB “DNA SEQ ID





NO:”


Defense System Ib
Gene
poly-
Table 8; Rows 1175-1830;


ZORYA Type I
Cassette
nucleotides
Column G





“genomic_accession” with





Start in Column AD





“Genomic Start Point” and





End in Column AE





“Genomic End Point”


Defense System II
ThsA
polypeptides
Table 9; Rows 2-2100;


Thoeris


Column I “ThsA





protein_accession” and





Column J “PRT SEQ ID





NO:”


Defense System II
ThsB
polypeptides
Table 9; Rows 2-2100;


Thoeris


Column M “ThsBi





protein_accession” and





Column N “PRT SEQ ID





NO:”, Column Q “ThsBii





protein_accession” and





Column R “PRT SEQ ID





NO:”, Column U “ThsBiii





protein_accession” and





Column V “PRT SEQ ID





NO:”, Column Y “ThsBiv





protein_accession” and





Column Z “PRT SEQ ID





NO:”, and Column AC





“ThsBv





protein_accession” and





Column AD “PRT SEQ ID





NO:”


Defense System II
thsA
poly-
Table 9; Rows 2-2100;


Thoeris

nucleotides
Column I “ThsA





protein_accession” and





Column K “DNA SEQ ID





NO:”


Defense System II
thsB
poly-
Table 9; Rows 2-2100;


Thoeris

nucleotides
Column M “ThsBi





protein_accession” and





Column O “DNA SEQ ID





NO:”, Column Q “ThsBii





protein_accession” and





Column S “DNA SEQ ID





NO:”, Column U “ThsBiii





protein_accession” and





Column W “DNA SEQ ID





NO:”, Column Y “ThsBiv





protein_accession” and





Column AA “DNA SEQ ID





NO:”, and Column AC





“ThsBv





protein_accession” and





Column AE “DNA SEQ ID





NO:”


Defense System II
Gene
poly-
Table 9; Rows 2-2100;


Thoeris
Cassette
nucleotides
Column G





“genomic_accession” with





Start in Column AG





“Genomic Start Point” and





End in Column AH





“Genomic End Point”


Defense System
DruA
polypeptides
Table 10; Rows 2-123;


IIIa Druantia


Column J “DruA


Type I


protein_accession” and





Column K “PRT SEQ ID





NO:”


Defense System
DruB
polypeptides
Table 10; Rows 2-123;


IIIa Druantia


Column N “DruB


Type I


protein_accession” and





Column O “PRT SEQ ID





NO:”


Defense System
DruC
polypeptides
Table 10; Rows 2-123;


IIIa Druantia


Column R “DruC


Type I


protein_accession” and





Column S “PRT SEQ ID





NO:”


Defense System
DruD
polypeptides
Table 10; Rows 2-123;


IIIa Druantia


Column V “DruD


Type I


protein_accession” and





Column W “PRT SEQ ID





NO:”


Defense System
DruE
polypeptides
Table 10; Rows 2-123;


IIIa Druantia


Column Z “DruE


Type I


protein_accession” and





Column AA “PRT SEQ ID





NO:”


Defense System
druA
poly-
Table 10; Rows 2-123;


IIIa Druantia

nucleotides
Column J “DruA


Type I


protein_accession” and





Column L “DNA SEQ ID





NO:”


Defense System
druB
poly-
Table 10; Rows 2-123;


IIIa Druantia

nucleotides
Column N “DruB


Type I


protein_accession” and





Column P “DNA SEQ ID





NO:”


Defense System
druC
poly-
Table 10; Rows 2-123;


IIIa Druantia

nucleotides
Column R “DruC


Type I


protein_accession” and





Column T “DNA SEQ ID





NO:”


Defense System
druD
poly-
Table 10; Rows 2-123;


IIIa Druantia

nucleotides
Column V “DruD


Type I


protein_accession” and





Column X “DNA SEQ ID





NO:”


Defense System
druE
poly-
Table 10; Rows 2-123;


IIIa Druantia

nucleotides
Column Z “DruE


Type I


protein_accession” and





Column AB “DNA SEQ ID





NO:”


Defense System
Gene
poly-
Table 10; Rows 2-123;


IIIa Druantia
Cassette
nucleotides
Column G


Type I


“genomic_accession” with





Start in Column AT





“Genomic Start Point” and





End in Column AU





“Genomic End Point”


Defense System
DruM
polypeptides
Table 10; Rows 124-295;


IIIb Druantia


Column AD “DruM


Type II


protein_accession” and





Column AE “PRT SEQ ID





NO:”


Defense System
DruF
polypeptides
Table 10; Rows 124-295;


IIIb Druantia


Column AH “DruF


Type II


protein_accession” and





Column AI “PRT SEQ ID





NO:”


Defense System
DruG
polypeptides
Table 10; Rows 124-295;


IIIb Druantia


Column AL “DruG


Type II


protein_accession” and





Column AM “PRT SEQ ID





NO:”


Defense System
DruE
polypeptides
Table 10; Rows 124-295;


IIIb Druantia


Column Z “DruE


Type II


protein_accession” and





Column AA “PRT SEQ ID





NO:”


Defense System
druM
poly-
Table 10; Rows 124-295;


IIIb Druantia

nucleotides
Column AD “DruM


Type II


protein_accession” and





Column AF “DNA SEQ ID





NO:”


Defense System
druF
poly-
Table 10; Rows 124-295;


IIIb Druantia

nucleotides
Column AH “DruF


Type II


protein_accession” and





Column AJ “DNA SEQ ID





NO:”


Defense System
druG
poly-
Table 10; Rows 124-295;


IIIb Druantia

nucleotides
Column AL “DruG


Type II


protein_accession” and





Column AN “DNA SEQ ID





NO:”


Defense System
druE
poly-
Table 10; Rows 124-295;


IIIb Druantia

nucleotides
Column Z “DruE


Type II


protein_accession” and





Column AB “DNA SEQ ID





NO:”


Defense System
Gene
poly-
Table 10; Rows 124-295;


IIIb Druantia
Cassette
nucleotides
Column G


Type II


“genomic_accession” with





Start in Column AT





“Genomic Start Point” and





End in Column AU





“Genomic End Point”


Defense System
DruH
polypeptides
Table 10; Rows 296-1343;


IIIc Druantia


Column AP “DruH


Type III


protein_accession” and





Column AQ “PRT SEQ ID





NO:”


Defense System
DruE
polypeptides
Table 10; Rows 296-1343;


IIIc Druantia


Column Z “DruE


Type III


protein_accession” and





Column AA “PRT SEQ ID





NO:”


Defense System
druH
poly-
Table 10; Rows 296-1343;


IIIc Druantia

nucleotides
Column AP “DruH


Type III


protein_accession” and





Column AR “DNA SEQ ID





NO:”


Defense System
druE
poly-
Table 10; Rows 296-1343;


IIIc Druantia

nucleotides
Column Z “DruE


Type III


protein_accession” and





Column AB “DNA SEQ ID





NO:”


Defense System
Gene
poly-
Table 10; Rows 296-1343;


IIIc Druantia
Cassette
nucleotides
Column G


Type III


“genomic_accession” with





Start in Column AT





“Genomic Start Point” and





End in Column AU





“Genomic End Point”


Defense System IV
HamA
polypeptides
Table 12; Rows 2-1782;


Hachiman


Column H “HamA





protein_accession” and





Column I “PRT SEQ ID





NO:”


Defense System
HamB
polypeptides
Table 12; Rows 2-1782;


IV Hachiman


Column L “HamB





protein_accession” and





Column M “PRT SEQ ID





NO:”


Defense System
hamA
poly-
Table 12; Rows 2-1782;


IV Hachiman

nucleotides
Column H “HamA





protein_accession” and





Column J “DNA SEQ ID





NO:”


Defense System
hamB
poly-
Table 12; Rows 2-1782;


IV Hachiman

nucleotides
Column L “HamB





protein_accession” and





Column N “DNA SEQ ID





NO:”


Defense System
Gene
poly-
Table 12; Rows 2-1782;


IV Hachiman
Cassette
nucleotides
Column G





“genomic_accession” with





Start in Column P





“Genomic Start Point”





and End in Column Q





“Genomic End Point”


Defense System V
SduA
polypeptides
Table 13; Rows 2-1247;


Shedu


Column H “SduA





protein_accession” and





Column I “PRT SEQ ID





NO:”


Defense System V
sduA
poly-
Table 13; Rows 2-1247;


Shedu

nucleotides
Column H “SduA





protein_accession” and





Column J “DNA SEQ ID





NO:”


Defense System V
Gene
poly-
Table 13; Rows 2-1782;


Shedu
Cassette
nucleotides
Column G





“genomic_accession” with





Start in Column L





“Genomic Start Point”





and End in Column M





“Genomic End Point”


Defense System
GajA
polypeptides
Table 14; Rows 2-4599;


VI Gabija


Column H “GajA





protein_accession” and





Column I “PRT SEQ ID





NO:”


Defense System
GajB
polypeptides
Table 14; Rows 2-4599;


VI Gabija


Column L “GajB





protein_accession” and





Column M “PRT SEQ ID





NO:”


Defense System
gajA
poly-
Table 14; Rows 2-4599;


VI Gabija

nucleotides
Column H “GajA





protein_accession” and





Column J “DNA SEQ ID





NO:”


Defense System
gajB
poly-
Table 14; Rows 2-4599;


VI Gabija

nucleotides
Column L “GajB





protein_accession” and





Column N “DNA SEQ ID





NO:”


Defense System
Gene
poly-
Table 14; Rows 2-4599;


VI Gabija
Cassette
nucleotides
Column G





“genomic_accession” with





Start in Column P





“Genomic Start Point”





and End in Column Q





“Genomic End Point”


Defense System
PtuA
polypeptides
Table 15; Rows 2-2507;


VII Septu


Column H “PtuA





protein_accession” and





Column I “PRT SEQ ID





NO:”


Defense System
PtuB
polypeptides
Table 15; Rows 2-2507;


VII Septu


Column L “PtuB





protein_accession” and





Column M “PRT SEQ ID





NO:”


Defense System
ptuA
poly-
Table 15; Rows 2-2507;


VII Septu

nucleotides
Column H “PtuA





protein_accession” and





Column J “DNA SEQ ID





NO:”


Defense System
ptuB
poly-
Table 15; Rows 2-2507;


VII Septu

nucleotides
Column L “PtuB





protein_accession” and





Column N “DNA SEQ ID





NO:”


Defense System
Gene
poly-
Table 15; Rows 2-2507;


VII Septu
Cassette
nucleotides
Column G





“genomic_accession” with





Start in Column P





“Genomic Start Point”





and End in Column Q





“Genomic End Point”


Defense System
LmuA
polypeptides
Table 16; Rows 2-698;


VIII Lamussa


Column H “LmuA





protein_accession” and





Column I “PRT SEQ ID





NO:”


Defense System
LmuB
polypeptides
Table 16; Rows 2-698;


VIII Lamussa


Column L “LmuB





protein_accession” and





Column M “PRT SEQ ID





NO:”


Defense System
lmuA
poly-
Table 16; Rows 2-698;


VIII Lamussa

nucleotides
Column H “LmuA





protein_accession” and





Column J “DNA SEQ ID





NO:”


Defense System
lmuB
poly-
Table 16; Rows 2-698;


VIII Lamussa

nucleotides
ColumnL “LmuB





protein_accession” and





Column N “DNA SEQ ID





NO:”


Defense System
Gene
poly-
Table 16; Rows 2-698;


VIII Lamussa
Cassette
nucleotides
Column G





“genomic_accession” with





Start in Column P





“Genomic Start Point”





and End in Column Q





“Genomic End Point”


Defense System
KwaA
polypeptides
Table 17; Rows 2-935;


IX Kiwa


Column H “KwaA





protein_accession” and





Column I “PRT SEQ ID





NO:”


Defense System
KwaB
polypeptides
Table 17; Rows 2-935;


IX Kiwa


Column L “KwaB





protein_accession” and





Column M “PRT SEQ ID





NO:”


Defense System
kwaA
poly-
Table 17; Rows 2-935;


IX Kiwa

nucleotides
Column H “KwaA





protein_accession” and





Column J “DNA SEQ ID





NO:”


Defense System
kwaB
poly-
Table 17; Rows 2-935;


IX Kiwa

nucleotides
Column L “KwaB





protein_accession” and





Column N “DNA SEQ ID





NO:”


Defense System
Gene
poly-
Table 17; Rows 2-935;


IX Kiwa
Cassette
nucleotides
Column G





“genomic_accession” with





Start in Column P





“Genomic Start Point”





and End in Column Q





“Genomic End Point”


Defense System
JetA
polypeptides
Table 11; Rows 2-2322;


Xa Wadjet type I


Column J “JetA





protein_accession” and





Column K “PRT SEQ ID





NO:”


Defense System
JetB
polypeptides
Table 11; Rows 2-2322;


Xa Wadjet type I


Column N “JetB





protein_accession” and





Column O “PRT SEQ ID





NO:”


Defense System
JetC
polypeptides
Table 11; Rows 2-2322;


Xa Wadjet type I


Column R “JetC





protein_accession” and





Column S “DNA SEQ ID





NO:”


Defense System
JetD
polypeptides
Table 11; Rows 2-2322;


Xa Wadjet type I


Column V “JetD





protein_accession” and





Column W “PRT SEQ ID





NO:”


Defense System
jetA
poly-
Table 11; Rows 2-2322;


Xa Wadjet type I

nucleotides
Column J “JetA





protein_accession” and





Column L “DNA SEQ ID





NO:”


Defense System
jetB
poly-
Table 11; Rows 2-2322;


Xa Wadjet type I

nucleotides
Column N “JetB





protein_accession” and





Column P “DNA SEQ ID





NO:”


Defense System
jetC
poly-
Table 11; Rows 2-2322;


Xa Wadjet type I

nucleotides
Column R “JetC





protein_accession” and





Column T “DNA SEQ ID





NO:”


Defense System
jetD
poly-
Table 11; Rows 2-2322;


Xa Wadjet type I

nucleotides
Column V “JetD





protein_accession” and





Column X “DNA SEQ ID





NO:”


Defense System
Gene
poly-
Table 11; Rows 2-2322;


Xa Wadjet type I
Cassette
nucleotides
Column G





“genomic_accession” with





Start in Column Z





“Genomic Start Point”





and End in Column AA





“Genomic End Point”


Defense System
JetAii
polypeptides
Table 11; Rows 2323-2844;


Xb Wadjet type II


Column J “JetA





protein_accession” and





Column K “PRT SEQ ID





NO:”


Defense System
JetBii
polypeptides
Table 11; Rows 2323-2844;


Xb Wadjet type II


Column N “JetB





protein_accession” and





Column O “DNA SEQ ID





NO:”


Defense System
JetCii
polypeptides
Table 11; Rows 2323-2844;


Xb Wadjet type II


Column R “JetC





protein_accession” and





Column S “PRT SEQ ID





NO:”


Defense System
JetDii
polypeptides
Table 11; Rows 2323-2844;


Xb Wadjet type II


Column V “JetD





protein_accession” and





Column W “PRT SEQ ID





NO:”


Defense System
jetAii
poly-
Table 11; Rows 2323-2844;


Xb Wadjet type II

nucleotides
Column J “JetA





protein_accession” and





Column L “DNA SEQ ID





NO:”


Defense System
jetBii
poly-
Table 11; Rows 2323-2844;


Xb Wadjet type II

nucleotides
Column N “JetB





protein_accession” and





Column P “DNA SEQ ID





NO:”


Defense System
jetCii
poly-
Table 11; Rows 2323-2844;


Xb Wadjet type II

nucleotides
Column R “JetC





protein_accession” and





Column T “DNA SEQ ID





NO:”


Defense System
jetDii
poly-
Table 11; Rows 2323-2844;


Xb Wadjet type II

nucleotides
Column V “JetD





protein_accession” and





Column X “DNA SEQ ID





NO:”


Defense System
Gene
poly-
Table 11; Rows 2323-2844;


Xb Wadjet type II
Cassette
nucleotides
Column G





“genomic_accession” with





Start in Column Z





“Genomic Start Point”





and End in Column AA





“Genomic End Point”


Defense System
JetAiii
polypeptides
Table 11; Rows 2845-3174;


Xc Wadjet type


Column J “JetA


III


protein_accession” and





Column K “PRT SEQ ID





NO:”


Defense System
JetBiii
polypeptides
Table 11; Rows 2845-3174;


Xc Wadjet type


Column N “JetB


III


protein_accession” and





Column O “PRT SEQ ID





NO:”


Defense System
JetCiii
polypeptides
Table 11; Rows 2845-3174;


Xc Wadjet type


Column R “JetC


III


protein_accession” and





Column S “PRT SEQ ID





NO:”


Defense System
JetDiii
polypeptides
Table 11; Rows 2845-3174;


Xc Wadjet type


Column V “JetD


III


protein_accession” and





Column W “PRT SEQ ID





NO:”


Defense System
jetAiii
poly-
Table 11; Rows 2845-3174;


Xc Wadjet type

nucleotides
Column J “JetA


III


protein_accession” and





Column L “DNA SEQ ID





NO:”


Defense System
jetBiii
poly-
Table 11; Rows 2845-3174;


Xc Wadjet type

nucleotides
Column N “JetB


III


protein_accession” and





Column P “DNA SEQ ID





NO:”


Defense System
jetCiii
poly-
Table 11; Rows 2845-3174;


Xc Wadjet type

nucleotides
Column R “JetC


III


protein_accession” and





Column T “DNA SEQ ID





NO:”


Defense System
jetDiii
poly-
Table 11; Rows 2845-3174;


Xc Wadjet type

nucleotides
Column V “JetD


III


protein_accession” and





Column X “DNA SEQ ID





NO:”


Defense System
Gene
poly-
Table 11; Rows 2845-3174;


Xc Wadjet type
Cassette
nucleotides
Column G


III


“genomic_accession” with





Start in Column Z





“Genomic Start Point”





and End in Column AA





“Genomic End Point”









Table 18 lists embodiments of the components of each Defense System and embodiments gene cassettes encoding the Defense Systems. Provided are the Sequence Numbers comprising the polypeptide and polynucleotide sequences, or explicit Reference to the Accession numbers provided in Tables 8-17, respectively for each Defense System, from which the skilled artisan can access the polypeptide and polynucleotide sequences. While Table 18 highlights polypeptide components of defense systems and the genes sequences that encode them, in some embodiments, defense system components include non-coding RNA and/or regulatory nucleic acid sequences.


Using the Reference locations provided in Table 18 and the “protein accession” numbers provided in Tables 8-17, one can reach both the amino acid and the nucleotide sequences of a Defense System component. For example, to access the polypeptide (amino acid) sequence of a component, a skilled artisan would find the Defense System and component of interest in Table 18. Next, they would use the Reference information provided in Table 18 to identify the series of accession numbers that encompass the polypeptide sequence of the component. Following that, the skilled artisan would query the NCBI “Protein” database: https://www.ncbi.nlm.nih.gov/protein, and enter the accession number provided for a component, for example but not limited to “ABS66238.1” (Table 8, row 2, column J), which would send them to https://www.ncbi.nlm.nih.gov/protein/CEP95570.1, wherein the amino acid sequence of the component is disclosed on this page, as follows:









(SEQ ID NO: 1)


MTVLKGLGRCVLFWTITGIFGVLYWLLPVVDMSALWGGTARAFSGDFSTV





GTQPYAFALAFALFATAVGFASAFLILHVGPIGWRLRRLRLRIAGTGDME





GFARTYDATRALMERDRLISHAWKQFDTVLVHRPDERIIRSTARAHAFFN





LGMAREKYFGLKMMGALPGYFVGIGLLLTFAGLVLALNKAAMAVNSSDAA





GMQGATRELLQVATFKFATSIAGLGASIALSLLFRIYTILMEGFFIGFCE





TVEDRVRYLSAQQIAAESRDFAAEQTDQLKSMSADFFARMGQELTPGMSR





MFETALDKVMSPVTTSIDQAVHRLADSSQSGMSEMLTRFTDSVQNGAGAE





LRGLAETLRGMQGAMVGVQQGLTGSGEDFGRRMSDAAENLNRLVTDAGAR





LGEGTDQSRAVLMDAVTAMRETFEQANRKVDEGLGAAAGGASARLEEVMG





RVLGSLEAQVGGFRESLSGFQEKMAGQLDETRVRVSAAQAEATDAVAQAS





AQAARALQDGLADALVRINGEIERFVVAMRASEVTLAAQAKAMMDATDKS





RQVADAFSRTAQDVRAASVPLAQSGERIAGATEKLGEAAGRSVAVLDKSQ





EEARRLAQALTGHVSNLDQVWRSYSARFEAVDEALGKAFERLTRGTDEQQ





DRIATFVRDVDVTFKEAVDTLAGCIGGLKDNTEEMVEAVDDLKRALRVEA





AE.






Similarly, to access the nucleotide (nucleic acid) sequence of a component, a skilled artisan would find the Defense System and component of interest in Table 18. Next, they would use the Reference information provided in Table 18 to identify the series of accession numbers that encompass the nucleotide sequence of the component. Following that, the skilled artisan would query the NCBI “Identical Protein Groups” database https://www.ncbi.nlm.nih.gov/ipg, and enter the accession number provided for a component, for example but not limited to “ABS66238.1” (Table 8, row 2, column J), which would send them to https://www.ncbi.nlm.nih.gov/ipg/?term=ABS66238.1, wherein any of the links under “CDS Region in Nucleotide” leads to the nucleotide sequence:


Origin










(SEQ ID NO: 2)










1
atgacggtct tgaagggttt ggggcgctgc gttctttttt ggacaatcat attcggcatc






61
ttcggcgtct tgtactggct ccttcctgtc gtcgacatga gcgcgctctg gggcgggacg





121
gcgcgcgcct tcagcggtga tttttccacc gtcggcaccc agccctatgc tttcgccctg





181
gccttcgccc tgttcgccac ggcggtcggc ttcgcctccg ctttcctcat cctgcatgtg





241
ggtccgatcg ggtggaggct gcggcgcctg cgattgcgta tcgcgggcac gggggacatg





301
gaaggcttcg ccagaaccta tgacgccacg cgcgcgctca tggagcgcga tcgactgatc





361
agccatgcgt ggaagcagtt cgacaccgtg ctcgttcatc ggccggatga acgcatcatc





421
cgcagcaccg cccgtgccca cgcctttttc aatctgggca tggcgcggga gaagtatttc





481
ggcctgaaga tgatgggcgc gctgccgggc tatttcgtcg gcatcggtct tctgctcacc





541
ttcgccggcc tcgtgctggc gctcaacaag gcggccatgg ccgtcaacag ctcggatgcc





601
gccggaatgc agggcgcgac gcgcgaactg cttcaggtgg cgaccttcaa gtttgccacc





661
tccatcgccg gccttggtgc ctccatcgcg ctctcgctgc tgttccgcat ctataccatc





721
ctgatggaag gcttcttcat cggcttctgc gagacggtgg aggaccgggt gcgctatctg





781
tcggcacagc agatcgcggc cgagagccgg gattttgccg ccgaacagac cgatcagctc





841
aagtcgatca acagcgccga cttcttcgcg cgcatggggc aggagctgac gccgggcatg





901
tcccgcatgt tcgagacggc gctcgacaag gtcatgtcgc cggtgaccac cagcatcgac





961
caggcggtcc ataggctcgc cgacagcagc cagagcggca tgtccgagat gctgacgcgc





1021
ttcaccgatt cggtgcagaa cggggccggg gccgagttgc gcgggctcgc cgagacgctc





1081
cggggcatgc agggtgccat ggtgggcgtg cagcaggggc tgaccgggtc cggcgaggat





1141
ttcggccggc gcatgtcgga tgccgcggaa aacctcaacc gcctcgtcac cgacgccggc





1201
gcacgcctgg gtgaaggcac ggaccagagc cgcgcggtcc tcatggatgc ggtcaccgcc





1261
atgcgggaga ccttcgagca agccaatcgc aaggtggacg agggtctcgg cgccgcggcg





1321
ggcggggctt cggcgcggct ggaggaggtc atggggcggg tgctcggcag cctcgaagcc





1381
caggtgggcg gctttcgcga gagcctgtcc ggcttccagg agaagatggc cggccagctc





1441
gatgagaccc gggtccgcgt ctccgccgcc caggcggagg cgaccgatgc cgtcgcccag





1501
gcctcggccc aggcggcgcg cgcgctccag gacgggcttg cggatgcgct cgtgcgcatc





1561
aacggcgaga tcgagcgttt cgtcgtcgcc atgcgggcca gcgaggtgac gctggcggcg





1621
caggccaagg cgatgatgga cgccaccgac aagtcgcgcc aggtggccga tgccttcagc





1681
cgcactgcgc aggatgtgcg cgcggctagc gtaccgctgg cccaatcggg cgagcgcatc





1741
gcgggggcga ccgagaagct cggcgaggcc gccggccggt cggtggcggt cctcgacaag





1801
agccaggagg aggcgcggcg gctggcccag gcgctgaccg gccatgtctc caacctcgat





1861
caggtctggc gcagctattc ggcccgcttc gaggcggtcg acgaggcgct gggcaaggcg





1921
ttcgagcgcc tgacgcgcgg aaccgacgag cagcaggacc ggatcgccac tttcgttcgc





1981
gacgtggacg tgaccttcaa ggaagcggtg gatacgctgg ccggctgcat cggcggcctg





2041
aaggacaata ccgaggagat ggtggaggcg gtggacgacc tgaaacgcgc gctgcgcgtc





2101
gaggccgcgg aatga.






Defense Systems & Combination of Defense Systems

Described above are non-limiting examples of defense systems, wherein each system comprises components that together make-up a defense system, wherein in some embodiments each component is encoded by a different gene. In some embodiments, the combination of components that make-up a Defense System, for example the components that make-up each of Defense Systems Ia-Xc disclosed above, may include components comprising nucleic acid sequences or amino acid sequences derived from different species (different donor species). In some embodiments, the combination of components that make-up a Defense System, for example the components that make-up each of Defense Systems Ia-Xc, may include homologs of the genes and/or polypeptides identified in donor species. In some embodiments, the combination of components that make-up a Defense System, for example the components that make-up each of Defense Systems Ia-Xc, differs from the combination of components found in donor species. In some embodiments, the components of a Defense System, for example the components that make-up each of Defense Systems Ia-Xc, comprises less than all the components found in donor species. In some embodiments, the components of a Defense System, for example the components that make-up each of Defense Systems Ia-Xc, comprises duplications of the components found in donor species, or multiple copies of one or more components found in a donor species. In some embodiments, the components of a Defense System, for example the components that make-up each of Defense Systems Ia-Xc, comprise functional portions of the components found in donor species, wherein a functional component comprise less than the full length of the components present in a donor species. In some embodiments, the order of components encoded on the nucleic acid sequence comprised within a construct comprising a Defense System, for example the order of the components the make-up each of Defense Systems Ia-Xc, differs from the order of the components found encoded on the nucleic acid sequences in donor species.


In some embodiments each Defense Systems Ia, Ib, II, III, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc comprising a nucleic acid construct comprising a nucleic acid sequence encoding the polypeptide components as disclosed herein, further comprises a regulatory element operably linked to said construct comprising a cis-acting regulatory element for directing expression of said nucleic acid sequence, or a transmissible element for directing transfer of said nucleic acid sequence from one cell to another, or a recombination element for integrating said nucleic acid sequence into a genome of a cell transfected with said construct, or an element providing episomal maintenance of said construct within a cell transfected with said construct, or any combination thereof.


In some embodiments, a construct further comprises a regulatory element operably linked to said construct comprising a cis-acting regulatory element for directing expression of said nucleic acid sequence. In some embodiment, the nucleic acid sequence of the regulatory element is from the same species as at least one component of the Defense System. In some embodiment, the nucleic acid sequence of the regulatory element is not from the same species as any of the components of the Defense System. In some embodiment, the nucleic acid sequence of the regulatory element is not from the donor species of the Defense System. In some embodiment, when a host cell comprises a Defense System, the nucleic acid sequence of the regulatory element is from the host species.


In some embodiments, cis-acting regulatory elements include those that direct constitutive expression of a nucleic acid sequence. In some embodiments, cis-acting regulatory elements comprise those that direct inducible expression of the nucleic acid sequence only under certain conditions.


According to some embodiments, the cis-acting regulatory element is heterologous to the genes encoding the components of a system. In some embodiments, the cis-acting regulatory element is heterologous to Defense System Ia genes zorA, zorB, zorC, and zorD. In some embodiments, the cis-acting regulatory element is heterologous to Defense System Ib genes zorA, zorB, and zorE. In some embodiments, the cis-acting regulatory element is heterologous to Defense System II genes thsA and thsB. In some embodiments, the cis-acting regulatory element is heterologous to Defense System IIIa genes druA, druB, druC, drub, and druE. In some embodiments, the cis-acting regulatory element is heterologous to Defense System IIIb genes druM, druF, druG, and druE. In some embodiments, the cis-acting regulatory element is heterologous to Defense System IIIc genes druH and druE. In some embodiments, the cis-acting regulatory element is heterologous to Defense System IV genes hamA and hamB. In some embodiments, the cis-acting regulatory element is heterologous to Defense System V component sduA. In some embodiments, the cis-acting regulatory element is heterologous to Defense System VI genes gajA and gajB. In some embodiments, the cis-acting regulatory element is heterologous to Defense System VII genes ptuA and ptuB. In some embodiments, the cis-acting regulatory element is heterologous to Defense System VIII genes lmuA and lmuB. In some embodiments, the cis-acting regulatory element is heterologous to Defense System IX genes kwaA and kwaB. In some embodiments, the cis-acting regulatory element is heterologous to Defense System Xa genes jetA, jetB, jetC, and jetD. In some embodiments, the cis-acting regulatory element is heterologous to Defense System Xb genes jetAii, jetBii, jetCii, and jetDii. In some embodiments, the cis-acting regulatory element is heterologous to Defense System Xc genes jetAiii, jetBiii, jetCiii, and jetDiii.


According to some embodiments, the nucleic acid construct includes a promoter sequence for directing transcription of the nucleic acid sequence in a host cell in a constitutive or inducible manner. In some embodiments, a promoter is a constitutive promoter. In some embodiments, a promoter is an inducible or regulatable promoter.


Constitutive promoters suitable for use with some embodiments of the Defense System constructs disclosed herein are promoter sequences which are active under most environmental conditions and most types of cells such as the cytomegalovirus (CMV) and Rous sarcoma virus (RSV). Inducible promoters suitable for use with some embodiments of Defense System constructs disclosed herein, include for example but not limited to the tetracycline-inducible promoter (Zabala M, et al., Cancer Res. 2004, 64(8): 2799-804) or pathogen-inducible promoters. Such promoters include those from pathogenesis-related proteins (PR proteins), which are induced following infection by a pathogen.


According to some embodiments, the promoter is bacterial nucleic acid (e.g., expression) construct.


A skilled artisan would appreciate that bacterial promoter encompasses any DNA sequence capable of binding bacterial RNA polymerase and initiating the downstream (3′) transcription of a coding sequence into mRNA. A promoter can have a transcription initiation region, which is usually placed proximal to the 5′ end of the coding sequence. This transcription initiation region typically includes an RNA polymerase binding site and a transcription initiation site. A bacterial promoter can also have a second domain called an operator, which can overlap an adjacent RNA polymerase binding site at which RNA synthesis begins. The operator permits negative regulated (inducible) transcription, as a gene repressor protein can bind the operator and thereby inhibit transcription of a specific gene. Constitutive expression can occur in the absence of negative regulatory elements, such as the operator. In addition, positive regulation can be achieved by a gene activator protein binding sequence, which, if present is usually proximal (5′) to the RNA polymerase binding sequence.


A non-limiting example of a gene activator protein is the catabolite activator protein (CAP), which helps initiate transcription of the lac operon in Escherichia coli (Raibaud et al. (1984) Annu. Rev. Genet. 18:173). Regulated expression can therefore be either positive or negative, thereby either enhancing or reducing transcription. Other examples of positive and negative regulatory elements are well known in the art. Various promoters that can be included in the protein expression system include, but are not limited to, a T7/LacO hybrid promoter, a trp promoter, a T7 promoter, a lac promoter, and a bacteriophage lambda promoter. Any suitable promoter can be used with the Defense systems disclosed herein, including the native promoter or a heterologous promoter. Heterologous promoters can be constitutively active or inducible. A non-limiting example of a heterologous promoter is given in U.S. Pat. No. 6,242,194 to Kullen and Klaenhammer.


Sequences encoding metabolic pathway enzymes provide particularly useful promoter sequences. Examples include promoter sequences derived from sugar metabolizing enzymes, such as galactose, lactose (lac) (Chang et al. (1987) Nature 198:1056), and maltose. Additional examples include promoter sequences derived from biosynthetic enzymes such as tryptophan (trp) (Goeddel et al. (1980) Nucleic Acids Res. 8:4057; Yelverton et al. (1981) Nucleic Acids Res. 9:731; U.S. Pat. No. 4,738,921; EPO Publication Nos. 36,776 and 121,775). The beta-lactamase (bla) promoter system (Weissmann, (1981) “The Cloning of Interferon and Other Mistakes,” in Interferon 3 (ed. I. Gresser); bacteriophage lambda PL (Shimatake et al. (1981) Nature 292:128); the arabinose-inducible araB promoter (U.S. Pat. No. 5,028,530); and T5 (U.S. Pat. No. 4,689,406) promoter systems also provide useful promoter sequences. See also Balbas (2001) Mol. Biotech. 19:251-267, where E. coli expression systems are discussed.


In addition, synthetic promoters that do not occur in nature also function as bacterial promoters. For example, transcription activation sequences of one bacterial or phage promoter can be joined with the operon sequences of another bacterial or phage promoter, creating a synthetic hybrid promoter (U.S. Pat. No. 4,551,433). For example, the tac (Amann et al. (1983) Gene 25:167; de Boer et al. (1983) Proc. Natl. Acad. Sci. 80:21) and trc (Brosius et al. (1985) J. Biol. Chem. 260:3539-3541) promoters are hybrid trp-lac promoters comprised of both trp promoter and lac operon sequences that are regulated by the lac repressor. The tac promoter has the additional feature of being an inducible regulatory sequence. Thus, for example, expression of a coding sequence operably linked to the tac promoter can be induced in a cell culture by adding isopropyl-1-thio-β-D-galactoside (IPTG). Furthermore, bacterial promoter can include naturally occurring promoters of non-bacterial origin that have the ability to bind bacterial RNA polymerase and initiate transcription. A naturally occurring promoter of non-bacterial origin can also be coupled with a compatible RNA polymerase to produce high levels of expression of some genes in prokaryotes. The phage T7 RNA polymerase/promoter system is an example of a coupled promoter system (Studier et al. (1986) J. Mol. Biol. 189:113; Tabor et al. (1985) Proc. Natl. Acad. Sci. 82:1074). In addition, a hybrid promoter can also be comprised of a phage promoter and an E. coli operator region (EPO Publication No. 267,851).


The nucleic acid construct can additionally contain a nucleic acid sequence encoding the repressor (or inducer) for that promoter. For example, an inducible construct can regulate transcription from the Lac operator (LacO) by expressing the nucleotide sequence encoding the Lad repressor protein. Other examples include the use of the lexA gene to regulate expression of pRecA, and the use of trpO to regulate ptrp. Alleles of such genes that increase the extent of repression (e.g., lacIq) or that modify the manner of induction (e.g., lambda CI857, rendering lambda pL thermo-inducible, or lambda CI+, rendering lambda pL chemo-inducible) can be employed.


In the construction of the construct, in some embodiments, the promoter is positioned approximately the same distance from the heterologous transcription start site as it is from the transcription start site in its natural setting. As is known in the art, however, some variation in this distance can be accommodated without loss of promoter function.


According to some embodiments, the nucleic acid construct includes a promoter sequence for directing transcription of the nucleic acid sequence in the cell in a constitutive or inducible manner. In some embodiments, the expression of a Defense System disclosed herein can be transient or consistent, episomal or integrated into the chromosome of a host cell. According to some embodiments, the expression is on a transmissible genetic element.


The nucleic acid construct of some embodiments of a Defense System disclosed herein may further include additional sequences which render this construct suitable for replication and integration in prokaryotes, eukaryotes, or preferably both (e.g., shuttle vectors).


In some embodiments, the construct comprises a recombination element for integrating the polynucleotide into a genome of a cell transfected with the construct.


A skilled artisan would appreciate that the term “recombination element” encompasses a nucleic acid sequence that allows the integration of the polynucleotide in the genome of a cell (e.g. bacteria) transfected with the construct.


In some embodiments, a construct may also contain a transcription and translation initiation sequence, transcription and translation terminator and a polyadenylation signal. By way of example, such constructs will typically include a 5′ LTR, a tRNA binding site, a packaging signal, an origin of second-strand DNA synthesis, and a 3′ LTR or a portion thereof.


In some embodiments, a construct further comprises a transmissible element for directing transfer of said nucleic acid sequence from one cell to another. In some embodiments, a Defense System Ia or the Defense System Ia component(s) is on a transmissible genetic element. In some embodiments, a Defense System Ib or the Defense System Ib component(s) is on a transmissible genetic element. In some embodiments, a Defense System IIIa or the Defense System IIIa component(s) is on a transmissible genetic element. In some embodiments, a Defense System IIIb or the Defense System IIIb component(s) is on a transmissible genetic element. In some embodiments, a Defense System IIIc or the Defense System IIIc component(s) is on a transmissible genetic element. In some embodiments, a Defense System IV or the Defense System IV component(s) is on a transmissible genetic element. In some embodiments, a Defense System V or the Defense System V component(s) is on a transmissible genetic element. In some embodiments, a Defense System VI or the Defense System VI component(s) is on a transmissible genetic element. In some embodiments, a Defense System VII or the Defense System VII component(s) is on a transmissible genetic element. In some embodiments, a Defense System VIII or the Defense System VIII component(s) is on a transmissible genetic element. In some embodiments, a Defense System IX or the Defense System IX component(s) is on a transmissible genetic element. In some embodiments, a Defense System Xa or the Defense System Xa component(s) is on a transmissible genetic element. In some embodiments, a Defense System Xb or the Defense System Xb component(s) is on a transmissible genetic element. In some embodiments, a Defense System Xc or the Defense System Xc component(s) is on a transmissible genetic element.


In some embodiments, a transmissible genetic element comprises the construct of a Defense System disclosed herein. In some embodiments, a transmissible genetic element comprises the construct of Defense System Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, or Xc. In some embodiments, a transmissible genetic element comprises the construct of Defense System Ia. In some embodiments, a transmissible genetic element comprises the construct of Defense System Ib. In some embodiments, a transmissible genetic element comprises the construct of Defense System II. In some embodiments, a transmissible genetic element comprises the construct of Defense System IIIa. In some embodiments, a transmissible genetic element comprises the construct of Defense System IIIb. In some embodiments, a transmissible genetic element comprises the construct of Defense System IIIc. In some embodiments, a transmissible genetic element comprises the construct of Defense System IV. In some embodiments, a transmissible genetic element comprises the construct of Defense System V. In some embodiments, a transmissible genetic element comprises the construct of Defense System VI. In some embodiments, a transmissible genetic element comprises the construct of Defense System VII. In some embodiments, a transmissible genetic element comprises the construct of Defense System VIII. In some embodiments, a transmissible genetic element comprises the construct of Defense System IX. In some embodiments, a transmissible genetic element comprises the construct of Defense System Xa. In some embodiments, a transmissible genetic element comprises the construct of Defense System Xb. In some embodiments, a transmissible genetic element comprises the construct of Defense System Xc.


A skilled artisan would appreciate that the term “transmissible element” or “transmissible genetic element”, which are interchangeably used, encompasses a polynucleotide that allows the transfer of the nucleic acid sequence from one cell to another, e.g. from one bacteria to another.


According to some embodiments, a transmissible genetic element comprises a conjugative genetic element or mobilizable genetic element. In some embodiments, a transmissible genetic element comprises a conjugative genetic element. In some embodiments, a transmissible genetic element comprises a mobilizable genetic element. The skilled artisan would appreciate that a “conjugative plasmid” encompasses a plasmid that is transferred from one cell (e.g. bacteria) to another during conjugation, and the term “mobilizable element” encompasses a transposon, which is a DNA sequence that can change its position within the genome.


In some embodiments, a nucleic acid construct disclosed herein, comprises an expression vector. In some embodiments, an “expression vector” or a “vector”, used interchangeably herein, comprises and expresses the Defense System components from a single or a plurality of constructs (i.e. construct). In some embodiments, expression comprises transient expression. In some embodiments, expression comprises constitutive expression. In some embodiments, expression is from an episomal nucleic acid sequence. In some embodiments, expression is from a nucleic acid sequence integrated into the chromosome of the cell. According to specific embodiments, the expression is on a transmissible genetic element.


According to some embodiments, a construct further comprises a recombination element for integrating the nucleic acid sequence into a genome of cell transfected with the construct. A skilled artisan would appreciate that the term “recombination element” encompasses a polynucleotide that allows the integration of the nucleic acid sequence in the genome of a cell (e.g. bacteria) transfected with the construct.


In addition, typical constructs may also, in certain embodiments, contain a transcription and translation initiation sequence, transcription and translation terminator and a polyadenylation signal. By way of example, such constructs will typically include a 5′ LTR, a tRNA binding site, a packaging signal, an origin of second-strand DNA synthesis, and a 3′ LTR or a portion thereof.


According to some embodiment, the nucleic acid construct comprises a plurality of cloning sites for ligating a nucleic acid sequence of a Defense System, such that it is under transcriptional regulation of the regulatory elements.


Selectable marker genes that ensure maintenance of a construct in a host cell can also be included in the construct. In some embodiments, selectable markers include those which confer resistance to drugs such as ampicillin, chloramphenicol, erythromycin, kanamycin (neomycin), and tetracycline (Davies et al. (1978) Annu. Rev. Microbiol. 32:469). Selectable markers can also allow a cell to grow on minimal medium, or in the presence of toxic metabolite and can include biosynthetic genes, such as those in the histidine, tryptophan, and leucine biosynthetic pathways.


Other than containing the necessary elements for the transcription and translation of the inserted coding sequence, the expression construct of some embodiments of Defense system can also include sequences engineered to enhance stability, production, purification, yield or toxicity of the expressed polypeptide. Where appropriate, the nucleic acid sequences may be optimized for increased expression in the transformed organism. For example, the nucleic acid sequences can be synthesized using preferred codons for improved expression.


Various methods known within the art can be used to introduce the construct of some embodiments of a Defense System disclosed herein into cells. Such methods are generally described in Sambrook et al., Molecular Cloning: A Laboratory Manual, Cold Springs Harbor Laboratory, New York (1989, 1992), in Ausubel et al., Current Protocols in Molecular Biology, John Wiley and Sons, Baltimore, Md. (1989), Chang et al., Somatic Gene Therapy, CRC Press, Ann Arbor, Mich. (1995), Vega et al., Gene Targeting, CRC Press, Ann Arbor Mich. (1995), Vectors: A Survey of Molecular Cloning Vectors and Their Uses, Butterworths, Boston Mass. (1988) and Gilboa et at. [Biotechniques 4 (6): 504-512, 1986] and include, for example, stable or transient transfection, natural or induced transformation, lipofection, electroporation and infection with recombinant viral vectors. In addition, see U.S. Pat. Nos. 5,464,764 and 5,487,992 for positive-negative selection methods.


Some methods of introducing a construct or constructs into bacterial cells include for example conventional transformation or transfection techniques, or by phage-mediated infection. A skilled artisan would appreciate that the terms “transformation”, “transduction”, “conjugation”, and “protoplast fusion” are intended to encompass a variety of art-recognized techniques for introducing foreign nucleic acid (e.g., DNA) into a cell, such as calcium chloride co-precipitation. A skilled artisan would appreciate that introduction of a construct or constructs into a bacterial cell, may in certain embodiments, result in expression of a polypeptide or polypeptides encoded by the construct or constructs.


Introduction of nucleic acids by phage infection offers several advantages over other methods such as transformation, since higher transfection efficiency can be obtained due to the infectious nature of phages. These methods are especially useful for rendering bacteria more sensitive to phage attack for antibiotics purposes as further described hereinbelow.


It will be appreciated that a Defense System polypeptide(s) can be introduced directly into the cell (e.g., bacterial cell) and not via recombinant expression to confer resistance. Thus, according to some embodiments, disclosed herein are isolated polypeptides of each of the Defense systems' components and functional fragments thereof as described herein. In some embodiments, a polypeptide component of a Defense System can be introduced directly into the cell (e.g., bacterial cell) and not via recombinant expression, to confer resistance. In some embodiments, at least two different polypeptide components of a Defense System can be introduced directly into the cell (e.g., bacterial cell) and not via recombinant expression, to confer resistance. In some embodiments, at least three different polypeptide components of a Defense System can be introduced directly into the cell (e.g., bacterial cell) and not via recombinant expression, to confer resistance. In some embodiments, at least four polypeptide components of a Defense System can be introduced directly into the cell (e.g., bacterial cell) and not via recombinant expression, to confer resistance. In some embodiments, at least five different polypeptide components of a Defense System can be introduced directly into the cell (e.g., bacterial cell) and not via recombinant expression, to confer resistance. In some embodiments, multiple polypeptide components of a Defense System can be introduced directly into the cell (e.g., bacterial cell) and not via recombinant expression, to confer resistance.


In some embodiments, a Defense System Ia polypeptides can be introduced directly into the cell (e.g., bacterial cell) and not via recombinant expression to confer resistance. In some embodiments, disclosed herein are isolated polypeptides of each of the Defense system Ia's components and functional fragments thereof as described herein. In some embodiments, a Defense System Ib polypeptides can be introduced directly into the cell (e.g., bacterial cell) and not via recombinant expression to confer resistance. In some embodiments, disclosed herein are isolated polypeptides of each of the Defense system Ib's components and functional fragments thereof as described herein. In some embodiments, Defense System II polypeptides can be introduced directly into the cell (e.g., bacterial cell) and not via recombinant expression to confer resistance. In some embodiments, disclosed herein are isolated polypeptides of each of the Defense system II's components and functional fragments thereof as described herein. In some embodiments, Defense System IIIa polypeptides can be introduced directly into the cell (e.g., bacterial cell) and not via recombinant expression to confer resistance. In some embodiments, disclosed herein are isolated polypeptides of each of the Defense system IIIa's components and functional fragments thereof as described herein. In some embodiments, Defense System IIIb polypeptides can be introduced directly into the cell (e.g., bacterial cell) and not via recombinant expression to confer resistance. In some embodiments, disclosed herein are isolated polypeptides of each of the Defense system IIIb's components and functional fragments thereof as described herein. In some embodiments, Defense System IIIc polypeptides can be introduced directly into the cell (e.g., bacterial cell) and not via recombinant expression to confer resistance. In some embodiments, disclosed herein are isolated polypeptides of each of the Defense system IIIc's components and functional fragments thereof as described herein. In some embodiments, Defense System IV polypeptides can be introduced directly into the cell (e.g., bacterial cell) and not via recombinant expression to confer resistance. In some embodiments, disclosed herein are isolated polypeptides of each of the Defense system IV components and functional fragments thereof as described herein. In some embodiments, Defense System V polypeptides can be introduced directly into the cell (e.g., bacterial cell) and not via recombinant expression to confer resistance. In some embodiments, disclosed herein are isolated polypeptides of each of the Defense System V components and functional fragments thereof as described herein. In some embodiments, Defense System VI polypeptides can be introduced directly into the cell (e.g., bacterial cell) and not via recombinant expression to confer resistance. In some embodiments, disclosed herein are isolated polypeptides of each of the Defense system VI's components and functional fragments thereof as described herein. In some embodiments, Defense System VII polypeptides can be introduced directly into the cell (e.g., bacterial cell) and not via recombinant expression to confer resistance. In some embodiments, disclosed herein are isolated polypeptides of each of the Defense system VII's components and functional fragments thereof as described herein. In some embodiments, Defense System VIII polypeptides can be introduced directly into the cell (e.g., bacterial cell) and not via recombinant expression to confer resistance. In some embodiments, disclosed herein are isolated polypeptides of each of the Defense system VIII's components and functional fragments thereof as described herein. In some embodiments, Defense System IX polypeptides can be introduced directly into the cell (e.g., bacterial cell) and not via recombinant expression to confer resistance. In some embodiments, disclosed herein are isolated polypeptides of each of the Defense system IX's components and functional fragments thereof as described herein. In some embodiments, a Defense System Xa polypeptides can be introduced directly into the cell (e.g., bacterial cell) and not via recombinant expression to confer resistance. In some embodiments, disclosed herein are isolated polypeptides of each of the Defense System Xa's components and functional fragments thereof as described herein. In some embodiments, a Defense System Xb polypeptides can be introduced directly into the cell (e.g., bacterial cell) and not via recombinant expression to confer resistance. In some embodiments, disclosed herein are isolated polypeptides of each of the Defense System Xb's components and functional fragments thereof as described herein. In some embodiments, a Defense System Xc polypeptides can be introduced directly into the cell (e.g., bacterial cell) and not via recombinant expression to confer resistance. In some embodiments, disclosed herein are isolated polypeptides of each of the Defense System Xc's components and functional fragments thereof as described herein.


In some embodiments, at least one Defense System component is on a transmissible genetic element. In some embodiments, more than one Defense System component, from the same Defense system, is on a transmissible genetic element. In some embodiments, two Defense System components, from the same Defense system, are on a transmissible genetic element. In some embodiments, three Defense System components, from the same Defense system, are on a transmissible genetic element. In some embodiments, four Defense System components, from the same Defense system, are on a transmissible genetic element. In some embodiments, five Defense System components, from the same Defense system, are on a transmissible genetic element. In some embodiments, all of the Defense System components from a single Defense system are on a transmissible genetic element. In some embodiments, the components are on the same transmissible genetic element. In some embodiments, the components are on different transmissible elements. In some embodiments, the order of the components on a transmissible genetic element is as found in a donor species. In some embodiments, the order of the components on a transmissible genetic element differs from the order found in a donor species.


In some embodiments, at least one Defense System Ia component is on a transmissible genetic element. In some embodiments, more than one Defense System Ia component, is on a transmissible genetic element. In some embodiments, two Defense System Ia components, are on a transmissible genetic element. In some embodiments, three Defense System Ia components, are on a transmissible genetic element. In some embodiments, four Defense System Ia components, are on a transmissible genetic element. In some embodiments, all of the Defense System Ia components are on a transmissible genetic element. In some embodiments, the nucleic acid construct of Defense System Ia is on a transmissible genetic element. In some embodiments, the components are on the same transmissible genetic element. In some embodiments, the components are on different transmissible elements. In some embodiments, the order of the components on a transmissible genetic element is as found in a donor species. In some embodiments, the order of the components on a transmissible genetic element differs from the order found in a donor species.


In some embodiments, at least one Defense System Ib component is on a transmissible genetic element. In some embodiments, more than one Defense System Ib component, is on a transmissible genetic element. In some embodiments, two Defense System Ib components, are on a transmissible genetic element. In some embodiments, three Defense System Ib components, are on a transmissible genetic element. In some embodiments, all of the Defense System Ib components are on a transmissible genetic element. In some embodiments, the nucleic acid construct of Defense System Ib is on a transmissible genetic element. In some embodiments, the components are on the same transmissible genetic element. In some embodiments, the components are on different transmissible elements. In some embodiments, the order of the components on a transmissible genetic element is as found in a donor species. In some embodiments, the order of the components on a transmissible genetic element differs from the order found in a donor species.


In some embodiments, at least one Defense System II component is on a transmissible genetic element. In some embodiments, more than one Defense System II component, is on a transmissible genetic element. In some embodiments, two Defense System II components, are on a transmissible genetic element. In some embodiments, all of the Defense System II components are on a transmissible genetic element. In some embodiments, the nucleic acid construct of Defense System II is on a transmissible genetic element. In some embodiments, the components are on the same transmissible genetic element. In some embodiments, the components are on different transmissible elements. In some embodiments, the order of the components on a transmissible genetic element is as found in a donor species. In some embodiments, the order of the components on a transmissible genetic element differs from the order found in a donor species.


In some embodiments, at least one Defense System IIIa component is on a transmissible genetic element. In some embodiments, more than one Defense System IIIa component, is on a transmissible genetic element. In some embodiments, two Defense System IIIa components, are on a transmissible genetic element. In some embodiments, three Defense System IIIa components, are on a transmissible genetic element. In some embodiments, four Defense System IIIa components, are on a transmissible genetic element. In some embodiments, five Defense System IIIa components, are on a transmissible genetic element. In some embodiments, all of the Defense System IIIa components are on a transmissible genetic element. In some embodiments, the nucleic acid construct of Defense System IIIa is on a transmissible genetic element. In some embodiments, the components are on the same transmissible genetic element. In some embodiments, the components are on different transmissible elements. In some embodiments, the order of the components on a transmissible genetic element is as found in a donor species. In some embodiments, the order of the components on a transmissible genetic element differs from the order found in a donor species.


In some embodiments, at least one Defense System IIIb component is on a transmissible genetic element. In some embodiments, more than one Defense System IIIb component, is on a transmissible genetic element. In some embodiments, two Defense System IIIb components, are on a transmissible genetic element. In some embodiments, three Defense System IIIb components, are on a transmissible genetic element. In some embodiments, four Defense System IIIb components, are on a transmissible genetic element. In some embodiments, five Defense System IIIb components, are on a transmissible genetic element. In some embodiments, all of the Defense System IIIb components are on a transmissible genetic element. In some embodiments, the nucleic acid construct of Defense System IIIb is on a transmissible genetic element. In some embodiments, the components are on the same transmissible genetic element. In some embodiments, the components are on different transmissible elements. In some embodiments, the order of the components on a transmissible genetic element is as found in a donor species. In some embodiments, the order of the components on a transmissible genetic element differs from the order found in a donor species.


In some embodiments, at least one Defense System IIIc component is on a transmissible genetic element. In some embodiments, more than one Defense System IIIc component, is on a transmissible genetic element. In some embodiments, two Defense System IIIc components, are on a transmissible genetic element. In some embodiments, three Defense System IIIc components, are on a transmissible genetic element. In some embodiments, four Defense System IIIc components, are on a transmissible genetic element. In some embodiments, five Defense System IIIc components, are on a transmissible genetic element. In some embodiments, all of the Defense System IIIc components are on a transmissible genetic element. In some embodiments, the nucleic acid construct of Defense System IIIc is on a transmissible genetic element. In some embodiments, the components are on the same transmissible genetic element. In some embodiments, the components are on different transmissible elements. In some embodiments, the order of the components on a transmissible genetic element is as found in a donor species. In some embodiments, the order of the components on a transmissible genetic element differs from the order found in a donor species.


In some embodiments, at least one Defense System IV component is on a transmissible genetic element. In some embodiments, more than one Defense System IV component, is on a transmissible genetic element. In some embodiments, two Defense System IV components, are on a transmissible genetic element. In some embodiments, all of the Defense System IV components are on a transmissible genetic element. In some embodiments, the nucleic acid construct of Defense System IV is on a transmissible genetic element. In some embodiments, the components are on the same transmissible genetic element. In some embodiments, the components are on different transmissible elements. In some embodiments, the order of the components on a transmissible genetic element is as found in a donor species. In some embodiments, the order of the components on a transmissible genetic element differs from the order found in a donor species.


In some embodiments, at least one Defense System V component is on a transmissible genetic element. In some embodiments, the nucleic acid construct of Defense System V is on a transmissible genetic element. In some embodiments, all of the Defense System V components are on a transmissible genetic element. In some embodiments, the components are on the same transmissible genetic element. In some embodiments, the components are on different transmissible elements. In some embodiments, the order of the components on a transmissible genetic element is as found in a donor species. In some embodiments, the order of the components on a transmissible genetic element differs from the order found in a donor species.


In some embodiments, at least one Defense System VI component is on a transmissible genetic element. In some embodiments, more than one Defense System VI component, is on a transmissible genetic element. In some embodiments, two Defense System VI components, are on a transmissible genetic element. In some embodiments, all of the Defense System VI components are on a transmissible genetic element. In some embodiments, the nucleic acid construct of Defense System VI is on a transmissible genetic element. In some embodiments, the components are on the same transmissible genetic element. In some embodiments, the components are on different transmissible elements. In some embodiments, the order of the components on a transmissible genetic element is as found in a donor species. In some embodiments, the order of the components on a transmissible genetic element differs from the order found in a donor species.


In some embodiments, at least one Defense System VII component is on a transmissible genetic element. In some embodiments, more than one Defense System VII component, is on a transmissible genetic element. In some embodiments, two Defense System VII components, are on a transmissible genetic element. In some embodiments, all of the Defense System VII components are on a transmissible genetic element. In some embodiments, the nucleic acid construct of Defense System VII is on a transmissible genetic element. In some embodiments, the components are on the same transmissible genetic element. In some embodiments, the components are on different transmissible elements. In some embodiments, the order of the components on a transmissible genetic element is as found in a donor species. In some embodiments, the order of the components on a transmissible genetic element differs from the order found in a donor species.


In some embodiments, at least one Defense System VIII component is on a transmissible genetic element. In some embodiments, more than one Defense System VIII component, is on a transmissible genetic element. In some embodiments, two Defense System VIII components, are on a transmissible genetic element. In some embodiments, all of the Defense System VIII components are on a transmissible genetic element. In some embodiments, the nucleic acid construct of Defense VIII is on a transmissible genetic element. In some embodiments, the components are on the same transmissible genetic element. In some embodiments, the components are on different transmissible elements. In some embodiments, the order of the components on a transmissible genetic element is as found in a donor species. In some embodiments, the order of the components on a transmissible genetic element differs from the order found in a donor species.


In some embodiments, at least one Defense System IX component is on a transmissible genetic element. In some embodiments, more than one Defense System IX component, is on a transmissible genetic element. In some embodiments, two Defense System IX components, are on a transmissible genetic element. In some embodiments, all of the Defense System IX components are on a transmissible genetic element. In some embodiments, the nucleic acid construct of Defense System IX is on a transmissible genetic element. In some embodiments, the components are on the same transmissible genetic element. In some embodiments, the components are on different transmissible elements. In some embodiments, the order of the components on a transmissible genetic element is as found in a donor species. In some embodiments, the order of the components on a transmissible genetic element differs from the order found in a donor species.


In some embodiments, at least one Defense System Xa component is on a transmissible genetic element. In some embodiments, more than one Defense System Xa component, is on a transmissible genetic element. In some embodiments, two Defense System Xa components, are on a transmissible genetic element. In some embodiments, three Defense System Xa components, are on a transmissible genetic element. In some embodiments, four Defense System Xa components, are on a transmissible genetic element. In some embodiments, all of the Defense System Xa components are on a transmissible genetic element. In some embodiments, the nucleic acid construct of Defense System Xa is on a transmissible genetic element. In some embodiments, the components are on the same transmissible genetic element. In some embodiments, the components are on different transmissible elements. In some embodiments, the order of the components on a transmissible genetic element is as found in a donor species. In some embodiments, the order of the components on a transmissible genetic element differs from the order found in a donor species.


In some embodiments, at least one Defense System Xb component is on a transmissible genetic element. In some embodiments, more than one Defense System Xb component, is on a transmissible genetic element. In some embodiments, two Defense System Xb components, are on a transmissible genetic element. In some embodiments, three Defense System Xb components, are on a transmissible genetic element. In some embodiments, four Defense System Xb components, are on a transmissible genetic element. In some embodiments, all of the Defense System Xb components are on a transmissible genetic element. In some embodiments, the nucleic acid construct of Defense System Xb is on a transmissible genetic element. In some embodiments, the components are on the same transmissible genetic element. In some embodiments, the components are on different transmissible elements. In some embodiments, the order of the components on a transmissible genetic element is as found in a donor species. In some embodiments, the order of the components on a transmissible genetic element differs from the order found in a donor species.


In some embodiments, at least one Defense System Xc component is on a transmissible genetic element. In some embodiments, more than one Defense System Xc component, is on a transmissible genetic element. In some embodiments, two Defense System Xc components, are on a transmissible genetic element. In some embodiments, three Defense System Xc components, are on a transmissible genetic element. In some embodiments, four Defense System Xc components, are on a transmissible genetic element. In some embodiments, all of the Defense System Xc components are on a transmissible genetic element. In some embodiments, the nucleic acid construct of Defense System Xc is on a transmissible genetic element. In some embodiments, the components are on the same transmissible genetic element. In some embodiments, the components are on different transmissible elements. In some embodiments, the order of the components on a transmissible genetic element is as found in a donor species. In some embodiments, the order of the components on a transmissible genetic element differs from the order found in a donor species.


In some embodiments, a construct disclosed herein, further comprises an element providing episomal maintenance of said construct within a cell transfected with said construct.


In some embodiments, a Defense System construct comprising a Defense System Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, or Xc further comprises a regulatory element operably linked to said construct comprising a cis-acting regulatory element for directing expression of said nucleic acid sequence. In some embodiments, a Defense System construct comprising a Defense System Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, or Xc further comprises a transmissible element for directing transfer of said nucleic acid sequence from one cell to another. In some embodiments, a Defense System construct comprising a Defense System Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, or Xc further comprises a recombination element for integrating said nucleic acid sequence into a genome of a cell transfected with said construct. In some embodiments, a Defense System construct comprising a Defense System Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, or Xc further comprises an element providing episomal maintenance of said construct within a cell transfected with said construct. In some embodiments, a Defense System construct comprising a Defense System Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, or Xc further comprises any combination of a regulatory element operably linked to said construct comprising a cis-acting regulatory element for directing expression of said nucleic acid sequence, or a transmissible element for directing transfer of said nucleic acid sequence from one cell to another, or a recombination element for integrating said nucleic acid sequence into a genome of a cell transfected with said construct, or an element providing episomal maintenance of said construct within a cell transfected with said construct, or any combination thereof.


In some embodiments, a defense system described herein comprises a combination of Defense Systems. In some embodiments, a defense system described herein comprises a combination of Defense Systems (Ia)-(Xc). In some embodiments, the combination of Defense Systems, for example but not limited to the combination of Defense Systems (Ia)-(Xc), provides advantageous properties including (1) resistance to a broader range of phages or (2) resistance to at least one phage and reduced transformation efficiency of plasmids or (3) both resistance to a broader range of phages and reduced transformation efficiency.


A skilled artisan would appreciate that the terms “anti-phage activity” or “resistant to infection by at least one phage” or “resistance to at least one phage” or “anti-phage defense” encompasses an activity provided by a Defense system to a host cell, for example but not limited to bacterial cell expressing a functional Defense System disclosed herein, wherein said bacterial cell then comprises an increased resistance to infection by at least one phage in comparison to bacteria of the same species under the same developmental stage (e.g. culture state) which does not express an endogenous functional Defense System. Resistance to infection, may be determined by for example but not limited to bacterial viability, phage lysogeny, phage genomic replication, or phage genomic degradation. The phage can be a lytic phage or a temperate (lysogenic) phage described herein. In some embodiments, the increase in resistance is at least 1.5 fold, at least 2 fold, at least 3 fold, at least 5 fold, at least 10 fold, or at least 20 fold as compared to same bacterial host in the absence of the functional Defense System.


In some embodiments, the increase in resistance is by at least 5%, by at least a 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90% or more than 100% as compared to same host bacteria in the absence of the functional Defense System.


Assays for testing phage resistance are well known in the art and are further described hereinbelow.


A skilled artisan would appreciate that the terms “anti-plasmid activity” or “defense against plasmid transformation” or “reduced transformation by a plasmid” or “anti-plasmid defense” or “plasmid resistance” encompasses an activity provided by a Defense System to a host cell, for example but not limited to bacterial cell expressing a functional Defense System disclosed herein, wherein the bacterial cell then comprises a decreased efficiency of transformation by at least one plasmid in comparison to bacteria of the same species under the same developmental stage (e.g. culture state) which does not express a functional Defense System. Decreased efficiency of plasmid transformation, may be determined by for example but not limited to a transformation efficiency assay comparing bacteria comprising a Defense System with those not comprising the Defense System. The plasmid may be an episomal plasmid. In some embodiments, the decreased transformation efficiency is at least 1.5 fold, at least 2 fold, at least 3 fold, at least 5 fold, at least 10 fold, or at least 20 fold as compared to same bacterial host in the absence of the functional Defense System.


In some embodiments, the decreased transformation efficiency is by at least 5%, by at least a 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90% or more than 100% as compared to same host bacteria in the absence of the functional Defense System.


A skilled artisan would appreciate that the term “donor species” may in certain embodiments, encompass the bacterial or archaeal species in which a Defense System was identified and sequenced. The skilled artisan would also appreciate that the term “host cell” may in certain embodiments, encompass bacterial or archaeal or eukaryotic cell in which a Defense System has been introduced. In some embodiments, the host cell does not endogenously comprise the Defense System introduced. In some embodiments, the host cell does not endogenously comprise a functional version of the Defense System introduced. In some embodiments, the host cell comprises the Defense System introduced but it is not functional in the host cell. In some embodiments, the host cell does not endogenously express the Defense System introduced. In some embodiments, the host cell does not endogenously express a functional version of the Defense System introduced.


Regardless of the method of introduction, in some embodiments provided herein are cells, for example but not limited to bacterial cells, which comprise a heterologous functional defense system, or components thereof. In some embodiments, the method of introduction is conjugation.


In some embodiments, the isolated cell is transformed or transfected with the described nucleic acid construct or nucleic acid construct Defense System, or a combination thereof.


In some embodiments, in some embodiments a combination of Defense Systems comprises a combination of the nucleic acid constructs comprising each Defense System. In some embodiments a combination of Defense systems comprises a combination of the nucleic acid constructs comprising a functional Defense System selected from Defense System Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments two defense systems are combined. In some embodiments 2-17 defense systems are combined. In some embodiments 2-5 defense systems are combined. In some embodiments 2-10 defense systems are combined. In some embodiments 5-10 defense systems are combined. In some embodiments 10-17 defense systems are combined. In some embodiments, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 defense systems are combined. In some embodiments 2-40 defense systems are combined. In some embodiments, multiple copies of the same Defense System are combined. In some embodiments, the combination comprises all different Defense Systems. In some embodiments a combination of Defense systems comprises any combination of the nucleic acid constructs comprising a functional Defense System selected from Defense System Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc.


In some embodiments, a combination comprising a Defense System Ia comprises a combination of Defense System Ia with any combination of Defense Systems Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System Ia comprises a combination of Defense System Ia with 1-16 defense systems selected from Defense Systems Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System Ia comprises a combination of Defense System Ia with 1 defense system selected from Defense Systems Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System Ia comprises a combination of Defense System Ia with 2 defense systems selected from Defense Systems Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System Ia comprises a combination of Defense System Ia with 3 defense systems selected from Defense Systems Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System Ia comprises a combination of Defense System Ia with 4 defense systems selected from Defense Systems Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System Ia comprises a combination of Defense System Ia with 5 defense systems selected from Defense Systems Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System Ia comprises a combination of Defense System Ia with 6 defense systems selected from Defense Systems Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System Ia comprises a combination of Defense System Ia with 7 defense systems selected from Defense Systems Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System Ia comprises a combination of Defense System Ia with 8 defense systems selected from Defense Systems Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System Ia comprises a combination of Defense System Ia with 9 defense systems selected from Defense Systems Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System Ia comprises a combination of Defense System Ia with 10 defense systems selected from Defense Systems Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System Ia comprises a combination of Defense System Ia with 11 defense systems selected from Defense Systems Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System Ia comprises a combination of Defense System Ia with 12 defense systems selected from Defense Systems Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System Ia comprises a combination of Defense System Ia with 13 defense systems selected from Defense Systems Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System Ia comprises a combination of Defense System Ia with 14 defense systems selected from Defense Systems Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System Ia comprises a combination of Defense System Ia with 15 defense systems selected from Defense Systems Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System Ia comprises a combination of Defense System Ia with 16 defense systems selected from Defense Systems Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc.


In some embodiments, a combination comprising a Defense System Ib comprises a combination of Defense System Ib with any combination of Defense Systems Ia, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System Ib comprises a combination of Defense System Ia with 1-16 defense systems selected from Defense Systems Ia, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System Ib comprises a combination of Defense System Ia with 1 defense system selected from Defense Systems Ia, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System Ib comprises a combination of Defense System Ib with 2 defense systems selected from Defense Systems Ia, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System Ib comprises a combination of Defense System Ib with 3 defense systems selected from Defense Systems Ia, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System Ib comprises a combination of Defense System Ib with 4 defense systems selected from Defense Systems Ia, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System Ib comprises a combination of Defense System Ib with 5 defense systems selected from Defense Systems Ia, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System Ib comprises a combination of Defense System Ib with 6 defense systems selected from Defense Systems Ia, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System Ib comprises a combination of Defense System Ib with 7 defense systems selected from Defense Systems Ia, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System Ib comprises a combination of Defense System Ib with 8 defense systems selected from Defense Systems Ia, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System Ib comprises a combination of Defense System Ib with 9 defense systems selected from Defense Systems Ia, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System Ib comprises a combination of Defense System Ib with 10 defense systems selected from Defense Systems Ia, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System Ib comprises a combination of Defense System Ib with 11 defense systems selected from Defense Systems Ia, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System Ib comprises a combination of Defense System Ib with 12 defense systems selected from Defense Systems Ia, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System Ib comprises a combination of Defense System Ib with 13 defense systems selected from Defense Systems Ia, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System Ib comprises a combination of Defense System Ib with 14 defense systems selected from Defense Systems Ia, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System Ib comprises a combination of Defense System Ib with 15 defense systems selected from Defense Systems Ia, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System Ib comprises a combination of Defense System Ib with 16 defense systems selected from Defense Systems Ia, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc.


In some embodiments, a combination comprising a Defense System II comprises a combination of Defense System II with any combination of Defense Systems Ia, Ib, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System II comprises a combination of Defense System II with 1-16 defense systems selected from Defense Systems Ia, Ib, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System II comprises a combination of Defense System II with 1 defense system selected from Defense Systems Ia, Ib, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System II comprises a combination of Defense System II with 2 defense systems selected from Defense Systems Ia, Ib, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System II comprises a combination of Defense System II with 3 defense systems selected from Defense Systems Ia, Ib, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System II comprises a combination of Defense System II with 4 defense systems selected from Defense Systems Ia, Ib, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System II comprises a combination of Defense System II with 5 defense systems selected from Defense Systems Ia, Ib, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System II comprises a combination of Defense System II with 6 defense systems selected from Defense Systems Ia, Ib, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System II comprises a combination of Defense System II with 7 defense systems selected from Defense Systems Ia, Ib, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System II comprises a combination of Defense System II with 8 defense systems selected from Defense Systems Ia, Ib, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System II comprises a combination of Defense System II with 9 defense systems selected from Defense Systems Ia, Ib, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System II comprises a combination of Defense System II with 10 defense systems selected from Defense Systems Ia, Ib, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System II comprises a combination of Defense System II with 11 defense systems selected from Defense Systems Ia, Ib, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System II comprises a combination of Defense System II with 12 defense systems selected from Defense Systems Ia, Ib, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System II comprises a combination of Defense System II with 13 defense systems selected from Defense Systems Ia, Ib, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System II comprises a combination of Defense System II with 14 defense systems selected from Defense Systems Ia, Ib, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System II comprises a combination of Defense System II with 15 defense systems selected from Defense Systems Ia, Ib, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System II comprises a combination of Defense System II with 16 defense systems selected from Defense Systems Ia, Ib, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc.


In some embodiments, a combination comprising a Defense System IIIa comprises a combination of Defense System IIIa with any combination of Defense Systems Ia, Ib, II, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IIIa comprises a combination of Defense System IIIa with 1-16 defense systems selected from Defense Systems Ia, Ib, II, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IIIa comprises a combination of Defense System IIIa with 1 defense system selected from Defense Systems Ia, Ib, II, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IIIa comprises a combination of Defense System IIIa with 2 defense systems selected from Defense Systems Ia, Ib, II, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IIIa comprises a combination of Defense System IIIa with 3 defense systems selected from Defense Systems Ia, Ib, II, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IIIa comprises a combination of Defense System IIIa with 4 defense systems selected from Defense Systems Ia, Ib, II, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IIIa comprises a combination of Defense System IIIa with 5 defense systems selected from Defense Systems Ia, Ib, II, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IIIa comprises a combination of Defense System IIIa with 6 defense systems selected from Defense Systems Ia, Ib, II, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IIIa comprises a combination of Defense System IIIa with 7 defense systems selected from Defense Systems Ia, Ib, II, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IIIa comprises a combination of Defense System IIIa with 8 defense systems selected from Defense Systems Ia, Ib, II, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IIIa comprises a combination of Defense System IIIa with 9 defense systems selected from Defense Systems Ia, Ib, II, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IIIa comprises a combination of Defense System IIIa with 10 defense systems selected from Defense Systems Ia, Ib, II, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IIIa comprises a combination of Defense System IIIa with 11 defense systems selected from Defense Systems Ia, Ib, II, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IIIa comprises a combination of Defense System IIIa with 12 defense systems selected from Defense Systems Ia, Ib, II, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IIIa comprises a combination of Defense System IIIa with 13 defense systems selected from Defense Systems Ia, Ib, II, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IIIa comprises a combination of Defense System IIIa with 14 defense systems selected from Defense Systems Ia, Ib, II, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IIIa comprises a combination of Defense System IIIa with 15 defense systems selected from Defense Systems Ia, Ib, II, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IIIa comprises a combination of Defense System IIIa with 16 defense systems selected from Defense Systems Ia, Ib, II, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc.


In some embodiments, a combination comprising a Defense System IIIb comprises a combination of Defense System IIIb with any combination of Defense Systems Ia, Ib, II, IIIa, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IIIb comprises a combination of Defense System IIIb with 1-16 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IIIb comprises a combination of Defense System IIIb with 1 defense system selected from Defense Systems Ia, Ib, II, IIIa, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IIIb comprises a combination of Defense System IIIb with 2 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IIIb comprises a combination of Defense System IIIb with 3 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IIIb comprises a combination of Defense System IIIb with 4 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IIIb comprises a combination of Defense System IIIb with 5 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IIIb comprises a combination of Defense System IIIb with 6 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IIIb comprises a combination of Defense System IIIb with 7 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IIIb comprises a combination of Defense System IIIb with 8 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IIIb comprises a combination of Defense System IIIb with 9 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IIIb comprises a combination of Defense System IIIb with 10 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IIIb comprises a combination of Defense System IIIb with 11 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IIIb comprises a combination of Defense System IIIb with 12 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IIIb comprises a combination of Defense System IIIb with 13 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IIIb comprises a combination of Defense System IIIb with 14 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IIIb comprises a combination of Defense System IIIb with 15 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IIIb comprises a combination of Defense System IIIb with 16 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc.


In some embodiments, a combination comprising a Defense System IIIc comprises a combination of Defense System IIIc with any combination of Defense Systems Ia, Ib, II, IIIa, IIIb, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IIIc comprises a combination of Defense System IIIc with 1-16 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IIIc comprises a combination of Defense System IIIc with 1 defense system selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IIIc comprises a combination of Defense System IIIc with 2 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IIIc comprises a combination of Defense System IIIc with 3 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IIIc comprises a combination of Defense System IIIc with 4 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IIIc comprises a combination of Defense System IIIc with 5 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IIIc comprises a combination of Defense System IIIc with 6 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IIIc comprises a combination of Defense System IIIc with 7 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IIIc comprises a combination of Defense System IIIc with 8 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IIIc comprises a combination of Defense System IIIc with 9 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IIIc comprises a combination of Defense System IIIc with 10 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IIIc comprises a combination of Defense System IIIc with 11 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IIIc comprises a combination of Defense System IIIc with 12 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IIIc comprises a combination of Defense System IIIc with 13 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IIIc comprises a combination of Defense System IIIc with 14 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IIIc comprises a combination of Defense System IIIc with 15 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IIIc comprises a combination of Defense System IIIc with 16 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc.


In some embodiments, a combination comprising a Defense System IV comprises a combination of Defense System IV with any combination of Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IV comprises a combination of Defense System IV with 1-16 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IV comprises a combination of Defense System IV with 1 defense system selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IV comprises a combination of Defense System IV with 2 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IV comprises a combination of Defense System IV with 3 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IV comprises a combination of Defense System IV with 4 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IV comprises a combination of Defense System IV with 5 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IV comprises a combination of Defense System IV with 6 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IV comprises a combination of Defense System IV with 7 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IV comprises a combination of Defense System IV with 8 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IV comprises a combination of Defense System IV with 9 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IV comprises a combination of Defense System IV with 10 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IV comprises a combination of Defense System IV with 11 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IV comprises a combination of Defense System IV with 12 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IV comprises a combination of Defense System IV with 13 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IV comprises a combination of Defense System IV with 14 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IV comprises a combination of Defense System IV with 15 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IV comprises a combination of Defense System IV with 16 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, V, VI, VII, VIII, IX, Xa, Xb, and Xc.


In some embodiments, a combination comprising a Defense System V comprises a combination of Defense System V with any combination of Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System V comprises a combination of Defense System V with 1-16 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System V comprises a combination of Defense System V with 1 defense system selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System V comprises a combination of Defense System V with 2 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System V comprises a combination of Defense System V with 3 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System V comprises a combination of Defense System V with 4 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System V comprises a combination of Defense System V with 5 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System V comprises a combination of Defense System V with 6 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System V comprises a combination of Defense System V with 7 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System V comprises a combination of Defense System V with 8 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System V comprises a combination of Defense System V with 9 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System V comprises a combination of Defense System V with 10 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System V comprises a combination of Defense System V with 11 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System V comprises a combination of Defense System V with 12 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System V comprises a combination of Defense System V with 13 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System V comprises a combination of Defense System V with 14 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System V comprises a combination of Defense System V with 15 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System V comprises a combination of Defense System V with 16 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, VII, VIII, IX, Xa, Xb, and Xc.


In some embodiments, a combination comprising a Defense System VI comprises a combination of Defense System VI with any combination of Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System VI comprises a combination of Defense System VI with 1-16 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System VI comprises a combination of Defense System VI with 1 defense system selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System VI comprises a combination of Defense System VI with 2 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System VI comprises a combination of Defense System VI with 3 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System VI comprises a combination of Defense System VI with 4 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System VI comprises a combination of Defense System VI with 5 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System VI comprises a combination of Defense System VI with 6 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System VI comprises a combination of Defense System VI with 7 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System VI comprises a combination of Defense System VI with 8 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System VI comprises a combination of Defense System VI with 9 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System VI comprises a combination of Defense System VI with 10 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System VI comprises a combination of Defense System VI with 11 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System VI comprises a combination of Defense System VI with 12 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System VI comprises a combination of Defense System VI with 13 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System VI comprises a combination of Defense System VI with 14 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System VI comprises a combination of Defense System VI with 15 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System VI comprises a combination of Defense System VI with 16 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VII, VIII, IX, Xa, Xb, and Xc.


In some embodiments, a combination comprising a Defense System VII comprises a combination of Defense System VII with any combination of Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System VII comprises a combination of Defense System VII with 1-16 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System VII comprises a combination of Defense System VII with 1 defense system selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System VII comprises a combination of Defense System VII with 2 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System VII comprises a combination of Defense System VII with 3 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System VII comprises a combination of Defense System VII with 4 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System VII comprises a combination of Defense System VII with 5 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System VII comprises a combination of Defense System VII with 6 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System VII comprises a combination of Defense System VII with 7 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System VII comprises a combination of Defense System VII with 8 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System VII comprises a combination of Defense System VII with 9 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System VII comprises a combination of Defense System VII with 10 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System VII comprises a combination of Defense System VII with 11 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System VII comprises a combination of Defense System VII with 12 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System VII comprises a combination of Defense System VII with 13 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System VII comprises a combination of Defense System VII with 14 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System VII comprises a combination of Defense System VII with 15 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VIII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System VII comprises a combination of Defense System VII with 16 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VIII, IX, Xa, Xb, and Xc.


In some embodiments, a combination comprising a Defense System VIII comprises a combination of Defense System VIII with any combination of Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System VIII comprises a combination of Defense System VIII with 1-16 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System VIII comprises a combination of Defense System VIII with 1 defense system selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System VIII comprises a combination of Defense System VIII with 2 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System VIII comprises a combination of Defense System VIII with 3 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System VIII comprises a combination of Defense System VIII with 4 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System VIII comprises a combination of Defense System VIII with 5 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System VIII comprises a combination of Defense System VIII with 6 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System VIII comprises a combination of Defense System VIII with 7 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System VIII comprises a combination of Defense System VIII with 8 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System VIII comprises a combination of Defense System VIII with 9 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System VIII comprises a combination of Defense System VIII with 10 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System VIII comprises a combination of Defense System VIII with 11 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System VIII comprises a combination of Defense System VIII with 12 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System VIII comprises a combination of Defense System VIII with 13 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System VIII comprises a combination of Defense System VIII with 14 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System VIII comprises a combination of Defense System VIII with 15 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VII, IX, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System VIII comprises a combination of Defense System VIII with 16 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VII, IX, Xa, Xb, and Xc.


In some embodiments, a combination comprising a Defense System IX comprises a combination of Defense System IX with any combination of Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VII, VIII, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IX comprises a combination of Defense System IX with 1-16 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VII, VIII, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IX comprises a combination of Defense System IX with 1 defense system selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VII, VIII, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IX comprises a combination of Defense System IX with 2 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VII, VIII, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IX comprises a combination of Defense System IX with 3 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VII, VIII, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IX comprises a combination of Defense System IX with 4 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VII, VIII, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IX comprises a combination of Defense System IX with 5 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VII, VIII, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IX comprises a combination of Defense System IX with 6 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VII, VIII, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IX comprises a combination of Defense System IX with 7 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VII, VIII, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IX comprises a combination of Defense System IX with 8 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VII, VIII, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IX comprises a combination of Defense System IX with 9 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VII, VIII, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IX comprises a combination of Defense System IX with 10 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VII, VIII, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IX comprises a combination of Defense System IX with 11 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VII, VIII, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IX comprises a combination of Defense System IX with 12 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VII, VIII, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IX comprises a combination of Defense System IX with 13 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VII, VIII, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IX comprises a combination of Defense System IX with 14 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VII, VIII, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IX comprises a combination of Defense System IX with 15 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VII, VIII, Xa, Xb, and Xc. In some embodiments, a combination comprising a Defense System IX comprises a combination of Defense System IX with 16 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VII, VIII, Xa, Xb, and Xc.


In some embodiments, a combination comprising a Defense System Xb comprises a combination of Defense System Xb with any combination of Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VII, VIII, IX, Xa, and Xc. In some embodiments, a combination comprising a Defense System Xb comprises a combination of Defense System Xb with 1-16 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VII, VIII, IX, Xa, and Xc. In some embodiments, a combination comprising a Defense System Xb comprises a combination of Defense System Xb with 1 defense system selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VII, VIII, IX, Xa, and Xc. In some embodiments, a combination comprising a Defense System Xb comprises a combination of Defense System Xb with 2 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VII, VIII, IX, Xa, and Xc. In some embodiments, a combination comprising a Defense System Xb comprises a combination of Defense System Xb with 3 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VII, VIII, IX, Xa, and Xc. In some embodiments, a combination comprising a Defense System Xb comprises a combination of Defense System Xb with 4 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VII, VIII, IX, Xa, and Xc. In some embodiments, a combination comprising a Defense System Xb comprises a combination of Defense System Xb with 5 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VII, VIII, IX, Xa, and Xc. In some embodiments, a combination comprising a Defense System Xb comprises a combination of Defense System Xb with 6 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VII, VIII, IX, Xa, and Xc. In some embodiments, a combination comprising a Defense System Xb comprises a combination of Defense System Xb with 7 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VII, VIII, IX, Xa, and Xc. In some embodiments, a combination comprising a Defense System Xb comprises a combination of Defense System Xb with 8 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VII, VIII, IX, Xa, and Xc. In some embodiments, a combination comprising a Defense System Xb comprises a combination of Defense System Xb with 9 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VII, VIII, IX, Xa, and Xc. In some embodiments, a combination comprising a Defense System Xb comprises a combination of Defense System Xb with 10 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VII, VIII, IX, Xa, and Xc. In some embodiments, a combination comprising a Defense System Xb comprises a combination of Defense System Xb with 11 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VII, VIII, IX, Xa, and Xc. In some embodiments, a combination comprising a Defense System Xb comprises a combination of Defense System Xb with 12 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VII, VIII, IX, Xa, and Xc. In some embodiments, a combination comprising a Defense System Xb comprises a combination of Defense System Xb with 13 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VII, VIII, IX, Xa, and Xc. In some embodiments, a combination comprising a Defense System Xb comprises a combination of Defense System Xb with 14 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VII, VIII, IX, Xa, and Xc. In some embodiments, a combination comprising a Defense System Xb comprises a combination of Defense System Xb with 15 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VII, VIII, IX, Xa, and Xc. In some embodiments, a combination comprising a Defense System Xb comprises a combination of Defense System Xb with 16 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VII, VIII, IX, Xa, and Xc.


In some embodiments, a combination comprising a Defense System Xc comprises a combination of Defense System Xc with any combination of Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VII, VIII, IX, Xa, and Xb. In some embodiments, a combination comprising a Defense System Xc comprises a combination of Defense System Xc with 1-16 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VII, VIII, IX, Xa, and Xb. In some embodiments, a combination comprising a Defense System Xc comprises a combination of Defense System Xc with 1 defense system selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VII, VIII, IX, Xa, and Xb. In some embodiments, a combination comprising a Defense System Xc comprises a combination of Defense System Xc with 2 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VII, VIII, IX, Xa, and Xb. In some embodiments, a combination comprising a Defense System Xc comprises a combination of Defense System Xc with 3 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VII, VIII, IX, Xa, and Xb. In some embodiments, a combination comprising a Defense System Xc comprises a combination of Defense System Xc with 4 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VII, VIII, IX, Xa, and Xb. In some embodiments, a combination comprising a Defense System Xc comprises a combination of Defense System Xc with 5 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VII, VIII, IX, Xa, and Xb. In some embodiments, a combination comprising a Defense System Xc comprises a combination of Defense System Xc with 6 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VII, VIII, IX, Xa, and Xb. In some embodiments, a combination comprising a Defense System Xc comprises a combination of Defense System Xc with 7 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VII, VIII, IX, Xa, and Xb. In some embodiments, a combination comprising a Defense System Xc comprises a combination of Defense System Xc with 8 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VII, VIII, IX, Xa, and Xb. In some embodiments, a combination comprising a Defense System Xc comprises a combination of Defense System Xc with 9 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VII, VIII, IX, Xa, and Xb. In some embodiments, a combination comprising a Defense System Xc comprises a combination of Defense System Xc with 10 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VII, VIII, IX, Xa, and Xb. In some embodiments, a combination comprising a Defense System Xc comprises a combination of Defense System Xc with 11 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VII, VIII, IX, Xa, and Xb. In some embodiments, a combination comprising a Defense System Xc comprises a combination of Defense System Xc with 12 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VII, VIII, IX, Xa, and Xb. In some embodiments, a combination comprising a Defense System Xc comprises a combination of Defense System Xc with 13 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VII, VIII, IX, Xa, and Xb. In some embodiments, a combination comprising a Defense System Xc comprises a combination of Defense System Xc with 14 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VII, VIII, IX, Xa, and Xb. In some embodiments, a combination comprising a Defense System Xc comprises a combination of Defense System Xc with 15 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VII, VIII, IX, Xa, and Xb. In some embodiments, a combination comprising a Defense System Xc comprises a combination of Defense System Xc with 16 defense systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, VI, V, VI, VII, VIII, IX, Xa, and Xb.


In some embodiments, a combination of Defense Systems disclosed herein above, does not naturally occur in nature. In some embodiments, a combination of Defense Systems disclosed herein above, does not naturally occur in a host cell. In some embodiments, a combination of Defense Systems disclosed herein above, does not naturally occur in bacterial cell. In some embodiments, a combination of Defense Systems disclosed herein above, does not naturally occur in an archaeal cell. In some embodiments, a combination of Defense Systems disclosed herein above, does not naturally occur in a eukaryotic cell. In some embodiments, a combination of Defense Systems disclosed herein above, does not naturally occur in a species disclosed in Tables 6-19C. In some embodiments, a combination of Defense Systems disclosed herein above, does not naturally occur in a host cell.


In some embodiments, a combination of Defense Systems disclosed herein above, is not expressed together in nature. In some embodiments, a combination of Defense Systems disclosed herein above, is not naturally expressed in a host cell. In some embodiments, a combination of Defense Systems disclosed herein above, is not naturally expressed in bacterial cell. In some embodiments, a combination of Defense Systems disclosed herein above, is not naturally expressed in an archaeal cell. In some embodiments, a combination of Defense Systems disclosed herein above, is not naturally expressed in a eukaryotic cell. In some embodiments, a combination of Defense Systems disclosed herein above, is not naturally expressed in a species disclosed in Tables 6-17.


In some embodiments, a combination of functional Defense Systems disclosed herein above, does not naturally occur in nature. In some embodiments, a combination of functional Defense Systems disclosed herein above, does not naturally occur in a host cell. In some embodiments, a combination of functional Defense Systems disclosed herein above, does not naturally occur in bacterial cell. In some embodiments, a combination of functional Defense Systems disclosed herein above, does not naturally occur in an archaeal cell. In some embodiments, a combination of functional Defense Systems disclosed herein above, does not naturally occur in a eukaryotic cell. In some embodiments, a combination of functional Defense Systems disclosed herein above, does not naturally occur in a species disclosed in Tables 6-19C. In some embodiments, a combination of functional Defense Systems disclosed herein above, does not naturally occur in a host cell.


In some embodiments, a cell comprising a combination of Defense Systems disclosed herein above, does not naturally occur in nature. In some embodiments, a cell comprising a combination of functional Defense Systems disclosed herein above, does not naturally occur in nature.


In some embodiments, a nucleic acid constructs, comprised in a Defense System Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, or Xc, encodes a polycistronic mRNA comprising said nucleic acid sequences. In some embodiments, a nucleic acid constructs, comprised in a Defense System Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, or Xc, encodes a polycistronic mRNA comprising said nucleic acid sequences encoding said polypeptides. In some embodiments, a nucleic acid constructs, comprised in a Defense System Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, or Xc, encodes a polycistronic mRNA comprising said nucleic acid sequences encoding components or functional portions thereof, of a Defense System.


Various construct schemes can be utilized to express few genes from a single nucleic acid construct. In some embodiments, the construct encodes a polycistronic mRNA comprising the nucleic acid sequences. In some embodiments, the nucleic acid sequences can be co-transcribed as a polycistronic message from a single promoter sequence of the nucleic acid construct. To enable co-translation of all the genes from a single polycistronic message, the different nucleic acid sequence segments can be transcriptionally fused via linker sequence including an internal ribosome entry site (IRES) sequence, which enables the translation of the nucleic acid sequence segment downstream of the IRES sequence. In this case, a transcribed polycistronic RNA molecule including the coding sequences of different combinations of the nucleic acid sequences, for example as disclosed herein, will be translated from both the capped 5′ end and the internal IRES sequence of the polycistronic RNA molecule.


In some embodiments, each two nucleic acid sequence segments can be translationally fused via protease recognition site cleavable by a protease expressed by the cell to be transformed with the nucleic acid construct. In this case, a chimeric polypeptide translated will be cleaved by the cell expressed protease.


In some embodiments, the nucleic acid construct can include at least two Cis acting regulatory elements each being for separately expressing a distinct nucleic acid sequence. These at least two Cis acting regulatory elements can be identical or distinct.


In some embodiments, disclosed herein is an isolated polypeptide comprising an amino acid sequence comprising one component of a Defense System disclosed herein. In some embodiments, disclosed herein is an isolated polypeptide comprising an amino acid sequence comprising two components of a Defense System disclosed herein. In some embodiments, disclosed herein is an isolated polypeptide comprising an amino acid sequence comprising three components of a Defense System disclosed herein. In some embodiments, disclosed herein is an isolated polypeptide comprising an amino acid sequence comprising four components of a Defense System disclosed herein. In some embodiments, disclosed herein is an isolated polypeptide comprising an amino acid sequence comprising five components of a Defense System disclosed herein.


In some embodiments, disclosed herein is an isolated polypeptide comprising an amino acid sequence comprising one component of a Defense System Ia or a Defense System Ib, said component selected from the group consisting of a ZorA polypeptide, a ZorB polypeptide, a ZorC polypeptide, a ZorD polypeptide, and a ZorE polypeptide. In some embodiments, is an isolated polypeptide comprising an amino acid sequence comprising two components of a Defense System Ia or a Defense System Ib, said component selected from the group consisting of a ZorA polypeptide, a ZorB polypeptide, a ZorC polypeptide, a ZorD polypeptide, and a ZorE polypeptide. In some embodiments, is an isolated polypeptide comprising an amino acid sequence comprising three components of a Defense System Ia or a Defense System Ib, said component selected from the group consisting of a ZorA polypeptide, a ZorB polypeptide, a ZorC polypeptide, a ZorD polypeptide, and a ZorE polypeptide. In some embodiments, is an isolated polypeptide comprising an amino acid sequence comprising four components of a Defense System Ia or a Defense System Ib, said component selected from the group consisting of a ZorA polypeptide, a ZorB polypeptide, a ZorC polypeptide, a ZorD polypeptide, and a ZorE polypeptide. In some embodiments, is an isolated polypeptide comprising an amino acid sequence comprising greater than four components of a Defense System Ia or a Defense System Ib, said component selected from the group consisting of a ZorA polypeptide, a ZorB polypeptide, a ZorC polypeptide, a ZorD polypeptide, and a ZorE polypeptide.


In some embodiments, disclosed herein is an isolated polypeptide comprising an amino acid sequence comprising one component of a Defense System II, said component selected from the group consisting of a ThsA polypeptide and a ThsB polypeptide. In some embodiments, is an isolated polypeptide comprising an amino acid sequence comprising two components of a Defense System II, said component selected from the group consisting of a ThsA polypeptide and a ThsB polypeptide. In some embodiments, is an isolated polypeptide comprising an amino acid sequence comprising more than two components of a Defense System II, said component selected from the group consisting of a ThsA polypeptide and a ThsB polypeptide.


In some embodiments, disclosed herein is an isolated polypeptide comprising an amino acid sequence comprising one component of a Defense System IIIa, said component selected from the group consisting of a DruA polypeptide, a DruB polypeptide, a DruC polypeptide, a DruD polypeptide, a DruE polypeptide. In some embodiments, is an isolated polypeptide comprising an amino acid sequence comprising two components of a Defense System IIIa, said component selected from the group consisting of a DruA polypeptide, a DruB polypeptide, a DruC polypeptide, a DruD polypeptide, a DruE polypeptide. In some embodiments, is an isolated polypeptide comprising an amino acid sequence comprising three components of a Defense System IIIa, said component selected from the group consisting of a DruA polypeptide, a DruB polypeptide, a DruC polypeptide, a DruD polypeptide, a DruE polypeptide. In some embodiments, is an isolated polypeptide comprising an amino acid sequence comprising four components of a Defense System IIIa, said component selected from the group consisting of a DruA polypeptide, a DruB polypeptide, a DruC polypeptide, a DruD polypeptide, a DruE polypeptide. In some embodiments, is an isolated polypeptide comprising an amino acid sequence comprising five components of a Defense System IIIa, said component selected from the group consisting of a DruA polypeptide, a DruB polypeptide, a DruC polypeptide, a DruD polypeptide, a DruE polypeptide. In some embodiments, is an isolated polypeptide comprising an amino acid sequence comprising more than five components of a Defense System IIIa, said component selected from the group consisting of a DruA polypeptide, a DruB polypeptide, a DruC polypeptide, a DruD polypeptide.


In some embodiments, disclosed herein is an isolated polypeptide comprising an amino acid sequence comprising one component of a Defense System IIIb, said component selected from the group consisting of a DruM polypeptide, a DruF polypeptide, a DruG polypeptide, a DruE polypeptide. In some embodiments, is an isolated polypeptide comprising an amino acid sequence comprising two components of a Defense System IIIb, said component selected from the group consisting of a DruM polypeptide, a DruF polypeptide, a DruG polypeptide, a DruE polypeptide. In some embodiments, is an isolated polypeptide comprising an amino acid sequence comprising three components of a Defense System IIIb, said component selected from the group consisting of a DruM polypeptide, a DruF polypeptide, a DruG polypeptide, a DruE polypeptide. In some embodiments, is an isolated polypeptide comprising an amino acid sequence comprising four components of a Defense System IIIb, said component selected from the group consisting of a DruM polypeptide, a DruF polypeptide, a DruG polypeptide, a DruE polypeptide. In some embodiments, is an isolated polypeptide comprising an amino acid sequence comprising five components of a Defense System IIIb, said component selected from the group consisting of a DruM polypeptide, a DruF polypeptide, a DruG polypeptide, a DruE polypeptide. In some embodiments, is an isolated polypeptide comprising an amino acid sequence comprising more than five components of a Defense System IIIb, said component selected from the group consisting of a DruM polypeptide, a DruF polypeptide, a DruG polypeptide, a DruE polypeptide.


In some embodiments, disclosed herein is an isolated polypeptide comprising an amino acid sequence comprising one component of a Defense System IIIc, said component selected from the group consisting of a DruH polypeptide a DruE polypeptide. In some embodiments, is an isolated polypeptide comprising an amino acid sequence comprising two components of a Defense System IIIc, said component selected from the group consisting of a DruH polypeptide a DruE polypeptide. In some embodiments, is an isolated polypeptide comprising an amino acid sequence comprising three components of a Defense System IIIc, said component selected from the group consisting of a DruH polypeptide a DruE polypeptide. In some embodiments, is an isolated polypeptide comprising an amino acid sequence comprising four components of a Defense System IIIc, said component selected from the group consisting of a DruH polypeptide a DruE polypeptide. In some embodiments, is an isolated polypeptide comprising an amino acid sequence comprising five components of a Defense System IIIc, said component selected from the group consisting of a DruH polypeptide a DruE polypeptide. In some embodiments, is an isolated polypeptide comprising an amino acid sequence comprising more than five components of a Defense System IIIc, said component selected from the group consisting of a DruH polypeptide a DruE polypeptide.


In some embodiments, disclosed herein is an isolated polypeptide comprising an amino acid sequence comprising one component of a Defense System IV, said component selected from the group consisting of a HamA polypeptide and a HamB polypeptide. In some embodiments, is an isolated polypeptide comprising an amino acid sequence comprising two components of a Defense System IV, said component selected from the group consisting of a HamA polypeptide and a HamB polypeptide. In some embodiments, is an isolated polypeptide comprising an amino acid sequence comprising more than two components of a Defense System IV, said component selected from the group consisting of a HamA polypeptide and a HamB polypeptide.


In some embodiments, disclosed herein is an isolated polypeptide comprising an amino acid sequence comprising one component of a Defense System V, said component selected from the group consisting of a SduA polypeptide. In some embodiments, is an isolated polypeptide comprising an amino acid sequence comprising more than one component of a Defense System V, said component selected from the group consisting of a SduA polypeptide.


In some embodiments, disclosed herein is an isolated polypeptide comprising an amino acid sequence comprising one component of a Defense System VI, said component selected from the group consisting of a GajA polypeptide and a GajB polypeptide. In some embodiments, is an isolated polypeptide comprising an amino acid sequence comprising two components of a Defense System VI, said component selected from the group consisting of a GajA polypeptide and a GajB polypeptide. In some embodiments, is an isolated polypeptide comprising an amino acid sequence comprising more than two components of a Defense System VI, said component selected from the group consisting of a GajA polypeptide and a GajB polypeptide.


In some embodiments, disclosed herein is an isolated polypeptide comprising an amino acid sequence comprising one component of a Defense System VII, said component selected from the group consisting of a PtuA polypeptide and a PtuB polypeptide. In some embodiments, is an isolated polypeptide comprising an amino acid sequence comprising two components of a Defense System VII, said component selected from the group consisting of a PtuA polypeptide and a PtuB polypeptide. In some embodiments, is an isolated polypeptide comprising an amino acid sequence comprising more than two components of a Defense System VII, said component selected from the group consisting of a PtuA polypeptide and a PtuB polypeptide.


In some embodiments, disclosed herein is an isolated polypeptide comprising an amino acid sequence comprising one component of a Defense System VIII, said component selected from the group consisting of a LmuA polypeptide and a LmuB polypeptide. In some embodiments, is an isolated polypeptide comprising an amino acid sequence comprising two components of a Defense System VIII, said component selected from the group consisting of a LmuA polypeptide and a LmuB polypeptide. In some embodiments, is an isolated polypeptide comprising an amino acid sequence comprising more than two components of a Defense System VIII, said component selected from the group consisting of a LmuA polypeptide and a LmuB polypeptide.


In some embodiments, disclosed herein is an isolated polypeptide comprising an amino acid sequence comprising one component of a Defense System IX, said component selected from the group consisting of a KwaA polypeptide and a KwaB polypeptide. In some embodiments, is an isolated polypeptide comprising an amino acid sequence comprising two components of a Defense System IX, said component selected from the group consisting of a KwaA polypeptide and a KwaB polypeptide. In some embodiments, is an isolated polypeptide comprising an amino acid sequence comprising more than two components of a Defense System IX, said component selected from the group consisting of a KwaA polypeptide and a KwaB polypeptide.


In some embodiments, disclosed herein is an isolated polypeptide comprising an amino acid sequence comprising one component of a Defense System Xa or a Defense System Xb or a Defense System Xc, said component selected from the group consisting of a JetA polypeptide, a JetB polypeptide, a JetC polypeptide, and a JetD polypeptide, and variants thereof. In some embodiments, is an isolated polypeptide comprising an amino acid sequence comprising two components of a Defense System Xa or a Defense System Xb or a Defense System Xc, said component selected from the group consisting of a JetA polypeptide, a JetB polypeptide, a JetC polypeptide, and a JetD polypeptide, and variants thereof. In some embodiments, is an isolated polypeptide comprising an amino acid sequence comprising three components of a Defense System Xa or a Defense System Xb or a Defense System Xc, said component selected from the group consisting of a JetA polypeptide, a JetB polypeptide, a JetC polypeptide, and a JetD polypeptide, and variants thereof. In some embodiments, is an isolated polypeptide comprising an amino acid sequence comprising four components of a Defense System Xa or a Defense System Xb or a Defense System Xc, said component selected from the group consisting of a JetA polypeptide, a JetB polypeptide, a JetC polypeptide, and a JetD polypeptide, and variants thereof. In some embodiments, is an isolated polypeptide comprising an amino acid sequence comprising more than four components of a Defense System Xa or a Defense System Xb or a Defense System Xc, said component selected from the group consisting of a JetA polypeptide, a JetB polypeptide, a JetC polypeptide, and a JetD polypeptide, and variants thereof.


In some embodiments, the isolated polypeptide comprising an amino acid sequence of a Defense System has an anti-phage activity. In some embodiments, the isolated polypeptide comprising an amino acid sequence of a Defense System has an anti-plasmid activity. In some embodiments, the isolated polypeptide comprising an amino acid sequence of a Defense System has an anti-phage activity and an anti-plasmid activity. In some embodiments, the anti-phage activity is against at least one phage. In some embodiments, the anti-phage activity is against more than one phage.


In some embodiments, any one of said constructs disclosed herein, comprises multiple nucleic acid sequences, each sequence encoding at least one of said polypeptides. In some embodiments, any one of said constructs disclosed herein, comprises multiple nucleic acid sequences, each sequence encoding at least a functional portion of one of said polypeptides. In some embodiments, any one of said constructs disclosed herein, comprises multiple nucleic acid sequences, each sequence encoding at least one component of a Defense System. In some embodiments, any one of said constructs disclosed herein, comprises multiple nucleic acid sequences, each sequence encoding at least one functional component of a Defense System. In some embodiments, any one of said constructs disclosed herein, comprises multiple nucleic acid sequences, each sequence encoding at least one functional portion of a component of a Defense System.


As used herein, the terms designating a polypeptide, for example the terms “ZorA”, “ZorB”, “ZorC”, “ZorD”, “ZorE”, “ThsA”, “ThsB”, “DruA”, “DruB”, “DruC”, “DruD”, “DruE”, DruM”, “DruF”, “DruG”, “DruH”, “HamA”, “HamB”, “SduA”, “GajA”, “GajB”, “PtuA”, “PtuB”, “LmuA”, “LmuB”, “KwaA”, “KwaB”, “JetA”, “JetB”, “JetC”, “JetD”, “JetAii”, “JetBii”, “JetCii”, “JetDii”, “JetAiii”, “JetBiii”, “JetCiii”, and “JetDiii”, in some embodiments comprise full length polypeptides, respectively. In some embodiments, the terms designating a polypeptide, for example the terms “ZorA”, “ZorB”, “ZorC”, “ZorD”, “ZorE”, “ThsA”, “ThsB”, “DruA”, “DruB”, “DruC”, “DruD”, “DruE”, DruM”, “DruF”, “DruG”, “DruH”, “HamA”, “HamB”, “SduA”, “GajA”, “GajB”, “PtuA”, “PtuB”, “LmuA”, “LmuB”, “KwaA”, “KwaB”, “JetA”, “JetB”, “JetC”, “JetD”, “JetAii”, “JetBii” “JetCii” “JetDii”, “JetAiii”, “JetBiii”, “JetCiii”, and “JetDiii”, comprise a fragment of the full length polypeptide, wherein the fragment maintains the activity as disclosed herein.


Similarly, the terms designating a gene, for example the terms “zorA”, “zorB”, “zorC”, “zorD”, “zorE”, “thsA”, “thsB”, “druA”, “druB”, “druC”, “druD”, “druE”, “druM”, “druF”, “druG”, “druH”, “hamA”, “hamB”, “sduA”, “gajA”, “gajB”, “ptuA”, “ptuB”, “lmuA”, “lmuB”, “kwaA”, “kwaB”, “jetA”, “jetB”, “jetC”, “jetD”, “jetAii”, “jetBii”, “jetCii”, “jetDi”, “jetAiii”, “jetBiii”, “jetCiii”, and “jetDiii”, in some embodiments comprise a full length gene, respectively. In some embodiments, the terms designating a gene, for example the terms “zorA”, “zorB”, “zorC”, “zorD”, “zorE”, “thsA”, “thsB”, “druA”, “druB”, “druC”, “druD”, “druE”, “druM”, “druF”, “druG”, “druH”, “hamA”, “hamB”, “sduA”, “gajA”, “gajB”, “ptuA”, “ptuB”, “lmuA”, “lmuB”, “kwaA”, “kwaB”, “jetA”, “jetB”, “jetC”, “jetD”, “jetAii”, “jetBii”, “jetCii”, “jetDii”, “jetAiii”, “jetBiii”, “jetCiii”, and “jetDiii”, comprise a fragment of the full length gene, wherein the fragment encodes a polypeptide, respectively, comprising the activity as disclosed herein.


In some embodiments, a construct comprising the nucleic acid sequence encoding the ZorA polypeptide, the ZorB polypeptide, the ZorC polypeptide, and the ZorD polypeptide, comprises a nucleic acid sequence having at least 80% homology with the sequence referenced in Table 8 rows 2-1174 columns G, AD, and AE or the sequence set forth in SEQ ID NO: 14, or comprises nucleic acid sequences having at least 80% homology to at least one of each of the sequences referenced in Table 8 rows 2-1830 columns J and L (encoding ZorA polypeptide), in Table 8 rows 2-1830 columns N and P (encoding ZorB polypeptide), in Table 8 rows 2-1174 columns R and T (encoding ZorC polypeptide), and in Table 8 rows 2-1174 columns V and X (encoding ZorD polypeptide).


In some embodiments, a construct comprising the nucleic acid sequence encoding the ZorA polypeptide, the ZorB polypeptide, and the ZorE polypeptide comprises a nucleic acid sequence having at least 80% homology to the sequence referenced in Table 8 rows 1175-1830 columns G, AD and AE, or the sequence set forth in SEQ ID NO: 15, or comprises nucleic acid sequences having at least 80% homology to the sequences referenced in Table 8 rows 2-1830 columns J and L (encoding ZorA polypeptide), in Table 8 rows 2-1830 columns N and P (encoding ZorB polypeptide), and in Table 8 rows 1175-1830 columns Z and AB (encoding ZorE polypeptide).


In some embodiments, a construct comprising the nucleic acid sequence encoding the ThsA polypeptide and the ThsB polypeptide comprises a nucleic acid sequence having at least 80% homology with the sequence referenced in Table 9 rows 2-2100 columns G, AG and AH, or the sequence set forth in SEQ ID NO: 10 or SEQ ID NO: 11, or comprises nucleic acid sequences having at least 80% homology to at least one of each of the sequences referenced in Table 9 rows 2-2100 columns I and K (encoding ThsA polypeptide) and the sequences referenced in Table 9 rows 2-2100 columns M and O, Q and S, U and W, Y and AA, and AC and AE (encoding ThsB polypeptide).


In some embodiments, a construct comprising the nucleic acid sequence encoding the DruA polypeptide, the DruB polypeptide, the DruC polypeptide, the DruD polypeptide, and the DruE polypeptide comprises a nucleic acid sequence having at least 80% homology with the sequences referenced in Table 10 rows 2-123 columns G, AT, and AU or the sequence set forth in SEQ ID NO: 16, or comprises nucleic acid sequences having at least 80% homology to at least one of each of the sequences referenced in Table 10 rows 2-123 columns J and L (encoding DruA polypeptide), referenced in Table 10 rows 2-123 columns N and P (encoding DruB polypeptide), referenced in Table 10 rows 2-123 columns R and T (encoding DruC polypeptide), referenced in Table 10 rows 2-123 columns V and X (encoding DruD polypeptide), and referenced in Table 10 rows 2-1343 columns Z and AB (encoding DruE polypeptide).


In some embodiments, a construct comprising the nucleic acid sequence encoding the DruM polypeptide, the DruF polypeptide, the DruG polypeptide, and the DruE polypeptide, comprises a nucleic acid sequence having at least 80% homology with the sequence referenced in Table 10 rows 124-295 columns G, AT, and AU, or comprises nucleic acid sequences having at least 80% homology to at least one of each of the sequences referenced in Table 10 rows 124-295 columns AD and AF (encoding DruM polypeptide), referenced in Table 10 rows 124-295 columns AH and AJ (encoding DruF polypeptide), referenced in Table 10 rows 124-295 columns AL and AN (encoding DruG polypeptide), and referenced in Table 10 rows 2-1343 columns Z and AB (encoding DruE polypeptide).


In some embodiments, a construct comprising the nucleic acid sequence encoding the DruH polypeptide and the DruE polypeptide, comprises a nucleic acid sequence having at least 80% homology with the sequence referenced in Table 10 rows 296-1343 columns G, AT, and AU, or comprises nucleic acid sequences having at least 80% homology to at least one of each of the sequences referenced in Table 10 rows 296-1343 columns AP and AR (encoding DruH polypeptide) and referenced in Table 10 rows 2-1343 columns Z and AB (encoding DruE polypeptide).


In some embodiments, a construct comprising the nucleic acid sequence encoding the HamA polypeptide and the HamB polypeptide comprises a nucleic acid sequence having at least 80% homology with the sequences referenced in Table 12 rows 2-1782 columns G, P, and Q or the sequence set forth in SEQ ID NO: 4, or comprises nucleic acid sequences having at least 80% homology to at least one of each of the sequences referenced in Table 12 rows 2-1782 column H and J (encoding HamA polypeptide) and referenced in Table 12 rows 2-1782 column L and N (encoding HamB polypeptide).


In some embodiments, a construct comprising the nucleic acid sequence encoding the SduA polypeptide comprises a nucleic acid sequence having at least 80% homology with the sequences referenced in Table 13 rows 2-1247 columns H and J or columns G, L, and M, or the sequences set forth in SEQ ID NO: 9.


In some embodiments, a construct comprising the nucleic acid sequence encoding the GajA polypeptide and the GajB polypeptide comprises a nucleic acid sequence having at least 80% homology with the sequences referenced in Table 14 rows 2-4599 columns G, P, and Q, or the sequence set forth in SEQ ID NO: 5 or SEQ ID NO: 6, or comprises nucleic acid sequences having at least 80% homology to at least one of each of sequences referenced in Table 14 rows 2-45-99 columns H and K (encoding GajA polypeptide) and referenced in Table 14 rows 2-45-99 columns L and N (encoding GajB polypeptide).


In some embodiments, a construct comprising the nucleic acid sequence encoding the PtuA polypeptide and the PtuB polypeptide comprises a nucleic acid sequence having at least 80% homology with the sequences referenced in Table 15 rows 2-2507 columns G, P and Q or the sequence set forth in SEQ ID NO: 12 or SEQ ID NO: 13, or comprises nucleic acid sequences having at least 80% homology to at least one of each of the sequences referenced in Table 15 rows 2-2507 columns H and J (encoding PtuA polypeptide) and referenced in Table 15 rows 2-2507 columns L and N (encoding PtuB polypeptide).


In some embodiments, a construct comprising the nucleic acid sequence encoding the LmuA polypeptide and the LmuB polypeptide comprises a nucleic acid sequence having at least 80% homology with the sequences referenced in Table 16 rows 2-698 columns G, P, and Q, or the sequence set forth in SEQ ID NO: 7 or SEQ ID NO: 8, or comprises nucleic acid sequences having at least 80% homology to at least one of each of the sequences referenced in Table 16 rows 2-698 column H (encoding LmuA polypeptide) and sequences referenced in Table 16 rows 2-698 column J (encoding LmuB polypeptide).


In some embodiments, a construct comprising the nucleic acid sequence encoding the KwaA polypeptide and the KwaB polypeptide comprises a nucleic acid sequence having at least 80% homology with the sequences referenced in Table 17 rows 2-935 columns G, P, and Q, or the sequence set forth in SEQ ID NO: 3, or comprises nucleic acid sequences having at least 80% homology to at least one of each of the sequences referenced in Table 17 rows 2-935 columns H and J (encoding KwaA polypeptide) and referenced in Table 17 rows 2-935 columns L and N (encoding KwaB polypeptide).


In some embodiments, a construct comprising the nucleic acid sequence encoding the JetA polypeptide, the JetB polypeptide, the JetC polypeptide, and the JetD comprises a nucleic acid sequence having at least 80% homology with the sequences referenced in Table 11 rows 2-2322 columns G, Z, and AA, or the sequence set forth in SEQ ID NO: 17, or comprises nucleic acid sequences having at least 80% homology to at least one of each of the sequences referenced in Table 11 rows 2-2322 columns J and L (encoding JetA polypeptide), referenced in Table 11 rows 2-2322 columns N and P (encoding JetB polypeptide), referenced in Table 11 rows 2-2322 columns R and T (encoding JetC polypeptide) and referenced in Table 11 rows 2-2322 columns V and X (encoding JetD polypeptide);


In some embodiments, a construct comprising the nucleic acid sequence encoding the JetAii polypeptide, the JetBii polypeptide, the JetCii polypeptide, and the JetDii comprises a nucleic acid sequence having at least 80% homology with the sequences referenced in Table 11 rows 2323-2844 columns G, Z, and AA, or the sequence set forth in SEQ ID NO: 18 or comprises nucleic acid sequences having at least 80% homology to at least one of each of the sequences referenced in Table 11 rows 2323-2844 columns J and L (encoding JetAii polypeptide), referenced in Table 11 rows 2323-2844 columns N and P (encoding JetBii polypeptide), referenced in Table 11 rows 2323-2844 columns R and T (encoding JetCii polypeptide) and referenced in Table 11 rows 2323-2844 columns V and X (encoding JetDii polypeptide);


In some embodiments, a construct comprising the nucleic acid sequence encoding the JetAiii polypeptide, the JetBiii polypeptide, the JetCiii polypeptide, and the JetDiii comprises a nucleic acid sequence having at least 80% homology with the sequences set forth in Table 11 rows 2845-3174 columns G, Z, and AA, or the sequence set forth in SEQ ID NO: 19 or comprises nucleic acid sequences having at least 80% homology to at least one of each of the sequences referenced in Table 11 rows 2845-3174 columns J and L (encoding JetAiii polypeptide), referenced in Table 11 rows 2845-3174 columns N and P (encoding JetBiii polypeptide), referenced in Table 11 rows 2845-3174 columns R and T (encoding JetC ill polypeptide) and referenced in Table 11 rows 2845-3174 columns V and X (encoding JetDiii polypeptide).


In some embodiments, a construct comprising a nucleic acid sequence comprises multiple copies of a nucleic acid sequence encoding a component of the Defense System. In some embodiments, a construct comprising a nucleic acid sequence comprises multiple copies of a nucleic acid sequence encoding two components of the Defense System. In some embodiments, a construct comprising a nucleic acid sequence comprises multiple copies of a nucleic acid sequence encoding three components of the Defense System. In some embodiments, a construct comprising a nucleic acid sequence comprises multiple copies of a nucleic acid sequence encoding four components of the Defense System. In some embodiments, a construct comprising a nucleic acid sequence comprises multiple copies of a nucleic acid sequence encoding five components of the Defense System. In some embodiments, a construct comprising a nucleic acid sequence comprises multiple copies of a nucleic acid sequence encoding more than components of the Defense System. In some embodiments, multiple copies comprise more than one copy. In some embodiments, multiple copies comprise 2 copies. In some embodiments, multiple copies comprise 2-10 copies. In some embodiments, multiple copies comprise 3 copies, 4 copies, 5 copies, 6 copies, 7 copies, 8 copies, 9 copies, or 10 copies.


In some embodiments, a Defense System disclosed herein provides a host cell with resistance to a foreign nucleic acid invasion. In some embodiments, a Defense System disclosed herein provides a bacterial cell with resistance to a foreign nucleic acid invasion. In some embodiments, a Defense System disclosed herein provides a bacterial cell with protection to foreign nucleic acid invasion.


In some embodiments, a method disclosed herein protects a host cell from foreign nucleic acid invasion, said method comprising a step of introducing into the host cell at least one defense system described herein. In some embodiments, a method disclosed herein protects a host cell from foreign nucleic acid invasion, said method comprising a step of introducing into the host cell at least one function defense system described herein. In some embodiments, a method disclosed herein protects a bacterial cell from foreign nucleic acid invasion, said method comprising a step of introducing into the bacterial cell at least one defense system described herein. In some embodiments, a method disclosed herein protects a bacterial cell from foreign nucleic acid invasion, said method comprising a step of introducing into the bacterial cell at least one function defense system described herein.


In some embodiments, protecting a host cell from foreign nucleic acid invasion comprises protecting from phage infection, protecting from plasmid transformation, or protection from conjugative element entry, or any combination thereof. In some embodiments, protecting a bacterial cell from foreign nucleic acid invasion comprises protecting from phage infection, protecting from plasmid transformation, or protection from conjugative element entry, or any combination thereof. In some embodiments, protection from phage infection comprises protection from at least one phage infection.


In some embodiments, a nucleic acid construct comprising any one of the defense systems described herein or any combination thereof, provides a host cell with resistance to foreign nucleic acid invasion. In some embodiments, a nucleic acid construct comprising any one of the defense systems described herein or any combination thereof, provides protection from foreign nucleic acid invasion to a host cells.


In some embodiments, a nucleic acid construct comprising any one of the defense systems described herein or any combination thereof, provides a bacterial cell with resistance to foreign nucleic acid invasion. In some embodiments, a nucleic acid construct comprising any one of the defense systems described herein or any combination thereof, provides protection from foreign nucleic acid invasion to a bacterial cells.


In some embodiments, a Defense System disclosed herein provides a host cell with resistance to at least one phage. In some embodiments, a Defense System disclosed herein provides a host cell with resistance to a plasmid. In some embodiments, a Defense System disclosed herein provides a host cell with resistance to a combination of at least one phage and a plasmid.


In some embodiments, a Defense System selected from a Defense System Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc, provides a host cell with resistance to at least one phage. In some embodiments, a Defense selected from a Defense System Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc, provides a host cell with resistance to a plasmid. In some embodiments, a Defense System selected from a Defense System Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc, provides a host cell with resistance to a combination of at least one phage and a plasmid.


In some embodiments, a defense system comprising a combination of Defense Systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc, provides a host cell with resistance to at least one phage. In some embodiments, a defense system comprising a combination of Defense Systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc, provides a host cell with resistance to a plasmid. In some embodiments, a defense system comprising a combination of Defense Systems selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc, provides a host cell with resistance to a combination of at least one phage and a plasmid.


In some embodiments, resistance is to at least one phage. In some embodiments, resistance to at least one phage comprises resistance to more than one phage. In some embodiments, resistance is to phage comprises resistance to phages from different families (See for example FIGS. 3B and 3C, and FIG. 5D).


A skilled artisan would appreciate that the term “phage” or “bacteriophage” refers to a virus that selectively infects one or more bacterial species. Many phages are specific to a particular genus or species or strain of bacteria. In some embodiments, a phage or a bacteriophage selectively infects one or more archaeal species. Many phages are specific to a particular genus or species or strain of archaea.


In some embodiments, the phage genome can be ssDNA, dsDNA, ssRNA, or dsRNA. In some embodiments, the phage genome is linear. In some embodiments, the phage genome is circular. In some embodiments, the phage is virulent to bacteria. In some embodiments, the phage is virulent to archaea. In some embodiments, the phage is virulent to bacteria and archaea.


In some embodiments, the phage is a lytic phage. In some embodiments, the phage is temperate (also referred to as lysogenic). In some embodiments, the phage is a lytic phage selected from the group consisting of Nf, SP82G and SPO1. In some embodiments, the phage is Nf. In some embodiments, the phage is SPO1. In some embodiments, the phage is a temperate phage selected from the group consisting of phi3T and phi105. In some embodiments, the phage is phi3T.


In some embodiments, phage as disclosed herein include, but are not limited to, phages that belong to any of the following virus families: Caudavirales, Corticoviridae, Cystoviridae, Inoviridae, Leviviridae, Microviridae, Myoviridae, Podoviridae, Siphoviridae, or Tectiviridae. In some embodiments, the phage is a podovirus, a myovirus or a siphovirus phage. In some embodiments, the phage is a T7 or a lambda-vir phage. In some embodiments, a phage comprises phage that infect bacteria that are pathogenic to plants and/or animals (including humans).


In some embodiments, the resistance of a host cell comprising a defense system against a phage is improved as compared to a host cell of the same species, which does not include a defense system disclosed herein.


Assays for testing phage resistance are well known in the art. Thus, for example, the lysogenic activity of a phage can be assessed by PCR or DNA sequencing. The DNA replication activity of a phage can be assessed e.g. by DNA sequencing or Southern blot analysis.


The lytic activity of a phage can be assessed e.g. by optical density, plaque assay or living dye indicators. The lytic activity of a phage can be measured indirectly by following the decrease in optical density of the bacterial cultures owing to lysis. This method involves introduction of phage into a fluid bacterial culture medium. After a period of incubation, the phage lyses the bacteria in the broth culture resulting in a clearing of the fluid medium resulting in decrease in optical density.


Another method, known as the plaque assay, introduces phage into a few milliliters of soft agar along with some bacterial host cells. This soft agar mixture is laid over a hard agar base (seeded-agar overlay). The phage adsorbs onto the host bacterial cells, infect and lyse the cells, and then begin the process anew with other bacterial cells in the vicinity. After 6-24 hours, zones of clearing on the plate, known as plaques, are observable within the lawn of bacterial growth on the plate. Each plaque represents a single infective phage particle in the original sample.


Yet another method is the one-step phage growth curve which allows determining the production of progeny virions by cells as a function of time after infection. The assay is based on the fact that cells in the culture are infected simultaneously with a low number of phages so that no cell can be infected with more than one phage. At various time intervals, samples are removed for a plaque assay allowing quantitative determination of the number of phages present in the medium.


Other methods use for example redox chemistry, employing cell respiration as a universal reporter. During active growth of bacteria, cellular respiration reduces a dye (e.g., tetrazolium dye) and produces a color change that can be measured in an automated fashion. On the other hand, successful phage infection and subsequent growth of the phage in its host bacterium results in reduced bacterial growth and respiration and a concomitant reduction in color.


Thus, nucleic acid sequences encoding a Defense System component(s) or functional fragments thereof, and the polypeptides and nucleic acid constructs disclosed herein can be used in conferring phage resistance thereby protecting bacteria from phage infection.


In some embodiments, “conferring phage resistance” refers to the level of phage infection and/or multiplication in the e.g. bacteria containing a functional Defense System as disclosed herein, that does not cause a deleterious effect to the bacteria e.g., growth arrest or death.


In some embodiments, the phage has about 10-10,000 times lower efficiency of plaquing on bacteria containing a functional Defense System. In some embodiments, the phage has about 100-100,000 times lower efficiency of plaquing on bacteria containing a functional Defense System ([EOP]=10−2), about 1000 times lower EOP (EOP=10−3), 10,000 times lower EOP (EOP=10−4), or 100,000 times lower EOP (EOP=10−5). In some embodiments, the level of phage multiplication in a culture is measured after about 6-14 hours incubation of the culture, e.g., after about 12 hours, after about 9 hours, after about 8 hours after about 7 hours, or after about 6 hours.


In some embodiments, the phage has about 100-100,000 times lower efficiency of plaquing on bacteria containing a functional Defense System Ia ([EOP]=10−2), about 1000 times lower EOP (EOP=10−3), 10,000 times lower EOP (EOP=10−4), or 100,000 times lower EOP (EOP=10−5). In some embodiments, the level of phage multiplication in a culture is measured after about 6-14 hours incubation of the culture, e.g., after about 12 hours, after about 9 hours, after about 8 hours after about 7 hours, or after about 6 hours.


In some embodiments, the phage has about 100-100,000 times lower efficiency of plaquing on bacteria containing a functional Defense System Ia ([EOP]=10−2), about 1000 times lower EOP (EOP=10−3), 10,000 times lower EOP (EOP=10−4), or 100,000 times lower EOP (EOP=10−5). In some embodiments, the level of phage multiplication in a culture is measured after about 6-14 hours incubation of the culture, e.g., after about 12 hours, after about 9 hours, after about 8 hours after about 7 hours, or after about 6 hours.


In some embodiments, the phage has about 100-100,000 times lower efficiency of plaquing on bacteria containing a functional Defense System Ia ([EOP]=10−2), about 1000 times lower EOP (EOP=10−3), 10,000 times lower EOP (EOP=10−4), or 100,000 times lower EOP (EOP=10−5). In some embodiments, the level of phage multiplication in a culture is measured after about 6-14 hours incubation of the culture, e.g., after about 12 hours, after about 9 hours, after about 8 hours after about 7 hours, or after about 6 hours.


In some embodiments, the phage has about 100-100,000 times lower efficiency of plaquing on bacteria containing a functional Defense System Ib ([EOP]=10−2), about 1000 times lower EOP (EOP=10−3), 10,000 times lower EOP (EOP=10−4), or 100,000 times lower EOP (EOP=10−5). In some embodiments, the level of phage multiplication in a culture is measured after about 6-14 hours incubation of the culture, e.g., after about 12 hours, after about 9 hours, after about 8 hours after about 7 hours, or after about 6 hours.


In some embodiments, the phage has about 100-100,000 times lower efficiency of plaquing on bacteria containing a functional Defense System II ([EOP]=10−2), about 1000 times lower EOP (EOP=10−3), 10,000 times lower EOP (EOP=10−4), or 100,000 times lower EOP (EOP=10−5). In some embodiments, the level of phage multiplication in a culture is measured after about 6-14 hours incubation of the culture, e.g., after about 12 hours, after about 9 hours, after about 8 hours after about 7 hours, or after about 6 hours.


In some embodiments, the phage has about 100-100,000 times lower efficiency of plaquing on bacteria containing a functional Defense System III (Type I, Type II, and Type III) ([EOP]=10−2), about 1000 times lower EOP (EOP=10−3), 10,000 times lower EOP (EOP=10−4), or 100,000 times lower EOP (EOP=10−5). In some embodiments, the level of phage multiplication in a culture is measured after about 6-14 hours incubation of the culture, e.g., after about 12 hours, after about 9 hours, after about 8 hours after about 7 hours, or after about 6 hours.


In some embodiments, the phage has about 100-100,000 times lower efficiency of plaquing on bacteria containing a functional Defense System IV ([EOP]=10−2), about 1000 times lower EOP (EOP=10−3), 10,000 times lower EOP (EOP=10−4), or 100,000 times lower EOP (EOP=10−5). In some embodiments, the level of phage multiplication in a culture is measured after about 6-14 hours incubation of the culture, e.g., after about 12 hours, after about 9 hours, after about 8 hours after about 7 hours, or after about 6 hours.


In some embodiments, the phage has about 100-100,000 times lower efficiency of plaquing on bacteria containing a functional Defense System V ([EOP]=10−2), about 1000 times lower EOP (EOP=10−3), 10,000 times lower EOP (EOP=10−4), or 100,000 times lower EOP (EOP=10−5). In some embodiments, the level of phage multiplication in a culture is measured after about 6-14 hours incubation of the culture, e.g., after about 12 hours, after about 9 hours, after about 8 hours after about 7 hours, or after about 6 hours.


In some embodiments, the phage has about 100-100,000 times lower efficiency of plaquing on bacteria containing a functional Defense System VI ([EOP]=10−2), about 1000 times lower EOP (EOP=10−3), 10,000 times lower EOP (EOP=10−4), or 100,000 times lower EOP (EOP=10−5). In some embodiments, the level of phage multiplication in a culture is measured after about 6-14 hours incubation of the culture, e.g., after about 12 hours, after about 9 hours, after about 8 hours after about 7 hours, or after about 6 hours.


In some embodiments, the phage has about 100-100,000 times lower efficiency of plaquing on bacteria containing a functional Defense System VII ([EOP]=10−2), about 1000 times lower EOP (EOP=10−3), 10,000 times lower EOP (EOP=10−4), or 100,000 times lower EOP (EOP=10−5). In some embodiments, the level of phage multiplication in a culture is measured after about 6-14 hours incubation of the culture, e.g., after about 12 hours, after about 9 hours, after about 8 hours after about 7 hours, or after about 6 hours.


In some embodiments, the phage has about 100-100,000 times lower efficiency of plaquing on bacteria containing a functional Defense System VIII ([EOP]=10−2), about 1000 times lower EOP (EOP=10−3), 10,000 times lower EOP (EOP=10−4), or 100,000 times lower EOP (EOP=10−5). In some embodiments, the level of phage multiplication in a culture is measured after about 6-14 hours incubation of the culture, e.g., after about 12 hours, after about 9 hours, after about 8 hours after about 7 hours, or after about 6 hours.


In some embodiments, the phage has about 100-100,000 times lower efficiency of plaquing on bacteria containing a functional Defense System IX ([EOP]=10−2), about 1000 times lower EOP (EOP=10−3), 10,000 times lower EOP (EOP=10−4), or 100,000 times lower EOP (EOP=10−5). In some embodiments, the level of phage multiplication in a culture is measured after about 6-14 hours incubation of the culture, e.g., after about 12 hours, after about 9 hours, after about 8 hours after about 7 hours, or after about 6 hours.


In some embodiments, the phage has about 100-100,000 times lower efficiency of plaquing on bacteria containing a functional Defense System Xa ([EOP]=10−2), about 1000 times lower EOP (EOP=10−3), 10,000 times lower EOP (EOP=10−4), or 100,000 times lower EOP (EOP=10−5). In some embodiments, the level of phage multiplication in a culture is measured after about 6-14 hours incubation of the culture, e.g., after about 12 hours, after about 9 hours, after about 8 hours after about 7 hours, or after about 6 hours.


In some embodiments, the phage has about 100-100,000 times lower efficiency of plaquing on bacteria containing a functional Defense System Xb ([EOP]=10−2), about 1000 times lower EOP (EOP=10−3), 10,000 times lower EOP (EOP=10−4), or 100,000 times lower EOP (EOP=10−5). In some embodiments, the level of phage multiplication in a culture is measured after about 6-14 hours incubation of the culture, e.g., after about 12 hours, after about 9 hours, after about 8 hours after about 7 hours, or after about 6 hours.


In some embodiments, the phage has about 100-100,000 times lower efficiency of plaquing on bacteria containing a functional Defense System Xc ([EOP]=10−2), about 1000 times lower EOP (EOP=10−3), 10,000 times lower EOP (EOP=10−4), or 100,000 times lower EOP (EOP=10−5). In some embodiments, the level of phage multiplication in a culture is measured after about 6-14 hours incubation of the culture, e.g., after about 12 hours, after about 9 hours, after about 8 hours after about 7 hours, or after about 6 hours.


In some embodiments, the phage has about 100-100,000 times lower efficiency of plaquing on bacteria containing a combination of functional Defense Systems ([EOP]=10−2), about 1000 times lower EOP (EOP=10−3), 10,000 times lower EOP (EOP=10−4), or 100,000 times lower EOP (EOP=10−5). In some embodiments, the level of phage multiplication in a culture is measured after about 6-14 hours incubation of the culture, e.g., after about 12 hours, after about 9 hours, after about 8 hours after about 7 hours, or after about 6 hours. In some embodiments, the combination of Defense Systems comprises any combination of Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc as described herein.


In some embodiments, a Defense System provides resistance is to a plasmid. In some embodiments, the resistance of a host cell comprising a defense system against a phage is improved as compared to a host cell of the same species, which does not include a defense system disclosed herein. In some embodiments, a plasmid comprises an episomal plasmid. In some embodiments, a plasmid comprises an integrative plasmid. In some embodiments, resistance to a plasmid comprises decrease transformation efficiency of the plasmid. In some embodiments, resistance to a plasmid comprises decrease transformation efficiency of the episomal plasmid.


In some embodiments, a nucleic acid sequences encoding a Defense System component(s) or functional fragments thereof, and the polypeptides and nucleic acid constructs disclosed herein can be used in protecting bacteria from conjugative elements. In some embodiments, disclosed herein is a method of protecting bacteria from conjugative elements, the method comprising the step of introducing into the bacteria a defense system selected from Defense Systems Ia-Xc, or a combination thereof. In some embodiments, disclosed herein is a method of protecting bacteria from conjugative elements, the method comprising the step of introducing into the bacteria a functional defense system selected from Defense Systems Ia-Xc, or a combination thereof. In some embodiments, disclosed herein is a method of protecting bacteria from conjugative elements, the method comprising the step of introducing into the bacteria at least one component of a defense systems selected from Defense Systems Ia-Xc, or a combination thereof.


A skilled artisan would appreciate that a method protecting bacteria from conjugative elements, would in some embodiments, encompass a reduction in the horizontal gene transfer between bacteria. The steps of conjugation known in the art comprise an initial step of cell-to-cell contact during mating pair formation, followed by a transfer of gene(s)/genetic elements in three steps. The DNA is nicked at the origin of transfer, wherein the nicking enzyme binds covalently to one of the DNA strands. The nucleoprotein filament is then coupled to the type 4 secretion system (T4SS) and transferred to the recipient cell. Finally, the element is replicated in the original and novel hosts leading to double stranded DNA molecules in each cell. (Cury et al. (2017) Nucleic Acids Res. September 6; 45(15): 8943-8956).


In some embodiments, a method of protecting bacteria from conjugative elements inhibits or reduces cell-to-cell contact or mating pair formation. In some embodiments, a method of protecting bacteria from conjugative elements inhibits or reduces nicking of the DNA strand. In some embodiments, a method of protecting bacteria from conjugative elements inhibits or reduces transfer of the DNA into the recipient cell. In some embodiments, a method of protecting bacteria from conjugative elements inhibits or reduces replication of the element in the novel host comprising a defense system described herein, a combination thereof, of at least one element thereof. In some embodiments, the conjugative element comprises a plasmid. In some embodiments, the conjugative element comprises a transposon.


In some embodiments, there is provided an article of manufacture or a kit identified for providing bacterial resistance, or plasmid transformation, or bacterial resistance and plasmid transformation to a microbial cell, for example but not limited to bacteria, comprising a defense system disclosed herein. In some embodiments, the article of manufacture or kit is for use producing bacteria resistant to at least one phage, wherein the bacteria do not naturally comprise the defense system. In some embodiments, the article of manufacture or kit is for use producing bacteria resistant to plasmid transformation, wherein the bacteria do not naturally comprise the defense system. In some embodiments, the article of manufacture or kit is for use producing bacteria resistant to at least one phage and resistant to plasmid transformation, wherein the bacteria do not naturally comprise the defense system.


In some embodiments, the defense system comprises at least 2 Defense Systems, wherein the bacteria do not naturally comprise the at least 2 Defense Systems. In some embodiments, the defense system comprises any of Defense Systems Ia-Xc or a combination thereof, wherein the bacteria do not naturally comprise the Defense System or combination of systems. In some embodiments, the defense system comprises a combination of Defense systems selected from Defense Systems Ia-Xc, wherein the bacteria do not naturally comprise the combination of Defense Systems present in the article of manufacture or the kit.


In some embodiments, a Defense System described herein is packaged in a container. In some embodiments, different Defense Systems are packaged in separate containers. In some embodiments, different Defense Systems are packaged in the same containers. In some embodiments, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 different Defense Systems are packaged in the same containers. In some embodiments, the different Defense Systems are in a co-formulation. In some embodiments, different Defense Systems are packaged in transportable containers.


In some embodiments, a container comprising a Defense Systems described herein comprises lyophilized components of said Defense System. In some embodiments, a container comprising at least two Defense Systems described herein comprises lyophilized components of said Defense Systems. In some embodiments, a container comprising at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 Defense Systems described herein comprises lyophilized components of said Defense Systems. In some embodiments, Defense Systems components are co-formulated and lyophilized and stored in a container.


In some embodiments, a container comprising a Defense Systems described herein comprises spray-dried components of said Defense System. In some embodiments, a container comprising at least two Defense Systems described herein comprises spray-dried components of said Defense Systems. In some embodiments, a container comprising at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 Defense Systems described herein comprises spray-dried components of said Defense Systems. In some embodiments, Defense Systems components are co-formulated and spray-dried and stored in a container.


In some embodiments, a container comprising a Defense Systems described herein comprises components of said Defense System in a liquid formulation. In some embodiments, a container comprising at least two Defense Systems described herein comprises components of said Defense Systems in a liquid formulation. In some embodiments, a container comprising at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 Defense Systems described herein comprises components of said Defense Systems in a liquid formulation. In some embodiments, Defense Systems components are co-formulated and stored in a container in a liquid formulation.


In some embodiments, a Defense system stored in a container comprises a full complement of components. In some embodiments, a Defense system stored in a container comprises less than a full complement of components. In some embodiments, a Defense system stored in a container comprises at least one component of the Defense system. In some embodiments, a Defense system stored in a container comprises at least 1, 2, 3, 4, or 5 component of the Defense system. In some embodiments, a Defense system stored in a container comprises between about 1-10 component of the Defense system. In some embodiments, a Defense system stored in a container comprises more than components of the Defense system. In some embodiments, a Defense system stored in a container comprises different numbers of components of different Defense systems. For example but not limited to, in some embodiments a container comprises a full complement of components of one Defense System and less than a full complement of components of another Defense system.


Methods of Use of a Defense System or Combinations Thereof

Defense systems have been described in detail above, as has the combination of Defense Systems each comprising a nucleic acid construct. In some embodiments, methods of use a defense system disclosed herein comprises use of a single Defense System comprising a nucleic acid construct, selected from Defense Systems Ia, Ib, II, IIIa, IIIa, IIIa, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, methods of use of a defense system comprises use of a combination of Defense Systems comprising nucleic acid constructs selected from Defense systems Ia, Ib, II, IIIa, IIIa, IIIa, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc, as disclosed herein.


Methods of use of a defense system described herein include but are not limited to, methods of protecting bacteria from phage infection, methods of protecting bacteria from plasmid transformation, methods of protecting bacteria from conjugative elements, methods of protecting bacteria from any combination of phage infection, conjugative elements, and plasmid transformation, methods of producing bacteria resistant to phage infection; methods of producing bacteria resistant to plasmids; methods of producing bacteria protected from conjugative elements, methods of producing bacteria resistant to phage infection, conjugative elements, or plasmids, or any combination thereof; and methods of making a food, a food additive, a feed, a nutritional supplement, a probiotic supplement, a personal care product, a health care product, and/or a veterinary product.


In some embodiments, a method of use described herein comprises a method of protecting a host cell from foreign nucleic acid invasion. A method of use described herein comprises a method of protecting a bacterial cell from foreign nucleic acid invasion.


In some embodiments, a method of protecting a host cell from foreign nucleic acid invasion comprises introducing into the host cells at least one defense system described herein. In some embodiments, a method of protecting a host cell from foreign nucleic acid invasion comprises introducing into the host cells a combination of defense systems described herein. In some embodiments, a method of protecting a host cell from foreign nucleic acid invasion comprises introducing into the host cells at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 defense system described herein.


In some embodiments, a method of protecting a host cell from foreign nucleic acid invasion comprises introducing into the host cells at least one functional defense system described herein. In some embodiments, a method of protecting a host cell from foreign nucleic acid invasion comprises introducing into the host cells a combination of functional defense systems described herein. In some embodiments, a method of protecting a host cell from foreign nucleic acid invasion comprises introducing into the host cells at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 functional defense system described herein. In some embodiments, a method of protecting a host cell from foreign nucleic acid invasion comprises introducing into the host cells at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 functional and non-functional defense system described herein.


In some embodiments, a method of protecting a bacterial cell from foreign nucleic acid invasion comprises introducing into the bacterial cells at least one defense system described herein. In some embodiments, a method of protecting a bacterial cell from foreign nucleic acid invasion comprises introducing into the bacterial cells a combination of defense systems described herein. In some embodiments, a method of protecting a bacterial cell from foreign nucleic acid invasion comprises introducing into the bacterial cells at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 defense system described herein.


In some embodiments, a method of protecting a bacterial cell from foreign nucleic acid invasion comprises introducing into the bacterial cells at least one functional defense system described herein. In some embodiments, a method of protecting a bacterial cell from foreign nucleic acid invasion comprises introducing into the bacterial cells a combination of functional defense systems described herein. In some embodiments, a method of protecting a bacterial cell from foreign nucleic acid invasion comprises introducing into the bacterial cells at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 functional defense system described herein. In some embodiments, a method of protecting a bacterial cell from foreign nucleic acid invasion comprises introducing into the bacterial cells at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 functional and non-functional defense system described herein.


In some embodiments, a method of protecting a host cell from foreign nucleic acid invasion comprises protecting said host cell from phage infection. In some embodiments, a method of protecting a host cell from foreign nucleic acid invasion comprises protecting said host cell from at least one phage infection. In some embodiments, a method of protecting a host cell from foreign nucleic acid invasion comprises protecting said host cell from more than one phage infection. In some embodiments, a method of protecting a host cell from foreign nucleic acid invasion comprises protecting said host cell from plasmid transformation. In some embodiments, a method of protecting a host cell from foreign nucleic acid invasion comprises protecting said host cell from at least one plasmid transformation. In some embodiments, a method of protecting a host cell from foreign nucleic acid invasion comprises protecting said host cell from more than one plasmid transformation. In some embodiments, a method of protecting a host cell from foreign nucleic acid invasion comprises protecting said host cell from entry of conjugative elements. In some embodiments, a method of protecting a host cell from foreign nucleic acid invasion comprises protecting said host cell from entry of at least one conjugative element. In some embodiments, a method of protecting a host cell from foreign nucleic acid invasion comprises protecting said host cell from entry of more than one conjugative elements. In some embodiments, a method of protecting a host cell from foreign nucleic acid invasion comprises protecting said host cell from any combination of phage infection, plasmid transformation, and entry of conjugative elements.


In some embodiments, a method of protecting a bacterial cell from foreign nucleic acid invasion comprises protecting said bacterial cell from phage infection. In some embodiments, a method of protecting a bacterial cell from foreign nucleic acid invasion comprises protecting said bacterial cell from at least one phage infection. In some embodiments, a method of protecting a bacterial cell from foreign nucleic acid invasion comprises protecting said bacterial cell from more than one phage infection. In some embodiments, a method of protecting a bacterial cell from foreign nucleic acid invasion comprises protecting said bacterial cell from plasmid transformation. In some embodiments, a method of protecting a bacterial cell from foreign nucleic acid invasion comprises protecting said bacterial cell from at least one plasmid transformation. In some embodiments, a method of protecting a bacterial cell from foreign nucleic acid invasion comprises protecting said bacterial cell from more than one plasmid transformation. In some embodiments, a method of protecting a bacterial cell from foreign nucleic acid invasion comprises protecting said bacterial cell from entry of conjugative elements. In some embodiments, a method of protecting a bacterial cell from foreign nucleic acid invasion comprises protecting said bacterial cell from entry of at least one conjugative element. In some embodiments, a method of protecting a bacterial cell from foreign nucleic acid invasion comprises protecting said bacterial cell from entry of more than one conjugative elements. In some embodiments, a method of protecting a bacterial cell from foreign nucleic acid invasion comprises protecting said bacterial cell from any combination of phage infection, plasmid transformation, and entry of conjugative elements.


In some embodiments, a method disclosed herein comprises the use of a defense system described herein, for protecting bacteria from phage infection. In some embodiments, a method disclosed herein comprises a method of protecting bacteria from plasmid transformation. In some embodiments, a method disclosed herein comprises a method of protecting bacteria from conjugative elements. In some embodiments, a method disclosed herein comprises a method of protecting bacteria from phage infection, and/or conjugative elements, and/or plasmid transformation. In some embodiments, a method disclosed herein comprises a method of producing bacteria resistant to phage infection. In some embodiments, a method disclosed herein comprises a method of producing bacteria resistant to plasmids. In some embodiments, a method disclosed herein comprises a method of producing bacteria resistant to conjugative elements. In some embodiments, a method disclosed herein comprises a method of producing bacteria resistant to phage infection, and/o conjugative elements, and/or plasmids.


In some embodiments, a method disclosed herein comprises a method of making a food. In some embodiments, a method disclosed herein comprises a method of making a food additive. In some embodiments, a method disclosed herein comprises a method of making a feed. In some embodiments, a method disclosed herein comprises a method of making a nutritional supplement. In some embodiments, a method disclosed herein comprises a method of making a probiotic supplement. In some embodiments, a method disclosed herein comprises a method of making a personal care product. In some embodiments, a method disclosed herein comprises a method of making a health care product. In some embodiments, a method disclosed herein comprises a method of making a veterinary product.


In some embodiments, disclosed herein is a method of protecting bacteria from phage infection, said method comprising the step of introducing into bacteria a defense system comprising at least one of a Defense System Ia, a Defense System Ib, a Defense System II, a Defense System IIIa, a Defense System IIIb, a Defense System IIIc, a Defense System IV, a Defense System V, a Defense System VI, a Defense System VII, a Defense System VIII, a Defense System IX, a Defense System Xa, a Defense System Xb, or a Defense System Xc, wherein each nucleic acid construct of each Defense System Ia-Xc further comprises a regulatory element operably linked to said construct comprising a cis-acting regulatory element for directing expression of said nucleic acid sequence, or a transmissible element for directing transfer of said nucleic acid sequence from one cell to another, or a recombination element for integrating said nucleic acid sequence into a genome of a cell transfected with said construct, or an element providing episomal maintenance of said construct within a cell transfected with said construct, or any combination thereof; wherein said method results in the bacteria being resistant to at least one phage, or being resistant to a plasmid, or being resistant to at least one phage and a plasmid.


In some embodiments, disclosed herein is a method of protecting bacteria from plasmid transformation, said method comprising the step of introducing into bacteria a defense system comprising at least one of a Defense System Ia, a Defense System Ib, a Defense System II, a Defense System IIIa, a Defense System IIIb, a Defense System IIIc, a Defense System IV, a Defense System V, a Defense System VI, a Defense System VII, a Defense System VIII, a Defense System IX, a Defense System Xa, a Defense System Xb, or a Defense System Xc, wherein each nucleic acid construct of each Defense System Ia-Xc further comprises a regulatory element operably linked to said construct comprising a cis-acting regulatory element for directing expression of said nucleic acid sequence, or a transmissible element for directing transfer of said nucleic acid sequence from one cell to another, or a recombination element for integrating said nucleic acid sequence into a genome of a cell transfected with said construct, or an element providing episomal maintenance of said construct within a cell transfected with said construct, or any combination thereof; wherein said method results in the bacteria being resistant to at least one phage, or being resistant to a plasmid, or being resistant to at least one phage and a plasmid.


In some embodiments, disclosed herein is a method of protecting bacteria from conjugative elements, said method comprising the step of introducing into bacteria a defense system comprising at least one of a Defense System Ia, a Defense System Ib, a Defense System II, a Defense System IIIa, a Defense System IIIb, a Defense System IIIc, a Defense System IV, a Defense System V, a Defense System VI, a Defense System VII, a Defense System VIII, a Defense System IX, a Defense System Xa, a Defense System Xb, or a Defense System Xc, wherein each nucleic acid construct of each Defense System Ia-Xc further comprises a regulatory element operably linked to said construct comprising a cis-acting regulatory element for directing expression of said nucleic acid sequence, or a transmissible element for directing transfer of said nucleic acid sequence from one cell to another, or a recombination element for integrating said nucleic acid sequence into a genome of a cell transfected with said construct, or an element providing episomal maintenance of said construct within a cell transfected with said construct, or any combination thereof; wherein said method results in the bacteria being resistant to at least one conjugative elements.


In some embodiments, disclosed herein is a method of protecting bacteria from any combination of phage infection, conjugative elements, and plasmid transformation, said method comprising the step of introducing into bacteria a defense system comprising at least one of a Defense System Ia, a Defense System Ib, a Defense System II, a Defense System IIIa, a Defense System IIIb, a Defense System IIIc, a Defense System IV, a Defense System V, a Defense System VI, a Defense System VII, a Defense System VIII, a Defense System IX, a Defense System Xa, a Defense System Xb, or a Defense System Xc, wherein each nucleic acid construct of each Defense System Ia-Xc further comprises a regulatory element operably linked to said construct comprising a cis-acting regulatory element for directing expression of said nucleic acid sequence, or a transmissible element for directing transfer of said nucleic acid sequence from one cell to another, or a recombination element for integrating said nucleic acid sequence into a genome of a cell transfected with said construct, or an element providing episomal maintenance of said construct within a cell transfected with said construct, or any combination thereof; wherein said method results in the bacteria being resistant to at least one phage, or being resistant to a plasmid, or being resistant to a conjugative element, or being resistant to a combination of at least one phage, a conjugative element, and a plasmid.


In some embodiments, disclosed herein is a method of producing bacteria resistant to phage infection, said method comprising the step of introducing into bacteria a defense system comprising at least one of a Defense System Ia, a Defense System Ib, a Defense System II, a Defense System IIIa, a Defense System IIIb, a Defense System IIIc, a Defense System IV, a Defense System V, a Defense System VI, a Defense System VII, a Defense System VIII, a Defense System IX, a Defense System Xa, a Defense System Xb, or a Defense System Xc, wherein each nucleic acid construct of each Defense System Ia-Xc further comprises a regulatory element operably linked to said construct comprising a cis-acting regulatory element for directing expression of said nucleic acid sequence, or a transmissible element for directing transfer of said nucleic acid sequence from one cell to another, or a recombination element for integrating said nucleic acid sequence into a genome of a cell transfected with said construct, or an element providing episomal maintenance of said construct within a cell transfected with said construct, or any combination thereof; wherein said method produces bacteria resistant to at least one phage.


In some embodiments, disclosed herein is a method of producing bacteria resistant to plasmid transformation, said method comprising the step of introducing into bacteria a defense system comprising at least one of a Defense System Ia, a Defense System Ib, a Defense System II, a Defense System IIIa, a Defense System IIIb, a Defense System IIIc, a Defense System IV, a Defense System V, a Defense System VI, a Defense System VII, a Defense System VIII, a Defense System IX, a Defense System Xa, a Defense System Xb, or a Defense System Xc, wherein each nucleic acid construct of each Defense System Ia-Xc further comprises a regulatory element operably linked to said construct comprising a cis-acting regulatory element for directing expression of said nucleic acid sequence, or a transmissible element for directing transfer of said nucleic acid sequence from one cell to another, or a recombination element for integrating said nucleic acid sequence into a genome of a cell transfected with said construct, or an element providing episomal maintenance of said construct within a cell transfected with said construct, or any combination thereof; wherein said method produces bacteria resistant to a plasmid transformation.


In some embodiments, disclosed herein is a method of producing bacteria resistant to conjugative elements, said method comprising the step of introducing into bacteria a defense system comprising at least one of a Defense System Ia, a Defense System Ib, a Defense System II, a Defense System IIIa, a Defense System IIIb, a Defense System IIIc, a Defense System IV, a Defense System V, a Defense System VI, a Defense System VII, a Defense System VIII, a Defense System IX, a Defense System Xa, a Defense System Xb, or a Defense System Xc, wherein each nucleic acid construct of each Defense System Ia-Xc further comprises a regulatory element operably linked to said construct comprising a cis-acting regulatory element for directing expression of said nucleic acid sequence, or a transmissible element for directing transfer of said nucleic acid sequence from one cell to another, or a recombination element for integrating said nucleic acid sequence into a genome of a cell transfected with said construct, or an element providing episomal maintenance of said construct within a cell transfected with said construct, or any combination thereof; wherein said method produces bacteria resistant to conjugative elements.


In some embodiments, disclosed herein is a method of producing bacteria resistant to any combination of phage infection, conjugative elements, and plasmid transformation, said method comprising the step of introducing into bacteria a defense system comprising at least one of a Defense System Ia, a Defense System Ib, a Defense System II, a Defense System IIIa, a Defense System IIIb, a Defense System IIIc, a Defense System IV, a Defense System V, a Defense System VI, a Defense System VII, a Defense System VIII, a Defense System IX, a Defense System Xa, a Defense System Xb, or a Defense System Xc, wherein each nucleic acid construct of each Defense System Ia-Xc further comprises a regulatory element operably linked to said construct comprising a cis-acting regulatory element for directing expression of said nucleic acid sequence, or a transmissible element for directing transfer of said nucleic acid sequence from one cell to another, or a recombination element for integrating said nucleic acid sequence into a genome of a cell transfected with said construct, or an element providing episomal maintenance of said construct within a cell transfected with said construct, or any combination thereof; wherein said method produces bacteria resistant to any combination of phage infection, conjugative elements, and plasmid transformation.


In some embodiments, the defense system used in a method disclosed herein comprises one of a Defense System Ia, a Defense System Ib, a Defense System II, a Defense System IIIa, a Defense System IIIb, a Defense System IIIc, a Defense System IV, a Defense System V, a Defense System VI, a Defense System VII, a Defense System VIII, a Defense System IX, a Defense System Xa, a Defense System Xb, and a Defense System Xc. In some embodiments, the defense system used in a method disclosed herein comprises a combination of Defense Systems selected from a Defense System Ia, a Defense System Ib, a Defense System II, a Defense System IIIa, a Defense System IIIb, a Defense System IIIc, a Defense System IV, a Defense System V, a Defense System VI, a Defense System VII, a Defense System VIII, a Defense System IX, a Defense System Xa, a Defense System Xb, and a Defense System Xc. In some embodiments, the defense system used in a method disclosed herein comprises between 2-5 Defense Systems selected from a Defense System Ia, a Defense System Ib, a Defense System II, a Defense System III, a Defense System IV, a Defense System V, a Defense System VI, a Defense System VII, a Defense System VIII, a Defense System IX, a Defense System Xa, a Defense System Xb, and a Defense System Xc. In some embodiments, the defense system used in a method disclosed herein comprises between 2-10 Defense Systems selected from a Defense System Ia, a Defense System Ib, a Defense System II, a Defense System IIIa, a Defense System IIIb, a Defense System IIIc, a Defense System IV, a Defense System V, a Defense System VI, a Defense System VII, a Defense System VIII, a Defense System IX, a Defense System Xa, a Defense System Xb, and a Defense System Xc. In some embodiments, the defense system used in a method disclosed herein comprises between 10-20 Defense Systems selected from a Defense System Ia, a Defense System Ib, a Defense System II, a Defense System IIIa, a Defense System IIIb, a Defense System IIIc, a Defense System IV, a Defense System V, a Defense System VI, a Defense System VII, a Defense System VIII, a Defense System IX, a Defense System Xa, a Defense System Xb, and a Defense System Xc.


In some embodiments, the defense system used in a method disclosed herein comprises a combination of Defense Systems, as described in detail herein, selected from a Defense System Ia, a Defense System Ib, a Defense System II, a Defense System IIIa, a Defense System IIIb, a Defense System IIIc, a Defense System IV, a Defense System V, a Defense System VI, a Defense System VII, a Defense System VIII, a Defense System IX, a Defense System Xa, a Defense System Xb, and a Defense System Xc.


In some embodiments, disclosed herein is a method of protecting bacteria from phage infection, said method comprising the step of introducing into bacteria a defense systems comprising a combination of Defense Systems, said combination comprising any combination of a Defense System Ia, a Defense System Ib, a Defense System II, a Defense System IIIa, a Defense System IIIb, a Defense System IIIc, a Defense System IV, a Defense System V, a Defense System VI, a Defense System VII, a Defense System VIII, a Defense System IX, a Defense System Xa, a Defense System Xb, or a Defense System Xc, wherein each nucleic acid construct of each Defense System Ia-Xc further comprises a regulatory element operably linked to said construct comprising a cis-acting regulatory element for directing expression of said nucleic acid sequence, or a transmissible element for directing transfer of said nucleic acid sequence from one cell to another, or a recombination element for integrating said nucleic acid sequence into a genome of a cell transfected with said construct, or an element providing episomal maintenance of said construct within a cell transfected with said construct, or any combination thereof; wherein said method results in the bacteria being resistant to at least one phage.


In some embodiments, disclosed herein is a method of protecting bacteria from plasmid transformation, said method comprising the step of introducing into bacteria a defense systems comprising a combination of Defense Systems, said combination comprising any combination of a Defense System Ia, a Defense System Ib, a Defense System II, a Defense System IIIa, a Defense System IIIb, a Defense System IIIc, a Defense System IV, a Defense System V, a Defense System VI, a Defense System VII, a Defense System VIII, a Defense System IX, a Defense System Xa, a Defense System Xb, or a Defense System Xc, wherein each nucleic acid construct of each Defense System Ia-Xc further comprises a regulatory element operably linked to said construct comprising a cis-acting regulatory element for directing expression of said nucleic acid sequence, or a transmissible element for directing transfer of said nucleic acid sequence from one cell to another, or a recombination element for integrating said nucleic acid sequence into a genome of a cell transfected with said construct, or an element providing episomal maintenance of said construct within a cell transfected with said construct, or any combination thereof; wherein said method results in the bacteria being resistant to a plasmid transformation.


In some embodiments, disclosed herein is a method of protecting bacteria from conjugative elements, said method comprising the step of introducing into bacteria a defense systems comprising a combination of Defense Systems, said combination comprising any combination of a Defense System Ia, a Defense System Ib, a Defense System II, a Defense System IIIa, a Defense System IIIb, a Defense System IIIc, a Defense System IV, a Defense System V, a Defense System VI, a Defense System VII, a Defense System VIII, a Defense System IX, a Defense System Xa, a Defense System Xb, or a Defense System Xc, wherein each nucleic acid construct of each Defense System Ia-Xc further comprises a regulatory element operably linked to said construct comprising a cis-acting regulatory element for directing expression of said nucleic acid sequence, or a transmissible element for directing transfer of said nucleic acid sequence from one cell to another, or a recombination element for integrating said nucleic acid sequence into a genome of a cell transfected with said construct, or an element providing episomal maintenance of said construct within a cell transfected with said construct, or any combination thereof; wherein said method results in the bacteria being resistant to conjugative elements.


In some embodiments, disclosed herein is a method of protecting bacteria from any combination of phage infection, conjugative elements, and plasmid transformation, said method comprising the step of introducing into bacteria a defense systems comprising a combination of Defense Systems, said combination comprising any combination of a Defense System Ia, a Defense System Ib, a Defense System II, a Defense System IIIa, a Defense System IIIb, a Defense System IIIc, a Defense System IV, a Defense System V, a Defense System VI, a Defense System VII, a Defense System VIII, a Defense System IX, a Defense System Xa, a Defense System Xb, or a Defense System Xc, wherein each nucleic acid construct of each Defense System Ia-Xc further comprises a regulatory element operably linked to said construct comprising a cis-acting regulatory element for directing expression of said nucleic acid sequence, or a transmissible element for directing transfer of said nucleic acid sequence from one cell to another, or a recombination element for integrating said nucleic acid sequence into a genome of a cell transfected with said construct, or an element providing episomal maintenance of said construct within a cell transfected with said construct, or any combination thereof; wherein said method results in the bacteria being resistant to any combination of phage infection, conjugative elements, and plasmid transformation.


In some embodiments, a method of protecting bacteria from phage infection produces bacteria resistant to phage infection. In some embodiments, the method of protecting bacteria from plasmid transformation produces bacteria having reduced transformation efficiency of a plasmid. In some embodiments, the method of protecting bacteria from conjugative elements produces bacteria resistant to horizontal gene transfer. In some embodiments, the method of protecting bacteria from phage infection, and/or conjugative elements, and/or plasmid transformation, produces bacteria resistant to phage infection, resistant to horizontal gene transfer, and having reduced transformation efficiency of a plasmid.


In some embodiments, a method of protecting bacteria from phage infection produces bacteria resistant to at least one phage. In some embodiments, a method of protecting bacteria from plasmid transformation produces bacteria resistant to plasmid transformation. In some embodiments, a method of protecting bacteria from phage infection and plasmid transformation produces bacteria resistant to at least one phage and resistant to entry of a plasmid.


In some embodiments, provided herein is a method of protecting bacteria from phage infection, the method comprising introducing into the bacteria a defense system having an anti-phage activity, the system comprising at least one component selected from the group consisting of the components of the defense system, thereby protecting the bacteria from phage infection. In some embodiments, a method of protecting bacteria from phage infection comprises introducing into the bacteria a defense system comprising a Defense System selected from a Defense System Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc, wherein said defense system comprises an anti-phage activity, the system comprising at least one component of said Defense System Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, or Xc, said at least one component selected from the group consisting of the components of the Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, or Xc, respectively, thereby protecting the bacteria from phage infection. In some embodiments, a method of protecting bacteria from phage infection comprises introducing into the bacteria a defense system comprising a combination of Defense Systems selected from Defense System Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc, wherein said defense system comprises an anti-phage activity, the system comprising at least one component of each of said Defense Systems in combination, said at least one component selected from the group consisting of the components of the Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, or Xc, respectively, thereby protecting the bacteria from phage infection.


In some embodiments, an at least one component comprises the components of a Defense System Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, or Xc, required for a functional Defense System, wherein said function comprises an anti-phage activity. In some embodiments, an at least one component comprises the components of the cassette of genes making up a Defense System Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, or Xc. In some embodiments, an at least one component comprises two components of a Defense System Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, or Xc. In some embodiments, an at least one component comprises three components of a Defense System Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, or Xc. In some embodiments, an at least one component comprises four components of a Defense System Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, or Xc. In some embodiments, an at least one component comprises five components of a Defense System Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, or Xc. In some embodiments, a component comprises the full-length component. In some embodiments, a component comprises a functional portion of the component. In some embodiments, a component comprises a component homolog.


In some embodiments, provided herein is a method of protecting bacteria from plasmid transformation, the method comprising introducing into the bacteria a defense system having an anti-plasmid activity, the system comprising at least one component selected from the group consisting of the components of the defense system, thereby protecting the bacteria from plasmid transformation. In some embodiments, a method of protecting bacteria from plasmid transformation comprises introducing into the bacteria a defense system comprising a Defense System selected from a Defense System Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc, wherein said defense system comprises an anti-plasmid activity, the system comprising at least one component of said Defense System Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, or Xc, said at least one component selected from the group consisting of the components of the Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, or Xc, respectively, thereby protecting the bacteria from plasmid transformation. In some embodiments, a method of protecting bacteria from plasmid transformation comprises introducing into the bacteria a defense system comprising a combination of Defense Systems selected from Defense System Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc, wherein said defense system comprises an anti-plasmid activity, the system comprising at least one component of each of said Defense Systems in combination, said at least one component selected from the group consisting of the components of the Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, or Xc, respectively, thereby protecting the bacteria from plasmid transformation.


In some embodiments, an at least one component comprises the components of a Defense System Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, or Xc, required for a functional Defense System, wherein said function comprises an anti-plasmid activity. In some embodiments, an at least one component comprises the components of the cassette of genes making up a Defense System Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, or Xc. In some embodiments, an at least one component comprises two components of a Defense System Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, or Xc. In some embodiments, an at least one component comprises three components of a Defense System Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, or Xc. In some embodiments, an at least one component comprises four components of a Defense System Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, or Xc. In some embodiments, an at least one component comprises five components of a Defense System Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, or Xc. In some embodiments, a component comprises the full-length component. In some embodiments, a component comprises a functional portion of the component. In some embodiments, a component comprises a component homolog.


In some embodiments, provided herein is a method of protecting bacteria from conjugative elements, the method comprising introducing into the bacteria a defense system having an anti-conjugation activity, the system comprising at least one component selected from the group consisting of the components of the defense system, thereby protecting the bacteria from conjugation. In some embodiments, a method of protecting bacteria from conjugative elements comprises introducing into the bacteria a defense system comprising a Defense System selected from a Defense System Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc, wherein said defense system comprises an anti-conjugation activity, the system comprising at least one component of said Defense System Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, or Xc, said at least one component selected from the group consisting of the components of the Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, or Xc, respectively, thereby protecting the bacteria from conjugation. In some embodiments, a method of protecting bacteria from conjugative elements comprises introducing into the bacteria a defense system comprising a combination of Defense Systems selected from Defense System Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc, wherein said defense system comprises an anti-conjugation activity, the system comprising at least one component of each of said Defense Systems in combination, said at least one component selected from the group consisting of the components of the Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, or Xc, respectively, thereby protecting the bacteria from conjugation.


In some embodiments, an at least one component comprises the components of a Defense System Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, or Xc, required for a functional Defense System, wherein said function comprises an anti-conjugation activity. In some embodiments, an at least one component comprises the components of the cassette of genes making up a Defense System Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, or Xc. In some embodiments, an at least one component comprises two components of a Defense System Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, or Xc. In some embodiments, an at least one component comprises three components of a Defense System Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, or Xc. In some embodiments, an at least one component comprises four components of a Defense System Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, or Xc. In some embodiments, an at least one component comprises five components of a Defense System Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, or Xc. In some embodiments, a component comprises the full-length component. In some embodiments, a component comprises a functional portion of the component. In some embodiments, a component comprises a component homolog.


In some embodiments, provided herein is a method of protecting bacteria from any combination of phage infection, conjugative elements, and plasmid transformation, the method comprising introducing into the bacteria a defense system having an anti-phage, anti-conjugation, and/or anti-plasmid activity, the system comprising at least one component selected from the group consisting of the components of the defense system, thereby protecting the bacteria from phage infection, conjugative elements, and plasmid transformation. In some embodiments, a method of protecting bacteria from phage infection, conjugative elements, and plasmid transformation comprises introducing into the bacteria a defense system comprising a Defense System selected from a Defense System Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc, wherein said defense system comprises an anti-phage, anti-conjugation, and/or anti-plasmid activity, the system comprising at least one component of said Defense System Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, or Xc, said at least one component selected from the group consisting of the components of the Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, or Xc, respectively, thereby protecting the bacteria from phage infection, conjugative elements, and/or plasmid transformation. In some embodiments, a method of protecting bacteria from phage infection, conjugative elements, and plasmid transformation comprises introducing into the bacteria a defense system comprising a combination of Defense Systems selected from Defense System Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc, wherein said defense system comprises an anti-phage, anti-conjugation, and anti-plasmid activity, the system comprising at least one component of each of said Defense Systems in combination, said at least one component selected from the group consisting of the components of the Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, or Xc, respectively, thereby protecting the bacteria from phage infection, bacterial conjugation, and/or plasmid transformation.


In some embodiments, an at least one component comprises the components of a Defense System Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, or Xc, required for a functional Defense System, wherein said function comprises an anti-phage, anti-conjugation, and/or anti-plasmid activity. In some embodiments, an at least one component comprises the components of the cassette of genes making up a Defense System Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, or Xc. In some embodiments, an at least one component comprises two components of a Defense System Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, or Xc. In some embodiments, an at least one component comprises three components of a Defense System Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, or Xc. In some embodiments, an at least one component comprises four components of a Defense System Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, or Xc. In some embodiments, an at least one component comprises five components of a Defense System Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, or Xc. In some embodiments, a component comprises the full-length component. In some embodiments, a component comprises a functional portion of the component. In some embodiments, a component comprises a component homolog.


The components of Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc have been described in detail above, as has the combination of these Defense systems. Methods of protecting bacteria comprising introducing into the bacteria a defense system comprising at least one components of a Defense System selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc, or a combination of Defense Systems thereof, comprises use of the components of the Defense Systems as described in detail above, and in Tables 6-18. The detailed description of the Defense Systems and components thereof, and combinations thereof, as described above, are incorporated in full in the method of use of protecting bacteria described herein. Briefly, a non-limiting description of Defense Systems and their components includes Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc and components thereof, including but are not limited to methods of protecting bacteria comprising introducing into the bacteria a defense system comprising at least one components of a Defense System selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc, or a combination of Defense Systems thereof, wherein in some embodiments:


a Defense System Ia comprises a nucleic acid construct comprising a nucleic acid sequence encoding a ZorA polypeptide comprising a pfam01618 domain, a ZorB polypeptide comprising a pfam13677 domain or a pfam00691 domain or a combination thereof, a ZorC polypeptide comprising a pfam15611 domain, and a ZorD polypeptide comprising a pfam00176 domain or a pfam00271 domain or a combination thereof;


a Defense System Ib comprises a nucleic acid construct comprising a nucleic acid sequence encoding a ZorA polypeptide comprising a pfam01618 domain, a ZorB polypeptide comprising a pfam13677 domain or a pfam00691 domain or a combination thereof, and a ZorE polypeptide comprising a pfam01844 domain or a COG3183 domain or a combination thereof;


a Defense System II comprises a nucleic acid construct comprising a nucleic acid sequence encoding a ThsA polypeptide comprising a pfam13289 domain or a pfam14519 domain or a combination thereof, and a KwaB polypeptide comprising a pfam13676 domain or a pfam08937 domain or a pfam08357 domain, or a combination thereof;


a Defense System IIIa comprises a nucleic acid construct comprising a nucleic acid sequence encoding a DruA polypeptide comprising a DUF4338 domain or a pfam14236 domain or a combination thereof, a DruB polypeptide, a DruC polypeptide, a DruD polypeptide, and a DruE polypeptide comprising a pfam00270 domain or a pfam00271 domain or a pfam09369 domain or a DUF1998 domain or any combination thereof;


a Defense System IIIa comprises a nucleic acid construct comprising a nucleic acid sequence encoding a DruA polypeptide comprising a DUF4338 domain or a pfam14236 domain or a combination thereof, a DruB polypeptide, a DruC polypeptide, a DruD polypeptide, and a DruE polypeptide comprising a pfam00270 domain or a pfam00271 domain or a pfam09369 domain or a DUF1998 domain or any combination thereof, said DruB polypeptide encoded by a gene positioned within 5 genes of a gene encoding DruA, DruD, and or DruE, and said DruC polypeptide encoded by a gene positioned within 5 genes of a gene encoding DruA, DruD, and or DruE;


a Defense System IIIb comprises a nucleic acid construct comprising a nucleic acid sequence encoding a DruM polypeptide comprising a pfam00145 domain or a COG0270 or a combination thereof, a DruF polypeptide, a DruG polypeptide, and a DruE polypeptide comprising a pfam00270 domain or a pfam00271 domain or a pfam09369 domain or a DUF1998 domain or any combination thereof;


a Defense System IIIb comprises a nucleic acid construct comprising a nucleic acid sequence encoding a DruM polypeptide comprising a pfam00145 domain or a COG0270 or a combination thereof, a DruF polypeptide, a DruG polypeptide, and a DruE polypeptide comprising a pfam00270 domain or a pfam00271 domain or a pfam09369 domain or a DUF1998 domain or any combination thereof, said DruF polypeptide encoded by a gene positioned within 5 genes of a gene encoding DruM and or DruE, and said DruG polypeptide encoded by a gene positioned within 5 genes of a gene encoding DruM and or DruE;


a Defense System IIIc comprises a nucleic acid construct comprising a nucleic acid sequence encoding a DruH polypeptide and a DruE polypeptide comprising a pfam00270 domain or a pfam00271 domain or a pfam09369 domain or a DUF1998 domain or any combination thereof;


a Defense System IIIc comprises a nucleic acid construct comprising a nucleic acid sequence encoding a DruH polypeptide and a DruE polypeptide comprising a pfam00270 domain or a pfam00271 domain or a pfam09369 domain or a DUF1998 domain or any combination thereof, said DruH polypeptide encoded by a gene positioned within 5 genes of a gene encoding DruE;


a Defense System IV comprises a nucleic acid construct comprising a nucleic acid sequence encoding a HamA polypeptide comprising a pfam08878 domain or a DUF1837 domain or a combination thereof, and a HamB polypeptide comprising COG1204 domain or a pfam00270 domain or a pfam00271 domain or any combination thereof;


a Defense System V comprises a nucleic acid construct comprising a nucleic acid sequence encoding a SduA polypeptide comprising a pfam14082 domain or a pfam01939 domain or a combination thereof;


a Defense System VI comprises a nucleic acid construct comprising a nucleic acid sequence encoding a GajA polypeptide comprising a pfam13175 domain or a COG3593 domain or a combination thereof, and a GajB polypeptide comprising a pfam04257 domain or a pfam00580 domain or a pfam13361 domain or a combination thereof;


a Defense System VII comprises a nucleic acid construct comprising a nucleic acid sequence encoding a PtuA polypeptide comprising a pfam13304 domain or a pfam02463 domain or a combination thereof, and a PtuB polypeptide comprising pfam13395 domain or a pfam 01844 domain or a combination thereof;


a Defense System VIII comprises a nucleic acid construct comprising a nucleic acid sequence encoding a LmuA polypeptide comprising a pfam14130 domain or a DUF4297 domain or a combination thereof, and a LmuB polypeptide comprising a pfam02463 domain;


a Defense System IX comprises a nucleic acid construct comprising a nucleic acid sequence encoding a KwaA polypeptide and a KwaB polypeptide comprising a pfam16162 domain or a DUF4868 domain or a combination thereof;


a Defense System IX comprises a nucleic acid construct comprising a nucleic acid sequence encoding a KwaA polypeptide and a KwaB polypeptide comprising a pfam16162 domain or a DUF4868 domain or a combination thereof, said KwaA polypeptide encoded by a gene positioned within 5 genes of a gene encoding KwaB;


a Defense System Xa comprises a nucleic acid construct comprising a nucleic acid sequence encoding a JetA polypeptide comprising a pfam11855 domain or a DUF3375 domain or any combination thereof, a JetB polypeptide comprising a pfam13835 domain or a DUF4194 domain or any combination thereof, a JetC polypeptide comprising a pfam13555 domain or a pfam13558 domain or a COG4913 domain or a combination thereof, and a JetD polypeptide comprising a pfam11795 domain or a DUF3322 domain or a pfam09983 domain or a DUF2220 domain or a COG4924 domain or any combination thereof;


a Defense System Xb comprises a nucleic acid construct comprising a nucleic acid sequence encoding a JetAii polypeptide comprising a pfam09660 domain or a DUF2397 domain or any combination thereof, a JetBii polypeptide comprising a pfam09661 domain or a DUF2398 domain or any combination thereof, a JetCii polypeptide comprising a pfam13558 domain, and a JetDii polypeptide comprising a pfam11796 domain or a DUF3323 domain or a pfam09664 domain or a DUF2399 domain or any combination thereof;


a Defense System Xc comprises a nucleic acid construct comprising a nucleic acid sequence encoding a JetAiii polypeptide, a JetBiii polypeptide, a JetCiii polypeptide comprising a COG1196 domain, a JetDiii polypeptide comprising a pfam09983 domain or a pfam09664 domain, or a DUF2220 domain, or a DUF2399 domain, or a combination thereof; or


a Defense System Xc comprises a nucleic acid construct comprising a nucleic acid sequence encoding a JetAiii polypeptide, a JetBiii polypeptide, a JetCiii polypeptide comprising a COG1196 domain, a JetDiii polypeptide comprising a pfam09983 domain or a pfam09664 domain, or a DUF2220 domain, or a DUF2399 domain, or a combination thereof, said JetAiii polypeptide and a JetBiii polypeptide each encoded by a gene positioned within 5 genes of a gene encoding JetCiii polypeptide or a JetDiii polypeptide;


wherein each nucleic acid construct of each Defense System Ia-Xc further comprises a regulatory element operably linked to said construct comprising a cis-acting regulatory element for directing expression of said nucleic acid sequence, or a transmissible element for directing transfer of said nucleic acid sequence from one cell to another, or a recombination element for integrating said nucleic acid sequence into a genome of a cell transfected with said construct, or an element providing episomal maintenance of said construct within a cell transfected with said construct, or any combination thereof; wherein said method results in protecting bacteria comprising the bacteria being resistant to at least one phage, or the bacteria having reduced efficacy of plasmid transformation, or a combination thereof.


In some embodiments, the bacteria do not express an endogenous version of the defense system being introduced. In some embodiments, the bacteria do not express a functional endogenous version of the defense system being introduced.


In some embodiments, the bacteria do not express an endogenous version of the Defense System Ia. In some embodiments, the bacteria do not express a functional endogenous version of the Defense System Ia. In some embodiments, the bacteria do not express an endogenous version of the Defense System Ib. In some embodiments, the bacteria do not express a functional endogenous version of the Defense System Ib. In some embodiments, the bacteria do not express an endogenous version of the Defense System II. In some embodiments, the bacteria do not express a functional endogenous version of the Defense System II. In some embodiments, the bacteria do not express an endogenous version of the Defense System IIIa. In some embodiments, the bacteria do not express a functional endogenous version of the Defense System IIIa. In some embodiments, the bacteria do not express an endogenous version of the Defense System IIIb. In some embodiments, the bacteria do not express a functional endogenous version of the Defense System IIIb. In some embodiments, the bacteria do not express an endogenous version of the Defense System IIIc. In some embodiments, the bacteria do not express a functional endogenous version of the Defense System IIIc. In some embodiments, the bacteria do not express an endogenous version of the Defense System IV. In some embodiments, the bacteria do not express a functional endogenous version of the Defense System IV. In some embodiments, the bacteria do not express an endogenous version of the Defense System V. In some embodiments, the bacteria do not express a functional endogenous version of the Defense System V. In some embodiments, the bacteria do not express an endogenous version of the Defense System VI. In some embodiments, the bacteria do not express a functional endogenous version of the Defense System VI. In some embodiments, the bacteria do not express an endogenous version of the Defense System VII. In some embodiments, the bacteria do not express a functional endogenous version of the Defense System VII. In some embodiments, the bacteria do not express an endogenous version of the Defense System VIII. In some embodiments, the bacteria do not express a functional endogenous version of the Defense System VIII. In some embodiments, the bacteria do not express an endogenous version of the Defense System IX. In some embodiments, the bacteria do not express a functional endogenous version of the Defense System IX. In some embodiments, the bacteria do not express an endogenous version of the Defense System Xa. In some embodiments, the bacteria do not express a functional endogenous version of the Defense System Xa. In some embodiments, the bacteria do not express an endogenous version of the Defense System Xb. In some embodiments, the bacteria do not express a functional endogenous version of the Defense System Xb. In some embodiments, the bacteria do not express an endogenous version of the Defense System Xc. In some embodiments, the bacteria do not express a functional endogenous version of the Defense System Xc.


In some embodiments, the bacteria do not express an endogenous version of the combination of Defense Systems selected from combinations disclosed herein above, of any of Defense Systems Ia-Xc. In some embodiments, the bacteria do not express a functional endogenous version of the combination of Defense Systems selected from combinations disclosed herein above, of any of Defense Systems Ia-Xc.


A skilled artisan would appreciate that various modalities may be used to introduce or express a defense system comprising a Defense System Ia-Xc or a combination thereof, or the components of a Defense System Ia-Xc, in the bacteria.


In some embodiments, the method is effected by expressing in the bacteria, an isolated nucleic acid sequence(s), nucleic acid construct or construct or alternatively introducing the component polypeptides of a Defense System or a combination of Defense Systems, as described herein, to confer protection. In some embodiments, protection comprises an anti-phage activity. In some embodiments, protection comprises an anti-plasmid activity. In some embodiments, protection comprises a combination of an anti-phage activity and an anti-plasmid activity. Alternatively, or additionally, the defense system comprising a Defense System or a combination of Defense Systems, is introduced into the bacteria via transmissible genetic element in a process of bacterial conjugation.


In some embodiments, there is provided a method of protecting bacteria from phage infection, or plasmid transformation, or phage infection and plasmid transformation, the method comprising introducing into the bacteria a defense system having an anti-phage activity, or an anti-plasmid activity, or an anti-phage activity and an anti-plasmid activity, wherein said bacteria is a first bacteria and said introducing into said bacteria said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, comprises contacting said first bacteria with a second bacteria expressing said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc on a transmissible genetic element.


In some embodiments, a transmissible genetic element comprises a defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, as described herein in detail above. In some embodiments, the transmissible genetic element comprises a conjugative genetic element or a mobilized genetic element. In some embodiments, a transmissible genetic element comprises a plasmid or a transposon.


A skilled artisan would appreciate that the phrase “bacterial conjugation” encompasses a direct transfer of genetic material between bacterial cells by cell-to-cell contact or by bridge-like connection between the cells. During conjugation the donor bacterium provides a transmissible genetic element, typically a plasmid or a transposon. The transfer of the transmissible genetic element takes advantage of the complementary nature of double stranded DNA. Thus, one strand of the transmissible genetic element is transferred, and the other remains in the original bacteria. Both strands have the complementary stranded added so that each bacterium ends up with a complete transmissible element.


According to some embodiments, contacting a first bacteria with second bacteria comprise the step of incubating the bacterial cell (e.g., first bacteria) with a substance or cell (e.g., second bacteria) such that the substance or a substance contained in the cell affects the bacterial cell resistance to phage infection, or to plasmid transformation, or to phage infection and plasmid transformation.


In some embodiments, the first bacteria and the second bacteria are non-identical.


In some embodiments, the first bacteria do not express an endogenous defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc. In some embodiments, the first bacteria do not express an endogenous functional defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc.


In some embodiments, the first bacteria is a commercially valuable bacteria such as those used for fermentation as described above. Thus, following the above teachings, in some embodiments, there is provided isolated bacteria comprising a nucleic acid sequence encoding a defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, said system having an anti-phage activity and a transmissible genetic element expressing the defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, wherein the isolated bacteria does not express an endogenous functional defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc.


In some embodiments, the first bacteria is a commercially valuable bacteria such as those used for fermentation as described above. Thus, following the above teachings, in some embodiments, there is provided isolated bacteria comprising a nucleic acid sequence encoding a defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, said system having an anti-plasmid activity and a transmissible genetic element expressing the defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, wherein the isolated bacteria does not express an endogenous functional defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc.


In some embodiments, the first bacteria is a commercially valuable bacteria such as those used for fermentation as described above. Thus, following the above teachings, in some embodiments, there is provided isolated bacteria comprising a nucleic acid sequence encoding a defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, said system having an anti-phage activity and anti-plasmid activity, and a transmissible genetic element expressing the defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, wherein the isolated bacteria does not express an endogenous functional defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc.


In some embodiments, a cell comprises a host cell. In some embodiments, a host cell comprises bacteria. In some embodiments, a cell comprises bacteria. In some embodiments, a host cell comprises a microbial cell. In some embodiments, a cell comprises a microbial cell. In some embodiments, the cell is an isolated cell. In some embodiments, bacteria are isolated bacteria. In some embodiments, a cell comprises isolated microbial cells. In some embodiments, the cell is a microbial cell such as bacteria, e.g., Gram-positive or Gram-negative bacteria. In some embodiments, the bacteria comprise Gram-negative bacteria or Negativicutes that stain negative in Gram stain. In some embodiments, a host cell comprises gram-positive bacteria, gram-negative bacteria, or archaea.


In some embodiments, Gram-negative bacteria comprise Acinetobacter calcoaceticus, Actinobacillus actinomycetemcomitans, Aeromonas hydrophila, Alcaligenes xylosoxidans, Bacteroides, Bacteroides fragilis, Bartonella bacilliformis, Bordetella spp., Borrelia burgdorferi, Branhamella catarrhalis, Brucella spp., Campylobacter spp., Chalmydia pneumoniae, Chlamydia psittaci, Chlamydia trachomatis, Chromobacterium violaceum, Citrobacter spp., Eikenella corrodens, Enterobacter aerogenes, Escherichia coli, Flavobacterium meningosepticum, Fusobacterium spp., Haemophilus influenzae, Haemophilus spp., Helicobacter pylori, Klebsiella spp., Legionella spp., Leptospira spp., Moraxella catarrhalis, Morganella morganii, Mycoplasma pneumoniae, Neisseria gonorrhoeae, Neisseria meningitidis, Pasteurella multocida, Plesiomonas shigelloides, Prevotella spp., Proteus spp., Providencia rettgeri, Pseudomonas aeruginosa, Pseudomonas spp., Rickettsia prowazekii, Rickettsia rickettsii, Rochalimaea spp., Salmonella spp., Salmonella typhi, Serratia marcescens, Shigella spp., Treponema carateum, Treponema pallidum, Treponema pallidum endemicum, Treponema pertenue, Veillonella spp., Vibrio cholerae, Vibrio vulnificus, Yersinia enterocolitica, Yersinia pestis.


In some embodiments, the bacteria comprise gammaproteobacteria (e.g. Escherichia coli, pseudomonas, vibrio and klebsiella) or Firmicutes (belonging to class Negativicutes that stain negative in Gram stain).


In some embodiments, Gram-positive bacteria comprise Actinomyces spp., Bacillus anthracis, Bifidobacterium spp., Clostridium botulinum, Clostridium perfringens, Clostridium spp., Clostridium tetani, Corynebacterium diphtheriae, Corynebacterium jeikeium, Enterococcus faecalis, Enterococcus faecium, Erysipelothrix rhusiopathiae, Eubacterium spp., Gardnerella vaginalis, Gemella morbillorum, Leuconostoc spp., Mycobacterium abcessus, Mycobacterium avium complex, Mycobacterium chelonae, Mycobacterium fortuitum, Mycobacterium haemophilium, Mycobacterium kansasii, Mycobacterium leprae, Mycobacterium marinum, Mycobacterium scrofulaceum, Mycobacterium smegmatis, Mycobacterium terrae, Mycobacterium tuberculosis, Mycobacterium ulcerans, Nocardia spp., Peptococcus niger, Peptostreptococcus spp., Proprionibacterium spp., Staphylococcus aureus, Staphylococcus auricularis, Staphylococcus capitis, Staphylococcus cohnii, Staphylococcus epidermidis, Staphylococcus haemolyticus, Staphylococcus hominis, Staphylococcus lugdanensis, Staphylococcus saccharolyticus, Staphylococcus saprophyticus, Staphylococcus schleiferi, Staphylococcus similans, Staphylococcus warneri, Staphylococcus xylosus, Streptococcus agalactiae (group B streptococcus), Streptococcus anginosus, Streptococcus bovis, Streptococcus canis, Streptococcus equi, Streptococcus milleri, Streptococcus mitior, Streptococcus mutans, Streptococcus pneumoniae, Streptococcus pyogenes (group A streptococcus), Streptococcus salivarius, Streptococcus sanguis.


In some embodiments the bacteria is a species selected from the group consisting of Escherichia, Shigella, Salmonella, Erwinia, Yersinia, Bacillus, Vibrio, Legionella, Pseudomonas, Neisseria, Bordetella, Helicobacter, Listeria, Agrobacterium, Staphylococcus, Streptococcus, Enterococcus, Clostridium, Corynebacterium, Mycobacterium, Treponema, Borrelia, Francisella, Brucella, Campylobacter, Klebsiella, Frankia, Bartonella, Rickettsia, Shewanella, Serratia, Enterobacter, Proteus, Providencia, Brochothrix, and Brevibacterium.


In some embodiments, there is provided herein a cell (e.g., bacteria) expressing at least one component of a defense system. In some embodiments, the cell is genetically modified. In some embodiments, the cell comprises an isolated cell. The components of defense systems comprising a Defense System Ia-Xc and combinations thereof, have been described in detail above. In some embodiments, polypeptide components of these systems include but are not limited to ZorA, ZorB, ZorC, ZorD, ZorE (Defense System Ia and Ib); ThsA and ThsB (Defense System II); DruA, DruB, DruC, DruD, DruE, DruH, DruM, DruG, DruF (Defense Systems IIIa, IIIb, IIIc); HamA and HamB (Defense System IV); SduA (Defense System V); GajA and GajB (Defense System VI); PtuA and PtuB (Defense System VII); LmuA and LmuB (Defense System VIII); KwaA and KwaB (Defense System IX); and JetA, JetB, JetC, and JetD, and variants thereof (Defense Systems Xa, Xb, Xc). In some embodiments, polynucleotide (e.g., gene) components, include but are not limited to zorA, zorB, zorC, zorD, zorE (Defense Systems Ia, Ib); thsA and thsB (Defense System II); druA, druB, druC, druD, druE, druF, druG, druH, druM (Defense Systems IIIa, IIIb, IIIc); hamA and hamB (Defense System IV); sduA (Defense System V); gajA and gajB (Defense System VI); ptuA and ptuB (Defense System VII); lmuA and lmuB (Defense System VIII); kwaA and kwaB (Defense System IX); and jetA, jetB, jetC, and jetD and variants thereof (Defense Systems Xa, Xb, Xc).


In some embodiments, a cell is genetically modified to express at least 2, at least 3, or at least 4 of the components of an anti-nucleic acid defense system comprising a Defense System of Ia-Xc, or a combination thereof. In some embodiments, the cell is genetically modified to express a functional anti-nucleic acid defense system. In some embodiments, the cell is genetically modified to express the components necessary for a functional anti-nucleic acid defense system. In some embodiments, the cell is genetically modified to expression any combination of components of a Defense System Ia, any combination of components of a Defense System Ib, any combination of components of a Defense System II, any combination of components of a Defense System IIIa, any combination of components of a Defense System IIIb, any combination of components of a Defense System IIIc, any combination of components of a Defense System IV, any combination of components of a Defense System V, any combination of components of a Defense System VI, any combination of components of a Defense System VII, any combination of components of a Defense System VIII, any combination of components of a Defense System IX, any combination of components of a Defense System Xa, any combination of components of a Defense System Xb, or any combination of components of a Defense System Xc. In some embodiments, a cell is genetically modified to express all of the components of a Defense System.


In some embodiments, a cell is genetically modified to express at least 2, 3, 4, or 5 components of a Defense System or combination of Defense systems, as described herein. In some embodiments, a cell is genetically modified to express at least 2, 3, 4, or 5 functional components of a Defense System or combination of Defense systems, as described herein, wherein the cell comprises the anti-phage, or anti-plasmid, or anti-phage and anti-plasmid resistance provide by each of the functional Defense Systems.


In some embodiments, a cell that has been genetically modified to express a defense system comprising a Defense System of Ia-Xc or a combination thereof, has an anti-phage activity. In some embodiments, a cell that has been genetically modified to express a defense system comprising a Defense System of Ia-Xc or a combination thereof, has an anti-plasmid activity. In some embodiments, a cell that has been genetically modified to express a defense system comprising a Defense System of Ia-Xc or a combination thereof, has an anti-phage activity and an anti-plasmid activity.


In some embodiments, a cell (e.g., bacterial cell) does not express an endogenous defense system comprising any one of Defense Systems Ia-Xc, or any combination thereof. In some embodiments, the cell expressing a defense system described herein (e.g., bacterial cell expressing a Defense System of Ia-Xc, or any combination thereof) does not endogenously express the defense system comprising any one of a the Defense Systems of Ia-Xc, or any combination thereof.


In some embodiments, the cell expressing a defense system (e.g., bacterial cell) is resistant to infection by at least one phage. In some embodiments the cell is resistant to at least one lytic phage. In some embodiments, the cell is resistant to at least one temperate (also referred as lysogenic) phage. In some embodiments, the cell is resistant to phage lysogeny. In some embodiments, the cell is resistant to phage DNA replication. In some embodiments, the cell is resistant to plasmid transformation. In some embodiments, the cell is resistant to infection by at least one phage and is resistant to plasmid transformation.


Phage contamination is now considered to be a main cause of slow fermentation or complete starter failure. The lack of bacteria which survive adequately can result in milk products which do not have a desirable taste. Thus, a goal of scientists working to produce better milk products lies in providing bacteria which have all the characteristics associated with production of a good flavor and which are able to resist infection by phages.


In some embodiments, the bacteria may be useful in the manufacture of dairy and fermentation processing such as, but not limited to, milk-derived products, such as cheeses, yogurt, fermented milk products, sour milks, and buttermilk. In some embodiments, the bacteria are useful as a part of the starter culture in the manufacture of dairy and fermentation processing. In some embodiments, the starter culture is a food grade starter culture.


A bacterium traditionally used in the production of milk products is S. thermophilus. It is particularly employed in the production of yogurt, mozzarella and Swiss type cheeses. One problem with S. thermophilus is that it is extremely sensitive to phage infection.


In some embodiments, the bacteria are lactic acid bacteria. A skilled artisan would appreciate that the term “lactic acid bacteria” encompasses Gram positive, microaerophillic or anaerobic bacteria which ferment sugar with the production of acids including lactic acid as the predominantly produced acid, acetic acid, formic acid and propionic acid.


In some embodiments, bacteria used in methods disclosed herein, are selected from a species selected from the group of the industrially most useful lactic acid bacteria comprising Lactococcus species, Streptococcus species, Lactobacillus species, Leuconostoc species, Oenococcus species, Pediococcus species, Bifidobacterium species, and Propionibacterium species. In some embodiments, bacteria protected in a method of protecting bacteria from phage infection comprises bacteria selected from a Lactococcus species, a Streptococcus species, a Lactobacillus species, a Leuconostoc species, a Oenococcus species, a Pediococcus species, a Bifidobacterium, and a Propionibacterium species. In some embodiments a method of protecting bacteria from phage infection comprises protecting a Lactococcus species of bacteria. In some embodiments a method of protecting bacteria from phage infection comprises protecting a Streptococcus species of bacteria. In some embodiments a method of protecting bacteria from phage infection comprises protecting a Lactobacillus species of bacteria. In some embodiments a method of protecting bacteria from phage infection comprises protecting a Leuconostoc species of bacteria. In some embodiments a method of protecting bacteria from phage infection comprises protecting a Oenococcus species of bacteria. In some embodiments a method of protecting bacteria from phage infection comprises protecting a Pediococcus species of bacteria. In some embodiments a method of protecting bacteria from phage infection comprises protecting a Bifidobacterium of bacteria. In some embodiments a method of protecting bacteria from phage infection comprises protecting a Propionibacterium species of bacteria.


In some embodiments, bacteria protected in a method of protecting bacteria from plasmid transformation comprises bacteria selected from a Lactococcus species, a Streptococcus species, a Lactobacillus species, a Leuconostoc species, a Oenococcus species, a Pediococcus species, a Bifidobacterium species, and a Propionibacterium species. In some embodiments, bacteria protected in a method of protecting bacteria from plasmid transformation comprises bacteria selected from a Lactococcus species, a Streptococcus species, a Lactobacillus species, a Leuconostoc species, a Oenococcus species, a Pediococcus species, a Bifidobacterium, and a Propionibacterium species. In some embodiments a method of protecting bacteria from plasmid transformation comprises protecting a Lactococcus species of bacteria. In some embodiments a method of protecting bacteria from plasmid transformation comprises protecting a Streptococcus species of bacteria. In some embodiments a method of protecting bacteria from plasmid transformation comprises protecting a Lactobacillus species of bacteria. In some embodiments a method of protecting bacteria from plasmid transformation comprises protecting a Leuconostoc species of bacteria. In some embodiments a method of protecting bacteria from plasmid transformation comprises protecting a Oenococcus species of bacteria. In some embodiments a method of protecting bacteria from plasmid transformation comprises protecting a Pediococcus species of bacteria. In some embodiments a method of protecting bacteria from plasmid transformation comprises protecting a Bifidobacterium of bacteria. In some embodiments a method of protecting bacteria from plasmid transformation comprises protecting a Propionibacterium species of bacteria.


In some embodiments, bacteria protected in a method of protecting bacteria from phage infection and plasmid transformation comprises bacteria selected from a Lactococcus species, a Streptococcus species, a Lactobacillus species, a Leuconostoc species, a Oenococcus species, a Pediococcus species, a Bifidobacterium species, and a Propionibacterium species. In some embodiments, bacteria protected in a method of protecting bacteria from phage infection and plasmid transformation comprises bacteria selected from a Lactococcus species, a Streptococcus species, a Lactobacillus species, a Leuconostoc species, a Oenococcus species, a Pediococcus species, a Bifidobacterium, and a Propionibacterium species. In some embodiments a method of protecting bacteria from phage infection and plasmid transformation comprises protecting a Lactococcus species of bacteria. In some embodiments a method of protecting bacteria from phage infection and plasmid transformation comprises protecting a Streptococcus species of bacteria. In some embodiments a method of protecting bacteria from phage infection and plasmid transformation comprises protecting a Lactobacillus species of bacteria. In some embodiments a method of protecting bacteria from phage infection and plasmid transformation comprises protecting a Leuconostoc species of bacteria. In some embodiments a method of protecting bacteria from phage infection and plasmid transformation comprises protecting a Oenococcus species of bacteria. In some embodiments a method of protecting bacteria from phage infection and plasmid transformation comprises protecting a Pediococcus species of bacteria. In some embodiments a method of protecting bacteria from phage infection and plasmid transformation comprises protecting a Bifidobacterium of bacteria. In some embodiments a method of protecting bacteria from phage infection and plasmid transformation comprises protecting a Propionibacterium species of bacteria.


In some embodiments, a host cell comprises a defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc. In some embodiments, a cell comprises a defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc. In some embodiments, bacteria comprise a defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc.


In some embodiments, a cell comprises a transmissible genetic element comprising a defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc. In some embodiments, bacteria comprise a transmissible genetic element comprising a defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc.


In some embodiments, an expression vector comprises a defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc. In some embodiments, a cell comprises an expression vector comprising a defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc. In some embodiments, bacteria comprise an expression vector comprising a defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc. In some embodiments, an expression vector comprises multiple vectors each comprising a construct comprising a Defense System selected from Ia-Xc. In some embodiments, an expression vector comprises multiple vectors each encoding a polypeptide component or functional portion of a polypeptide component of a Defense System Ia-Xc construct.


In some embodiments, a cell comprising a defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, as disclosed herein, is resistant to at least one phage. In some embodiments, a cell comprising a defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, as disclosed herein, is resistant to plasmid transformation. In some embodiments, a cell comprising a defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, as disclosed herein, is resistant to at least one phage and is resistant to plasmid transformation.


In some embodiments, a cell comprising a transmissible element comprising a defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, as disclosed herein, is resistant to at least one phage. In some embodiments, a cell comprising a transmissible element comprising a defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, as disclosed herein, is resistant to plasmid transformation. In some embodiments, a cell comprising a transmissible element comprising a defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, as disclosed herein, is resistant to at least one phage and is resistant to plasmid transformation.


In some embodiments, a cell comprising an expression vector comprising a defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, as disclosed herein, is resistant to at least one phage. In some embodiments, a cell comprising an expression vector comprising a defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, as disclosed herein, is resistant to plasmid transformation. In some embodiments, a cell comprising an expression vector comprising a defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, as disclosed herein, is resistant to at least one phage and is resistant to plasmid transformation.


Cultures, and starter cultures, in particular are used extensively in the food industry in the manufacture of fermented products including milk products (e.g., yogurt, buttermilk, and cheese), meat products, bakery products, wine, and vegetable products. The preparation of cultures is labor intensive, occupying much space and equipment, and there is a considerable risk of contamination with spoilage bacteria and/or phages during the propagation steps. The failure of bacterial cultures due to phage infection and multiplication is a major problem with the industrial use of bacterial cultures. There are many different types of phages and new strains continue to emerge. Indeed, despite advances in culture development, there is a continuing need to improve cultures for use in industry.


In some embodiments, there is provided a method of preparing a food, the method comprising adding to the food at least one defense system, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, thereby preparing the food. In some embodiments, a food comprises an alcoholic beverage.


In some embodiments, an alcoholic beverage comprises a wine or a sake. In some embodiments, provided herein is a method of preparing an alcoholic beverage, the method comprising adding to the alcoholic beverage at least on defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, thereby preparing the alcoholic beverage. In some embodiments, provided herein is a method of preparing a wine, the method comprising adding to the wine at least on defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, thereby preparing the wine. In some embodiments, provided herein is a method of preparing a sake, the method comprising adding to the sake at least on defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, thereby preparing the sake.


In some embodiments, a food comprises a dairy product. In some embodiments, a dairy product comprises a milk product, a sour milk, a buttermilk, a milk, a cheese, a yogurt, viili, yakult, or casein. In some embodiments, a food comprises natto.


In some embodiments, provided herein is a method of preparing a dairy product, the method comprising adding to the dairy product at least on defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, thereby preparing the dairy product. In some embodiments, provided herein is a method of preparing a milk product, the method comprising adding to the milk product at least on defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, thereby preparing the milk product. In some embodiments, provided herein is a method of preparing milk, the method comprising adding to the milk at least on defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, thereby preparing the milk. In some embodiments, provided herein is a method of preparing a sour milk, the method comprising adding to the sour milk at least on defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, thereby preparing the sour milk. In some embodiments, provided herein is a method of preparing a butter milk, the method comprising adding to the butter milk at least on defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, thereby preparing the butter milk. In some embodiments, provided herein is a method of preparing a cheese, the method comprising adding to the cheese at least on defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, thereby preparing the cheese. In some embodiments, provided herein is a method of preparing a yogurt the method comprising adding to the yogurt at least on defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, thereby preparing the yogurt. In some embodiments, provided herein is a method of preparing a viili the method comprising adding to the viili at least on defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, thereby preparing the viili. In some embodiments, provided herein is a method of preparing a yakult the method comprising adding to the yakult at least on defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, thereby preparing the yakult. In some embodiments, provided herein is a method of preparing a casein, the method comprising adding to the casein at least on defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, thereby preparing the casein.


In some embodiments, provided herein is a method of preparing a natto, the method comprising adding to the natto at least on defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, thereby preparing the natto.


In some embodiments, there is provided a method of preparing a food additive, the method comprising adding to the food additive, at least one defense system components, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, thereby preparing the food additive.


In some embodiments, there is provided a method of preparing a feed, the method comprising adding to the feed at least one defense system components, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, thereby preparing the feed.


In some embodiments, there is provided a method of preparing a nutritional supplement, the method comprising adding to the nutritional supplement at least one defense system components, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, thereby preparing the nutritional supplement.


In some embodiments, there is provided a method of preparing a probiotic supplement, the method comprising adding to the probiotic supplement, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, thereby preparing the probiotic supplement.


In some embodiments, there is provided a method of preparing a health care product, the method comprising adding to the health care product at least one defense system components, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, thereby preparing the health care product. In some embodiments, a health care product comprises an antibiotic.


In some embodiments, there is provided a method of preparing an antibiotic, the method comprising adding to the antibiotic, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, thereby preparing the antibiotic. In some embodiments, an antibiotic comprises a polymyxin, a colistin, or a bacitracin.


In some embodiments, there is provided a method of preparing a polymyxin, the method comprising adding to the polymyxin, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, thereby preparing the polymyxin. In some embodiments, there is provided a method of preparing colistin, the method comprising adding to the colistin, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, thereby preparing the colistin. In some embodiments, there is provided a method of preparing a bacitracin, the method comprising adding to the bacitracin, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, thereby preparing the bacitracin.


In some embodiments, there is provided a method of preparing a personal care product, the method comprising adding to the personal care product at least one defense system components, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, thereby preparing the personal care product.


In some embodiments, there is provided a method of preparing a veterinary product, the method comprising adding to the veterinary product at least one defense system components, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, thereby preparing veterinary product.


In some embodiments, there is provided a method of preparing a L-glutamine, the method comprising adding to the L-glutamine at least one defense system components, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, thereby preparing L-glutamine.


In some embodiments, there is provided a method of preparing acetone, the method comprising adding to the acetone at least one defense system components, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, thereby preparing acetone.


In some embodiments, there is provided a method of preparing butanol, the method comprising adding to the butanol at least one defense system components, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, thereby preparing butanol.


Thus, following the above teachings, in some embodiments, there is provided a food, food additive, feed, nutritional supplement, probiotic supplement, personal care product, health care product and veterinary product comprising at least one components of a defense system, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, as described in details herein. In some embodiments, a food, food additive, feed, nutritional supplement, probiotic supplement, personal care product, health care product and veterinary product comprises at least one functional component of a defense system, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein. In some embodiments, there is provided a food, food additive, feed, nutritional supplement, probiotic supplement, personal care product, health care product and veterinary product comprising a functional defense system, said defense system comprising a functional Defense System selected from Defense Systems Ia-Xc or a combination of functional Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein.


In some embodiments, there is provided a starter culture comprising at least one components of a defense system, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein. In some embodiments, a started culture comprises at least one functional component of a defense system, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein. In some embodiments, there is provided a starter culture comprising a functional defense system, said defense system comprising a functional Defense System selected from Defense Systems Ia-Xc or a combination of functional Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein.


In some embodiments, there is provided a food comprising at least one components of a defense system, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein. In some embodiments, a food comprises at least one functional component of a defense system, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein. In some embodiments, there is provided a food comprising a functional defense system, said defense system comprising a functional Defense System selected from Defense Systems Ia-Xc or a combination of functional Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein.


In some embodiments, a food comprises a dairy product. In some embodiments, a food comprises an alcoholic beverage. In some embodiments, a food comprises a natto.


In some embodiments, there is provided a dairy product comprising at least one components of a defense system, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein. In some embodiments, a dairy product comprises at least one functional component of a defense system, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein. In some embodiments, there is provided a dairy product comprising a functional defense system, said defense system comprising a functional Defense System selected from Defense Systems Ia-Xc or a combination of functional Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein.


In some embodiments, there is provided a milk comprising at least one components of a defense system, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein. In some embodiments, a milk comprises at least one functional component of a defense system, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein. In some embodiments, there is provided a milk comprising a functional defense system, said defense system comprising a functional Defense System selected from Defense Systems Ia-Xc or a combination of functional Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein.


In some embodiments, there is provided a milk product comprising at least one components of a defense system, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein. In some embodiments, a milk product comprises at least one functional component of a defense system, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein. In some embodiments, there is provided a milk product comprising a functional defense system, said defense system comprising a functional Defense System selected from Defense Systems Ia-Xc or a combination of functional Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein.


In some embodiments, there is provided a sour milk comprising at least one components of a defense system, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein. In some embodiments, a sour milk comprises at least one functional component of a defense system, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein. In some embodiments, there is provided a sour milk comprising a functional defense system, said defense system comprising a functional Defense System selected from Defense Systems Ia-Xc or a combination of functional Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein.


In some embodiments, there is provided a butter milk comprising at least one components of a defense system, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein. In some embodiments, a butter milk comprises at least one functional component of a defense system, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein. In some embodiments, there is provided a butter milk comprising a functional defense system, said defense system comprising a functional Defense System selected from Defense Systems Ia-Xc or a combination of functional Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein.


In some embodiments, there is provided a cheese comprising at least one components of a defense system, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein. In some embodiments, a cheese comprises at least one functional component of a defense system, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein. In some embodiments, there is provided a cheese comprising a functional defense system, said defense system comprising a functional Defense System selected from Defense Systems Ia-Xc or a combination of functional Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein.


In some embodiments, there is provided a yogurt comprising at least one components of a defense system, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein. In some embodiments, a yogurt comprises at least one functional component of a defense system, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein. In some embodiments, there is provided a yogurt comprising a functional defense system, said defense system comprising a functional Defense System selected from Defense Systems Ia-Xc or a combination of functional Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein.


In some embodiments, there is provided a viili comprising at least one components of a defense system, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein. In some embodiments, a viili comprises at least one functional component of a defense system, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein. In some embodiments, there is provided a viili comprising a functional defense system, said defense system comprising a functional Defense System selected from Defense Systems Ia-Xc or a combination of functional Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein.


In some embodiments, there is provided a yakult comprising at least one components of a defense system, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein. In some embodiments, a yakult comprises at least one functional component of a defense system, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein. In some embodiments, there is provided a yakult comprising a functional defense system, said defense system comprising a functional Defense System selected from Defense Systems Ia-Xc or a combination of functional Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein.


In some embodiments, there is provided a casein comprising at least one components of a defense system, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein. In some embodiments, a casein comprises at least one functional component of a defense system, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein. In some embodiments, there is provided a casein comprising a functional defense system, said defense system comprising a functional Defense System selected from Defense Systems Ia-Xc or a combination of functional Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein.


In some embodiments, there is provided an alcoholic beverage comprising at least one components of a defense system, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein. In some embodiments, an alcoholic beverage comprises at least one functional component of a defense system, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein. In some embodiments, there is provided an alcoholic beverage comprising a functional defense system, said defense system comprising a functional Defense System selected from Defense Systems Ia-Xc or a combination of functional Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein. In some embodiments, an alcoholic beverage comprises a wine or a sake. In some embodiments, there is provided a wine comprising at least one components of a defense system, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein. In some embodiments, a wine comprises at least one functional component of a defense system, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein. In some embodiments, there is provided a wine comprising a functional defense system, said defense system comprising a functional Defense System selected from Defense Systems Ia-Xc or a combination of functional Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein. In some embodiments, there is provided a sake comprising at least one components of a defense system, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein. In some embodiments, a sake comprises at least one functional component of a defense system, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein. In some embodiments, there is provided a sake comprising a functional defense system, said defense system comprising a functional Defense System selected from Defense Systems Ia-Xc or a combination of functional Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein.


In some embodiments, there is provided a natto comprising at least one components of a defense system, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein. In some embodiments, a natto comprises at least one functional component of a defense system, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein. In some embodiments, there is provided a natto comprising a functional defense system, said defense system comprising a functional Defense System selected from Defense Systems Ia-Xc or a combination of functional Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein.


In some embodiments, there is provided a food additive comprising at least one components of a defense system, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein. In some embodiments, a food additive comprises at least one functional component of a defense system, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein. In some embodiments, there is provided a food additive comprising a functional defense system, said defense system comprising a functional Defense System selected from Defense Systems Ia-Xc or a combination of functional Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein.


In some embodiments, there is provided feed comprising at least one components of a defense system, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein. In some embodiments, feed comprises at least one functional component of a defense system, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein. In some embodiments, there is provided feed comprising a functional defense system, said defense system comprising a functional Defense System selected from Defense Systems Ia-Xc or a combination of functional Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein.


In some embodiments, there is provided a nutritional supplement comprising at least one components of a defense system, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein. In some embodiments, a nutritional supplement comprises at least one functional component of a defense system, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein. In some embodiments, there is provided a nutritional supplement comprising a functional defense system, said defense system comprising a functional Defense System selected from Defense Systems Ia-Xc or a combination of functional Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein.


In some embodiments, there is provided a probiotic supplement comprising at least one components of a defense system, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein. In some embodiments, a probiotic supplement comprises at least one functional component of a defense system, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein. In some embodiments, there is provided a probiotic supplement comprising a functional defense system, said defense system comprising a functional Defense System selected from Defense Systems Ia-Xc or a combination of functional Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein.


In some embodiments, there is provided a health care product comprising at least one components of a defense system, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein. In some embodiments, a health care product comprises at least one functional component of a defense system, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein. In some embodiments, there is provided a health care product comprising a functional defense system, said defense system comprising a functional Defense System selected from Defense Systems Ia-Xc or a combination of functional Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein.


In some embodiments, a health care product comprises an antibiotic. In some embodiments, there is provided an antibiotic comprising at least one components of a defense system, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein. In some embodiments, an antibiotic comprises at least one functional component of a defense system, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein. In some embodiments, there is provided an antibiotic comprising a functional defense system, said defense system comprising a functional Defense System selected from Defense Systems Ia-Xc or a combination of functional Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein.


In some embodiments, an antibiotic comprises a polymyxin, a colistin, or a bacitracin. In some embodiments, there is provided a polymyxin comprising at least one components of a defense system, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein. In some embodiments, a polymyxin comprises at least one functional component of a defense system, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein. In some embodiments, there is provided a polymyxin comprising a functional defense system, said defense system comprising a functional Defense System selected from Defense Systems Ia-Xc or a combination of functional Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein.


In some embodiments, there is provided a colistin comprising at least one components of a defense system, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein. In some embodiments, a colistin comprises at least one functional component of a defense system, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein. In some embodiments, there is provided a colistin comprising a functional defense system, said defense system comprising a functional Defense System selected from Defense Systems Ia-Xc or a combination of functional Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein.


In some embodiments, there is provided a bacitracin comprising at least one components of a defense system, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein. In some embodiments, a bacitracin comprises at least one functional component of a defense system, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein. In some embodiments, there is provided a bacitracin comprising a functional defense system, said defense system comprising a functional Defense System selected from Defense Systems Ia-Xc or a combination of functional Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein.


In some embodiments, there is provided a personal care product comprising at least one components of a defense system, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein. In some embodiments, a personal care product comprises at least one functional component of a defense system, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein. In some embodiments, there is provided a personal care product comprising a functional defense system, said defense system comprising a functional Defense System selected from Defense Systems Ia-Xc or a combination of functional Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein.


In some embodiments, there is provided a veterinary product comprising at least one components of a defense system, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein. In some embodiments, a veterinary product comprises at least one functional component of a defense system, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein. In some embodiments, there is provided a veterinary product comprising a functional defense system, said defense system comprising a functional Defense System selected from Defense Systems Ia-Xc or a combination of functional Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein.


In some embodiments, there is provided a L-glutamine comprising at least one components of a defense system, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein. In some embodiments, a L-glutamine comprises at least one functional component of a defense system, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein. In some embodiments, there is provided a L-glutamine comprising a functional defense system, said defense system comprising a functional Defense System selected from Defense Systems Ia-Xc or a combination of functional Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein.


In some embodiments, there is provided an acetone comprising at least one components of a defense system, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein. In some embodiments, an acetone comprises at least one functional component of a defense system, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein. In some embodiments, there is provided an acetone comprising a functional defense system, said defense system comprising a functional Defense System selected from Defense Systems Ia-Xc or a combination of functional Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein.


In some embodiments, there is provided butanol comprising at least one components of a defense system, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein. In some embodiments, a butanol comprises at least one functional component of a defense system, said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein. In some embodiments, there is provided a butanol comprising a functional defense system, said defense system comprising a functional Defense System selected from Defense Systems Ia-Xc or a combination of functional Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein.


In some embodiments, the nucleic acid construct of the Defense Systems Ia-Xb comprises a regulatory element operably linked to said construct comprising a cis-acting regulatory element for directing expression of said nucleic acid sequence, or a transmissible element for directing transfer of said nucleic acid sequence from one cell to another, or a recombination element for integrating said nucleic acid sequence into a genome of a cell transfected with said construct, or an element providing episomal maintenance of said construct within a cell transfected with said construct, or any combination thereof.


In some embodiments, a method of preparing a food, food additive, feed, nutritional supplement, probiotic supplement, personal care product, health care product and veterinary product, comprises adding to the food, food additive, feed, nutritional supplement, probiotic supplement, personal care product, health care product and veterinary product at least one component selected from the group consisting of the components of the defense system, thereby preparing a food, food additive, feed, nutritional supplement, probiotic supplement, personal care product, health care product and veterinary product. In some embodiments, a method of preparing a food, food additive, feed, nutritional supplement, probiotic supplement, personal care product, health care product and veterinary product comprises introducing into the bacteria a defense system comprising a Defense System selected from a Defense System Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc, wherein said defense system comprises an anti-phage activity, or an anti-plasmid activity, or an anti-phage and an anti-plasmid activity, the system comprising at least one component of said Defense System Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, or Xc, said at least one component selected from the group consisting of the components of the Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, or Xc, respectively, thereby preparing the food, food additive, feed, nutritional supplement, probiotic supplement, personal care product, health care product and veterinary product.


In some embodiments, a method of preparing a food, food additive, feed, nutritional supplement, probiotic supplement, personal care product, health care product and veterinary product comprises introducing into the bacteria a defense system comprising a combination of Defense Systems selected from Defense System Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc, wherein said defense system comprises an anti-phage activity, an anti-plasmid activity, or an anti-phage and an anti-plasmid activity, the system comprising at least one component of each of said Defense Systems in a combination, said at least one component selected from the group consisting of the components of the Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, or Xc, respectively, thereby preparing a food, food additive, feed, nutritional supplement, probiotic supplement, personal care product, health care product and veterinary product.


In some embodiments, an at least one component comprises the components of a Defense System Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, or Xc, required for a functional Defense System, wherein said function comprises an anti-phage activity, an anti-plasmid activity, or an anti-phage and an anti-plasmid activity. In some embodiments, an at least one component comprises the components of the cassette of genes making up a Defense System Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, or Xc. In some embodiments, an at least one component comprises two components of a Defense System Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, or Xc. In some embodiments, an at least one component comprises three components of a Defense System Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, or Xc. In some embodiments, an at least one component comprises four components of a Defense System Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, or Xc. In some embodiments, an at least one component comprises five components of a Defense System Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, or Xc. In some embodiments, a component comprises the full-length component. In some embodiments, a component comprises a functional portion of the component. In some embodiments, a component comprises a component homolog. Defense System components, nucleic acid sequences thereof, and amino acid sequences thereof are presented herein in Table 18.


In some embodiments, for a method of use disclosed herein, the at least one defense system component is comprised in cell (e.g. bacteria) genetically modified to express the component.


In some embodiments, there is provided a method of preparing a food, food additive, feed, nutritional supplement, probiotic supplement, personal care product, health care product and veterinary product, the method comprising adding to the food, food additive, feed, nutritional supplement, probiotic supplement, personal care product, health care product and veterinary product a cell comprising a defense system disclosed herein, thereby preparing the food, food additive, feed, nutritional supplement, probiotic supplement, personal care product, health care product and veterinary product. In some embodiments, said use comprises use of an isolated cell comprising a defense system disclosed herein.


In some embodiments, there is provided a food, food additive, feed, nutritional supplement, probiotic supplement, personal care product, health care product and veterinary product comprising the cell comprising a defense system disclosed herein.


In some embodiments, there is provided a method of preparing a food, food additive, feed, nutritional supplement, probiotic supplement, personal care product, health care product and veterinary product comprising adding to the food, food additive, feed, nutritional supplement, probiotic supplement, personal care product, health care product and veterinary product bacteria which expresses on a transmissible genetic element at least one component of a defense system disclosed herein, wherein said defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc, as described in detail herein, thereby preparing the food, food additive, feed, nutritional supplement, probiotic supplement, personal care product, health care product and veterinary product.


In some embodiments, an at least one component comprises the components of a Defense System Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, or Xc, required for a functional Defense System, wherein said function comprises an anti-phage activity, an anti-plasmid activity, or an anti-phage and an anti-plasmid activity. In some embodiments, an at least one component comprises the components of the cassette of genes making up a Defense System Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, or Xc. In some embodiments, an at least one component comprises two components of a Defense System Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, or Xc. In some embodiments, an at least one component comprises three components of a Defense System Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, or Xc. In some embodiments, an at least one component comprises four components of a Defense System Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, or Xc. In some embodiments, an at least one component comprises five components of a Defense System Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, or Xc. In some embodiments, a component comprises the full-length component. In some embodiments, a component comprises a functional portion of the component. In some embodiments, a component comprises a component homolog. Defense System components, nucleic acid sequences thereof, and amino acid sequences thereof are presented herein in Table 18.


In some embodiments, there is provided a food, food additive, feed, nutritional supplement, probiotic supplement, personal care product, health care product and veterinary product comprising bacteria which expresses on a transmissible genetic element at least one component of a defense system comprising a Defense System selected from Defense Systems Ia-Xc or a combination of Defense Systems selected from Defense Systems Ia-Xc.


In some embodiments, an at least one component comprises the components of a Defense System Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, or Xc, required for a functional Defense System, wherein said function comprises an anti-phage activity, an anti-plasmid activity, or an anti-phage and an anti-plasmid activity. In some embodiments, an at least one component comprises the components of the cassette of genes making up a Defense System Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, or Xc. In some embodiments, an at least one component comprises two components of a Defense System Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, or Xc. In some embodiments, an at least one component comprises three components of a Defense System Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, or Xc. In some embodiments, an at least one component comprises four components of a Defense System Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, or Xc. In some embodiments, an at least one component comprises five components of a Defense System Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, or Xc. In some embodiments, a component comprises the full-length component. In some embodiments, a component comprises a functional portion of the component. In some embodiments, a component comprises a component homolog. Defense System components, nucleic acid sequences thereof, and amino acid sequences thereof are presented herein in Table 18.


In some embodiments, a food or feed disclosed herein, comprises a dairy product. In some embodiments, a food additive comprises an additive to be added to a dairy product or to an ingredient used to prepare a dairy product.


The preparation of starter cultures of such bacteria, and methods of fermenting substrates, particularly food substrates such as milk, can be carried out in accordance with known techniques, including but not limited to those described in Mayra-Makinen and Bigret (1993) Lactic Acid Bacteria; Salminen and vonWright eds. Marcel Dekker, Inc. New York. 65-96; Sandine (1996) Dairy Starter Cultures Cogan and Accolas eds. VCH Publishers, New York. 191-206; Gilliland (1985) Bacterial Starter Cultures for Food. CRC Press, Boca Raton, Fla.


The term “fermenting” refers to the energy-yielding, metabolic breakdown of organic compounds by microorganisms that generally proceeds under anaerobic conditions and with the evolution of gas.


Products produced by fermentation which have been known to experience phage infection, and the corresponding infected fermentation bacteria, include cheddar and cottage cheese (Lactococcus lactis subsp. lactis, Lactococcus lactis subsp. cremoris), yogurt (Lactobacillus delbrueckii subsp. bulgaricus, Streptococcus thermophilus), Swiss cheese (S. thermophilus, Lactobacillus lactis, Lactobacillus helveticus), blue cheese (Leuconostoc cremoris), Italian cheese (L. bulgaricus, S. thermophilus), viili (Lactococcus lactis subsp. cremoris, Lactococcus lactis subsp. lactis biovar diacetylactis, Leuconostoc cremoris), yakult (Lactobacillus casei), casein (Lactococcus lactis subsp. cremoris), natto (Bacillus subtilis var. natto), wine (Leuconostoc oenos), sake (Leuconostoc mesenteroides), polymyxin (Bacillus polymyxa), colistin (Bacillus colistrium), bacitracin (Bacillus licheniformis), L-glutamic acid (Brevibacterium lactofermentum, Microbacterium ammoniaphilum), and acetone and butanol (Clostridium acetobutylicum, Clostridium saccharoperbutylacetonicum).


In some embodiments, provided herein are bacteria resistant to phage infection, said bacteria including but not limited to Lactococcus lactis subsp. lactis, Lactococcus lactis subsp. cremoris Lactobacillus delbrueckii subsp. bulgaricus, Streptococcus thermophilus, S. thermophilus, Lactobacillus lactis, Lactobacillus helveticus, Leuconostoc cremoris, L. bulgaricus, S. thermophilus, Lactococcus lactis subsp. cremoris, Lactococcus lactis subsp. lactis biovar diacetylactis, Leuconostoc cremoris, Lactobacillus casei, Lactococcus lactis subsp. cremoris, Bacillus subtilis var. natto, Leuconostoc oenos, Leuconostoc mesenteroides, polymyxin Bacillus polymyxa, Bacillus colistrium, Bacillus licheniformis, L-Brevibacterium lactofermentum, Microbacterium ammoniaphilum, and acetone and butanol Clostridium acetobutylicum, Clostridium saccharoperbutylacetonicum.


In some embodiments, provided here are starter cultures comprising bacteria resistant to phage infection, said bacteria including but not limited to Lactococcus lactis subsp. lactis, Lactococcus lactis subsp. cremoris Lactobacillus delbrueckii subsp. bulgaricus, Streptococcus thermophilus, S. thermophilus, Lactobacillus lactis, Lactobacillus helveticus, Leuconostoc cremoris, L. bulgaricus, S. thermophilus, Lactococcus lactis subsp. cremoris, Lactococcus lactis subsp. lactis biovar diacetylactis, Leuconostoc cremoris, Lactobacillus casei, Lactococcus lactis subsp. cremoris, Bacillus subtilis var. natto, Leuconostoc oenos, Leuconostoc mesenteroides, polymyxin Bacillus polymyxa, Bacillus colistrium, Bacillus licheniformis, L-Brevibacterium lactofermentum, Microbacterium ammoniaphilum, and acetone and butanol Clostridium acetobutylicum, Clostridium saccharoperbutylacetonicum.


In some embodiments, a method of protecting a bacteria from phage infection, comprises protecting bacteria selected from Lactococcus lactis subsp. lactis, Lactococcus lactis subsp. cremoris Lactobacillus delbrueckii subsp. bulgaricus, Streptococcus thermophilus, S. thermophilus, Lactobacillus lactis, Lactobacillus helveticus, Leuconostoc cremoris, L. bulgaricus, S. thermophilus, Lactococcus lactis subsp. cremoris, Lactococcus lactis subsp. lactis biovar diacetylactis, Leuconostoc cremoris, Lactobacillus casei, Lactococcus lactis subsp. cremoris, Bacillus subtilis var. natto, Leuconostoc oenos, Leuconostoc mesenteroides, polymyxin Bacillus polymyxa, Bacillus colistrium, Bacillus licheniformis, L-Brevibacterium lactofermentum, Microbacterium ammoniaphilum, and acetone and butanol Clostridium acetobutylicum, and Clostridium saccharoperbutylacetonicum.


In some embodiments, a method of protecting a bacteria from plasmid transformation, comprises protecting bacteria selected from Lactococcus lactis subsp. lactis, Lactococcus lactis subsp. cremoris Lactobacillus delbrueckii subsp. bulgaricus, Streptococcus thermophilus, S. thermophilus, Lactobacillus lactis, Lactobacillus helveticus, Leuconostoc cremoris, L. bulgaricus, S. thermophilus, Lactococcus lactis subsp. cremoris, Lactococcus lactis subsp. lactis biovar diacetylactis, Leuconostoc cremoris, Lactobacillus casei, Lactococcus lactis subsp. cremoris, Bacillus subtilis var. natto, Leuconostoc oenos, Leuconostoc mesenteroides, polymyxin Bacillus polymyxa, Bacillus colistrium, Bacillus licheniformis, L-Brevibacterium lactofermentum, Microbacterium ammoniaphilum, and acetone and butanol Clostridium acetobutylicum, and Clostridium saccharoperbutylacetonicum.


In some embodiments, a method of protecting a bacteria from phage infection and plasmid transformation, comprises protecting bacteria selected from Lactococcus lactis subsp. lactis, Lactococcus lactis subsp. cremoris Lactobacillus delbrueckii subsp. bulgaricus, Streptococcus thermophilus, S. thermophilus, Lactobacillus lactis, Lactobacillus helveticus, Leuconostoc cremoris, L. bulgaricus, S. thermophilus, Lactococcus lactis subsp. cremoris, Lactococcus lactis subsp. lactis biovar diacetylactis, Leuconostoc cremoris, Lactobacillus casei, Lactococcus lactis subsp. cremoris, Bacillus subtilis var. natto, Leuconostoc oenos, Leuconostoc mesenteroides, polymyxin Bacillus polymyxa, Bacillus colistrium, Bacillus licheniformis, L-Brevibacterium lactofermentum, Microbacterium ammoniaphilum, and acetone and butanol Clostridium acetobutylicum, and Clostridium saccharoperbutylacetonicum.


In some embodiments, a cell comprising a defense system described herein, comprises a Lactococcus lactis subsp. Lactis cell, a Lactococcus lactis subsp. cremoris cell, a Lactobacillus delbrueckii subsp. bulgaricus cell, a Streptococcus thermophilus cell, a S. thermophilus cell, a Lactobacillus lactis cell, a Lactobacillus helveticus cell, a Leuconostoc cremoris cell, a L. bulgaricus cell, a S. thermophilus cell, a Lactococcus lactis subsp. cremoris cell, a Lactococcus lactis subsp. lactis biovar diacetylactis cell, a Leuconostoc cremoris cell, a Lactobacillus case cell, a, Lactococcus lactis subsp. cremoris cell, a Bacillus subtilis var. natto cell, a Leuconostoc oenos cell, a Leuconostoc mesenteroides cell, a polymyxin Bacillus polymyxa cell, a Bacillus colistrium cell, a Bacillus licheniformis cell, a L-Brevibacterium lactofermentum cell, a Microbacterium ammoniaphilum cell, a Clostridium acetobutylicum cell, and a Clostridium saccharoperbutylacetonicum cell


As exemplified herein below in Examples 1-8, transformation of bacteria with a defense system confers either phage resistance or plasmid resistance to the bacteria. For example, but not limited to the results presented in FIGS. 3B, 3C, 3D, 3E, 5D, and 7C. These results suggest that the use of anti-defense system as a method to induce phage sensitivity.


In some embodiments, addition of nucleic acid sequences to the genome of a bacteria provides phage resistance. In some embodiments, addition of a nucleic acid construct, as disclosed herein, to the genome of a bacteria provides phage resistance. In some embodiments, addition of a nucleic acid construct, as disclosed herein, to the genome of a bacteria comprising Lactococcus lactis subsp. lactis, Lactococcus lactis subsp. cremoris Lactobacillus delbrueckii subsp. bulgaricus, Streptococcus thermophilus, S. thermophilus, Lactobacillus lactis, Lactobacillus helveticus, Leuconostoc cremoris, L. bulgaricus, S. thermophilus, Lactococcus lactis subsp. cremoris, Lactococcus lactis subsp. lactis biovar diacetylactis, Leuconostoc cremoris, Lactobacillus casei, Lactococcus lactis subsp. cremoris, Bacillus subtilis var. natto, Leuconostoc oenos, Leuconostoc mesenteroides, polymyxin Bacillus polymyxa, Bacillus colistrium, Bacillus licheniformis, L-Brevibacterium lactofermentum, Microbacterium ammoniaphilum, and acetone and butanol Clostridium acetobutylicum, Clostridium saccharoperbutylacetonicum, provides phage resistance to the bacteria.


As used herein, “inducing phage sensitivity” refers to an increase of at least 5% in bacterial susceptibility towards a phage, as compared to same in the absence of the defense system agent, as may be manifested e.g. in growth arrest, death or prevention of lysogeny. According to a specific embodiment, the increase is in at least 10%, 20%, 30%, 40% or even higher say, 50%, 60%, 70%, 80%, 90% or more than 100%.


Methods of Identifying Defense Systems

Disclosed herein, in some embodiments is a computational approach to identify new defense systems localized in the vicinity of annotated defense systems.


In some embodiments, there is provided a method for identifying a defense system in a prokaryotic cell, comprising the steps of:

    • (a) selecting, in-silico, a gene located in close proximity to a known defense-related gene family present in a plurality of prokaryotic genomes;
    • (b) analyzing, in-silico, the DNA upstream and downstream of said gene; and
    • (c) identifying, in-silico, a cassette of genes within the upstream and downstream DNA analyzed in step (b) comprising said gene of step (a), wherein said cassette of genes has conserved synteny in said plurality of prokaryotic genomes.


In some embodiments, a method for identifying a defense system comprises the steps of:

    • (a) in-silico selecting a gene in location proximity to an annotated defense system of a plurality of prokaryotic genomes; and
    • (b) in-silico selecting a cassette of genes comprising said gene with conserved synteny in said plurality of prokaryotic genomes.


In some embodiments, the defense system comprises an anti-phage defense system. In some embodiments, the defense system comprises an anti-plasmid defense system. In some embodiments, the defense system comprises an anti-phage defense system and an anti-plasmid defense system.


In some embodiments, a gene in location proximity comprises a gene positioned within less than 10 genes upstream (5′) or 10 genes downstream (3′) to the annotated defense system. In some embodiments, the location proximity is positioned within 10 genes upstream or downstream to said annotated defense system in said prokaryotic genome.


Annotated defense systems are disclosed in scientific papers and databases known to the skilled in the art (see e.g. Makarova et al. J Bacteriol. 2011 November; 193(21): 6039-6056; Swarts et al. Nature (2014) 507, 258-261; and Goldfarb et al. EMBO J. (2015) 34, 169-83]. Non-limiting examples of annotated defense systems that can be used with some embodiments of the methods for identifying defense systems include, but are not limited to surface modifications to prevent adsorption of phages, restriction-modification (RIM) systems, infection (Abi) mechanisms, the CRISPR/Cas adaptive defense system, the prokaryotic argonaute and the BREX system.


In some embodiments, the annotated defense system is selected from the group consisting of a restriction-modification (R/M) system, an infection (Abi) system, a CRISPR/Cas adaptive defense system, a prokaryotic argonaute and a BREX system.


In some embodiments, the plurality comprises at least 2. In some embodiments, the plurality comprises at least 5, at least 10, at least 20, at least 50, at least 100 or at least 500.


A skilled artisan would appreciate that the term “conserved synteny” encompasses a conserved gene order in the genomes of different species.


In some embodiments, the method for identifying a defense system further comprises a step of validating a defensive effect of the selected (identified) cassette of genes.


Validating a defensive effect may be effected in any method known in the art.


In some embodiments, validating the defensive effect is effected by genetically modifying a prokaryotic cell to express the selected cassette of genes and subjecting the prokaryotic cell to phage infection or plasmid transformation, wherein a decrease in phage or plasmid sensitivity below a predetermined threshold as compared to a prokaryotic cell of the same origin not genetically modified to express the selected cassette of genes is indicative of a defensive effect.


In some embodiments, validating the defensive effect is effected by contacting a prokaryotic cell with an agent capable of downregulating expression and/or activity of at least one gene of the selected cassette of genes in a prokaryotic cell and subjecting the prokaryotic cell to phage infection or plasmid transformation, wherein an increase in phage or plasmid sensitivity above a predetermined threshold as compared to a prokaryotic cell of the same origin not contacted with the agent is indicative of a defensive effect.


In some embodiments, the decrease/increase below or above a predetermined threshold is statistically significant.


In some embodiments, the predetermined threshold is at least at least 1.5 fold, at least 2 fold, at least 3 fold, at least 5 fold, at least 10 fold, or at least 20 fold. In some embodiments, the predetermined threshold is at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, e.g., 100%, at least 200%, at least 300%, at least 400%, at least 500%, at least 600%.


A non-limiting example of a method of identifying a defense system, which can be used according to embodiments disclosed herein, is described at least in the Materials and Methods hereinbelow, Example 1, Example 2, and in FIG. 1, which is to be understood as forming an integral part of the present section.


Once selected, the identified cassette of genes comprising said gene with conserved synteny in said plurality of prokaryotic genomes can be cloned or synthesized.


The gene(s) can be ligated into expression constructs and used in a variety of applications e.g., for conferring phage resistance in for example, but not limited to the food, feed, medical and veterinary industries.


In some embodiments, an identified cassette of gene confers phage resistance to a starter culture. In some embodiments, an identified cassette of gene confers phage resistance to a food product. In some embodiments, a food product comprises a dairy product, an alcoholic beverage, or a natto. In some embodiments, an identified cassette of gene confers phage resistance to a dairy product. In some embodiments, an identified cassette of gene confers phage resistance to an alcoholic beverage. In some embodiments, an identified cassette of gene confers phage resistance to a natto.


In some embodiments, an identified cassette of gene confers phage resistance to a milk product. In some embodiments, an identified cassette of gene confers phage resistance to milk. In some embodiments, an identified cassette of gene confers phage resistance to a sour milk. In some embodiments, an identified cassette of gene confers phage resistance to a milk butter milk. In some embodiments, an identified cassette of gene confers phage resistance to a cheese. In some embodiments, an identified cassette of gene confers phage resistance to a yogurt. In some embodiments, an identified cassette of gene confers phage resistance to a viili. In some embodiments, an identified cassette of gene confers phage resistance to yakult. In some embodiments, an identified cassette of gene confers phage resistance to a casein. In some embodiments, an identified cassette of gene confers phage resistance to a wine. In some embodiments, an identified cassette of gene confers phage resistance to a sake. In some embodiments, an identified cassette of gene confers phage resistance to a food additive. In some embodiments, an identified cassette of gene confers phage resistance to a feed. In some embodiments, an identified cassette of gene confers phage resistance to a nutritional supplement. In some embodiments, an identified cassette of gene confers phage resistance to a probiotic supplement. In some embodiments, an identified cassette of gene confers phage resistance to a health care product. In some embodiments, an identified cassette of gene confers phage resistance to an antibiotic. In some embodiments, an identified cassette of gene confers phage resistance to polymyxin. In some embodiments, an identified cassette of gene confers phage resistance to a colistin. In some embodiments, an identified cassette of gene confers phage resistance to a bacitracin. In some embodiments, an identified cassette of gene confers phage resistance to a personal care product. In some embodiments, an identified cassette of gene confers phage resistance to a veterinary product.


Antagonists of Defense Systems and Methods of Use Thereof

In some embodiments, there is provided an antagonist of a defense system disclosed herein, an “anti-defense system agent”. A skilled artisan would appreciate that the terms “anti-defense system agent” and “anti-Defense System agent” and “agent” may in some embodiments, be used interchangeably having all the same elements and qualities. In some embodiments, an anti-defense system agent may antagonize more than one Defense System function. In some embodiments, an anti-defense system agent may antagonize more than one Defense System function, selected from Defense systems Ia-Xc. In some embodiments, an anti-Defense System agent may antagonize more than one Defense System. In some embodiments, an anti-Defense System agent may antagonize more than one Defense System selected from Defense systems Ia-Xc.


In some embodiments, an anti-Defense System agent is capable of down regulating expression and/or activity of at least one Defense System component. In some embodiments, an anti-Defense System agent is capable of down regulating expression and/or activity of at least one Defense System component, wherein said Defense System is selected from Defense Systems Ia-Xc.


In some embodiments, the anti-defense system agent is directed against a defense system component comprising an enzyme activity, for example but not limited to a HamB polypeptide, a SduA polypeptide, a GajA polypeptide, a GajB polypeptide, a PtuA polypeptide, a PtuB polypeptide, a LmuB polypeptide, a ZorD polypeptide, a ZorE polypeptide, a DruE polypeptide, a DruM polypeptide, or a JetC polypeptide. For example, the anti-defense agent may interfere with the expression of an active defense system component or, for example in its DNA methyltransferase function, helicase function, exonuclease function, or endonuclease function. For example, in some embodiments, a methylase activity may be inhibited by the use of common inhibitors of such an enzyme e.g., 5-Azacytidine, Decitabine Zebularine, RG108, Hydralazine hydrochloride, and Psammaplin A.


In some embodiments, an at least one component comprises a component selected from Defense Systems Ia, Ib, II, IIIa, IIIb, IIIc, IV, V, VI, VII, VIII, IX, Xa, Xb, and Xc. In some embodiments, a component comprises a functional component. In some embodiments, a component comprises an essential component. In some embodiments, a component comprises the full-length component. In some embodiments, a component comprises a functional portion of the component.


The components of defense systems comprising a Defense System Ia-Xc and combinations thereof, have been described in detail above. In some embodiments, polypeptide components of these systems include but are not limited to ZorA, ZorB, ZorC, ZorD, ZorE (Defense System Ia and Ib); ThsA and ThsB (Defense System II); DruA, DruB, DruC, DruD, DruE, DruH, DruM, DruG, DruF (Defense Systems IIIa, IIIb, IIIc); HamA and HamB (Defense System IV); SduA (Defense System V); GajA and GajB (Defense System VI); PtuA and PtuB (Defense System VII); LmuA and LmuB (Defense System VIII); KwaA and KwaB (Defense System IX); and JetA, JetB, JetC, and JetD, and variants thereof (Defense Systems Xa, Xb, Xc). In some embodiments, polynucleotide (e.g., gene) components, include but are not limited to zorA, zorB, zorC, zorD, zorE (Defense Systems Ia, Ib); thsA and thsB (Defense System II); druA, druB, druC, drub, druE, druF, druG, druH, druM (Defense Systems IIIa, IIIb, IIIc); hamA and hamB (Defense System IV); sduA (Defense System V); gajA and gajB (Defense System VI); ptuA and ptuB (Defense System VII); lmuA and lmuB (Defense System VIII); kwaA and kwaB (Defense System IX); and jetA, jetB, jetC, and jetD and variants thereof (Defense Systems Xa, Xb, Xc). In some embodiments, a component comprises a component homolog. Defense System components, nucleic acid sequences thereof, and amino acid sequences thereof are presented herein in Table 18.


In some embodiments, a Defense System described herein comprises at least two different polypeptide components. The polypeptide components of the Defense Systems described herein, and the nucleic acids encoding them are described in detail above, and in Tables 8-18. In some embodiments, a Defense System described herein comprises at least three different polypeptide components. In some embodiments, a Defense System described herein comprises at least four different polypeptide components. In some embodiments, a Defense System described herein comprises at least five different polypeptide components. In some embodiments, a Defense System described herein comprises multiple polypeptide components, wherein the components comprise different polypeptides. In some embodiments, a Defense System described herein comprises multiple polypeptide components, wherein the components comprise different polypeptides and duplications of a same polypeptide. In some embodiments, components comprising duplication of a same polypeptide comprise homologues of that polypeptide.


In some embodiments, a Defense System comprising at least two different polypeptide components provides a functional defense activity (protection from foreign nucleic acid) for a cell. In some embodiments, a Defense System described herein comprises at least three different polypeptide components provides a functional defense activity (protection from foreign nucleic acid) for a cell. In some embodiments, a Defense System described herein comprises at least four different polypeptide components provides a functional defense activity (protection from foreign nucleic acid) for a cell. In some embodiments, a Defense System described herein comprises at least five different polypeptide components provides a functional defense activity (protection from foreign nucleic acid) for a cell. In some embodiments, a Defense System described herein comprises multiple polypeptide components, wherein the components comprise different polypeptides, and wherein the Defense System provides a functional defense activity (protection from foreign nucleic acid) for a cell. In some embodiments, a Defense System described herein comprises multiple polypeptide components, wherein the components comprise different polypeptides and duplications of a same polypeptide, wherein said Defense System provides a functional defense activity (protection from foreign nucleic acid) for a cell. In some embodiments, components comprising duplication of a same polypeptide comprise homologues of that polypeptide.


In some embodiments, an agent is capable of down regulating expression and/or activity of at least two components of a defense system. In some embodiments, an agent is capable of down regulating at least one components of at least two different Defense Systems. In some embodiments, an agent is capable of down regulating expression and/or activity of at least two components of a Defense System. In some embodiments, an agent is capable of down regulating at least two components of the same Defense System. In some embodiments, an agent is capable of down regulating expression and/or activity of at least two components of a Defense System selected from the components of Defense Systems Ia-Xc.


In some embodiments, an agent is capable of down regulating expression and/or activity of 1-40 components of a defense system. In some embodiments, an agent is capable of down regulating expression and/or activity of 1-4 components of a defense system. In some embodiments, an agent is capable of down regulating expression and/or activity of 1-5 components of a defense system. In some embodiments, an agent is capable of down regulating expression and/or activity of 1-10 components of a defense system. In some embodiments, an agent is capable of down regulating expression and/or activity of 10-20 components of a defense system. In some embodiments, an agent is capable of down regulating expression and/or activity of 20-30 components of a defense system. In some embodiments, an agent is capable of down regulating expression and/or activity of 30-40 components of a defense system. In some embodiments, an agent is capable of down regulating expression and/or activity of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, or 43 components of a defense system. In some embodiments, an agent is capable of down regulating at least one components of at least two different Defense Systems. In some embodiments, an agent is capable of down regulating expression and/or activity of at least two components of a Defense System. In some embodiments, an agent is capable of down regulating at least two components of the same Defense System. In some embodiments, an agent is capable of down regulating expression and/or activity of at least two components of a Defense System selected from the components of Defense Systems Ia-Xc.


A skilled artisan would recognize that the phrase “anti-Defense agent” encompasses an agent capable of specifically inhibiting the expression of a target Defense System gene (at the DNA or RNA level) or alternatively specifically impairing the functionality of the target Defense System protein. In some embodiments, an agent is capable of specifically inhibiting the expression of a target Defense System component (at the DNA or RNA level) or alternatively specifically impairing the functionality of the target Defense System component polypeptide.


In some embodiments, the anti-Defense system agent is directed against one of the Defense System components. In some embodiments, the anti-Defense System agent is directed against multiple components of a Defense System. In some embodiments, the anti-Defense System agent is directed against at least 2 components of a Defense System. In some embodiments, the anti-Defense System agent is directed against at least 3 components of a Defense System. In some embodiments, the anti-Defense System agent is directed against at least 4 components of a Defense System. In some embodiments, the anti-Defense System agent is directed against at least 5 components of a Defense System.


In some embodiments, the anti-Defense system agent is directed against any of the components disclosed in Table 18. In some embodiments, the anti-Defense system agent is directed against any combination of the components disclosed in Table 18. In some embodiments, the combination of components may be from a same Defense System selected from Defense Systems Ia-Xc. In some embodiments, the combination of components may be from different Defense Systems selected from Defense Systems Ia-Xc. In some embodiments, the combination of components may be from the same and different Defense Systems selected from Defense Systems Ia-Xc.


In some embodiments, the agent is directed against all of the components of a single Defense System. In some embodiments, the agent is directed against all of the essential components of a single Defense System. In some embodiments, the agent is directed against all of the components of a single Defense System selected from Defense Systems Ia-Xc. In some embodiments, the agent is directed against all of the essential components of a single Defense System, selected from Defense Systems Ia-Xc.


Down regulation of a Defense System can be effected on the genomic and/or the transcript level using a variety of molecules that interfere with transcription and/or translation (e.g., RNA silencing agents), or on the protein level using e.g., aptamers, small molecules and inhibitory peptides, antagonists, enzymes that cleave the polypeptide and the like.


In some embodiments the anti-Defense System agent is selected from the group consisting of a nucleic acid suitable for silencing expression, aptamers, small molecules and inhibitory peptides.


A skilled artisan would appreciate that the phrase “nucleic acid suitable for silencing expression” refers to regulatory mechanisms mediated by nucleic acid molecules, which result in the inhibition or “silencing” of the expression of a corresponding protein-coding gene.


Methods for qualifying efficacy and detecting inhibition or “silencing” of the expression of a corresponding protein-coding gene are well known in the art and include, but are not limited to, DNA sequencing, electrophoresis, an enzyme-based mismatch detection assay and hybridization assay such as PCR, RT-PCR, RNase protection, in-situ hybridization, primer extension, Southern blot, Northern Blot and dot blot analysis. Inhibition or “silencing” of the expression of a specific protein-coding gene can also be determined at the protein level using e.g. chromatography, electrophoretic methods, immunodetection assays such as ELISA and Western blot analysis or immunohistochemistry. In addition, one ordinarily skilled in the art can readily design a knock-in/knock-out construct including positive and/or negative selection markers for efficiently selecting transformed cells that e.g. underwent a homologous recombination event with the construct.


In some embodiments, downregulation can be achieved by DNA silencing.


Methods of introducing nucleic acid alterations to a gene of interest are well known in the art [see for example Menke D. Genesis (2013) 51: 618; Capecchi, Science (1989) 244:1288-1292; Santiago et al. Proc Natl Acad Sci USA (2008) 105:5809-5814; International Patent Application Nos. WO 2014085593, WO 2009071334 and WO 2011146121; U.S. Pat. Nos. 8,771,945, 8,586,526, 6,774,279 and UP Patent Application Publication Nos. 20030232410, 20050026157, US20060014264; the contents of which are incorporated by reference in their entireties] and include targeted homologous recombination, site specific recombinases, PB transposases and genome editing by engineered nucleases.


Non-limiting examples of DNA silencing agents that can be used In some embodiments include: the “Hit and run” or “in-out” strategy; the “double-replacement” or “tag and exchange” strategy; site-specific recombinases such as, but not limited to, cre recombinase and Flp recombinase; genome editing using engineered endonucleases such as, but not limited to, meganucleases, Zinc finger nucleases (ZFNs), transcription-activator like effector nucleases (TALENs) and CRISPR/Cas system; transposases; and genome editing using recombinant adeno-associated virus (rAAV) platform.


It will be appreciated that the agent can be a mutagen that causes random mutations and the cells exhibiting downregulation of the expression level and/or activity of a component or components of a Defense System disclosed herein, for example but not limited to the components and Defense Systems disclosed in Table 18. The mutagens may be, but are not limited to, genetic, chemical or radiation agents.


Downregulation can also be achieved by RNA silencing.


In certain embodiments, the RNA silencing agent is capable of preventing complete processing (e.g., the full translation and/or expression) of an mRNA molecule through a post-transcriptional silencing mechanism. RNA silencing agents include non-coding RNA molecules, for example RNA duplexes comprising paired strands, as well as precursor RNAs from which such small non-coding RNAs can be generated. Exemplary RNA silencing agents include dsRNAs such as siRNAs, miRNAs and shRNAs.


In some embodiments, the RNA silencing agent is capable of inducing RNA interference. In some embodiments, the RNA silencing agent is capable of mediating translational repression.


In some embodiments, the RNA silencing agent is specific to the target RNA of a component of a Defense System disclosed herein, and does not cross inhibit or silence other targets or a splice variant which exhibits 99% or less global homology to the target gene, e.g., less than 98%, 97%, 96%, 95%, 94%, 93%, 92%, 91%, 90%, 89%, 88%, 87%, 86%, 85%, 84%, 83%, 82%, 81% global homology to the target gene; as determined by PCR, Western blot, Immunohistochemistry and/or flow cytometry.


Non-limiting examples of RNA silencing agents that can be used in some embodiments include but are not limited to antisense, DsRNA, siRNA, shRNA, miRNA and miRNA mimics.


Numerous methods are known in the art for gene silencing particularly in prokaryotes; examples include but are not limited to U.S. Patent Application 20040053289 which teaches the use of si hybrids to down-regulate prokaryotic genes, and U.S. Patent Application PCT/US09/69258 which teaches the use of CRISPR to downregulate prokaryotic genes.


In some embodiments, the inhibition can be carried out at the protein level which interferes with protein activity, such as by the use of aptamers. Various methods are known in the art which can be used to design protein specific aptamers. The skilled artisan can employ SELEX (Systematic Evolution of Ligands by Exponential Enrichment) for efficient selection as described in Stoltenburg R, Reinemann C, and Strehlitz B (Biomolecular engineering (2007) 24(4):381-403).


In some embodiments, a small molecule, peptides or antibodies can be used which interfere with the Defense System component(s) protein function (e.g., catalytic or interaction).


In some embodiments, an anti-Defense agent comprises any molecule which binds to and/or cleaves a Defense System component gene or component polypeptide. Such molecules can be, for example, a small molecule, antagonists, or inhibitory peptide.


It will be appreciated that a non-functional analogue of at least a catalytic or binding portion of a Defense System polypeptide component can be also used as an anti-Defense System agent.


In some embodiments, there is provided a method of inducing phage sensitivity in bacteria, the method comprising introducing the agent disclosed herein into bacteria, which expresses a defense system having an anti-phage activity, said system comprising at least one component selected from the group consisting of said component polypeptides of said Defense System, thereby inducing sensitivity of the bacteria to phage infection.


In some embodiments, there is provided a method of killing bacteria, the method comprising introducing into bacteria, which expresses a defense system having an anti-phage activity, as described herein, an anti-defense system agent capable of down regulating expression and/or activity of a component polypeptide of the defense system, thereby killing the bacteria.


In another embodiment, there is provided an isolated anti-defense system agent capable of down regulating expression and/or activity of at least two defense system components. In some embodiments, the bacteria express the at least one Defense System component for which the anti-Defense System agent is directed against.


In some embodiments, the method further comprises infecting said bacteria with a phage.


Specifically, introducing an anti-Defense System agent is effected such that the positioning of the anti-Defense System agent is in direct or indirect contact with the bacterial cell. In some embodiments, both applying the anti-Defense System agent or agents disclosed herein to a desirable surface and/or directly to the bacterial cells. In some embodiments, the surface is comprised in a biological tissue, such as for example, mammalian tissues e.g. the skin.


It will be appreciated that the bacteria may be comprised inside a particular organism, (e.g. intracellularly or extracellularly) for example inside a mammalian body or inside a plant. In this case, the introducing may be effected by administering the anti-Defense System agent per se or by transfecting the cells of the organism with the anti-Defense System agents.


In some embodiments, introducing with an anti-Defense System agent is effected in-vivo. In some embodiments, introducing with an anti-Defense System agent is effected ex-vivo. In some embodiments, introducing with an anti-Defense System agent is effected in-vitro.


In some embodiments, there is provided isolated bacteria generated by introducing into bacteria an anti-Defense System agent as described above. In some embodiments, there is provided isolated bacteria generated by introducing into the bacteria an anti-Defense System agent in-vitro or ex-vivo.


Thus, following the above teachings there is provided isolated bacteria comprising the anti-Defense System agent.


According to some embodiments, a Defense System or an anti-Defense System agent is provided in a formulation suitable for cell penetration that enhances intracellular delivery of the system or the agent.


Any suitable penetrating agent for enhancing penetration of a Defense System or its components or an anti-Defense System agent to cell (e.g., bacteria) may be used, as known by those of skill in the art. Examples include but are not limited to:


Phages—Phages offer several advantages including lateral infection, higher efficiency of transformation, and targeting to, and propagation in, specific bacteria.


Cell-Penetrating Peptides (CPPs)—CPPs, for example TAT (transcription activator from HIV-1) are short peptides (≤40 amino acids), with the ability to gain access to the interior of almost any cell. They are highly cationic and usually rich in arginine and lysine amino acids. They have the exceptional property of carrying into the cells a wide variety of covalently and noncovalently conjugated cargoes such as proteins, oligonucleotides, and even 200 nm liposomes. Protocols for producing CPPs-cargos conjugates and for infecting cells with such conjugates can be found, for example L. Theodore et al. [The Journal of Neuroscience, (1995) 15(11): 7158-7167], Fawell S, et al. [Proc Natl Acad Sci USA, (1994) 91:664-668], and Jing Bian et al. [Circulation Research. (2007) 100: 1626-1633].


The expression level and/or activity level of the Defense System components expressed in the cells of some embodiments can be determined using methods known in the arts, e.g. but not limited to selectable marker gene, Northern blot analysis, PCR analysis, DNA sequencing, RNA sequencing, Western blot analysis or Immunohistochemistry.


In some embodiments, there is provided a method of treating bacterial infection in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of the anti-Defense System agent, thereby treating the bacterial infection in the subject. In some embodiments, there is provided the agent, for use in the treatment of bacterial infection in a subject in need thereof.


A skilled artisan would appreciate that the term “treating” encompasses in some embodiments, curing, reversing, attenuating, alleviating, minimizing, suppressing or halting the deleterious effects of a pathogen infection. Those of skill in the art will understand that various methodologies and assays can be used to assess the development of the pathology, and similarly, various methodologies and assays may be used to assess the reversal, attenuation, alleviation or suppression of the pathology.


In some embodiments, a “subject in need thereof” includes but is not limited to mammals. In some embodiments, the subject comprises a human being of any gender and at any age which suffer from pathogen infection.


The anti-Defense System agent may be used alone or together with additional antimicrobial agents (e.g. phage therapy, antibiotic and/or additional anti-microbial peptides).


In some embodiments, a method disclosed herein further comprises administering to the subject a phage therapy and/or an antibiotic. In some embodiments, the uses further comprise a phage therapy and/or an antibiotic.


In some embodiments, antibiotics include, but are not limited to aminoglycoside antibiotics, cephalosporins, quinolone antibiotics, macrolide antibiotics, penicillin, sulfonamides, tetracyclines and carbapenems. It will be appreciated that since the agents disclosed herein, enhance the anti-bacterial effect of the antibiotic, doses of the antibiotic may be lower (e.g. 20% lower, 30% lower, 40% lower, 50% lower, 60% lower, 70% lower, 80% lower or even 90% lower) than those currently in use.


In the context of manufacturing of food products and especially fermented products in the food industry, an anti-Defense System agent can be used to eliminate spoilage bacteria or the end product from traces of used bacteria.


Thus, in some embodiments, there is provided a method of preparing a food, food additive, feed, nutritional supplement, probiotic supplement, personal care product, health care product and veterinary product, the method comprising adding to the food, food additive, feed, nutritional supplement, probiotic supplement, personal care product, health care product and veterinary product the anti-Defense System agent, thereby preparing the food, food additive, feed, nutritional supplement, probiotic supplement, personal care product, health care product and veterinary product.


Following the above teachings there is provided a food, food additive, feed, nutritional supplement, probiotic supplement, personal care product, health care product and veterinary product comprising the anti-Defense System agent.


The nucleic acid sequences, constructs, transmissible elements, polypeptides and cells comprising the Defense System components or the anti-Defense System agent of some embodiments, can be administered to a starter culture, a fermentation vat or an organism per se, or in a composition where it is mixed with suitable carriers or excipients.


The phrase “pharmaceutical composition” as used herein refers to a preparation of one or more of the active ingredients described herein with other chemical components such as physiologically suitable carriers and excipients. The purpose of a pharmaceutical composition is to facilitate administration of a compound to an organism.


Hereinafter, the phrases “physiologically acceptable carrier” and “pharmaceutically acceptable carrier” which may be interchangeably used refer to a carrier or a diluent that does not cause significant irritation to an organism and does not abrogate the biological activity and properties of the administered compound. An adjuvant is included under these phrases.


Herein, the term “excipient” refers to an inert substance added to a pharmaceutical composition to further facilitate administration of an active ingredient. Examples, without limitation, of excipients include calcium carbonate, calcium phosphate, various sugars and types of starch, cellulose derivatives, gelatin, vegetable oils, and polyethylene glycols.


As used herein the term “active ingredient” refers to any one of the component polypeptides or polynucleotides of a Defense System, an anti-Defense System agent, or cells generated according to the methods disclosed herein, accountable for the biological effect.


Techniques for formulation and administration of drugs may be found in the latest edition of “Remington's Pharmaceutical Sciences,” Mack Publishing Co., Easton, Pa., which is herein fully incorporated by reference and are further described herein below.


It will be appreciated that the polypeptides, polynucleotides, nucleic acid construct(s) or other agents can be provided to the individual with additional active agents to achieve an improved therapeutic effect as compared to treatment with each agent by itself.


In some embodiments, additional agents include phage therapy and antibiotics (e.g. rifampicin, chloramphenicol and spectinomycin).


In some embodiments, the composition further comprises a phage.


Suitable routes of administration may, for example, include oral, rectal, transmucosal, especially transnasal, intestinal or parenteral delivery, including intramuscular, subcutaneous and intramedullary injections as well as intrathecal, direct intraventricular, intracardiac, e.g., into the right or left ventricular cavity, into the common coronary artery, intravenous, intraperitoneal, intranasal, or intraocular injections.


Conventional approaches for drug delivery to the central nervous system (CNS) include: neurosurgical strategies (e.g., intracerebral injection or intracerebroventricular infusion); molecular manipulation of the agent (e.g., production of a chimeric fusion protein that comprises a transport peptide that has an affinity for an endothelial cell surface molecule in combination with an agent that is itself incapable of crossing the BBB) in an attempt to exploit one of the endogenous transport pathways of the BBB; pharmacological strategies designed to increase the lipid solubility of an agent (e.g., conjugation of water-soluble agents to lipid or cholesterol carriers); and the transitory disruption of the integrity of the BBB by hyperosmotic disruption (resulting from the infusion of a mannitol solution into the carotid artery or the use of a biologically active agent such as an angiotensin peptide). However, each of these strategies has limitations, such as the inherent risks associated with an invasive surgical procedure, a size limitation imposed by a limitation inherent in the endogenous transport systems, potentially undesirable biological side effects associated with the systemic administration of a chimeric molecule comprised of a carrier motif that could be active outside of the CNS, and the possible risk of brain damage within regions of the brain where the BBB is disrupted, which renders it a suboptimal delivery method.


Alternately, one may administer the pharmaceutical composition in a local rather than systemic manner, for example, via injection of the pharmaceutical composition directly into a tissue region of a patient.


Pharmaceutical compositions may be manufactured by processes well known in the art, e.g., by means of conventional mixing, dissolving, granulating, dragee-making, levigating, emulsifying, encapsulating, entrapping or lyophilizing processes.


Pharmaceutical compositions for use in accordance with the disclosure herein, may be formulated in conventional manner using one or more physiologically acceptable carriers comprising excipients and auxiliaries, which facilitate processing of the active ingredients into preparations which, can be used pharmaceutically. Proper formulation is dependent upon the route of administration chosen.


For injection, the active ingredients may be formulated in aqueous solutions, preferably in physiologically compatible buffers such as Hank's solution, Ringer's solution, or physiological salt buffer. For transmucosal administration, penetrants appropriate to the barrier to be permeated are used in the formulation. Such penetrants are generally known in the art.


For oral administration, the compounds can be formulated readily by combining the active compounds with pharmaceutically acceptable carriers well known in the art. Such carriers enable the compounds to be formulated as tablets, pills, dragees, capsules, liquids, gels, syrups, slurries, suspensions, and the like, for oral ingestion by a patient. Pharmacological preparations for oral use can be made using a solid excipient, optionally grinding the resulting mixture, and processing the mixture of granules, after adding suitable auxiliaries if desired, to obtain tablets or dragee cores. Suitable excipients are, in particular, fillers such as sugars, including lactose, sucrose, mannitol, or sorbitol; cellulose preparations such as, for example, maize starch, wheat starch, rice starch, potato starch, gelatin, gum tragacanth, methyl cellulose, hydroxypropylmethyl-cellulose, sodium carbomethylcellulose; and/or physiologically acceptable polymers such as polyvinylpyrrolidone (PVP). If desired, disintegrating agents may be added, such as cross-linked polyvinyl pyrrolidone, agar, or alginic acid or a salt thereof such as sodium alginate.


Dragee cores are provided with suitable coatings. For this purpose, concentrated sugar solutions may be used which may optionally contain gum arabic, talc, polyvinyl pyrrolidone, carbopol gel, polyethylene glycol, titanium dioxide, lacquer solutions and suitable organic solvents or solvent mixtures. Dyestuffs or pigments may be added to the tablets or dragee coatings for identification or to characterize different combinations of active compound doses.


Pharmaceutical compositions, which can be used orally, include push-fit capsules made of gelatin as well as soft, sealed capsules made of gelatin and a plasticizer, such as glycerol or sorbitol. The push-fit capsules may contain the active ingredients in admixture with filler such as lactose, binders such as starches, lubricants such as talc or magnesium stearate and, optionally, stabilizers. In soft capsules, the active ingredients may be dissolved or suspended in suitable liquids, such as fatty oils, liquid paraffin, or liquid polyethylene glycols. In addition, stabilizers may be added. All formulations for oral administration should be in dosages suitable for the chosen route of administration.


For buccal administration, the compositions may take the form of tablets or lozenges formulated in conventional manner.


For administration by nasal inhalation, the active ingredients for use according to the disclosure herein are conveniently delivered in the form of an aerosol spray presentation from a pressurized pack or a nebulizer with the use of a suitable propellant, e.g., dichlorodifluoromethane, trichlorofluoromethane, dichloro-tetrafluoroethane or carbon dioxide. In the case of a pressurized aerosol, the dosage unit may be determined by providing a valve to deliver a metered amount. Capsules and cartridges of, e.g., gelatin for use in a dispenser may be formulated containing a powder mix of the compound and a suitable powder base such as lactose or starch.


The preparations described herein may be formulated for parenteral administration, e.g., by bolus injection or continuous infusion. Formulations for injection may be presented in unit dosage form, e.g., in ampoules or in multidose containers with optionally, an added preservative. The compositions may be suspensions, solutions or emulsions in oily or aqueous vehicles, and may contain formulatory agents such as suspending, stabilizing and/or dispersing agents.


Pharmaceutical compositions for parenteral administration include aqueous solutions of the active preparation in water-soluble form. Additionally, suspensions of the active ingredients may be prepared as appropriate oily or water based injection suspensions. Suitable lipophilic solvents or vehicles include fatty oils such as sesame oil, or synthetic fatty acids esters such as ethyl oleate, triglycerides or liposomes. Aqueous injection suspensions may contain substances, which increase the viscosity of the suspension, such as sodium carboxymethyl cellulose, sorbitol or dextran. Optionally, the suspension may also contain suitable stabilizers or agents which increase the solubility of the active ingredients to allow for the preparation of highly concentrated solutions.


Alternatively, the active ingredient may be in powder form for constitution with a suitable vehicle, e.g., sterile, pyrogen-free water based solution, before use.


The preparation may also be formulated in rectal compositions such as suppositories or retention enemas, using, e.g., conventional suppository bases such as cocoa butter or other glycerides.


The preparation may also be formulated as a topical composition, such as a spray, a cream, a mouthwash, a wipe, a foam, a soap, an oil, a solution, a lotion, an ointment, a paste, a gel and a patch.


Pharmaceutical compositions suitable for use in context include compositions wherein the active ingredients are contained in an amount effective to achieve the intended purpose. More specifically, a therapeutically effective amount means an amount of active ingredients effective to prevent, alleviate or ameliorate symptoms of disease (e.g., bacterial infection) or prolong the survival of the subject being treated.


Determination of a therapeutically effective amount is well within the capability of those skilled in the art.


For any preparation used in the methods disclosed herein, the therapeutically effective amount or dose can be estimated initially from in vitro assays. For example, a dose can be formulated in animal models and such information can be used to more accurately determine useful doses in humans.


Toxicity and therapeutic efficacy of the active ingredients described herein can be determined by standard pharmaceutical procedures in vitro, in cell cultures or experimental animals. The data obtained from these in vitro and cell culture assays and animal studies can be used in formulating a range of dosage for use in human. The dosage may vary depending upon the dosage form employed and the route of administration utilized. The exact formulation, route of administration and dosage can be chosen by the individual physician in view of the patient's condition. [See e.g., Fingl, et al., (1975) “The Pharmacological Basis of Therapeutics”, Ch. 1 p. 1].


Depending on the severity and responsiveness of the condition to be treated, dosing can be of a single or a plurality of administrations, with course of treatment lasting from several days to several weeks or until cure is effected or diminution of the disease state is achieved.


The amount of a composition to be administered will, of course, be dependent on e.g. the subject being treated, the severity of the affliction, the manner of administration, the judgment of the prescribing physician, etc.


Compositions of some embodiments, may, if desired, be presented in a pack or dispenser device, such as an FDA approved kit, which may contain one or more unit dosage forms containing the active ingredient. The pack may, for example, comprise metal or plastic foil, such as a blister pack. The pack or dispenser device may be accompanied by instructions for administration. The pack or dispenser may also be accommodated by a notice associated with the container in a form prescribed by a governmental agency regulating the manufacture, use or sale of pharmaceuticals, which notice is reflective of approval by the agency of the form of the compositions or human or veterinary administration. Such notice, for example, may be of labeling approved by the U.S. Food and Drug Administration for prescription drugs or of an approved product insert. Compositions comprising a preparation formulated in a compatible pharmaceutical carrier may also be prepared, placed in an appropriate container, and labeled for treatment of an indicated condition, as is further detailed above.


In some embodiments, there is provided an article of manufacture or a kit identified for treating bacterial infection comprising the anti-Defense System agent; and a phage and/or an antibiotic. In some embodiments, the anti-Defense System agent and the phage and/or the antibiotic are packaged in separate containers. In some embodiments, the anti-Defense System agent and the phage and/or the antibiotic are in co-formulation.


In some embodiments, there is provided a method of screening for identifying phage useful for infecting bacteria, the method comprising:


(a) contacting a phage with bacteria expressing a Defense System; and


(b) determining deleterious effects induced in said bacteria, wherein an increase in deleterious effects of said bacteria in the presence of said phage compared to deleterious effects in the absence of said phage is indicative of a phage useful for infecting said bacteria.


In some embodiments, the method comprising further isolating the phage, characterizing it in terms of sequencing and compatibility with phages species and the ability to infect different bacterial species.


Use of a Defense System or Components Thereof, for Gene Editing

In some embodiments, disclosed herein is a method of gene editing, the method comprising contacting a nucleic acid sequence with a defense system component, as described herein, wherein said contact edits a gene sequence within the nucleic acid. In some embodiments, said editing comprises deleting a gene, deleting a portion of a gene, deleting upstream regulatory sequences of a gene, deleting downstream regulatory sequences of a gene, deleting upstream and downstream regulatory sequences of a gene, repairing a gene sequence, replacing a gene, replacing a part of a gene, replacing an upstream sequence of a gene, replacing a downstream sequence of a gene, replacing an upstream and a downstream sequence of a gene, modifying a gene sequence, modifying a sequence upstream of a gene, modifying a sequence downstream of a gene, modifying a sequence upstream and downstream of a gene, or a combination thereof.


In some embodiments, use of a defense system component, as described herein, for gene editing provides greater precision in editing a nucleotide sequence. In some embodiments, gene editing provides greater precision of cutting the nucleotide sequence at a cleavage site. In some embodiments, gene editing comprising cutting the nucleic acid sequence at a specific cleavage site. In some embodiments, gene editing comprising cutting the nucleic acid sequence based on the modification of nucleotides within the nucleic acid. In some embodiments, gene editing comprising inhibition of cutting the nucleic acid sequence based on the modification of nucleotides within the nucleic acid. In some embodiments, cleavage comprises cleavage of the phosphodiester bond within a nucleotide sequence. In some embodiments, cleavage is ATP dependent.


In some embodiments, use of a defense system component, as described herein, for gene editing provides separation of two annealed nucleic acid strands. In some embodiments, gene editing comprises separation of double stranded DNA. In some embodiments, gene editing comprises separation of double stranded RNA. In some embodiments, gene editing comprises separation of a double stranded RNA-DNA hybrid. In some embodiments, separation uses energy derived from ATP hydrolysis. In some embodiments, separation of a double stranded sequence is based on the specific sequence of the double stranded sequence. In some embodiments, separation of a double stranded sequence is based on the methylation pattern within the double stranded sequence. In some embodiments, separation of a double stranded sequence is based on the modification pattern within the double stranded sequence.


In some embodiments, use of a defense system component, as described herein, for gene editing provides unwinding of a double stranded nucleic acid sequence one base at a time. In some embodiments, unwinding is of a double stranded DNA. In some embodiments, unwinding is of a double stranded RNA. In some embodiments, unwinding is of a hybrid double stranded RNA-DNA. In some embodiments, unwinding uses energy derived from ATP hydrolysis. In some embodiments, unwinding of a double stranded sequence is based on the specific sequence of the double stranded sequence. In some embodiments, unwinding of a double stranded sequence is based on the methylation pattern within the double stranded sequence. In some embodiments, unwinding of a double stranded sequence is based on the modification pattern within the double stranded sequence.


In some embodiments, use of a defense system component, as described herein, for gene editing provides cleaving nucleotides one at a time from the end of a polynucleotide chain. In some embodiments, the polynucleotide change comprises DNA. In some embodiments, the polynucleotide chain comprises RNA. In some embodiments, the polynucleotide chain comprises a hybrid RNA-DNA construct. In some embodiments, cleavage is based on the specific sequence of the double stranded sequence. In some embodiments, cleavage is based on the methylation pattern within the double stranded sequence. In some embodiments, cleavage is based on the modification pattern within the double stranded sequence.


In some embodiments, use of a defense system component, as described herein, for gene editing provides overwinding or underwinding of DNA. In some embodiments, the overwinding or underwinding comprises cleavage of the phosphate backbone of one of the DNA strands. In some embodiments, the overwinding or underwinding comprises cleavage of the phosphagen backbone of both of the DNA strands. In some embodiments, overwinding or underwinding is based on the specific sequence of the double stranded sequence. In some embodiments, overwinding or underwinding is based on the methylation pattern within the double stranded sequence. In some embodiments, overwinding or underwinding is based on the modification pattern within the double stranded sequence.


In some embodiments, modifications comprise methylation and acetylation. In some embodiments, methylation comprises methylation of adenine bases. In some embodiments, methylation comprises methylation of cytosine bases.


In some embodiments, gene editing comprises cutting the nucleic acid sequence based on the methylation pattern of the nucleic acid. In some embodiments, gene editing comprising cutting the nucleic acid sequence based on the lack of methylation of the nucleic acid. In some embodiments, gene editing comprises inhibition of cutting the nucleic acid sequence based on the methylation pattern of the nucleic acid. In some embodiments, gene editing comprising inhibition of cutting the nucleic acid sequence based on the lack of methylation of the nucleic acid.


A skilled artisan would appreciate that the terms “cutting” and “cleaving” may be used interchangeably in some embodiments, having all the qualities and meanings.


In some embodiments, cutting a nucleic acid sequence comprises cleavage of a single stranded nucleic acid. In some embodiments, cutting a nucleic acid sequence comprises cleavage of a double stranded nucleic acid. In some embodiments, cutting a nucleic acid sequence comprises cleavage of a DNA molecule. In some embodiments, cutting a nucleic acid sequence comprises cleavage of an RNA molecule.


In some embodiments, cutting a nucleic acid sequence comprises recognizing a specific nucleotide sequence. In some embodiments, cutting a nucleic acid sequence comprises recognizing a specific pattern of methylation of a nucleotide sequence. In some embodiments, editing comprising inhibiting cleavage of a nucleic acid sequence, wherein said inhibition of cleavage comprises recognizing a specific pattern of methylation of the nucleotide sequence.


In some embodiments, the nucleotide sequence being edited is comprised in a cell. In some embodiments, the nucleotide sequence being edited is not comprised within a cell. In some embodiments, editing of a nucleotide sequence within a cell, comprises genetically engineering the cell.


In some embodiments, genetic engineering of a cell comprises deleting a gene, deleting a portion of a gene, deleting upstream regulatory sequences of a gene, deleting downstream regulatory sequences of a gene, deleting upstream and downstream regulatory sequences of a gene, repairing a gene sequence, replacing a gene, replacing a part of a gene, replacing an upstream sequence of a gene, replacing a downstream sequence of a gene, replacing an upstream and a downstream sequence of a gene, modifying a gene sequence, modifying a sequence upstream of a gene, modifying a sequence downstream of a gene, modifying a sequence upstream and downstream of a gene, or a combination thereof, within the cell.


In some embodiments, a cell comprises a eukaryotic cell. In some embodiments, a cell comprises a prokaryotic cell. In some embodiments, a cell comprises a plant cell. In some embodiments, a cell comprises a yeast cell. In some embodiments, a cell comprises a protozoa cell.


In some embodiments, genetic engineering of a cell provides cells useful in treating a disease.


In some embodiments, genetic engineering of a plant cell provides for improved plant growth. In some embodiments, genetic engineering of a plant cell provides for improved plant growth under adverse conditions, including but not limited to extreme heat, extreme cold, drought, high salt content, lack of nutrients, or any combination thereof. In some embodiments, genetic engineering of a plant cell provides for higher crop yield. In some embodiments, genetic engineering of a plant cell provides for higher crop yield under adverse conditions, including but not limited to extreme heat, extreme cold, drought, high salt content, lack of nutrients, or any combination thereof.


In some embodiments, gene editing provides improved identification and validation of therapeutic agents. In some embodiments, gene editing provides improved development and production of animal models of human disease. In some embodiments, uses of gene editing leading to improvements comprises performing the work in a shorter amount of time and with more precision.


In some embodiments, a method of gene editing a nucleic acid sequence comprises contacting the nucleic acid sequence with a component of a defense system as described herein, thereby editing the nucleic acid sequence. In some embodiments, a method of cutting a nucleic acid sequence comprises contacting the nucleic acid sequence with a component of a defense system as described herein, thereby cutting the nucleic acid sequence.


Components of defense systems have been described in detail here (Tables 7-17 and 18).


In some embodiments, a method of editing a nucleic acid sequence comprises contacting the nucleic acid sequence with a component of a Defense System Ia, said component comprising a ZorA polypeptide, a ZorB polypeptide, a ZorC polypeptide, or a ZorD polypeptide, thereby editing the nucleic acid sequence.


In some embodiments, a method of editing a nucleic acid sequence comprises contacting the nucleic acid sequence with a component of a Defense System Ib, said component comprising a ZorA polypeptide, a ZorB polypeptide, or a ZorD polypeptide, thereby editing the nucleic acid sequence.


In some embodiments, a method of editing a nucleic acid sequence comprises contacting the nucleic acid sequence with a component of a Defense System II, said component comprising a ThsA polypeptide or a ThsB polypeptide, thereby editing the nucleic acid sequence.


In some embodiments, a method of editing a nucleic acid sequence comprises contacting the nucleic acid sequence with a component of a Defense System IIIa, said component comprising a DruA polypeptide, a DruB polypeptide, a DruC polypeptide, a DruD polypeptide, or a DruE polypeptide, thereby editing the nucleic acid sequence.


In some embodiments, a method of editing a nucleic acid sequence comprises contacting the nucleic acid sequence with a component of a Defense System IIIb, said component comprising a DruM polypeptide, a DruF polypeptide, a DruG polypeptide, or a DruE polypeptide, thereby editing the nucleic acid sequence.


In some embodiments, a method of editing a nucleic acid sequence comprises contacting the nucleic acid sequence with a component of a Defense System IIIc, said component comprising a DruH polypeptide, or a DruE polypeptide, thereby editing the nucleic acid sequence.


In some embodiments, a method of editing a nucleic acid sequence comprises contacting the nucleic acid sequence with a component of a Defense System IV, said component comprising a HamA polypeptide or a HamB polypeptide, thereby editing the nucleic acid sequence.


In some embodiments, a method of editing a nucleic acid sequence comprises contacting the nucleic acid sequence with a component of a Defense System V, said component comprising a SduA polypeptide, thereby editing the nucleic acid sequence.


In some embodiments, a method of editing a nucleic acid sequence comprises contacting the nucleic acid sequence with a component of a Defense System VI, said component comprising a GajA polypeptide or a GajB polypeptide, thereby editing the nucleic acid sequence.


In some embodiments, a method of editing a nucleic acid sequence comprises contacting the nucleic acid sequence with a component of a Defense System VII, said component comprising a PtuA polypeptide or a PtuB polypeptide, thereby editing the nucleic acid sequence.


In some embodiments, a method of editing a nucleic acid sequence comprises contacting the nucleic acid sequence with a component of a Defense System VIII, said component comprising a LmuA polypeptide or a LmuB polypeptide, thereby editing the nucleic acid sequence.


In some embodiments, a method of editing a nucleic acid sequence comprises contacting the nucleic acid sequence with a component of a Defense System IX, said component comprising a KwaA polypeptide or a KwaB polypeptide, thereby editing the nucleic acid sequence.


In some embodiments, a method of editing a nucleic acid sequence comprises contacting the nucleic acid sequence with a component of a Defense System Xa, said component comprising a JetA polypeptide, a JetB polypeptide, a JetC polypeptide, or a JetD polypeptide, thereby editing the nucleic acid sequence.


In some embodiments, a method of editing a nucleic acid sequence comprises contacting the nucleic acid sequence with a component of a Defense System Xb, said component comprising a JetAii polypeptide, a JetBii polypeptide, a JetCii polypeptide, or a JetDii polypeptide, thereby editing the nucleic acid sequence.


In some embodiments, a method of editing a nucleic acid sequence comprises contacting the nucleic acid sequence with a component of a Defense System Xc, said component comprising a JetAiii polypeptide, a JetBiii polypeptide, a JetCiii polypeptide, or a JetDii polypeptide, thereby editing the nucleic acid sequence.


In some embodiments, a method of editing a nucleic acid sequence comprises editing said sequence within a cell. One skilled in the art would appreciate that a method of editing a nucleic acid sequence within a cell comprises in some embodiments, expressing a component of a defense system in the cell. Genes encoding the components of defense systems described herein, have been described in detail (Tables 7-17 and 18).


In some embodiments, contacting the nucleic acid sequence with the defense system component can be performed by any in vitro conditions including for example, adding a defense system polypeptide to a naked nucleic acid sequence, adding a defense system polypeptide to a cell expressing the nucleic acid sequence, or introducing a defense system gene nucleotide sequence into a cell and expressing the gene sequence, such that the defense system component is in or comes into direct contact with the nucleic acid sequence to be edited.


The contacting may be effected with at least 1, at least 2, at least 3, or at least 4 defense system components.


In some embodiments, the contacting is effected with a ZorA, ZorB, ZorC, or ZorD polypeptide, or any combination thereof. In some embodiments, the contacting is effected with a ZorA, ZorB, or ZorE polypeptide, or any combination thereof. In some embodiments, the contacting is effected with a ThsA or a ThsB polypeptide, or any combination thereof. In some embodiments, the contacting is effected with a DruA, DruB, DruC, DruD, or DruE polypeptide, or any combination thereof. In some embodiments, the contacting is effected with a DruM, DruF, DruG, or DruE polypeptide, or any combination thereof. In some embodiments, the contacting is effected with a DruH or a DruE polypeptide, or any combination thereof. In some embodiments, the contacting is effected with a HamA or a HamB polypeptide, or any combination thereof. In some embodiments, the contacting is affected with a SduA polypeptide, or any combination thereof. In some embodiments, the contacting is effected with a GajA or a GajB polypeptide, or any combination thereof. In some embodiments, the contacting is effected with a PtuA or a PtuB polypeptide, or any combination thereof. In some embodiments, the contacting is affected with a Lmu or a LmuB polypeptide, or any combination thereof. In some embodiments, the contacting is effected with a KwaA or a KwaB polypeptide, or any combination thereof. In some embodiments, the contacting is effected with a JetA, JetB, JetC, or JetD polypeptide, or any combination thereof. In some embodiments, the contacting is effected with a JetAii, JetBii, JetCii, or JetDii polypeptide, or any combination thereof. In some embodiments, the contacting is effected with a JetAiii, JetBiii, JetCiii, or JetDiii polypeptide, or any combination thereof.


In some embodiments, the nucleic acid sequence being edited is comprised in a cell. In some embodiments, the nucleic acid sequence being edited is comprised in a cell that is not expressing an endogenous defense system or components thereof. In some embodiments, the nucleic acid sequence being edited is comprised in a cell that is not expressing an endogenous functional defense system or components thereof.


In some embodiments, the nucleic acid sequence being edited is not comprised in a cell expressing an endogenous defense system or components thereof. In some embodiments, the nucleic acid sequence being edited is not comprised in a cell expressing an endogenous functional defense system or components thereof.


In some embodiments, wherein the nucleic acid being edited is comprised in a cell expressing a component polypeptide of a defense system, the method further comprises introducing into the cell an agent capable of downregulating expression and/or activity of the expressed component polypeptide.


In some embodiments, a method of editing a nucleic acid sequence within a cell comprises expressing a component of a Defense System Ia within said cell, said component comprising a ZorA polypeptide, a ZorB polypeptide, a ZorC polypeptide, or a ZorD polypeptide, thereby editing the nucleic acid sequence.


In some embodiments, a method of editing a nucleic acid sequence within a cell comprises expressing a component of a Defense System Ib within said cell, said component comprising a ZorA polypeptide, a ZorB polypeptide, or a ZorD polypeptide, thereby editing the nucleic acid sequence.


In some embodiments, a method of editing a nucleic acid sequence within a cell comprises expressing a component of a Defense System II within said cell, said component comprising a ThsA polypeptide or a ThsB polypeptide, thereby editing the nucleic acid sequence.


In some embodiments, a method of editing a nucleic acid sequence within a cell comprises expressing a component of a Defense System IIIa within said cell, said component comprising a DruA polypeptide, a DruB polypeptide, a DruC polypeptide, a DruD polypeptide, or a DruE polypeptide, thereby editing the nucleic acid sequence.


In some embodiments, a method of editing a nucleic acid sequence within a cell comprises expressing a component of a Defense System IIIb within said cell, said component comprising a DruM polypeptide, a DruF polypeptide, a DruG polypeptide, or a DruE polypeptide, thereby editing the nucleic acid sequence.


In some embodiments, a method of editing a nucleic acid sequence within a cell comprises expressing a component of a Defense System IIIc within said cell, said component comprising a DruH polypeptide, or a DruE polypeptide, thereby editing the nucleic acid sequence.


In some embodiments, a method of editing a nucleic acid sequence within a cell comprises expressing a component of a Defense System IV within said cell, said component comprising a HamA polypeptide or a HamB polypeptide, thereby editing the nucleic acid sequence.


In some embodiments, a method of editing a nucleic acid sequence within a cell comprises expressing a component of a Defense System V within said cell, said component comprising a SduA polypeptide, thereby editing the nucleic acid sequence.


In some embodiments, a method of editing a nucleic acid sequence within a cell comprises expressing a component of a Defense System VI within said cell, said component comprising a GajA polypeptide or a GajB polypeptide, thereby editing the nucleic acid sequence.


In some embodiments, a method of editing a nucleic acid sequence within a cell comprises expressing a component of a Defense System VII within said cell, said component comprising a PtuA polypeptide or a PtuB polypeptide, thereby editing the nucleic acid sequence.


In some embodiments, a method of editing a nucleic acid sequence within a cell comprises expressing a component of a Defense System VIII within said cell, said component comprising a LmuA polypeptide or a LmuB polypeptide, thereby editing the nucleic acid sequence.


In some embodiments, a method of editing a nucleic acid sequence within a cell comprises expressing a component of a Defense System IX within said cell, said component comprising a KwaA polypeptide or a KwaB polypeptide, thereby editing the nucleic acid sequence.


In some embodiments, a method of editing a nucleic acid sequence within a cell comprises expressing a component of a Defense System Xa within said cell, said component comprising a JetA polypeptide, a JetB polypeptide, a JetC polypeptide, or a JetD polypeptide, thereby editing the nucleic acid sequence.


In some embodiments, a method of editing a nucleic acid sequence within a cell comprises expressing a component of a Defense System Xb within said cell, said component comprising a JetAii polypeptide, a JetBii polypeptide, a JetCii polypeptide, or a JetDii polypeptide, thereby editing the nucleic acid sequence.


In some embodiments, a method of editing a nucleic acid sequence within a cell comprises expressing a component of a Defense System Xc within said cell, said component comprising a JetAiii polypeptide, a JetBiii polypeptide, a JetCiii polypeptide, or a JetDii polypeptide, thereby editing the nucleic acid sequence.


In some embodiments, a method of editing a nucleic acid sequence within a cell comprises expressing a gene encoding a component of a Defense System Ia within said cell, said gene comprising a zorA gene, a zorB gene, a zorC gene, or a zorD gene, thereby editing the nucleic acid sequence.


In some embodiments, a method of editing a nucleic acid sequence within a cell comprises expressing a gene encoding a component of a Defense System Ib within said cell, said gene comprising a zorA gene, a zorB gene, or a zorD gene, thereby editing the nucleic acid sequence.


In some embodiments, a method of editing a nucleic acid sequence within a cell comprises expressing a gene encoding a component of a Defense System II within said cell, said gene comprising a thsA gene or a thsB gene, thereby editing the nucleic acid sequence.


In some embodiments, a method of editing a nucleic acid sequence within a cell comprises expressing a gene encoding a component of a Defense System IIIa within said cell, said gene comprising a druA gene, a druB gene, a druC gene, a druD polypeptide, or a druE gene, thereby editing the nucleic acid sequence.


In some embodiments, a method of editing a nucleic acid sequence within a cell comprises expressing a gene encoding a component of a Defense System IIIb within said cell, said gene comprising a druM gene, a druF gene, a druG gene, or a druE gene, thereby editing the nucleic acid sequence.


In some embodiments, a method of editing a nucleic acid sequence within a cell comprises expressing a gene encoding a component of a Defense System IIIc within said cell, said gene comprising a druH gene, or a druE gene, thereby editing the nucleic acid sequence.


In some embodiments, a method of editing a nucleic acid sequence within a cell comprises expressing a gene encoding a component of a Defense System IV within said cell, said gene comprising a hamA gene or a hamB gene, thereby editing the nucleic acid sequence.


In some embodiments, a method of editing a nucleic acid sequence within a cell comprises expressing a gene encoding a component of a Defense System V within said cell, said gene comprising a sduA gene, thereby editing the nucleic acid sequence.


In some embodiments, a method of editing a nucleic acid sequence within a cell comprises expressing a gene encoding a component of a Defense System VI within said cell, said gene comprising a gajA gene or a gajB gene, thereby editing the nucleic acid sequence.


In some embodiments, a method of editing a nucleic acid sequence within a cell comprises expressing a gene encoding a component of a Defense System VII within said cell, said gene comprising a ptuA gene or a ptuB gene, thereby editing the nucleic acid sequence.


In some embodiments, a method of editing a nucleic acid sequence within a cell comprises expressing a gene encoding a component of a Defense System VIII within said cell, said gene comprising a lmuA gene or a lmuB gene, thereby editing the nucleic acid sequence.


In some embodiments, a method of editing a nucleic acid sequence within a cell comprises expressing a gene encoding a component of a Defense System IX within said cell, said gene comprising a kwaA gene or a kwaB gene, thereby editing the nucleic acid sequence.


In some embodiments, a method of editing a nucleic acid sequence within a cell comprises expressing a gene encoding a component of a Defense System Xa within said cell, said gene comprising a jetA gene, a jetB gene, a jetC gene, or a jetD gene, thereby editing the nucleic acid sequence.


In some embodiments, a method of editing a nucleic acid sequence within a cell comprises expressing a gene encoding a component of a Defense System Xb within said cell, said gene comprising a jetAii gene, a jetBii gene, a jetCii gene, or a jetDii gene, thereby editing the nucleic acid sequence.


In some embodiments, a method of editing a nucleic acid sequence within a cell comprises expressing a gene encoding a component of a Defense System Xc within said cell, said gene comprising a jetAiii gene, a jetBiii gene, a jetCiii gene, or a jetDiii gene, thereby editing the nucleic acid sequence.


In some embodiments, the nucleic acid sequence being editing is not comprised in a cell expressing the defense system component. In some embodiments, the nucleic acid sequence being editing is not comprised in a cell expression a defense system polypeptide component comprising a ZorA, ZorB, ZorC, ZorD, ZorE, ThsA, ThsB, DruA, DruB, DruC, DruD, DruE, DruM, DruF, DruG, DruH, HamA, HamB, SduA, GajA, GajB, PtuA, PtuB, LmuA, LmuB, KwaA, KwaB, JetA, JetB, JetC, JetD, JetAii, JetBii, JetCii, JetDii, JetAiii, JetBiii, JetCiii, or JetDiii polypeptide.


In some embodiments, the nucleic acid sequence being editing is not comprised in a cell expressing a defense system gene encoding the polypeptide component, said gene comprising a zorA, zorB, zorC, zorD, zorE, thsA, thsB, druA, druB, druC, druD, druE, druM, druF, druG, druH, hamA, hamB, sduA, gajA, gajB, ptuA, ptuB, lmuA, lmuB, kwaA, kwaB, jetA, jetB, jetC, jetD, jetAii, jetBii, jetCii, jetDii, jetAiii, jetBiii, jetCiii, or jetDiii gene.


In some embodiments, the nucleic acid sequence being editing is not comprised in a cell expressing a functional defense system component. In some embodiments, the nucleic acid sequence being editing is not comprised in a cell expression a functional defense system polypeptide component comprising a ZorA, ZorB, ZorC, ZorD, ZorE, ThsA, ThsB, DruA, DruB, DruC, DruD, DruE, DruM, DruF, DruG, DruH, HamA, HamB, SduA, GajA, GajB, PtuA, PtuB, LmuA, LmuB, KwaA, KwaB, JetA, JetB, JetC, JetD, JetAii, JetBii, JetCii, JetDii, JetAiii, JetBiii, JetCiii, or JetDiii.


In some embodiments, the nucleic acid sequence being editing is not comprised in a cell expressing a functional defense system gene encoding the polypeptide component, said gene comprising a zorA, zorB, zorC, zorD, zorE, thsA, thsB, druA, druB, druC, druD, druE, druM, druF, druG, druH, hamA, hamB, sduA, gajA, gajB, ptuA, ptuB, lmuA, lmuB, kwaA, kwaB, jetA, jetB, jetC, jetD, jetAii, jetBii, jetCii, jetDii, jetAiii, jetBiii, jetCiii, or jetDiii gene.


In some embodiments, there is provided a method of cloning an expression product of interest, the method comprising:


(a) introducing into a nucleic acid construct a polynucleotide encoding the expression product of interest and a defense system component comprising a nucleic acid cleavage activity, or an unwinding activity; and


(b) further introducing into said nucleic acid construct an additional at least one component of the defense system, thereby cloning the expression product of interest.


In some embodiments, step (b) comprises introducing into said nucleic acid construct any other component of the defense system. In some embodiments, step (b) comprises introducing into said nucleic acid construct all other component of the defense system. In some embodiments, step (b) comprises introducing into said nucleic acid construct component of the defense system to form a functional defense system. According to some embodiments the cell does not express an endogenous defense system. In some embodiments, the nucleic acid sequence being edited is not comprised in a cell expressing an endogenous functional version of the defense system.


In a non-limited example, in some embodiments, there is provided a method of cloning an expression product of interest, the method comprising:


(a) introducing into a nucleic acid construct a polynucleotide encoding the expression product of interest and a DruM; and


(b) introducing into said nucleic acid construct a Druantia (Type II) system component selected from the group consisting of: a DruF polypeptide; a DruG polypeptide; and a DruE polypeptide; or any combination thereof, thereby cloning the expression product of interest.


According to some embodiments the cell does not express an endogenous Druantia system. In some embodiments, the nucleic acid sequence being edited is not comprised in a cell expressing an endogenous functional Druantia (Type II) system.


As used herein the term “about” refers to ±10%


As used herein, the singular form “a”, “an” and “the” include plural references unless the context clearly dictates otherwise. For example, the term “a compound” or “at least one compound” may include a plurality of compounds, including mixtures thereof.


Throughout this application, various embodiments are disclosed that may be presented in a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope. Accordingly, the description of a range should be considered to have specifically disclosed all the possible subranges as well as individual numerical values within that range. For example, description of a range such as from 1 to 6 should be considered to have specifically disclosed subranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6 etc., as well as individual numbers within that range, for example, 1, 2, 3, 4, 5, and 6. This applies regardless of the breadth of the range.


Whenever a numerical range is indicated herein, it is meant to include any cited numeral (fractional or integral) within the indicated range. The phrases “ranging/ranges between” a first indicate number and a second indicate number and “ranging/ranges from” a first indicate number “to” a second indicate number are used herein interchangeably and are meant to include the first and second indicated numbers and all the fractional and integral numerals therebetween.


As used herein the term “method” refers to manners, means, techniques and procedures for accomplishing a given task including, but not limited to, those manners, means, techniques and procedures either known to, or readily developed from known manners, means, techniques and procedures by practitioners of the chemical, pharmacological, biological, biochemical and medical arts.


When reference is made to particular sequence listings, such reference is to be understood to also encompass sequences that substantially correspond to its complementary sequence as including minor sequence variations, resulting from, e.g., sequencing errors, cloning errors, or other alterations resulting in base substitution, base deletion or base addition, provided that the frequency of such variations is less than 1 in 50 nucleotides, alternatively, less than 1 in 100 nucleotides, alternatively, less than 1 in 200 nucleotides, alternatively, less than 1 in 500 nucleotides, alternatively, less than 1 in 1000 nucleotides, alternatively, less than 1 in 5,000 nucleotides, alternatively, less than 1 in 10,000 nucleotides.


EXAMPLES

Reference is now made to the following examples, which together with the above descriptions illustrate some embodiments in a non-limiting fashion.


Generally, the nomenclature used herein, and the laboratory procedures utilized, include molecular, biochemical, microbiological and recombinant DNA techniques. Such techniques are thoroughly explained in the literature. See, for example, “Molecular Cloning: A laboratory Manual” Sambrook et al., (1989); “Current Protocols in Molecular Biology” Volumes I-III Ausubel, R. M., ed. (1994); Ausubel et al., “Current Protocols in Molecular Biology”, John Wiley and Sons, Baltimore, Md. (1989); Perbal, “A Practical Guide to Molecular Cloning”, John Wiley & Sons, New York (1988); Watson et al., “Recombinant DNA”, Scientific American Books, New York; Birren et al. (eds) “Genome Analysis: A Laboratory Manual Series”, Vols. 1-4, Cold Spring Harbor Laboratory Press, New York (1998); methodologies as set forth in U.S. Pat. Nos. 4,666,828; 4,683,202; 4,801,531; 5,192,659 and 5,272,057; “Cell Biology: A Laboratory Handbook”, Volumes I-III Cellis, J. E., ed. (1994); “Culture of Animal Cells—A Manual of Basic Technique” by Freshney, Wiley-Liss, N.Y. (1994), Third Edition; “Current Protocols in Immunology” Volumes I-III Coligan J. E., ed. (1994); Stites et al. (eds), “Basic and Clinical Immunology” (8th Edition), Appleton & Lange, Norwalk, Conn. (1994); Mishell and Shiigi (eds), “Selected Methods in Cellular Immunology”, W. H. Freeman and Co., New York (1980); available immunoassays are extensively described in the patent and scientific literature, see, for example, U.S. Pat. Nos. 3,791,932; 3,839,153; 3,850,752; 3,850,578; 3,853,987; 3,867,517; 3,879,262; 3,901,654; 3,935,074; 3,984,533; 3,996,345; 4,034,074; 4,098,876; 4,879,219; 5,011,771 and 5,281,521; “Oligonucleotide Synthesis” Gait, M. J., ed. (1984); “nucleic Acid Hybridization” Hames, B. D., and Higgins S. J., eds. (1985); “Transcription and Translation” Hames, B. D., and Higgins S. J., eds. (1984); “Animal Cell Culture” Freshney, R. I., ed. (1986); “Immobilized Cells and Enzymes” IRL Press, (1986); “A Practical Guide to Molecular Cloning” Perbal, B., (1984) and “Methods in Enzymology” Vol. 1-317, Academic Press; “PCR Protocols: A Guide To Methods And Applications”, Academic Press, San Diego, Calif. (1990); Marshak et al., “Strategies for Protein Purification and Characterization—A Laboratory Course Manual” CSHL Press (1996); all of which are incorporated by reference as if fully set forth herein. Other general references are provided throughout this document. The procedures therein are well known in the art and are provided for the convenience of the reader. All the information contained therein is incorporated herein by reference.


Materials and Methods

Computational Prediction of Defense Systems


A Set of Gene Families Known to Participate in Defense:


A set of pfams and COGs that are known to participate in anti-phage defense was compiled based on the gene families present in Table S10 from Makarova et al. (2011) Defense islands in bacterial and archaeal genomes and prediction of novel defense systems. J Bacteriol. 193: 6039-56, with the addition of pfams/COGs present in the BREX (Goldfarb T, et al. (2015) BREX is a novel phage resistance system widespread in microbial genomes. EMBO J. EMBO Press; 34: 169-83) and DISARM (Ofir G, et al. (2017) DISARM is a widespread bacterial defense system with broad anti-phage activities. Nat Microbiology 2017 doi: 10.1038/s41564-017-0051-0). This set is found in Table 1.









TABLE 1







Known Defense-associated gene families














Used in








prediction

Defense

Defense
Variability


Family
cycle #
Source
system type
Annotation/Comments
score
score
















pfam12183
1
Makarova et
RM
Restriction endonuclease NotI
95.9%
0.38




al. (2011)1






pfam12161
1
Makarova et
RM
HsdM N-terminal domain
93.4%
0.21




al. (2011)






pfam12008
1
Makarova et
RM
Type I restriction and
85.7%
0.19




al. (2011)

modification enzyme-subunit








R C terminal




pfam11663
1
Makarova et
TA
Toxin with endonuclease
75.5%
0.14




al. (2011)

activity YhaV




pfam11487
1
Makarova et
RM
Type II restriction enzyme
pfam < 20
pfam < 20




al. (2011)

SfiI
members
members


pfam11455
1
Makarova et
new_system
Protein of unknown function
97.1%
0.10




al. (2011)

(DUF3018); probable








antitoxin associated with








Toxin COG2337




pfam11198
1
Makarova et
new_system
Protein of unknown function
80.0%
0.14




al. (2011)

(DUF2857), associated with








COG1475, Spo0J




pfam11171
1
Makarova et
new_RM
Protein of unknown function
79.5%
0.34




al. (2011)

(DUF2958), fused to








Methylase, helicase




pfam10832
1
Makarova et
TA
Protein of unknown function
96.8%
0.03




al. (2011)

(DUF2559), TA system








component YhfG




pfam10784
1
Makarova et
TA
Plasmid stability protein
55.1%
0.20




al. (2011)






pfam10593
1
Makarova et
RM
Z1 domain
95.3%
0.42




al. (2011)






pfam10592
1
Makarova et
Abi
AIPR protein; abortive
72.4%
0.39




al. (2011)

infection phage resistance








protein often found in








restriction modification








system operons; PMID:








18346280




pfam10544
1
Makarova et
RM
Type III restriction enzyme,
55.1%
0.35




al. (2011)

res subunit




pfam10543
1
Makarova et
new_system
ORF6N domain
55.9%
0.26




al. (2011)






pfam10387
1
Makarova et
new_TA
Xre family, TA; Protein of
59.3%
0.42




al. (2011)

unknown function (DUF2442)




pfam10047
1
Makarova et
TA
Protein of unknown function
86.9%
0.53




al. (2011)

(DUF2281), same as








COG2442 (wHTH)




pfam10040
1
Makarova et
CRISPR
RAMP, CRISPR related;
94.6%
0.34




al. (2011)

Uncharacterized conserved








protein (DUF2276)




pfam09957
1
Makarova et
TA
RHH; Uncharacterized
96.9%
0.06




al. (2011)

protein conserved in bacteria








(DUF2191); Bacterial








antitoxin of type II TA








system, VapB




pfam09827
1
Makarova et
CRISPR
CRISPR associated protein
93.0%
0.31




al. (2011)

Cas2




pfam09823
1
Makarova et
new_system
Domain of unknown function
69.1%
0.52




al. (2011)

(DUF2357) (often fused to








recB-like nuclease domain GI:








218891088)




pfam09720
1
Makarova et
TA
Putative addiction module
81.8%
0.44




al. (2011)

component




pfam09709
1
Makarova et
CRISPR
CRISPR-associated protein
97.4%
0.27




al. (2011)

(Cas_Csd1)




pfam09707
1
Makarova et
CRISPR
CRISPR-associated protein
98.3%
0.16




al. (2011)

(Cas_Cas2CT1978)




pfam09706
1
Makarova et
CRISPR
CRISPR-associated protein
99.4%
0.33




al. (2011)

(Cas_CXXC_CXXC)




pfam09704
1
Makarova et
CRISPR
CRISPR-associated protein
99.2%
0.25




al. (2011)

(Cas_Cas5)




pfam09703
1
Makarova et
CRISPR
CRISPR-associated protein
100.0%
0.58




al. (2011)

(Cas_Csa4)




pfam09702
1
Makarova et
CRISPR
CRISPR-associated protein
71.1%
0.72




al. (2011)

(Cas_Csa5)




pfam09701
1
Makarova et
CRISPR
CRISPR-associated protein
99.5%
0.69




al. (2011)

(Cas_Cmr5)




pfam09700
1
Makarova et
CRISPR
CRISPR-associated protein
98.2%
0.65




al. (2011)

(Cas_Cmr3)




pfam09670
1
Makarova et
CRISPR
CRISPR-associated protein
89.8%
0.76




al. (2011)

(Cas_Cas02710)




pfam09665
1
Makarova et
RM
Type II restriction
97.4%
0.18




al. (2011)

endonuclease








(RE_Alw26IDE)




pfam09659
1
Makarova et
CRISPR
CRISPR-associated protein
78.8%
0.13




al. (2011)

(Cas_Csm6)




pfam09658
1
Makarova et
CRISPR
CRISPR-associated protein
pfam < 20
pfam < 20




al. (2011)

(Cas_Csx9)
members
members


pfam09657
1
Makarova et
CRISPR
CRISPR-associated protein
99.2%
0.33




al. (2011)

Csx8 (Cas_Csx8)




pfam09652
1
Makarova et
CRISPR
Putative CRISPR-associated
94.5%
0.86




al. (2011)

protein (Cas_VVA1548)




pfam09651
1
Makarova et
CRISPR
CRISPR-associated protein
93.0%
0.76




al. (2011)

(Cas_APE2256)




pfam09623
1
Makarova et
CRISPR
CRISPR-associated protein
89.2%
0.79




al. (2011)

NE0113 (Cas_NE0113)




pfam09620
1
Makarova et
CRISPR
CRISPR-associated protein
91.4%
0.82




al. (2011)

(Cas_c5x3)




pfam09618
1
Makarova et
CRISPR
CRISPR-associated protein
98.3%
0.21




al. (2011)

(Cas_Csy4)




pfam09617
1
Makarova et
CRISPR
CRISPR-associated protein
95.9%
0.47




al. (2011)

GSU0053 (Cas_GSU0053)




pfam09615
1
Makarova et
CRISPR
CRISPR-associated protein
99.7%
0.21




al. (2011)

(Cas_Csy3)




pfam09614
1
Makarova et
CRISPR
CRISPR-associated protein
99.8%
0.19




al. (2011)

(Cas_Csy2)




pfam09611
1
Makarova et
CRISPR
CRISPR-associated protein
98.6%
0.17




al. (2011)

(Cas_Csy1)




pfam09609
1
Makarova et
CRISPR
CRISPR-associated protein,
95.0%
0.47




al. (2011)

GSU0054 family








(Cas_GSU0054)




pfam09573
1
Makarova et
RM
TaqI restriction endonuclease
85.5%
0.51




al. (2011)






pfam09572
1
Makarova et
RM
XamI restriction endonuclease
92.3%
0.36




al. (2011)






pfam09571
1
Makarova et
RM
XcyI restriction endonuclease
91.0%
0.51




al. (2011)






pfam09569
1
Makarova et
RM
ScaI restriction endonuclease
97.7%
0.33




al. (2011)






pfam09568
1
Makarova et
RM
MjaI restriction endonuclease
85.0%
0.34




al. (2011)






pfam09565
1
Makarova et
RM
NgoFVII restriction
95.1%
0.42




al. (2011)

endonuclease




pfam09563
1
Makarova et
RM
LlaJI restriction endonuclease
94.0%
0.45




al. (2011)






pfam09559
1
Makarova et
CRISPR
Cas6 Crispr
80.0%
0.40




al. (2011)






pfam09556
1
Makarova et
RM
HaeIII restriction
97.1%
0.34




al. (2011)

endonuclease




pfam09549
1
Makarova et
RM
Bpu10I restriction
96.1%
0.50




al. (2011)

endonuclease




pfam09530
1
Makarova et
CRISPR
CRISPR-associated protein
pfam < 20
pfam < 20




al. (2011)

(cas_TM1812)
members
members


pfam09520
1
Makarova et
RM
MjaII restriction endonuclease
89.7%
0.41




al. (2011)






pfam09517
1
Makarova et
RM
Eco29kI restriction
95.5%
0.32




al. (2011)

endonuclease




pfam09516
1
Makarova et
RM
CfrBI restriction
95.5%
0.16




al. (2011)

endonuclease




pfam09491
1
Makarova et
RM
AlwI restriction endonuclease
90.5%
0.28




al. (2011)






pfam09485
1
Makarova et
CRISPR
CRISPR-associated protein
99.6%
0.16




al. (2011)

Cse2 (CRISPR_cse2)




pfam09484
1
Makarova et
CRISPR
CRISPR-associated protein
93.0%
0.51




al. (2011)

TM1802 (cas_TM1802)




pfam09481
1
Makarova et
CRISPR
CRISPR-associated protein
98.4%
0.17




al. (2011)

Cse1 (CRISPR_cse1)




pfam09455
1
Makarova et
CRISPR
CRISPR-associated (Cas)
91.5%
0.71




al. (2011)

DxTHG family




pfam09369
1
Makarova et
new_RM
Contains a number of Zn-
66.2%
0.26




al. (2011)

binding domains; Domain of








unknown function








(DUF1998); DISARM








system: DrmB




pfam09344
1
Makarova et
CRISPR
CT1975-like protein
99.3%
0.17




al. (2011)






pfam09233
1
Makarova et
RM
Restriction endonuclease
91.6%
0.39




al. (2011)

EcoRV




pfam09225
1
Makarova et
RM
Restriction endonuclease
99.5%
0.16




al. (2011)

PvuII




pfam09217
1
Makarova et
RM
Restriction endonuclease
98.0%
0.25




al. (2011)

EcoRII, N-terminal




pfam09208
1
Makarova et
RM
Restriction endonuclease
96.7%
0.69




al. (2011)

MspI




pfam09195
1
Makarova et
RM
Restriction endonuclease
69.2%
0.41




al. (2011)

BglII




pfam09194
1
Makarova et
RM
Restriction endonuclease
93.8%
0.50




al. (2011)

BsobI




pfam09019
1
Makarova et
RM
EcoRII C terminal
97.7%
0.17




al. (2011)






pfam09002
1
Makarova et
new_system
COG1517 contains RecB
46.1%
0.50




al. (2011)

family nuclease and wHTH;








Domain of unknown function








(DUF1887)




pfam08972
1
Makarova et
TA
HicA; Domain of unknown
73.2%
0.47




al. (2011)

function (DUF1902)




pfam08849
1
Makarova et
“new system”,
Same as DUF3387; which is
95.2%
0.39




al. (2011),
BREX
fused to RM (GI:






Goldfarb et

209527353); Putative inner






al. (2015)

membrane protein








(DUF1819); pdb: 3BHW;








BrxA-Unknown function




pfam08843
1
Makarova et
new_Abi
Same as COG2253, AbiG;
70.1%
0.20




al. (2011)

Domain of unknown function








(DUF1814); Nucleotidyl








transferase AbiEii toxin, Type








IV TA system




pfam08808
1
Makarova et
TA
RES domain
66.6%
0.14




al. (2011)






pfam08798
1
Makarova et
CRISPR
CRISPR associated protein
98.6%
0.18




al. (2011)






pfam08780
1
Makarova et
TA
HEPN; Nucleotidyltransferase
91.2%
0.32




al. (2011)

substrate binding protein like




pfam08747
1
Makarova et
new_RM,
Domain of unknown function
97.9%
0.45




al. (2011),
BREX
(DUF1788); BrxB-Unknown






Goldfarb et

function






al. (2015)






pfam08665
1
Makarova et
“new system”
PglZ domain, Alkaline
69.4%
0.45




al. (2011)

phosphatase clan. BREX








system: PglZ




pfam08463
1
Makarova et
RM
EcoEI R protein C-terminal
97.3%
0.28




al. (2011)






pfam07927
1
Makarova et
TA
toxin component, HicA
89.7%
0.24




al. (2011)

family; YcfA-like protein;








HicA toxin of bacterial toxin-








antitoxin




pfam07805
1
Makarova et
TA
HipA-like N-terminal domain
57.3%
0.24




al. (2011)






pfam07804
1
Makarova et
TA
HipA-like C-terminal domain
56.2%
0.24




al. (2011)






pfam07751
1
Makarova et
Abi
Abi-like protein
66.3%
0.17




al. (2011)






pfam07669
1
Makarova et
RM
Eco57I restriction
74.2%
0.29




al. (2011)

endonuclease




pfam07215
1
Makarova et
new_RM
Protein of unknown function
88.1%
0.53




al. (2011)

(DUF1419) linked to








methylase COG0827




pfam06616
1
Makarova et
RM
BsuBI/PstI restriction
81.7%
0.34




al. (2011)

endonuclease C-terminus




pfam06414
1
Makarova et
TA
Zeta toxin
35.1%
0.27




al. (2011)






pfam06296
1
Makarova et
TA
Toxin component, RelE
90.5%
0.13




al. (2011)

family Protein of unknown








function (DUF1044)




pfam06114
1
Makarova et
TA
Same as COG2856; Domain
48.5%
0.16




al. (2011)

of unknown function








(DUF955)




pfam05942
1
Makarova et
TA
Archaeal PaREP1/PaREP8
70.7%
0.34




al. (2011)

family




pfam05534
1
Makarova et
TA
HicB family
76.4%
0.21




al. (2011)






pfam05016
1
Makarova et
TA
Plasmid stabilisation system
77.4%
0.18




al. (2011)

protein; ParE toxin of type II








toxin-antitoxin system, parDE




pfam04851
1
Makarova et
RM
Type III restriction enzyme,
55.5%
0.16




al. (2011)

res subunit




pfam04556
1
Makarova et
RM
DpnII restriction
93.8%
0.19




al. (2011)

endonuclease




pfam04555
1
Makarova et
RM
Restriction endonuclease
90.0%
0.39




al. (2011)

XhoI




pfam04149
1
Makarova et
TA
DUF397, see our TA paper
51.5%
0.12




al. (2011)






pfam04014
1
Makarova et
TA
SpoVT/AbrB like domain;
77.3%
0.16




al. (2011)

Antidote-toxin recognition








MazE, bacterial antitoxin




pfam03787
1
Makarova et
CRISPR
RAMP superfamily
98.4%
0.44




al. (2011)






pfam03681
1
Makarova et
TA
HicB family; Uncharacterized
pfam < 20
pfam < 20




al. (2011)

protein family (UPF0150)
members
members


pfam03230
1
Makarova et
RM
Antirestriction protein
57.8%
0.14




al. (2011)






pfam02963
1
Makarova et
RM
Restriction endonuclease
61.6%
0.40




al. (2011)

EcoRI




pfam02923
1
Makarova et
RM
Restriction endonuclease
97.4%
0.47




al. (2011)

BamHI




pfam02604
1
Makarova et
TA
Antitoxin Phd_Yet-M, type II
90.5%
0.13




al. (2011)

toxin-antitoxin system




pfam01930
1
Makarova et
CRISPR
Domain of unknown function
90.5%
0.37




al. (2011)

DUF83




pfam01909
1
Makarova et
TA
Nucleotidyltransferase
47.6%
0.26




al. (2011)

domain, COG1669




pfam01867
1
Makarova et
CRISPR
CRISPR associated protein
97.4%
0.26




al. (2011)

Cas1




pfam01850
1
Makarova et
TA
PIN domain
76.0%
0.11




al. (2011)






pfam01845
1
Makarova et
TA
CcdB protein
89.4%
0.15




al. (2011)






pfam01420
1
Makarova et
RM
Type I restriction
91.8%
0.20




al. (2011)

modification DNA specificity








domain




pfam14390
1
Ofir et al.
DISARM-
Putative PD-(D/E)XK family
98.9%
0.42




(2017)
associated
member, (DUF4420)




pfam13659
1
Goldfarb et
BREX,
PglX-Adenine-specific
63.3%
0.21




al. (2015)2,
DISARM
methylase; DrmMI-






Ofir et al.

Superfamily SSF5335 (S-






(2017)3

adenosyl-L-methionine-








dependent








methyltransferases);








Methyltransferase domain




pfam13589
1
Ofir et al.
DISARM-
Histidine kinase-, DNA
33.5%
0.21




(2017)
associated
gyrase B-, and HSP90-like








ATPase




pfam13361
1
Ofir et al.
DISARM-
UvrD-like helicase C-terminal
50.2%
0.08




(2017)
associated
domain




pfam13182
1
Goldfarb et
BREX
Protein of unknown function
94.9%
0.31




al. (2015)

(DUF4007); BrxP-








Phosphoadenosine








phosphosulfate reductase




pfam10923
1
Goldfarb et
BREX
BrxC/PglY, BrxD-ATP
93.1%
0.28




al. (2015)

binding; P-loop Domain of








unknown function (DUF2791)




pfam04465
1
Goldfarb et
BREX
BrxC/PglY-ATP binding;
93.1%
0.50




al. (2015)

Protein of unknown function








(DUF499)




pfam03852
1
Ofir et al.
DISARM-
DNA mismatch endonuclease
93.0%
0.18




(2017)
associated
Vsr




pfam01555
1
Goldfarb et
BREX
DNA methylase; PglXI-
64.4%
0.20




al. (2015)

Adenine-specific methylase




pfam01507
1
Goldfarb et
BREX
Phosphoadenosine
62.9%
0.07




al. (2015)

phosphosulfate reductase








family; BrxP-








Phosphoadenosine








phosphosulfate reductase




pfam00580
1
Ofir et al.
DISARM-
UvrD/REP helicase N-
47.4%
0.09




(2017)
associated
terminal domain




pfam00271
1
Ofir et al.
DISARM
DrmA; Helicase conserved C-
39.0%
0.10




(2017)

terminal domain




pfam00176
1
Ofir et al.
DISARM
DrmD; SNF2 family N-
46.8%
0.23




(2017)

terminal domain




pfam00145
1
Ofir et al.
DISARM
DrmMII; C-5 cytosine-
72.5%
0.19




(2017)

specific DNA methylase




pfam00004
1
Ofir et al.
DISARM-
ATPase family associated
30.1%
0.07




(2017)
associated
with various cellular activities








(AAA)




COG5654
1
Makarova et
TA
Uncharacterized conserved






al. (2011)

protein




COG5642
1
Makarova et
TA
Uncharacterized conserved






al. (2011)

protein




COG4861
1
Makarova et
Abi
Uncharacterized protein






al. (2011)

conserved in bacteria




COG5611
1
Makarova et
TA
PIN domain






al. (2011)






COG4849
1
Makarova et
Abi
Uncharacterized protein






al. (2011)

conserved in bacteria




COG5606
1
Makarova et
TA
Uncharacterized conserved






al. (2011)

small protein




COG4823
1
Makarova et
Abi
Abortive infection






al. (2011)

bacteriophage resistance








protein




COG5573
1
Makarova et
TA
Predicted nucleic-acid-






al. (2011)

binding protein, contains PIN








domain




COG4804
1
Makarova et
new_system
Predicted nuclease of






al. (2011)

restriction endonuclease-like








fold




COG5551
1
Makarova et
CRISPR
CRISPR system related






al. (2011)

protein, RAMP superfamily




COG4748
1
Makarova et
RM
Uncharacterized conserved






al. (2011)

protein




COG5519
1
Makarova et
new_system
Superfamily II helicase or






al. (2011)

inactivated derivatives, fused








to primase




COG4737
1
Makarova et
TA
Uncharacterized protein






al. (2011)

conserved in bacteria




COG5499
1
Makarova et
TA
Predicted transcription






al. (2011)

regulator containing HTH








domain




COG4710
1
Makarova et
TA
Predicted DNA-binding






al. (2011)

protein with an HTH domain




COG5464
1
Makarova et
new_RM
RecB-family nuclease domain






al. (2011)

(see TIGR01784), linked to








COG1479




COG4694
1
Makarova et
Abi
Wobble nucleotide-excising






al. (2011)

tRNase




COG5450
1
Makarova et
TA
Transcription regulator of the






al. (2011)

Arc/MetJ class




COG4691
1
Makarova et
TA
Plasmid stability protein






al. (2011)






COG5340
1
Makarova et
Abi
Predicted transcriptional






al. (2011)

regulator




COG4683
1
Makarova et
TA
Uncharacterized protein






al. (2011)

conserved in bacteria




COG5304
1
Makarova et
TA
Uncharacterized protein






al. (2011)

conserved in bacteria




COG4680
1
Makarova et
TA
Uncharacterized protein






al. (2011)

conserved in bacteria




COG5302
1
Makarova et
TA
Post-segregation antitoxin






al. (2011)

(ccd killing mechanism








protein) encoded by the F








plasmid




COG4679
1
Makarova et
TA
Phage-related protein






al. (2011)






COG4951
1
Makarova et
RM
Uncharacterized protein






al. (2011)

conserved in bacteria




COG4646
1
Makarova et
new_system
DNA methylase, see






al. (2011)

COG0553




COG4914
1
Makarova et
Abi
Predicted






al. (2011)

nucleotidyltransferase




COG4636
1
Makarova et
TA
Endonuclease, Uma2 family






al. (2011)

(restriction endonuclease fold)




COG4889
1
Makarova et
RM
Predicted helicase






al. (2011)






COG4634
1
Makarova et
TA
PIN family nuclease, potential






al. (2011)

toxin-antitoxin system








component




COG4456
1
Makarova et
TA
Virulence-associated protein






al. (2011)

or related protein




COG4453
1
Makarova et
TA
Uncharacterized protein






al. (2011)

conserved in bacteria




COG4423
1
Makarova et
TA
Uncharacterized protein






al. (2011)

conserved in bacteria




COG4374
1
Makarova et
TA
PIN domain nuclease, a






al. (2011)

component of toxin-antitoxin








system (PIN domain)




COG4343
1
Makarova et
CRISPR
CRISPR-associated protein,






al. (2011)

RecB family exonuclease




COG4268
1
Makarova et
RM
McrBC 5-methylcytosine






al. (2011)

restriction system component




COG4227
1
Makarova et
new_system
Antirestriction protein






al. (2011)






COG4226
1
Makarova et
TA
Predicted nuclease of the






al. (2011)

RNAse H fold, HicB family




COG4127
1
Makarova et
new_RM
Mrr restriction endonuclease






al. (2011)

domain




COG4118
1
Makarova et
TA
Antitoxin (DNA binding






al. (2011)

domain) of toxin-antitoxin








stability system




COG4115
1
Makarova et
TA
Uncharacterized protein






al. (2011)

conserved in bacteria




COG4113
1
Makarova et
TA
Predicted nucleic acid-binding






al. (2011)

protein, contains PIN domain




COG4096
1
Makarova et
RM
Type I site-specific






al. (2011)

restriction-modification








system, R (restriction) subunit








or related helicase




COG4006
1
Makarova et
CRISPR
Uncharacterized protein






al. (2011)

conserved in archaea




COG3950
1
Makarova et
new_system
Predicted ATP-binding






al. (2011)

protein involved in virulence




COG3943
1
Makarova et
new_TA
Virulence protein






al. (2011)






COG3905
1
Makarova et
TA
Predicted transcriptional






al. (2011)

regulator




COG3886
1
Makarova et
RM
Predicted HKD family






al. (2011)

nuclease; type III restriction








protein res subunit




COG3832
1
Makarova et
TA
Uncharacterized conserved






al. (2011)

protein




COG3744
1
Makarova et
TA
PIN domain nuclease, a






al. (2011)

component of toxin-antitoxin








system (PIN domain)




COG3742
1
Makarova et
TA
Uncharacterized protein






al. (2011)

conserved in bacteria




COG3692
1
Makarova et
TA
Uncharacterized protein






al. (2011)

conserved in bacteria




COG3668
1
Makarova et
TA
Plasmid stabilization system






al. (2011)

protein




COG3657
1
Makarova et
TA
Uncharacterized protein






al. (2011)

conserved in bacteria




COG3654
1
Makarova et
TA
Prophage maintenance system






al. (2011)

killer protein




COG3649
1
Makarova et
CRISPR
CRISPR system related






al. (2011)

protein




COG3636
1
Makarova et
TA
Predicted transcriptional






al. (2011)

regulator




COG3609
1
Makarova et
TA
Predicted transcriptional






al. (2011)

regulators containing the








CopG/Arc/MetJ DNA-binding








domain




COG3598
1
Makarova et
new_system
RecA-family ATPase, fused






al. (2011)

to TOPRIM




COG3587
1
Makarova et
RM
Restriction endonuclease






al. (2011)






COG3586
1
Makarova et
new_system
Some protein fused to






al. (2011)

domains similar to N terminal








regions found in type I








restriction enzyme R (HSDR)








proteins and RloF (gi:








93006430)




COG3550
1
Makarova et
TA
Toxin module HipA, protein






al. (2011)

kinase of phosphatidylinositol








3/4-kinase superfamily




COG3549
1
Makarova et
TA
Plasmid maintenance system






al. (2011)

killer protein




COG3514
1
Makarova et
TA
Uncharacterized protein






al. (2011)

conserved in bacteria




COG3513
1
Makarova et
CRISPR
Predicted CRISPR-associated






al. (2011)

nuclease, contains








McrA/HNH-nuclease and








RuvC-like nuclease domain




COG3512
1
Makarova et
CRISPR
CRISPR-associated protein,






al. (2011)

Cas2 homolog




COG3472
1
Makarova et
new_system
Uncharacterized; often fused






al. (2011)

to COG1479




COG3440
1
Makarova et
RM
Predicted restriction






al. (2011)

endonuclease




COG3410
1
Makarova et
Abi
Uncharacterized conserved






al. (2011)

protein




COG3392
1
Makarova et
RM
Adenine-specific DNA






al. (2011)

methylase




COG3372
1
Makarova et
new_RM
Predicted nuclease of






al. (2011)

restriction endonuclease-like








fold; associated with








COG1061 (RM)




COG3344
1
Makarova et
Abi
Retron-type reverse






al. (2011)

transcriptase




COG3337
1
Makarova et
CRISPR
CRISPR system related






al. (2011)

protein




COG3311
1
Makarova et
TA
HTH_MerR_SF






al. (2011)






COG3183
1
Makarova et
RM
Predicted restriction






al. (2011)

endonuclease




COG3177
1
Makarova et
TA
Fic family protein






al. (2011)






COG3093
1
Makarova et
TA
Plasmid maintenance system






al. (2011)

antidote protein




COG3077
1
Makarova et
TA
DNA-damage-inducible






al. (2011)

protein J




COG3041
1
Makarova et
TA
Uncharacterized protein






al. (2011)

conserved in bacteria




COG2944
1
Makarova et
TA
Predicted transcriptional






al. (2011)

regulator




COG2929
1
Makarova et
TA
Uncharacterized protein






al. (2011)

conserved in bacteria




COG2886
1
Makarova et
TA
Uncharacterized small protein






al. (2011)






COG2880
1
Makarova et
TA
Uncharacterized protein






al. (2011)

conserved in archaea




COG2865
1
Makarova et
new_system
Predicted transcriptional






al. (2011)

regulator containing an HTH








domain and diverged ATP-








binding domain (Schlafen-








like)




COG2856
1
Makarova et
TA
Predicted Zn peptidase






al. (2011)






COG2852
1
Makarova et
RM
Very-short-patch-repair






al. (2011)

endonuclease




COG2810
1
Makarova et
RM
Predicted type IV restriction






al. (2011)

endonuclease




COG2521
1
Makarova et
new_RM
Predicted archaeal






al. (2011)

methyltransferase




COG2445
1
Makarova et
TA
Uncharacterized conserved






al. (2011)

protein




COG2442
1
Makarova et
TA
Uncharacterized conserved






al. (2011)

protein




COG2405
1
Makarova et
TA
Predicted nucleic acid-binding






al. (2011)

protein, contains PIN domain




COG2402
1
Makarova et
TA
Predicted nucleic acid-binding






al. (2011)

protein, contains PIN domain




COG2361
1
Makarova et
TA
Uncharacterized conserved






al. (2011)

protein




COG2337
1
Makarova et
TA
Toxin-antitoxin addiction






al. (2011)

module toxin component








MazF (an endoRNAse)




COG2336
1
Makarova et
TA
Toxin-antitoxin addiction






al. (2011)

module antitoxin component








MazE




COG2254
1
Makarova et
CRISPR
Predicted HD superfamily






al. (2011)

hydrolase, possibly a nuclease




COG2253
1
Makarova et
Abi
Uncharacterized conserved






al. (2011)

protein




COG2250
1
Makarova et
TA
HEPN domain






al. (2011)






COG2189
1
Makarova et
RM
Adenine specific DNA






al. (2011)

methylase Mod




COG2184
1
Makarova et
TA
Protein involved in cell






al. (2011)

division




COG2161
1
Makarova et
TA
Antitoxin (DNA-binding






al. (2011)

domain) of toxin-antitoxin








stability system




COG2026
1
Makarova et
TA
Cytotoxic translational






al. (2011)

repressor of toxin-antitoxin








stability system




COG2002
1
Makarova et
TA
Transcriptional regulator






al. (2011)

AbrB




COG1895
1
Makarova et
TA
Uncharacterized conserved






al. (2011)

protein related to C-terminal








domain of eukaryotic








chaperone, SACSIN




COG1857
1
Makarova et
CRISPR
CRISPR system related






al. (2011)

protein




COG1848
1
Makarova et
TA
Predicted nucleic acid-binding






al. (2011)

protein, contains PIN domain




COG1787
1
Makarova et
RM
Endonuclease, HJR/Mrr/RecB






al. (2011)

family




COG1769
1
Makarova et
CRISPR
CRISPR system related






al. (2011)

protein, RAMP superfamily




COG1753
1
Makarova et
TA
Predicted antitoxin, copG






al. (2011)

family




COG1743
1
Makarova et
RM, BREX
Adenine-specific DNA






al. (2011),

methylase containing a Zn-






Goldfarb et

ribbon; PglXI-Adenine-






al. (2015)

specific methylase




COG1724
1
Makarova et
TA
Predicted RNA binding






al. (2011)

protein (dsRBD-like fold),








HicA family




COG1715
1
Makarova et
RM
Restriction endonuclease






al. (2011)






COG1708
1
Makarova et
TA
Predicted






al. (2011)

nucleotidyltransferase




COG1700
1
Makarova et
new_RM
Contains PD_(D/E)xK






al. (2011)

nuclease odmain, DUF524




COG1688
1
Makarova et
CRISPR
CRISPR system related






al. (2011)

protein, RAMP superfamily




COG1669
1
Makarova et
TA
Nucleotidyltransferase






al. (2011)






COG1604
1
Makarova et
CRISPR
CRISPR system related






al. (2011)

protein, RAMP superfamily




COG1598
1
Makarova et
TA
Predicted nuclease of the






al. (2011)

RNAse H fold, HicB family




COG1583
1
Makarova et
CRISPR
CRISPR system related






al. (2011)

protein, RAMP superfamily




COG1569
1
Makarova et
TA
Predicted nucleic acid-binding






al. (2011)

protein, contains PIN domain




COG1567
1
Makarova et
CRISPR
CRISPR system related






al. (2011)

protein, RAMP superfamily




COG1518
1
Makarova et
CRISPR
CRISPR-associated protein






al. (2011)

Cas1




COG1517
1
Makarova et
CRISPR
CRISPR system related






al. (2011)

protein




COG1487
1
Makarova et
TA
Predicted nucleic acid-binding






al. (2011)

protein, contains PIN domain




COG1479
1
Makarova et
new_system
RloF-like, possible RM






al. (2011)

component (contains HNH-








type nuclease domain)




COG1476
1
Makarova et
TA
Predicted transcriptional






al. (2011)

regulator, xre family




COG1475
1
Makarova et
new_system
Stage 0 sporulation protein J






al. (2011)

(antagonist of Soj); contains








ParB-like nuclease domain




COG1468
1
Makarova et
CRISPR
CRISPR-associated protein






al. (2011)

Cas4 (RecB family








exonuclease)




COG1431
1
Makarova et
pAgo
Argonaute homolog,






al. (2011)

implicated in RNA








metabolism




COG1421
1
Makarova et
CRISPR
CRISPR system related






al. (2011)

protein




COG1403
1
Makarova et
RM
Restriction endonuclease,






al. (2011)

McrA/HNH family




COG1401
1
Makarova et
RM
GTPase subunit of restriction






al. (2011)

endonuclease




COG1396
1
Makarova et
TA
Predicted transcriptional






al. (2011)

regulator, xre family




COG1367
1
Makarova et
CRISPR
CRISPR system related






al. (2011)

protein, RAMP superfamily




COG1353
1
Makarova et
CRISPR
Predicted CRISPR-associated






al. (2011)

polymerase




COG1343
1
Makarova et
CRISPR
CRISPR-associated protein






al. (2011)

Cas2




COG1337
1
Makarova et
CRISPR
CRISPR system related






al. (2011)

protein, RAMP superfamily




COG1336
1
Makarova et
CRISPR
CRISPR system related






al. (2011)

protein, RAMP superfamily




COG1332
1
Makarova et
CRISPR
CRISPR system related






al. (2011)

protein, RAMP superfamily




COG1203
1
Makarova et
CRISPR
CRISPR-associated helicase






al. (2011)

Cas3




COG1112
1
Makarova et
new_system
Superfamily I DNA/RNA






al. (2011)

helicase




COG1106
1
Makarova et
Abi
Predicted ATPase






al. (2011)






COG1061
1
Makarova et
RM
DNA or RNA helicase of






al. (2011)

superfamily II




COG1002
1
Makarova et
RM, BREX
Type II restriction enzyme,






al. (2011),

methylase subunit; PglX-






Goldfarb et

Adenine-specific methylase






al. (2015)






COG0864
1
Makarova et
TA
Transcriptional regulator,






al. (2011)

CopG/Arc/MetJ family








(DNA-binding and a metal-








binding domains)




COG0863
1
Makarova et
RM, BREX
DNA modification methylase;






al. (2011),

PglXI-Adenine-specific






Goldfarb et

methylase






al. (2015)






COG0827
1
Makarova et
RM
Adenine-specific DNA






al. (2011)

methylase




COG0732
1
Makarova et
RM
Restriction endonuclease S






al. (2011)

subunit




COG0640
1
Makarova et
TA
Transcriptional regulator






al. (2011)

containing HTH domain,








ArsR family




COG0610
1
Makarova et
RM
Type I site-specific






al. (2011)

restriction-modification








system, R (restriction) subunit








or related helicase




COG0338
1
Makarova et
RM
Site-specific DNA methylase






al. (2011)






COG0286
1
Makarova et
RM, BREX
Type I restriction-






al. (2011),

modification system






Goldfarb et

methyltransferase subunit;






al. (2015)

PglX-Adenine-specific








methylase




COG0270
1
Makarova et
RM,
Dcm, Site-specific DNA-






al. (2011),
DISARM
cytosine methylase; DrmMII






Ofir et al.








(2017)






COG4930
1
Goldfarb et
BREX
BrxL-Lon-like protease






al. (2015)






COG3655
1
Ofir et al.
DISARM-
DNA-binding transcriptional






(2017)
associated
regulator, XRE family




COG1404
1
Ofir et al.
DISARM-
Serine protease, subtilisin






(2017)
associated
family




COG1205
1
Ofir et al.
DISARM-
ATP-dependent helicase






(2017)
associated
YprA, contains C-terminal








metal-binding DUF1998








domain




COG1201
1
Goldfarb et
BREX
BrxHI-Lhr-like helicase






al. (2015)






COG0553
1
Goldfarb et
BREX,
BrxHII-DNA/RNA






al. (2015),
DISARM
helicases; DrmD; HepA,






Ofir et al.

Superfamily II DNA or RNA






(2017)

helicase, SNF2 family




COG0515
1
Goldfarb et
BREX
PglW-Serine/threonine






al. (2015)

protein kinase




COG0210
1
Ofir et al.
DISARM-
UvrD, Superfamily I DNA or






(2017)
associated
RNA helicase




COG0175
1
Goldfarb et
BREX
BrxP-Phosphoadenosine






al. (2015)

phosphosulfate reductase




pfam13091
2
Ofir et al.
DISARM
DrmC; PLD-like domain
44.2%
0.14




(2017)






pfam01881
2
known
CRISPR
CRISPR associated protein
92.3%
0.44




system

Cas6






found in








round 1






pfam01905
2
known
CRISPR
CRISPR-associated negative
99.3%
0.41




system

auto-regulator DevR/Csa2






found in








round 1






pfam01954
2
known
TA
Protein of unknown function
89.8%
0.59




system

DUF104. Probably a new






found in

antitoxin; the associated gene






round 1

is a PIN-domain protein,








known toxin




pfam02697
2
known
TA
Uncharacterized ACR,
89.6%
0.42




system

COG1753






found in








round 1






pfam02980
2
known
RM
Restriction endonuclease
74.4%
0.63




system

FokI, catalytic domain






found in








round 1






pfam02981
2
known
RM
Restriction endonuclease
75.0%
0.64




system

FokI, recognition domain






found in








round 1






pfam03235
2
known
RM
Protein of unknown function
78.8%
0.38




system

DUF262






found in








round 1,








putative








system








found in








round 1






pfam03683
2
known
TA
predicted
88.3%
0.54




system








found in








round 1






pfam03693
2
known
TA
Bacterial antitoxin of ParD
88.1%
0.19




system

toxin-antitoxin type II system






found in

and RHH






round 1






pfam03750
2
known
CRISPR
Protein of unknown function
99.9%
0.26




system

(DUF310)






found in








round 1






pfam04255
2
known
TA
Protein of unknown function
69.0%
0.36




system

(DUF433)






found in








round 1






pfam04365
2
known
TA
Ribonuclease toxin, BmT, of
91.1%
0.33




system

type II toxin-antitoxin system






found in








round 1






pfam04411
2
known
RM
PD-(D/E)XK nuclease
84.0%
0.57




system

superfamily






found in








round 1






pfam05015
2
known
TA
HigAB; RelE-like toxin of
96.9%
0.26




system

type II toxin-antitoxin system






found in

HigB






round 1






pfam05107
2
known
CRISPR
CRISPR-associated protein
98.5%
0.41




system

Cas7






found in








round 1






pfam05168
2
known
TA
HEPN domain
84.9%
0.36




system








found in








round 1






pfam05315
2
known
RM
ICEA Protein
98.7%
0.17




system








found in








round 1






pfam06023
2
known
CRISPR
Archaeal protein of unknown
93.9%
0.71




system

function (DUF911)






found in








round 1






pfam06154
2
known
TA
CbeA_antitoxin, type IV,
97.2%
0.11




system

cytoskeleton bundling-






found in

enhancing factor A






round 1






pfam06300
2
known
RM
Tsp45I type II restriction
97.1%
0.33




system

enzyme






found in








round 1






pfam06634
2
known
RM, System
Protein of unknown function
95.5%
0.66




system
around
(DUF1156)






found in
anchors







round 1,
pfam06634,







putative
COG1483,







system
pfam12635







found in








round 1






pfam06755
2
known
TA
CbtA_toxin of type IV toxin-
96.6%
0.12




system

antitoxin system






found in








round 1






pfam07362
2
known
TA
Post-segregation antitoxin
94.5%
0.15




system

CcdA






found in








round 1






pfam07510
2
known
RM
Protein of unknown function
72.8%
0.29




system

(DUF1524)






found in








round 1,








putative








system








found in








round 1






pfam07704
2
known
TA
Rv0623-like transcription
99.3%
0.05




system

factor






found in








round 1






pfam07832
2
known
RM
Cfr10I/Bse634I restriction
100.0%
0.57




system

endonuclease






found in








round 1






pfam08870
2
known
DND
Domain of unknown function
96.1%
0.52




system

(DUF1832)






found in








round 1






pfam08998
2
known
TA
Bacterial epsilon antitoxin
92.0%
0.22




system








found in








round 1






pfam09015
2
known
RM
NgoMIV restriction enzyme
98.1%
0.34




system








found in








round 1






pfam09126
2
known
RM
Restriction endonuclease NaeI
95.9%
0.50




system








found in








round 1






pfam09226
2
known
RM
Restriction endonuclease
97.1%
0.47




system

HincII






found in








round 1






pfam09254
2
known
RM
Restriction endonuclease
78.3%
0.73




system

FokI, C terminal






found in








round 1






pfam09386
2
known
TA
Antitoxin ParD
92.1%
0.58




system








found in








round 1






pfam09499
2
known
RM
ApaLI-like restriction
99.1%
0.10




system

endonuclease






found in








round 1






pfam09518
2
known
RM
HindIII restriction
84.8%
0.46




system

endonuclease






found in








round 1






pfam09519
2
known
RM
Hind VP restriction
93.8%
0.56




system

endonuclease






found in








round 1






pfam09521
2
known
RM
NgoPII restriction
96.4%
0.18




system

endonuclease






found in








round 1






pfam09545
2
known
RM
AccI restriction endonuclease
95.2%
0.68




system








found in








round 1






pfam09553
2
known
RM
Eco47II restriction
97.6%
0.36




system

endonuclease






found in








round 1






pfam09554
2
known
RM
HaeII restriction endonuclease
97.5%
0.33




system








found in








round 1






pfam09561
2
known
RM
HpaII restriction
82.0%
0.33




system

endonuclease






found in








round 1






pfam09564
2
known
RM
NgoBV restriction
99.6%
0.13




system

endonuclease






found in








round 1






pfam09566
2
known
RM
SacI restriction endonuclease
95.8%
0.41




system








found in








round 1






pfam09570
2
known
RM
SinI restriction endonuclease
95.1%
0.49




system








found in








round 1






pfam09711
2
known
CRISPR
CRISPR-associated protein
98.9%
0.15




system

(Cas_Csn2)






found in








round 1






pfam09722
2
known
TA
Protein of unknown function
92.7%
0.16




system

(DUF2384)






found in








round 1






pfam09907
2
known
TA
HigAB
97.8%
0.18




system








found in








round 1






pfam09946
2
known
TA
predicted
97.9%
0.16




system








found in








round 1






pfam09952
2
known
TA
putative toxin has a
94.2%
0.13




system

nucleotidyl transferase






found in

domain






round 1






pfam10117
2
known
RM
McrBC 5-methylcytosine
75.9%
0.40




system

restriction system component






found in








round 1






pfam10884
2
known
TA
Protein of unknown function
80.7%
0.44




system

(DUF2683)






found in








round 1






pfam10959
2
known
TA
Protein of unknown function
91.3%
0.33




system

(DUF2761)






found in








round 1






pfam11463
2
known
RM
R.HinP1I restriction
90.9%
0.36




system

endonuclease






found in








round 1






pfam11564
2
known
RM
Restriction endonuclease
100.0%
0.58




system

BpuJI-N terminal






found in








round 1






pfam11848
2
known
TA
contains PIN domain. Two
95.9%
0.54




system

small proteins






found in








round 1






pfam11867
2
known
RM
Domain of unknown function
86.9%
0.37




system

(DUF3387)






found in








round 1






pfam12102
2
known
RM
Domain of unknown function
46.0%
0.23




system

(DUF3578)






found in








round 1






pfam12441
2
known
TA
CopG antitoxin of type II
89.9%
0.46




system

toxin-antitoxin system






found in








round 1






pfam12469
2
known
CRISPR
CRISPR-associated protein
98.2%
0.70




system








found in








round 1






pfam12564
2
known
RM
Type III
95.3%
0.25




system

restriction/modification






found in

enzyme methylation subunit






round 1






pfam12676
2
known
TA
Protein of unknown function
96.5%
0.08




system

(DUF3796)






found in








round 1






pfam13156
2
known
RM
maybe a type IIG gene;
82.5%
0.19




system

Restriction endonuclease






found in








round 1






pfam13337
2
known
BREX
Putative ATP-dependent Lon
91.8%
0.56




system

protease






found in








round 1






pfam13391
2
known
RM
HNH_2, HNH endonuclease
75.3%
0.36




system








found in








round 1






pfam13395
2
known
CRISPR
HNH endonuclease
85.4%
0.34




system








found in








round 1






pfam13643
2
known
RM
Domain of unknown function
70.9%
0.44




system

(DUF4145)






found in








round 1






pfam13957
2
known
TA
Toxin YafO, type II toxin-
79.6%
0.11




system

antitoxin system






found in








round 1






pfam14072
2
known
DND
DndB, DNA-sulfur
86.1%
0.44




system

modification-associated






found in








round 1






pfam14076
2
known
TA
Domain of unknown function
78.5%
0.38




system

(DUF4258)






found in








round 1






pfam14335
2
known
RM
Domain of unknown function
92.8%
0.54




system

(DUF4391)






found in








round 1






pfam14338
2
known
RM
Mrr N-terminal domain
87.8%
0.27




system








found in








round 1






pfam14350
2
known
TA
Nearby gene is HigA
71.2%
0.39




system

antitoxin






found in








round 1






pfam14355
2
known
Abi
Abortive infection C-terminus
73.1%
0.41




system








found in








round 1






pfam14367
2
known
TA
Domain of unknown function
98.0%
0.17




system

(DUF4411)






found in








round 1






pfam14384
2
known
TA
BrnA antitoxin of type II
88.9%
0.26




system

toxin-antitoxin system






found in








round 1






pfam14487
2
known
TA
pmen type TA system
88.7%
0.22




system








found in








round 1






pfam14511
2
known
RM
Type II restriction
95.1%
0.42




system

endonuclease EcoO109I






found in








round 1






pfam14809
2
known
tgtA
C1 domain of tRNA-guanine
81.1%
0.57




system
(deazaguanine
transglycosylase dimerisation






found in
tRNA







round 1
modification)





pfam15514
2
known
RM
Restriction endonuclease ThaI
95.1%
0.33




system








found in








round 1






pfam15515
2
known
RM
MvaI/BcnI restriction
95.0%
0.44




system

endonuclease family






found in








round 1






pfam15723
2
known
TA
Motility quorum-sensing
81.1%
0.19




system

regulator, toxin of MqsA






found in








round 1






pfam15738
2
known
TA
Bacterial toxin of type II
87.0%
0.22




system

toxin-antitoxin system, YafQ






found in








round 1






pfam16277
2
known
TA
Domain of unknown function
87.5%
0.22




system

(DUF4926)






found in








round 1






pfam16565
2
known
BREX
Lon Protease; Phospholipase
85.5%
0.74




system

D-like domain at C-terminus






found in

of MIT






round 1






pfam16592
2
known
CRISPR
REC lobe of CRISPR-
98.0%
0.17




system

associated endonuclease Cas9






found in








round 1






pfam16593
2
known
CRISPR
Bridge helix of CRISPR-
97.8%
0.14




system

associated endonuclease Cas9






found in








round 1






pfam16595
2
known
CRISPR
PAM-interacting domain of
99.4%
0.14




system

CRISPR-associated






found in

endonuclease Cas9






round 1






pfam16762
2
known
TA
PIN domain; Ribbon-helix-
96.6%
0.38




system

helix domain






found in








round 1






pfam16813
2
known
CRISPR
CRISPR-associated protein
98.8%
0.28




system

Csn2 subfamily St






found in








round 1






pfam16902
2
known
RM
FokI; Type-2 restriction
73.5%
0.62




system

enzyme D3 domain






found in








round 1






pfam16948
2
known
TA
HipAB; Cell translocating
73.9%
0.56




system

kinase A N-terminus






found in








round 1






pfam02384
2
known
RM
N-6 DNA Methylase
79.5%
0.31




system








found in








round 1






pfam01541
2
putative
single-gene
GIY-YIG catalytic domain
38.0%
0.12




system
“system” of







found in
pfam14267







round 1






pfam01618
2
putative
Zorya
ZorA; MotA/TolQ/ExbB
66.5%
0.06




system

proton channel family






found in








round 1






pfam01863
2
putative
single-gene
Protein of unknown function
62.3%
0.18




system
“system” of
DUF45






found in
COG1451







round 1






pfam00691
2
putative
Zorya
ZorB; OmpA family
60.7%
0.06




system








found in








round 1






pfam03174
2
putative
System
Chitobiase/beta-
41.9%
0.24




system
around
hexosaminidase C-terminal






found in
anchors
domain






round 1
pfam06634,








COG1483,








pfam12635





pfam04383
2
putative
single-gene
KilA-N domain
43.1%
0.31




system
“system” of







found in
pfam04383







round 1






pfam04471
2
putative
Zorya
ZorD (in some cases);
66.7%
0.31




system

Restriction endonuclease






found in








round 1






pfam06250
2
putative
single-gene
Protein of unknown function
55.6%
0.42




system
“system”of
(DUF1016)






found in
COG4804







round 1






pfam08878
2
putative
Hachiman
HamA; Domain of unknown
89.5%
0.48




system

function (DUF1837)






found in








round 1






pfam09414
2
putative
System
RNA ligase
34.5%
0.39




system
around anchor







found in
pfam12476







round 1






pfam09983
2
putative
Wadjet
JetD; Uncharacterized protein
87.5%
0.45




system

conserved in bacteria C-






found in

term(DUF2220)






round 1






pfam10088
2
putative
Lamassu
LmuB; Uncharacterized
57.3%
0.52




system

protein conserved in bacteria






found in

(DUF2326)






round 1






pfam11795
2
putative
Wadjet
JetD; Uncharacterized protein
95.3%
0.40




system

conserved in bacteria N-term






found in

(DUF3322)






round 1






pfam11855
2
putative
Wadjet
JetA; Protein of unknown
97.6%
0.31




system

function (DUF3375)






found in








round 1






pfam12476
2
putative
System
Protein of unknown function
89.0%
0.45




system
around anchor
(DUF3696)






found in
pfam12476







round 1






pfam12635
2
putative
System
Protein of unknown function
98.8%
0.69




system
around
(DUF3780)






found in
anchors







round 1
pfam06634,








COG1483,








pfam12635





pfam13020
2
putative
System
Domain of unknown function
52.6%
0.41




system
around
(DUF3883)






found in
anchors







round 1
pfam06634,








COG1483





pfam13175
2
putative
Septu + System
PtuA; AAA ATPase domain
73.9%
0.37




system
around anchor







found in
pfam12476







round 1






pfam13208
2
putative
System
TerB N-terminal domain
89.6%
0.29




system
around anchor







found in
pfam13208







round 1






pfam13304
2
putative
Septu + System
PtuA; AAA domain, putative
63.8%
0.33




system
around anchor
AbiEii toxin, Type IV TA






found in
pfam12476
system






round 1






pfam13476
2
putative
Septu
PtuA; AAA domain
47.1%
0.24




system








found in








round 1






pfam13677
2
putative
Zorya
ZorB; Membrane MotB of
92.5%
0.04




system

proton-channel complex






found in

MotA/MotB






round 1






pfam13835
2
putative
Wadjet
JetB; Domain of unknown
98.0%
0.32




system

function (DUF4194)






found in








round 1






pfam13910
2
putative
single-gene
Domain of unknown function
69.0%
0.34




system
“system” of
(DUF4209)






found in
pfam13910







round 1






pfam14130
2
putative
Lamassu
LmuA; Domain of unknown
74.8%
0.45




system

function (DUF4297)






found in








round 1






pfam14267
2
putative
single-gene
Domain of unknown function
78.8%
0.60




system
“system” of
(DUF4357)






found in
pfam14267







round 1






pfam14491
2
putative
Septu-
Protein of unknown function
92.4%
0.29




system
associated
(DUF4435)






found in








round 1






pfam15611
2
putative
Zorya
ZorC; EH_Signature domain
98.3%
0.55




system








found in








round 1






pfam15615
2
putative
System
TerB-C domain
92.1%
0.29




system
around anchor







found in
pfam13208







round 1






pfam13280
2
putative
System
exists in subtypes; WYL
57.6%
0.19




system
around
domain






found in
anchors







round 1
pfam06634,








COG1483





COG1483
2
known
RM, System
Predicted ATPase, AAA +






system
around
superfamily






found in
anchors







round 1,
pfam06634,







putative
COG1483,







system
pfam12635







found in








round 1






COG0419
2
putative
Lamassu
LmuB; SbcC, DNA repair






system

exonuclease SbcCD ATPase






found in

subunit






round 1






COG3727
2
known
RM
Vsr accompanying C






system

methylase, auxilary to RM;






found in

G:T-mismatch repair DNA






round 1

endonuclease, very short








patch repair protein




COG0840
2
putative
Zorya
ZorA; Methyl-accepting






system

chemotaxis protein






found in








round 1






COG1196
2
putative
Lamassu
LmuB; Smc, Chromosome






system

segregation ATPase






found in








round 1






COG1204
2
putative
Lamassu-
Replicative superfamily II






system
associated
helicase






found in








round 1






COG1360
2
putative
Zorya
ZorB; Flagellar motor protein






system

MotB






found in








round 1






COG1451
2
putative
single-gene
Predicted metal-dependent






system
“system” of
hydrolase






found in
COG1451







round 1






COG2378
2
putative
System
Predicted DNA-binding






system
around
transcriptional regulator






found in
anchors
YafY, contains an HTH and






round 1
pfam06634,
WYL domains







COG1483





COG2885
2
putative
Zorya
ZorB; Outer membrane






system

protein OmpA and related






found in

peptidoglycan-associated






round 1

(lipo)proteins




COG4913
2
putative
Wadjet
JetC; Uncharacterized protein,






system

contains a C-terminal ATPase






found in

domain






round 1






COG4924
2
putative
Wadjet
JetD; Uncharacterized protein






system








found in








round 1






COG4938
2
putative
System
Predicted ATPase






system
around anchor







found in
pfam12476







round 1






COG5293
2
putative
Lamassu
LmuB; Uncharacterized






system

protein YydD, contains






found in

DUF2326 domain






round 1

(pfam10088)






1Makarova et al. J Bacteriol. 2011 November; 193(21): 6039-6056



2Goldfarb T, et al. (2015) BREX is a novel phage resistance system widespread in microbial genomes. EMBO J. EMBO Press; 34: 169-83



3Submitted






Identification of Pfams Enriched Near Defense Genes:


The genome sequences, gene annotations and taxonomy annotations of all publicly available sequenced bacterial and archaeal genomes were downloaded from the NCBI FTP site (ftp.ncbi.nih.gov/genomes/genbank/bacteria/ and ftp.ncbi.nih.gov/genomes/genbank/archaea/, respectively) on April 2016. pfam annotations for bacterial and archaeal genes were obtained from the Integrated Microbial Genomes (IMG) database (Markowitz V M, et al. (2012) IMG: the Integrated Microbial Genomes database and comparative analysis system. nucleic Acids Res. Oxford University Press; 40: D115-22) on December 2015, and cross-referenced to the genes in the genomes downloaded from NCBI using the locus_tag Genbank field. All pfams annotated in at least 20 genes (“members”) across the analyzed genomes (14,083 pfams) were scanned. For each pfam, the number of member genes for which a gene having an annotation of a known defense gene family (Table 1) was present in proximity (up to ten genes upstream and ten genes downstream) was recorded. The fraction of defense-associated members out of total members (“defense score”) was calculated per pfam. A second score (“defense context variability score”) was calculated for each pfam as follows: for each member gene occurring with at least one defense gene in proximity, a list of the proximal defense genes was recorded, and the fraction of unique lists out of total number of lists for that pfam represents the score (for example: if pfamX is found within 20 genes in our set, with 15 of them having Cas9 nearby and 5 having type I R-M nearby, the number of unique lists is 2, and the “defense context variability score” is 2/20=0.1). Pfams with defense score >=65% and defense context variability score >=0.1 were taken for further analysis. This list was supplemented with 35 non-pfam gene families that were predicted to be associated with defense by Makarova et al. (2011) ibid, as well as 23 pfams that were predicted in the same study but did not pass the thresholds above (Table 2).









TABLE 2







Scanned Families












Defense
Variability




Family
score
score
Family source
Classification














pfam10802
65.4%
0.82
Prediction cycle 1
Likely mobilome


pfam10657
96.4%
0.15
Prediction cycle 1
Likely non-defense function


pfam09226
94.3%
0.30
Prediction cycle 1
Known system


pfam14809
70.3%
0.58
Prediction cycle 1
Likely known system


pfam11572
92.1%
0.23
Prediction cycle 1
Likely non-defense function


pfam14455
67.4%
0.79
Prediction cycle 1
Likely mobilome


pfam07832
100.0%
0.53
Prediction cycle 1
Known system


pfam10959
84.8%
0.31
Prediction cycle 1
Likely known system


pfam04033
85.7%
0.77
Prediction cycle 1
Possibly belongs to a new defense






system


pfam09629
70.9%
0.26
Prediction cycle 1
Likely mobilome


pfam01304
74.6%
0.41
Prediction cycle 1
Likely non-defense function


pfam11536
75.0%
0.60
Prediction cycle 1
Possibly belongs to a new defense






system


pfam09545
80.6%
0.70
Prediction cycle 1
Known system


pfam11564
100.0%
0.48
Prediction cycle 1
Known system


pfam09566
95.8%
0.38
Prediction cycle 1
Known system


pfam16902
69.9%
0.45
Prediction cycle 1
Known system


pfam12942
78.2%
0.13
Prediction cycle 1
Likely non-defense function


pfam02981
71.6%
0.46
Prediction cycle 1
Known system


pfam16992
86.5%
0.18
Prediction cycle 1
Likely non-defense function


pfam02980
71.1%
0.44
Prediction cycle 1
Known system


pfam12962
67.0%
0.34
Prediction cycle 1
Likely mobilome


pfam09518
76.8%
0.43
Prediction cycle 1
Known system


pfam10473
78.3%
0.18
Prediction cycle 1
Likely mobilome


pfam14466
84.6%
0.28
Prediction cycle 1
Likely mobilome


pfam14456
78.3%
0.34
Prediction cycle 1
Likely mobilome


pfam10876
66.7%
0.40
Prediction cycle 1
Likely mobilome


pfam09543
67.9%
0.24
Prediction cycle 1
Likely non-defense function


pfam09254
76.1%
0.58
Prediction cycle 1
Known system


pfam09973
65.5%
0.23
Prediction cycle 1
Likely non-defense function


pfam09570
92.3%
0.42
Prediction cycle 1
Known system


pfam15514
95.1%
0.29
Prediction cycle 1
Known system


pfam08078
66.7%
0.36
Prediction cycle 1
Likely non-defense function


pfam09519
93.2%
0.45
Prediction cycle 1
Known system


pfam09554
97.5%
0.29
Prediction cycle 1
Known system


pfam11428
67.7%
0.13
Prediction cycle 1
Likely non-defense function


pfam16813
98.8%
0.20
Prediction cycle 1
Known system


pfam09895
71.4%
0.18
Prediction cycle 1
Likely non-defense function


pfam11463
88.2%
0.26
Prediction cycle 1
Known system


pfam09436
84.7%
0.28
Prediction cycle 1
Likely mobilome


pfam10884
75.6%
0.40
Prediction cycle 1
Known system


pfam10907
85.1%
0.15
Prediction cycle 1
Likely mobilome


pfam12963
67.1%
0.32
Prediction cycle 1
Likely mobilome


pfam16827
81.6%
0.37
Prediction cycle 1
Likely non-defense function


pfam09871
66.0%
0.16
Prediction cycle 1
Likely non-defense function


pfam12635
94.7%
0.55
Prediction cycle 1
Possibly belongs to a new defense






system


pfam09126
95.5%
0.40
Prediction cycle 1
Known system


pfam06023
93.9%
0.69
Prediction cycle 1
Known system


pfam11645
67.2%
0.21
Prediction cycle 1
Likely non-defense function


pfam12959
87.7%
0.48
Prediction cycle 1
Likely mobilome


pfam06300
95.0%
0.26
Prediction cycle 1
Known system


pfam16948
68.6%
0.49
Prediction cycle 1
Known system


pfam09386
91.1%
0.52
Prediction cycle 1
Known system


pfam09466
89.4%
0.23
Prediction cycle 1
Likely mobilome


pfam16468
92.3%
0.28
Prediction cycle 1
Likely mobilome


pfam09015
98.1%
0.29
Prediction cycle 1
Known system


pfam09544
81.4%
0.19
Prediction cycle 1
Possibly belongs to a new defense






system


pfam05315
98.1%
0.13
Prediction cycle 1
Known system


pfam11426
66.1%
0.36
Prediction cycle 1
Likely mobilome


pfam09553
97.3%
0.29
Prediction cycle 1
Known system


pfam14462
81.4%
0.53
Prediction cycle 1
Likely non-defense function


pfam12960
90.8%
0.46
Prediction cycle 1
Likely mobilome


pfam12997
80.4%
0.17
Prediction cycle 1
Likely non-defense function


pfam09521
95.3%
0.15
Prediction cycle 1
Known system


pfam07015
69.5%
0.61
Prediction cycle 1
Likely mobilome


pfam14457
71.2%
0.51
Prediction cycle 1
Likely mobilome


pfam08998
91.0%
0.19
Prediction cycle 1
Known system


pfam14511
93.2%
0.34
Prediction cycle 1
Known system


pfam09946
97.7%
0.12
Prediction cycle 1
Likely known system


pfam10398
93.2%
0.26
Prediction cycle 1
Likely non-defense function


pfam16762
96.4%
0.33
Prediction cycle 1
Known system


pfam03513
68.1%
0.29
Prediction cycle 1
Likely non-defense function


pfam07820
68.8%
0.41
Prediction cycle 1
Likely mobilome


pfam11320
69.8%
0.27
Prediction cycle 1
Likely non-defense function


pfam16565
81.7%
0.61
Prediction cycle 1
Known system


pfam11341
67.9%
0.27
Prediction cycle 1
Likely non-defense function


pfam09561
80.1%
0.25
Prediction cycle 1
Known system


pfam14386
71.5%
0.45
Prediction cycle 1
Likely mobilome


pfam14192
89.7%
0.30
Prediction cycle 1
Likely mobilome


pfam12617
73.3%
0.24
Prediction cycle 1
Likely non-defense function


pfam14203
88.3%
0.37
Prediction cycle 1
Likely mobilome


pfam07550
67.6%
0.12
Prediction cycle 1
Likely non-defense function


pfam15515
93.8%
0.37
Prediction cycle 1
Known system


pfam14101
76.9%
0.11
Prediction cycle 1
Likely non-defense function


pfam16509
79.5%
0.34
Prediction cycle 1
Likely mobilome


pfam08950
65.4%
0.12
Prediction cycle 1
Likely non-defense function


pfam09274
70.3%
0.39
Prediction cycle 1
Likely mobilome


pfam07764
78.8%
0.19
Prediction cycle 1
Likely mobilome


pfam11083
80.5%
0.11
Prediction cycle 1
Likely mobilome


pfam12957
68.2%
0.48
Prediction cycle 1
Likely mobilome


pfam14194
73.8%
0.29
Prediction cycle 1
Likely mobilome


pfam14461
67.1%
0.35
Prediction cycle 1
Likely mobilome


pfam12599
72.6%
0.55
Prediction cycle 1
Likely mobilome


pfam16734
66.7%
0.39
Prediction cycle 1
Likely non-defense function


pfam14452
85.5%
0.47
Prediction cycle 1
Likely non-defense function


pfam14193
80.3%
0.31
Prediction cycle 1
Likely mobilome


pfam14195
77.6%
0.39
Prediction cycle 1
Likely mobilome


pfam02697
88.4%
0.38
Prediction cycle 1
Known system


pfam14217
67.9%
0.30
Prediction cycle 1
Likely non-defense function


pfam15611
92.5%
0.41
Prediction cycle 1
Possibly belongs to a new defense






system


pfam13910
65.1%
0.27
Prediction cycle 1
Possibly belongs to a new defense






system


pfam12958
67.2%
0.29
Prediction cycle 1
Likely mobilome


pfam14130
66.5%
0.35
Prediction cycle 1
Possibly belongs to a new defense






system


pfam14460
65.9%
0.30
Prediction cycle 1
Likely mobilome


pfam05626
83.4%
0.23
Prediction cycle 1
Uncertain


pfam12664
72.1%
0.17
Prediction cycle 1
Likely mobilome


pfam16560
73.7%
0.11
Prediction cycle 1
Likely mobilome


pfam04796
69.8%
0.42
Prediction cycle 1
Likely mobilome


pfam14271
66.0%
0.15
Prediction cycle 1
Likely non-defense function


pfam08870
92.8%
0.32
Prediction cycle 1
Known system


pfam11211
65.2%
0.29
Prediction cycle 1
Likely mobilome


pfam12469
97.8%
0.67
Prediction cycle 1
Known system


pfam05037
74.5%
0.21
Prediction cycle 1
Likely mobilome


pfam06666
78.2%
0.32
Prediction cycle 1
Likely mobilome


pfam06868
67.3%
0.30
Prediction cycle 1
Likely mobilome


pfam08989
73.7%
0.28
Prediction cycle 1
Uncertain


pfam04411
69.9%
0.54
Prediction cycle 1
Likely known system


pfam11225
73.4%
0.16
Prediction cycle 1
Likely non-defense function


pfam14350
68.9%
0.31
Prediction cycle 1
Known system


pfam14335
91.7%
0.45
Prediction cycle 1
Possibly belongs to a new defense






system


pfam12476
72.9%
0.41
Prediction cycle 1
Possibly belongs to a new defense






system


pfam12750
77.7%
0.31
Prediction cycle 1
Likely mobilome


pfam12564
94.5%
0.19
Prediction cycle 1
Known system


pfam14198
70.8%
0.44
Prediction cycle 1
Likely mobilome


pfam13872
71.6%
0.45
Prediction cycle 1
Likely mobilome


pfam06634
91.9%
0.50
Prediction cycle 1
Possibly belongs to a new defense






system


pfam13871
72.8%
0.46
Prediction cycle 1
Likely mobilome


pfam14283
81.6%
0.35
Prediction cycle 1
Likely mobilome


pfam10987
70.9%
0.14
Prediction cycle 1
Likely non-defense function


pfam08878
86.8%
0.38
Prediction cycle 1
Possibly belongs to a new defense






system


pfam13208
83.0%
0.24
Prediction cycle 1
Possibly belongs to a new defense






system


pfam09509
68.3%
0.39
Prediction cycle 1
Likely known system


pfam12358
70.0%
0.34
Prediction cycle 1
Likely mobilome


pfam15723
76.6%
0.17
Prediction cycle 1
Known system


pfam10980
78.5%
0.22
Prediction cycle 1
Possibly belongs to a new defense






system


pfam15615
85.9%
0.23
Prediction cycle 1
Possibly belongs to a new defense






system


pfam08775
70.6%
0.23
Prediction cycle 1
Likely mobilome


pfam08814
70.1%
0.48
Prediction cycle 1
Possibly belongs to a new defense






system


pfam11848
82.8%
0.53
Prediction cycle 1
Likely known system


pfam12441
81.8%
0.42
Prediction cycle 1
Known system


pfam14267
72.7%
0.54
Prediction cycle 1
Possibly belongs to a new defense






system


pfam14065
65.4%
0.14
Prediction cycle 1
Likely mobilome


pfam13101
70.3%
0.25
Prediction cycle 1
Likely mobilome


pfam01905
99.0%
0.37
Prediction cycle 1
Known system


pfam13351
67.1%
0.25
Prediction cycle 1
Likely mobilome


pfam13337
89.2%
0.44
Prediction cycle 1
Known system


pfam11103
68.9%
0.36
Prediction cycle 1
Likely non-defense function


pfam12083
85.2%
0.20
Prediction cycle 1
Likely mobilome


pfam09035
73.8%
0.17
Prediction cycle 1
Likely mobilome


pfam13707
93.3%
0.26
Prediction cycle 1
Likely known system


pfam07638
67.4%
0.17
Prediction cycle 1
Likely non-defense function


pfam08869
72.6%
0.43
Prediction cycle 1
Possibly belongs to a new defense






system


pfam14355
67.4%
0.33
Prediction cycle 1
Known system


pfam03750
99.9%
0.25
Prediction cycle 1
Known system


pfam06892
71.1%
0.12
Prediction cycle 1
Likely mobilome


pfam14076
73.9%
0.33
Prediction cycle 1
Likely known system


pfam07515
77.4%
0.20
Prediction cycle 1
Likely mobilome


pfam02920
67.7%
0.17
Prediction cycle 1
Likely mobilome


pfam10134
72.8%
0.34
Prediction cycle 1
Likely mobilome


pfam11140
71.2%
0.13
Prediction cycle 1
Likely non-defense function


pfam01881
90.7%
0.40
Prediction cycle 1
Known system


pfam14072
80.6%
0.31
Prediction cycle 1
Known system


pfam10552
72.0%
0.11
Prediction cycle 1
Likely mobilome


pfam09952
92.9%
0.11
Prediction cycle 1
Known system


pfam06290
87.1%
0.12
Prediction cycle 1
Likely mobilome


pfam16277
85.0%
0.19
Prediction cycle 1
Likely known system


pfam14367
97.4%
0.14
Prediction cycle 1
Known system


pfam03683
85.0%
0.46
Prediction cycle 1
Known system


pfam15937
96.2%
0.14
Prediction cycle 1
Likely mobilome


pfam13156
79.4%
0.16
Prediction cycle 1
Likely known system


pfam06952
84.0%
0.12
Prediction cycle 1
Likely mobilome


pfam06953
78.6%
0.10
Prediction cycle 1
Likely non-defense function


pfam14487
82.1%
0.18
Prediction cycle 1
Known system


pfam05107
98.5%
0.35
Prediction cycle 1
Known system


pfam13711
92.8%
0.32
Prediction cycle 1
Likely mobilome


pfam10554
73.2%
0.12
Prediction cycle 1
Likely mobilome


pfam07514
76.0%
0.21
Prediction cycle 1
Likely mobilome


pfam05284
73.1%
0.36
Prediction cycle 1
Likely mobilome


pfam13154
68.0%
0.28
Prediction cycle 1
Likely mobilome


pfam14261
66.3%
0.35
Prediction cycle 1
Likely mobilome


pfam07128
96.0%
0.13
Prediction cycle 1
Likely mobilome


pfam08273
79.8%
0.13
Prediction cycle 1
Likely mobilome


pfam13395
81.0%
0.25
Prediction cycle 1
Known system


pfam06406
79.1%
0.16
Prediction cycle 1
Likely mobilome


pfam14338
84.2%
0.23
Prediction cycle 1
Known system


pfam10117
65.1%
0.35
Prediction cycle 1
Known system


pfam13643
66.4%
0.35
Prediction cycle 1
Likely known system


pfam08401
69.4%
0.33
Prediction cycle 1
Likely mobilome


pfam09907
97.4%
0.14
Prediction cycle 1
Known system


pfam13148
68.0%
0.25
Prediction cycle 1
Uncertain


pfam07275
75.3%
0.14
Prediction cycle 1
Likely mobilome


pfam15738
85.6%
0.18
Prediction cycle 1
Known system


pfam13708
75.2%
0.11
Prediction cycle 1
Uncertain


pfam14384
84.4%
0.22
Prediction cycle 1
Known system


pfam07362
93.8%
0.12
Prediction cycle 1
Known system


pfam03288
70.3%
0.13
Prediction cycle 1
Likely mobilome


pfam05015
96.4%
0.21
Prediction cycle 1
Known system


pfam13310
68.4%
0.36
Prediction cycle 1
Likely known system


pfam11867
78.7%
0.29
Prediction cycle 1
Known system


pfam05168
82.0%
0.31
Prediction cycle 1
Likely known system


pfam04365
80.6%
0.28
Prediction cycle 1
Known system


pfam13391
67.8%
0.28
Prediction cycle 1
Known system


pfam13362
76.6%
0.19
Prediction cycle 1
Likely mobilome


pfam08706
65.4%
0.16
Prediction cycle 1
Likely mobilome


pfam08774
69.9%
0.11
Prediction cycle 1
Likely mobilome


pfam03693
86.8%
0.16
Prediction cycle 1
Known system


pfam04255
66.4%
0.32
Prediction cycle 1
Likely known system


pfam13744
87.2%
0.15
Prediction cycle 1
Known system


pfam06067
76.7%
0.15
Prediction cycle 1
Possibly belongs to a new defense






system


pfam14657
67.2%
0.11
Prediction cycle 1
Likely mobilome


pfam15919
75.6%
0.26
Prediction cycle 1
Likely non-defense function


pfam04221
84.2%
0.18
Prediction cycle 1
Known system


pfam05973
78.5%
0.17
Prediction cycle 1
Known system


pfam03235
66.7%
0.28
Prediction cycle 1
Possibly belongs to a new defense






system


pfam13635
68.0%
0.19
Prediction cycle 1
Possibly belongs to a new defense






system


pfam11657
78.9%
0.37
Prediction cycle 1
Likely mobilome


pfam14662
72.0%
0.53
Prediction cycle 1
Likely non-defense function


pfam04313
90.7%
0.23
Prediction cycle 1
Known system


pfam08130
65.0%
0.31
Prediction cycle 1
Likely non-defense function


pfam09116
94.7%
0.39
Prediction cycle 1
Likely mobilome


pfam04582
85.1%
0.19
Prediction cycle 1
Likely mobilome


pfam04875
79.3%
0.26
Prediction cycle 1
Likely mobilome


pfam11592
68.2%
0.31
Prediction cycle 1
Likely non-defense function


pfam09552
92.7%
0.47
Prediction cycle 1
Known system


pfam10892
93.8%
0.29
Prediction cycle 1
Likely mobilome


pfam09567
72.7%
0.53
Prediction cycle 1
Known system


pfam02691
78.6%
0.12
Prediction cycle 1
Likely non-defense function


pfam08046
78.9%
0.10
Prediction cycle 1
Likely non-defense function


pfam11570
71.0%
0.24
Prediction cycle 1
Likely non-defense function


pfam10083
81.9%
0.19
Prediction cycle 1
Likely mobilome


pfam02048
68.5%
0.44
Prediction cycle 1
Likely non-defense function


pfam13604
66.3%
0.10
Prediction cycle 1
Possibly belongs to a new defense






system


pfam11770
73.5%
0.32
Prediction cycle 1
Likely non-defense function


pfam06709
86.8%
0.36
Prediction cycle 1
Possibly belongs to a new defense






system


pfam16790
84.2%
0.50
Prediction cycle 1
Likely mobilome


pfam04604
65.0%
0.13
Prediction cycle 1
Likely non-defense function


pfam12113
66.1%
0.17
Prediction cycle 1
Likely mobilome


pfam14459
66.7%
0.68
Prediction cycle 1
Likely mobilome


pfam12703
88.5%
0.28
Prediction cycle 1
Known system


pfam02384
77.6%
0.22
Prediction cycle 1
Known system


pfam16848
80.2%
0.15
Prediction cycle 1
Likely non-defense function


pfam11056
76.2%
0.31
Prediction cycle 1
Likely mobilome


pfam07339
95.1%
0.36
Prediction cycle 1
Likely mobilome


pfam14562
96.9%
0.39
Prediction cycle 1
Known system


pfam09185
82.9%
0.14
Prediction cycle 1
Likely non-defense function


pfam12493
82.3%
0.32
Prediction cycle 1
Likely mobilome


pfam16831
68.0%
0.28
Prediction cycle 1
Likely non-defense function


pfam01818
75.0%
0.50
Prediction cycle 1
Likely mobilome


pfam11554
67.2%
0.69
Prediction cycle 1
Likely mobilome


pfam09504
97.8%
0.34
Prediction cycle 1
Known system


pfam16243
100.0%
0.22
Prediction cycle 1
Likely mobilome


pfam16280
90.9%
0.34
Prediction cycle 1
Likely known system


pfam09020
98.5%
0.14
Prediction cycle 1
Likely mobilome


pfam09562
80.0%
0.55
Prediction cycle 1
Known system


pfam07154
75.5%
0.45
Prediction cycle 1
Possibly belongs to a new defense






system


pfam06443
77.1%
0.12
Prediction cycle 1
Likely non-defense function


pfam03295
100.0%
0.50
Prediction cycle 1
Likely mobilome


pfam13128
68.4%
0.15
Prediction cycle 1
Likely mobilome


pfam11504
74.8%
0.18
Prediction cycle 1
Likely non-defense function


pfam12136
98.2%
0.14
Prediction cycle 1
Likely non-defense function


pfam07042
74.7%
0.50
Prediction cycle 1
Likely mobilome


pfam11459
87.6%
0.24
Prediction cycle 1 +
Likely known system





Makarova et al. (2011)4



pfam11726
79.5%
0.12
Prediction cycle 1 +
Likely mobilome





Makarova et al. (2011)



pfam01954
87.5%
0.54
Prediction cycle 1 +
Known system





Makarova et al. (2011)



pfam03428
86.2%
0.26
Prediction cycle 1 +
Likely mobilome





Makarova et al. (2011)



pfam06924
91.9%
0.19
Prediction cycle 1 +
Likely mobilome





Makarova et al. (2011)



pfam07183
77.6%
0.59
Prediction cycle 1 +
Likely mobilome





Makarova et al. (2011)



pfam11800
84.5%
0.26
Prediction cycle 1 +
Likely mobilome





Makarova et al. (2011)



pfam09722
90.4%
0.12
Prediction cycle 1 +
Known system





Makarova et al. (2011)



pfam11994
72.6%
0.39
Prediction cycle 1 +
Possibly belongs to a new defense





Makarova et al. (2011)
system


pfam12101
84.6%
0.19
Prediction cycle 1 +
Likely mobilome





Makarova et al. (2011)



pfam08900
90.5%
0.17
Prediction cycle 1 +30
Likely mobilome





Makarova et al. (2011)



pfam10074
83.5%
0.24
Prediction cycle 1 +
Likely mobilome





Makarova et al. (2011)



pfam11000
71.8%
0.22
Prediction cycle 1 +
Likely mobilome





Makarova et al. (2011)



pfam11284
86.2%
0.21
Prediction cycle 1 +
Likely mobilome





Makarova et al. (2011)



pfam11358
95.8%
0.17
Prediction cycle 1 +
Likely mobilome





Makarova et al. (2011)



pfam11679
93.3%
0.18
Prediction cycle 1 +
Likely mobilome





Makarova et al. (2011)



pfam12553
86.9%
0.19
Prediction cycle 1 +
Likely mobilome





Makarova et al. (2011)



COG4688


Makarova et al. (2011)
Likely mobilome


COG4190


Makarova et al. (2011)
Likely known system


COG5428


Makarova et al. (2011)
Likely known system


COG3756


Makarova et al. (2011)
Likely mobilome


COG4185


Makarova et al. (2011)
Likely non-defense function


COG4854


Makarova et al. (2011)
Likely non-defense function


COG5532


Makarova et al. (2011)
Likely mobilome


COG5545


Makarova et al. (2011)
Likely mobilome


COG5658


Makarova et al. (2011)
Likely non-defense function


pfam01724
64.0%
0.34
Makarova et al. (2011)
Likely non-defense function


pfam03432
62.3%
0.27
Makarova et al. (2011)
Likely mobilome


pfam09588
40.7%
0.25
Makarova et al. (2011)
Likely mobilome


pfam11238
37.1%
0.10
Makarova et al. (2011)
Likely non-defense function


COG1205


Makarova et al. (2011)
Possibly belongs to a new defense






system


COG4913


Makarova et al. (2011)
Possibly belongs to a new defense






system


COG4924


Makarova et al. (2011)
Possibly belongs to a new defense






system


pfam04383
32.4%
0.28
Makarova et al. (2011)
Possibly belongs to a new defense






system


COG1112


Makarova et al. (2011)
Uncertain


COG1373


Makarova et al. (2011)
Uncertain


COG2865


Makarova et al. (2011)
Uncertain


COG3598


Makarova et al. (2011)
Likely mobilome


pfam10543
55.9%
0.26
Makarova et al. (2011)
Uncertain


pfam11185
50.8%
0.35
Makarova et al. (2011)
Uncertain


pfam09823
69.1%
0.52
Makarova et al. (2011)
Likely known system


COG5519


Makarova et al. (2011)
Likely mobilome


pfam10711
29.6%
0.18
Makarova et al. (2011)
Likely mobilome


COG1483


Makarova et al. (2011)
Possibly belongs to a new defense






system


COG3586


Makarova et al. (2011)
Possibly belongs to a new defense






system


COG3950


Makarova et al. (2011)
Possibly belongs to a new defense






system


COG4804


Makarova et al. (2011)
Possibly belongs to a new defense






system


pfam01541
31.4%
0.10
Makarova et al. (2011)
Uncertain


COG1475


Makarova et al. (2011)
Likely mobilome


COG0507


Makarova et al. (2011)
Likely non-defense function


COG0553


Makarova et al. (2011)
Possibly belongs to a new defense






system


COG1192


Makarova et al. (2011)
Likely mobilome


COG1451


Makarova et al. (2011)
Possibly belongs to a new defense






system


COG3727


Makarova et al. (2011)
Known system


pfam01464
22.2%
0.10
Makarova et al. (2011)
Likely mobilome


pfam02876
60.9%
0.01
Makarova et al. (2011)
Likely non-defense function


pfam03837
33.5%
0.12
Makarova et al. (2011)
Likely mobilome


pfam08861
30.3%
0.09
Makarova et al. (2011)
Likely known system


pfam09199
92.0%
0.00
Makarova et al. (2011)
Likely non-defense function


pfam09954
21.0%
0.31
Makarova et al. (2011)
Possibly belongs to a new defense






system


COG3505


Makarova et al. (2011)
Likely mobilome


COG3843


Makarova et al. (2011)
Likely mobilome


COG4227


Makarova et al. (2011)
Likely mobilome


COG4646


Makarova et al. (2011)
Likely mobilome


COG4930


Makarova et al. (2011)
Known system


COG5489


Makarova et al. (2011)
Likely mobilome


pfam07895
42.0%
0.03
Makarova et al. (2011)
Likely non-defense function


pfam08849
95.2%
0.39
Makarova et al. (2011)
Known system


pfam09002
46.1%
0.50
Makarova et al. (2011)
Known system


pfam11198
80.0%
0.14
Makarova et al. (2011)
Likely mobilome


pfam11455
97.1%
0.10
Makarova et al. (2011)
Known system


pfam11985
22.7%
0.18
Makarova et al. (2011)
Likely mobilome


COG1479


Makarova et al. (2011)
Known system


COG3472


Makarova et al. (2011)
Known system


pfam10923
93.1%
0.28
Makarova et al. (2011)
Possibly belongs to a new defense






system


pfam12495
85.7%
0.17
Prediction cycle 2
Likely non-defense function


pfam04787
100.0%
1.00
Prediction cycle 2
Likely mobilome


pfam15541
69.0%
0.40
Prediction cycle 2
Likely mobilome


pfam04778
68.8%
0.36
Prediction cycle 2
Likely non-defense function


pfam07199
69.7%
0.26
Prediction cycle 2
Likely non-defense function


pfam10790
68.4%
0.65
Prediction cycle 2
Likely mobilome


pfam09131
79.5%
0.19
Prediction cycle 2
Likely non-defense function


pfam16445
66.7%
0.19
Prediction cycle 2
Likely non-defense function


pfam11519
69.0%
0.28
Prediction cycle 2
Likely non-defense function


pfam11516
95.3%
0.17
Prediction cycle 2
Likely non-defense function


pfam16904
76.5%
0.10
Prediction cycle 2
Likely non-defense function


pfam07046
90.4%
0.11
Prediction cycle 2
Likely non-defense function


pfam16436
86.8%
0.11
Prediction cycle 2
Likely non-defense function


pfam14590
72.2%
0.15
Prediction cycle 2
Likely non-defense function


pfam12772
69.8%
0.22
Prediction cycle 2
Likely non-defense function


pfam11263
98.3%
0.10
Prediction cycle 2
Likely non-defense function


pfam10913
69.7%
0.11
Prediction cycle 2
Likely mobilome


pfam16390
68.8%
0.13
Prediction cycle 2
Uncertain


pfam16847
65.0%
0.38
Prediction cycle 2
Likely non-defense function


pfam11565
92.0%
0.11
Prediction cycle 2
Likely non-defense function


pfam03857
65.7%
0.52
Prediction cycle 2
Likely non-defense function


pfam13497
92.2%
0.19
Prediction cycle 2
Likely mobilome


pfam08048
85.3%
0.33
Prediction cycle 2
Likely mobilome


pfam09264
83.5%
0.11
Prediction cycle 2
Likely non-defense function


pfam05946
72.9%
0.13
Prediction cycle 2
Likely non-defense function


pfam09930
97.8%
0.16
Prediction cycle 2
Likely non-defense function


pfam16163
68.5%
0.68
Prediction cycle 2
Likely non-defense function


pfam16754
75.7%
0.29
Prediction cycle 2
Known system


pfam16416
65.2%
0.48
Prediction cycle 2
Possibly belongs to a new defense






system


pfam06613
82.2%
0.36
Prediction cycle 2
Likely mobilome


pfam16479
88.9%
0.11
Prediction cycle 2
Likely non-defense function


pfam05969
65.3%
0.40
Prediction cycle 2
Likely non-defense function


pfam15538
66.0%
0.10
Prediction cycle 2
Likely non-defense function


pfam10865
68.9%
0.41
Prediction cycle 2
Likely non-defense function


pfam07828
85.5%
0.12
Prediction cycle 2
Likely non-defense function


pfam11580
85.6%
0.10
Prediction cycle 2
Likely non-defense function


pfam08017
68.3%
0.10
Prediction cycle 2
Likely non-defense function


pfam05265
88.7%
0.12
Prediction cycle 2
Likely mobilome


pfam13009
66.7%
0.53
Prediction cycle 2
Likely mobilome


pfam09016
65.9%
0.19
Prediction cycle 2
Likely non-defense function


pfam10726
67.3%
0.29
Prediction cycle 2
Likely non-defense function


pfam10130
69.0%
0.71
Prediction cycle 2
Known system


pfam10616
78.4%
0.10
Prediction cycle 2
Likely non-defense function


pfam13314
69.8%
0.11
Prediction cycle 2
Likely non-defense function


pfam04485
65.1%
0.35
Prediction cycle 2
Possibly belongs to a new defense






system


pfam12655
65.6%
0.12
Prediction cycle 2
Likely non-defense function


pfam13079
69.0%
0.11
Prediction cycle 2
Likely non-defense function


pfam14275
67.6%
0.13
Prediction cycle 2
Likely non-defense function


pfam11686
70.8%
0.11
Prediction cycle 2
Likely non-defense function


pfam11397
67.0%
0.13
Prediction cycle 2
Likely non-defense function


pfam11796
65.0%
0.59
Prediction cycle 2
Possibly belongs to a new defense






system


pfam09000
66.3%
0.28
Prediction cycle 2
Likely non-defense function


pfam14453
65.8%
0.12
Prediction cycle 2
Likely non-defense function


pfam13651
85.8%
0.46
Prediction cycle 2
Known system


pfam11173
66.6%
0.11
Prediction cycle 2
Likely non-defense function


pfam16162
70.6%
0.46
Prediction cycle 2
Possibly belongs to a new defense






system


pfam12975
68.1%
0.11
Prediction cycle 2
Likely non-defense function


pfam14133
71.1%
0.18
Prediction cycle 2
Likely non-defense function


pfam16082
65.4%
0.15
Prediction cycle 2
Likely mobilome


pfam16223
66.3%
0.11
Prediction cycle 2
Likely non-defense function


pfam12545
65.6%
0.11
Prediction cycle 2
Likely non-defense function


pfam09664
67.9%
0.50
Prediction cycle 2
Possibly belongs to a new defense






system


pfam11813
79.5%
0.10
Prediction cycle 2
Likely non-defense function


pfam11149
69.5%
0.52
Prediction cycle 2
Likely mobilome


pfam16263
76.4%
0.35
Prediction cycle 2
Possibly belongs to a new defense






system


pfam12119
72.8%
0.11
Prediction cycle 2
Likely non-defense function


pfam10893
91.7%
0.13
Prediction cycle 2
Likely mobilome


pfam14790
67.2%
0.11
Prediction cycle 2
Likely non-defense function


pfam12668
68.0%
0.38
Prediction cycle 2
Possibly belongs to a new defense






system


pfam14082
65.3%
0.57
Prediction cycle 2
Possibly belongs to a new defense






system


pfam06698
79.9%
0.12
Prediction cycle 2
Likely non-defense function


pfam07509
65.6%
0.12
Prediction cycle 2
Likely non-defense function


pfam07323
77.8%
0.12
Prediction cycle 2
Likely non-defense function


pfam09919
98.4%
0.11
Prediction cycle 2
Likely non-defense function


pfam16930
85.1%
0.11
Prediction cycle 2
Likely non-defense function


pfam14113
71.7%
0.14
Prediction cycle 2
Likely non-defense function


pfam13151
65.5%
0.40
Prediction cycle 2
Possibly belongs to a new defense






system


pfam14328
71.3%
0.13
Prediction cycle 2
Likely non-defense function


pfam07511
68.4%
0.23
Prediction cycle 2
Likely mobilome


pfam14281
71.4%
0.59
Prediction cycle 2
Possibly belongs to a new defense






system


pfam14584
79.8%
0.12
Prediction cycle 2
Likely non-defense function


pfam11047
78.1%
0.11
Prediction cycle 2
Likely non-defense function


pfam11660
70.4%
0.20
Prediction cycle 2
Likely mobilome


pfam11190
67.1%
0.20
Prediction cycle 2
Likely mobilome


pfam14103
97.7%
0.39
Prediction cycle 2
Likely known system


pfam09686
68.6%
0.20
Prediction cycle 2
Likely mobilome


pfam15978
75.8%
0.25
Prediction cycle 2
Likely mobilome


pfam09376
67.6%
0.33
Prediction cycle 2
Possibly belongs to a new defense






system


pfam12602
69.9%
0.18
Prediction cycle 2
Likely mobilome


pfam07455
91.6%
0.11
Prediction cycle 2
Likely mobilome


pfam16452
82.1%
0.13
Prediction cycle 2
Likely mobilome


pfam11072
75.0%
0.20
Prediction cycle 2
Likely mobilome


pfam14253
69.7%
0.30
Prediction cycle 2
Known system


pfam15731
83.3%
0.28
Prediction cycle 2
Known system


pfam05419
65.3%
0.43
Prediction cycle 2
Possibly belongs to a new defense






system


pfam12870
65.4%
0.18
Prediction cycle 2
Likely non-defense function


pfam10723
78.2%
0.20
Prediction cycle 2
Likely mobilome


pfam14302
67.0%
0.10
Prediction cycle 2
Likely non-defense function


pfam14348
69.7%
0.23
Prediction cycle 2
Likely mobilome


pfam10049
75.1%
0.51
Prediction cycle 2
Likely known system


pfam13814
65.5%
0.25
Prediction cycle 2
Likely mobilome


pfam12834
67.9%
0.27
Prediction cycle 2
Likely mobilome


pfam09937
66.2%
0.10
Prediction cycle 2
Likely non-defense function


pfam08937
67.8%
0.33
Prediction cycle 2
Possibly belongs to a new defense






system


pfam09903
65.6%
0.26
Prediction cycle 2
Possibly belongs to a new defense






system


pfam02521
90.4%
0.11
Prediction cycle 2
Likely non-defense function


pfam12835
70.7%
0.31
Prediction cycle 2
Likely mobilome


pfam02387
75.9%
0.20
Prediction cycle 2
Likely mobilome


pfam13784
65.1%
0.47
Prediction cycle 2
Possibly belongs to a new defense






system


pfam09848
65.6%
0.45
Prediction cycle 2
Known system


pfam12950
67.4%
0.39
Prediction cycle 2
Known system


pfam13166
75.6%
0.39
Prediction cycle 2
Known system


pfam13555
70.4%
0.27
Prediction cycle 2
Possibly belongs to a new defense






system


pfam01927
65.2%
0.19
Prediction cycle 2
Likely known system


pfam06006
93.4%
0.14
Prediction cycle 2
Likely mobilome


pfam06174
98.7%
0.10
Prediction cycle 2
Likely mobilome


pfam11398
85.9%
0.10
Prediction cycle 2
Likely non-defense function


pfam12686
65.4%
0.32
Prediction cycle 2
Likely mobilome


pfam03596
70.8%
0.12
Prediction cycle 2
Likely non-defense function


pfam06527
68.3%
0.31
Prediction cycle 2
Likely mobilome


pfam07799
70.7%
0.12
Prediction cycle 2
Likely mobilome


pfam13470
67.0%
0.43
Prediction cycle 2
Known system


pfam13588
68.3%
0.37
Prediction cycle 2
Known system


pfam05713
65.0%
0.39
Prediction cycle 2
Likely mobilome


pfam05272
68.0%
0.17
Prediction cycle 2
Uncertain


pfam13749
69.0%
0.43
Prediction cycle 2
Possibly belongs to a new defense






system


pfam13657
69.5%
0.30
Prediction cycle 2
Known system


pfam04326
65.1%
0.39
Prediction cycle 2
Possibly belongs to a new defense






system


pfam06769
96.5%
0.12
Prediction cycle 2
Known system


pfam02498
66.8%
0.17
Prediction cycle 2
Likely mobilome


pfam13173
68.3%
0.26
Prediction cycle 2
Possibly belongs to a new defense






system


pfam05685
67.2%
0.27
Prediction cycle 2
Uncertain


pfam13538
66.9%
0.13
Prediction cycle 2
Possibly belongs to a new defense






system


pfam01402
67.6%
0.12
Prediction cycle 2
Likely non-defense function


pfam12705
76.4%
0.10
Prediction cycle 2
Likely non-defense function


pfam13175
73.9%
0.37
Prediction cycle 2
Possibly belongs to a new defense






system


pfam13304
63.8%
0.33
Prediction cycle 2
Possibly belongs to a new defense






system






4Makarova et al. J Bacteriol. 2011 Nov; 193(21): 6039-6056






From genes to systems: Each of the putative defense-related gene families was used as an anchor to search for multi-gene systems, as follows. The protein coding sequences for neighboring genes (+/−10 genes) for all family members were clustered based on sequence homology (for example, if pfamY is found within 50 genomes in our set, the 20 neighboring genes in each genome, plus the pfamY gene in each genome, were taken—altogether 50*21=1050 genes to be clustered). Clustering was done with OrthoMCL software v2.0.9 (Li L, Stoeckert C J, Roos D S. (2003) OrthoMCL: identification of ortholog groups for eukaryotic genomes. Genome Res. 13: 2178-89) with blastp parameters [-F ′m S′-v 100000 -b 100000 -e 1e-5 -m 8] and with mcl v12.068 downloaded from http://micans.org/mcl/ (Enright A J, Van Dongen S, Ouzounis C A. (2002) An efficient algorithm for large-scale detection of protein families. nucleic Acids Res. 30: 1575-84; van Dongen S, Abreu-Goodger C. (2012) Using MCL to Extract Clusters from Networks. Methods in molecular biology (Clifton, N.J.). pp. 281-295) with inflation value of 1.1. When the number of blastp hits for a given anchor pfam was too large and prohibitive for OrthoMCL to generate clusters (>75 million blastp hits), a subset of genomes, containing only bacterial and archaeal genomes annotated as “complete” (rather than “draft”) was used for clustering.


To detect the most prevalent genes around the anchor pfam, only the 10% largest clusters (“frequent clusters”) were considered. For the sake of cluster size calculation, genes originating from the same species (derived from the strain name in the NCBI annotation) were counted as one gene, to prevent organisms for which many strains have been sequenced from inflating the cluster size. An edge between cluster(i) and cluster(j) was defined if a gene from cluster(j) followed a gene from cluster(i) in a given genome with no other genes belonging to frequent clusters found in between, with edge weight (“thickness”) defined as the number of such adjacency cases. Again, edge weights were adjusted such that multiple appearances of a cluster pair originating from the same species were recorded as a single appearance. Only the 10% thickest edges were retained for further analysis. In each genome, the maximal “path” that included the anchor pfam gene and was composed of the retained (largest) clusters and the retained (thickest) edges was recorded. Such a “path”, representing a set of genes appearing in a conserved order in multiple genomes, was considered a candidate multi-gene system. Infrequent variations on the gene order and composition of common systems were merged into the common system if they shared at least 50% of their clusters and had less than 25% appearances than the common system. Only systems with five or more appearances from different species were further analyzed.


The domains within the gene members of each system were analyzed bioinformatically using the tools HHpred (Soding J, Biegert A, Lupas A N. (2005) The HHpred interactive server for protein homology detection and structure prediction. nucleic Acids Res. 33: W244-W248; Alva V, Nam S-Z, Soding J, Lupas A N, I. S, S. C, et al. (2016) The MPI bioinformatics Toolkit as an integrative platform for advanced protein sequence and structure analysis. nucleic Acids Res. Oxford University Press; 44: W410-W415), Phyre2 (Kelley L A, Mezulis S, Yates C M, Wass M N, Sternberg M J E. (2015) The Phyre2 web portal for protein modeling, prediction and analysis. Nat Protoc. Nature Research; 10: 845-858), PSI-BLAST (Altschul S F, Madden T L, Schïffer A A, Zhang J, Zhang Z, Miller W, et al. (1997) Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. nucleic Acids Res. 25: 3389-402), and NCBI's Conserved Domain Database (CDD) (Marchler-Bauer A, Lu S, Anderson J B, Chitsaz F, Derbyshire M K, DeWeese-Scott C, et al. (2011) CDD: a Conserved Domain Database for the functional annotation of proteins. nucleic Acids Res. 39: D225-D229). The systems were then manually filtered, based on this analysis, to remove (i) known defense systems whose domains did not appear in our initial set of gene families known to participate in defense; (ii) systems likely representing mobile genetic elements (“mobilome”) and; (iii) systems likely participating in non-defensive functions or house-keeping systems (Table 2).


A second cycle of prediction was then performed, expanding the set of “positive” gene families from Table 1 to include the gene families participating in the candidate new defense systems, as well as the gene families participating in known defense systems that were previously missing from our set and detected in the first round. All pfams were again scanned and the same thresholds were applied (defense score 65%, context variability score 0.1). New pfams retrieved from the second cycle were analyzed as above to generate and annotate multi-gene systems.


Candidate new systems were further prioritized to select instances for experimental validations. Systems tagged as “questionable”, due to uncertainty whether they represent defense genes or mobile genetic elements, were filtered out (Table 3). Systems existing in only a narrow range of organisms, as well as systems that were not found in organisms phylogenetically close either to E. coli or B. subtilis, were not tested experimentally (Table 3).









TABLE 3







Candidate Defense Systems












Included/





Excluded from



Anchor protein
Number
experimental



families
of genes?
study
Reason for exclusion





pfam04033
1
Excluded
Archaea specific


pfam11536
2
Excluded

Thermococcus specific


pfam12635;
3-4
Included
—


pfam06634;





COG1483





pfam09544
3-4
Excluded

Myxococcales specific


pfam15611;
3-4
Included
—


COG0553





pfam13910
1
Included
—


pfam14130
2
Included
—


pfam14335
1-2
Excluded
No locus that is a stand-





alone gene, always





within R-M systems


pfam12476;
3
Included
—


pfam03235





pfam08878
2
included
—


pfam13208;
3
Included
—


pfam15615;





pfam10923





pfam10980
7
Included
—


pfam08814;
2
Excluded

Cyanobacteria specific


pfam08869





pfam14267
1
Included
—


pfam06067
1-2
Excluded
Loci in Bacillus are in





phage/mobilome





context


pfam13635;
1
Included
—


pfam13173





pfam13604;
1
Included
—


pfam13538





pfam06709
1
Excluded

Vibrio specific


pfam07154
1
Excluded

Cyanobacteria specific


pfam11994
3
Excluded
Not found in





bacillus/coli


COG1205
2-5
Included
—


COG4913;
3-4
Included
—


COG4924;





pfam11796;





pfam09664;





pfam13555





pfam04383
1
Included
—


COG3586
1
Included
—


COG3950
2
Included
—


COG4804
1
Included
—


COG1451
1
Included
—


pfam09954
1
Excluded
No appropriate locus





that is a stand-alone





gene, always comes





with other genes +





already exists in





BEST7003


pfam16416;
2-4
Excluded

Cyanobacteria specific


pfam05419





pfam04485
4
Excluded

Cyanobacteria specific


pfam16162
2
Included
—


pfam16263
1
Excluded
Loci in Bacillus are in





phage/mobilome





context


pfam12668;
2
Included
—


pfam13151





pfam14082
1
Included
—


pfam14281
1
Included
—


pfam09376
3
Included
—


pfam08937
2
Included
—


pfam09903
1
Included
—


pfam13784
1
Included
—


pfam13749;
1
Included
—


pfam04326





pfam13175;
2
included
—


pfam13304









Phylogenetic Distribution Analysis of New Systems:


For each validated defense system, several loci including the locus that was experimentally verified were taken as seeds for psi-Blast. psi-Blast version 2.5.0 of BLAST+ (Altschul S F, Madden T L, Schïffer A A, Zhang J, Zhang Z, Miller W, Lipman D J. (1997) Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. nucleic Acids Res.; 25: 3389-402; Camacho C, Coulouris G, Avagyan V, Ma N, Papadopoulos J, Bealer K, Madden TL. (2009) BLAST+: architecture and applications. BMC Bioinformatics. 10: 421. doi: 10.1186/1471 -2105-10-421) with parameters [-num_iterations 10 -max_hsps 1 -max_target_seqs 100000 -evalue 1e-10] was performed for each protein of each system, against all microbial genomes downloaded from NCBI on April 2016. When the hits of all proteins of a system were found closely localized on a genome, spanning no more than 150% of the length of the original system, this genome was recorded as containing the system. For the Druantia and Wadjet systems, -evalue 1e-5 was used to enable detection of distant homologs. For systems with 4 or 5 genes (Zorya type I, Druantia types I and II, Wadjet), systems were reported if at least 3 of their genes were identified. For the Druantia system, systems with hits to the DruE protein were retained if the DruE size was >1300aa. For the Thoeris system, multiple thsB genes near the thsA gene were recorded if they were within 10 kb of genomic DNA around the identified thsA. Phylum for each genome was obtained using the JGI taxonomy server (https://taxonomyjgi-psf.org/).


Experimental Validation of Defense Systems


Cloning of the Systems into E. coli MG1655 and/or B. subtilis BEST7003


A cloning shuttle vector for large fragments was constructed as previously described (Ofir G, Melamed S, Sberro H, Silverman S, Doron S, Yaakov G, Mukamel Z, Sorek R. (2017) DISARM, a novel bacterial defense system with broad anti-phage activities, submitted). The vector contains a p15a origin of replication and ampicillin resistance for plasmid propagation in E. coli, and amyE integration cassette with spectinomycin resistance for genomic integration into B. subtilis. The backbone of this vector was amplified using primers OGO309+OGO310, adding to it a BamHI restriction site and a terminator site upstream to the insert cloning site. The multiple cloning site of plasmid pBS1C (Radeck J, Kraft K, Bartels J, Cikovic T, Dürr F, Emenegger J, Kelterborn S, Sauer C, Fritz G, Gebhard S, Mascher T. (2013) The Bacillus BioBrick Box: generation and evaluation of essential genetic building blocks for standardized work with Bacillus subtilis. J Biol Eng. BioMed Central; 7: 29. doi:10.1186/1754-1611-7-29), received from BGSC (accession ECE257), was amplified using primers OGO311+OGO312. Both fragments were digested using AscI and BamHI, ligated using T4 ligase and transformed into E. coli, resulting in plasmid pSG1-rfp.


The loci of most systems were commercially synthesized by Genscript and cloned, also by Genscript, directly into pSG1-rfp between the AscI and NotI sites of the multiple cloning site (Table 4: “Cloning method” column).









TABLE 4





Loci for Candidate Systems




















Anchor

Construct
Donor bacteria




protein
System
number
(IMG
Position
Length


families
name
(C.N.)
accession)
(strand)
in bp





pfam16162
Kiwa
1

Bacillus sp.
1801073-1803310
2238





FJAT-27997
(+)





(Ga0081961_11)



Kiwa
2

E. coli O55:H7
5120652-5122819
2168





RM12579
(−)





(CP003109)


pfam08878
Hachiman
3

B. cereus

106560-111167
5122





B4087
(−)





(phylogroup





III-12 9)





(LCYM01000053)



Hachiman
4

B. cereus

77887-82731
4845





H3081.97
(+)





(ABDL02000007)


pfam13749;

5

B. iranensis

391132-393430
2299


pfam04326


DSM 23995
(+)





(Ga0075261_103)




6

B. boroniphilus

3453-5851
2399





JCM 21738
(−)





(Ga0054992_1085)


pfam13175;
Gabija
7

B. cereus

172515-177839
5325


pfam13304


HuB5-5
(+)





(AHEG01000016)



Gabija
8

B. cereus

93871-97763
3893





VD045
(+)





(AHET01000033)


pfam13208;

9

B. methanolicus

1037084-1043201
6118


pfam15615;


PB1
(−)


pfam10923


(AFEU01000001)




10

B. cereus

118058-124729
6672





NVH0597-99
(−)





ABDK02000013





(ABDK02000013)


pfam04383

11

Enterococcus

142827-143797
970






faecalis TR197
(+)





(ASDV01000010)




12

Lactobacillus

785262-786580
1320






plantarum

(−)





subsp.






plantarum ST-





III chromosome





(NC_014554)


pfam14130
Lamassu
13

Bacillus sp.
104996-108335
3358





NIO-1130
(−)





(Ga0061086_109)



Lamassu
14

B. cereus

52399-56035
3637





VD014
(+)





(AHER01000061)


pfam10980

15

Pseudoalteromonas

119710-124196
4486






marina

(−)





mano4





(AHCB02000060)




16

E. coli UMEA
116829-122750
5921





3355-1
(−)





(AWDK01000015)


pfam13604;

17

B. cereus

120797-124381
3585


pfam13538


HuA2-1
(+)





(AHDV01000009)




18

B. paralicheniformis

4324128-4327523
3382





ATCC 9945a
(−)





(CP005965





(NC 021362))


pfam13635;

19

Bacillus sp.
420-2978
2559


pfam13173


L1(2012)
(−)





(BLTDRAFT_ANNK01000002_1.2)




20

Bacillus sp.
98213-100268
2056





MT2
(+)





(Ga0058649_116)


pfam12668;

21

B. cereus

4327581-4328881
1301


pfam13151


G9241
(−)





(Ga0077877_11)




22

B. cereus

92524-94334
1811





R309803
(−)





(NZ_ACLY01000076)


pfam09376

23

B. cereus Q1
1003565-1008191
4627





(NC_011969)
(+)




24

B. subtilis Hall
25333-30937
5605





(A921DRAFT_AMCA01000155_1.155)
(−)


pfam13784

25

E. coli H397
928-2724
1797





(AEXH01000043)
(−)




26

E. coli UMEA
254125-256825
2000





3108-1
(+)





(AWBD01000001)


pfam14082
Shedu
27

B. cereus

186286-187555
1270





BAG2O-2
(−)





(AHCX01000044)



Shedu
28

B. cereus

954837-957049
2213





B4264
(−)





(NC_011725)


pfam12635;

29

Paenibacillus

743619-754251
10633


pfam06634;



sabinae T27

(+)


COG1483


(CP004078)


COG4804

30

Paenibacillus

649-3948
3300






sophorae S27
(+)





(L689DRAFT_ASSF01000040_1.18)


pfam08937
Thoeris
31

B. cereus MSX-
16453-19685
2477





D12
(+)





(AHEQ01000050)



Thoeris
32

B. amyloliquefaciens

2071378-2073427
2050





Y2
(−)





(CP003332)



Thoeris
33

B. cereus

93628-95745
1689





HuB4-4
(+)





(AHEF01000014)



Thoeris
34

B. thuringiensis

134769-136361
1590





serovar
(−)






finitimus YBT-





020 plasmid





pBMB26





(CP002509)


pfam14267

35

Paenibacillus

94753-96069
1316






macerans 8244
(−)





(Ga0097770_129)




36

B. cereus

57053-58320
1154





BAG2X1-1
(−)





(AHCZ01000031)


pfam12476;

37

Solibacillus

1395361-1399023
3663


pfam03235



silvestris

(+)





(AP012157)




38

Tumebacillus

100864-104082
3219






flagellatus

(−)





GST4





(JMIR01000008)




39

Paenibacillus

23305-26493
3189





sp. FSL R7-269
(+)





(ASPS01000025)


COG1451

40

B. cereus

119987-121875
1888





MC67
(+)





(AHEN01000008)




41

B. cereus IS195
240659-242023
1364





(AHEH01000058)
(+)


COG3950
Septu
42

B. thuringiensis

2740820-2743903
3083





HD12
(+)





(Ga0125139_15)



Septu
43

B. weihenstephanensis

3499862-3504110
3745





KBAB4
(−)





(NC_010184)



Septu
44

B. cereus

90978-93642
2665





m1293
(−)





(NZ_ACLS01000104)


COG3586

45

B. paralicheniformis

829842-834035
4194





ATCC 9945a
(+)





(CP005965





(NC_021362))




46

B. vallismortis

121062-122280
1219





DV1-F-3
(+)





(GYSDRAFT_AFSH01000055_1.55)




47

Bacillus sp.
1839870-1841334
1465





BC15
(+)





(Ga0066720_10)


pfam09903

48

Geobacter sulfurreducens

72105-73998
1894





AM-1
(+)





(Ga0098194_11)


pfam15611;
Zorya
49

E. coli

298890-307639
8750


COG0553


E24377A
(−)





(NC_009801)



Zorya
50

E. coli KOEGE
522466-531355
8890





71 (186a)
(+)





(AWAO01000003)



Zorya
51

E. coli ATCC
4265695-4269611
3917





8739
(+)





(NC_010468)


pfam14281

52

B. cereus LK9
37579-39692
2114





(Ga0081098-108)
(−)




53

B. cereus

14516-15854
1339





VD200
(+)





(AHFM01000019)




54

B. subtilis HM-
187758-189194
1437





66
(−)





(Ga0124450_104)


COG1205
Druantia
55

E. coli KTE181
35990-46193
10204





(ANTC01000054)
(+)



Druantia
56

E. coli UMEA
219529-231495
11967





4076-1
(+)





(AWEM01000032)



Druantia
57

B. cereus LK9
4022-14331
10310





(Ga0081098_108)
(−)


pfam13910

58

B. megaterium

3517210-3519233
2024





Q3
(−)





(Ga0081752_11)


COG4913;
Wadjet
59

B. cereus Q1
1011280-1018329
7050


COG4924;


(NC_011969)
(+)


pfam11796;


pfam09664;


pfam13555



Wadjet
60

B. vireti LMG
67917-76250
8334





21834
(−)





(ALAN01000059)



Wadjet
61

B. thuringiensis

1018412-1025427
7013





serovar
(+)






finitimus YBT-





020 plasmid





pBMB26





(CP002508)


Controls


Type III

63

Lactobacillus

1034479-1039919
5441


RM system



rhamnosus GG
(+)


(BceSI)


(AP011548)


Type III

64

B. thuringiensis

52683-53616
934


TA system


sv. kurstaki
(+)


(ToxIN)


HD-1





(CP004874)


Type II RM

65

B. amyloliquefaciens

3187589-3190876
3192


system


DSM 7
(+)


(BamHI)


(NC_014551)


Abi system

66

B. cereus

18460-19683
1224


(AbiH)


ATCC 10876
(−)





(NZ_ACLT01000157)


Type I RM

67

B. glycinifermentans

59672-66665
6994


system


TH008
(−)


(BliDi)


(Ga0077513_1025)


DISARM

68

B. paralicheniformis

815730-826377
10648





ATCC 9945a
(+)





(CP005965





(NC_021362))


Negative

69
(empty vector)

0


Control






















NA

Open


Anchor

Construct


SEQ

Reading


protein
System
number
Cloning
Cloning
ID

Frame


families
name
(C.N.)
method
successful?
NO:
Expressed?
Coordinates





pfam16162
Kiwa
1
Synthesis
yes

yes



Kiwa
2
Synthesis
yes
SEQ
yes
kwaA: 572-1159







ID

kwaB: 1156-2103







NO: 3


pfam08878
Hachiman
3
Synthesis
yes
SEQ
yes
hamA: 339-1154







ID

hamB: 1114-4506







NO: 4



Hachiman
4
Synthesis
yes

yes


pfam13749;

5
Synthesis
yes

yes


pfam04326




6
Synthesis
yes

yes


pfam13175;
Gabija
7
Synthesis
yes
SEQ
yes
gajA: 810-2870


pfam13304




ID

gajB: 2873-4927







NO: 5



Gabija
8
Synthesis
yes
SEQ
yes
gajA: 320-2056







ID

gajB: 2058-3542







NO: 6


pfam13208;

9
Synthesis
yes

yes


pfam15615;


pfam10923




10
Synthesis
yes

yes


pfam04383

11
Synthesis
yes

yes




12
Synthesis
yes

yes


pfam14130
Lamassu
13
Strain
yes
SEQ
yes
lmuA: 361-1308





obtained

ID

lmuB: 1314-3002





from

NO: 7





DSMZ





(DSM





25149)



Lamassu
14
Synthesis
yes
SEQ
yes
lmuA: 877-1863







ID

lmuB: 1868-3562







NO: 8


pfam10980

15
Synthesis
yes

yes




16
Synthesis
no

—


pfam13604;

17
Synthesis
yes

yes


pfam13538




18
Strain
yes

yes





obtained





from





ATCC





(9945a)


pfam13635;

19
Synthesis
yes

yes


pfam13173




20
Synthesis
yes

yes


pfam12668;

21
Synthesis
yes

yes


pfam13151




22
Synthesis
yes

yes


pfam09376

23
Synthesis
yes

yes




24
Synthesis
yes

yes


pfam13784

25
Synthesis
yes

yes




26
Synthesis
yes

yes


pfam14082
Shedu
27
Synthesis
yes

yes



Shedu
28
Synthesis
yes
SEQ
yes
sduA: 760-1902







ID







NO: 9


pfam12635;

29
Strain
no

—


pfam06634;


obtained


COG1483


from





DSMZ





(DSM





17841)


COG4804

30
Synthesis
yes

yes


pfam08937
Thoeris
31
Synthesis
yes
SEQ
yes
thsA: 205-1635







ID

thsB: 1674-2252







NO:







10



Thoeris
32
Synthesis
yes
SEQ
yes
thsA: 298-1191







ID

thsB: 1181-1753







NO:







11



Thoeris
33
Synthesis
yes

yes



Thoeris
34
Strain
yes

no





obtained





from BGSC





(4B4)


pfam14267

35
Synthesis
yes

no




36
Synthesis
yes

no


pfam12476;

37
Synthesis
yes

yes


pfam03235




38
Synthesis
no

—




39
Synthesis
no

—


COG1451

40
Synthesis
yes

yes




41
Synthesis
yes

yes


COG3950
Septu
42
Strain
yes
SEQ
yes
ptuA: 434-1624





obtained

ID

ptuB: 1621-2394





from BGSC

NO:





(4K1)

12



Septu
43
Synthesis
yes
SEQ
yes
ptuA: 251-2380







ID

ptuB: 2389-3276







NO:







13



Septu
44
Strain
no

—





obtained





from BGSC





(6A54)


COG3586

45
Strain
yes

yes





obtained





from





ATCC





(9945a)




46
Strain
yes

yes





obtained





from BGSC





(28A4)




47
Synthesis
yes

yes


pfam09903

48
Synthesis
yes

yes


pfam15611;
Zorya
49
Synthesis
yes
SEQ
yes
zorA: 364-2553


COG0553




ID

zorB: 2567-3307







NO:

zorC: 3304-4986







14

zorD: 4986-8228



Zorya
50
Synthesis
yes

yes



Zorya
51
Strain
yes
SEQ
yes
zorA: 213-1865





obtained

ID

zorB: 1872-2579





from

NO:

zorE: 2583-3686





ATCC

15





(8739)


pfam14281

52
Synthesis
yes

yes




53
Synthesis
yes

yes




54
Synthesis
yes

no


COG1205
Druantia
55
Strain
yes

yes





obtained





from BEI





Resources





(NR-





32771)



Druantia
56
Synthesis
yes
SEQ
yes
druA: 378-1592





(fragments)

ID

druB: 1614-3260







NO:

druC: 3272-5155







16

druD: 5167-6210









druE: 6207-11717



Druantia
57
Synthesis
yes

yes





(fragments)


pfam13910

58
Synthesis
yes

yes


COG4913;
Wadjet
59
Synthesis
yes
SEQ
yes
jetA: 146-1552


COG4924;


(fragments),

ID

jetB: 1562-2155


pfam11796;


by Gen9

NO:

jetC: 2133-5447


pfam09664;




17

jetD: 5551-6636


pfam13555



Wadjet
60
Synthesis
yes
SEQ
yes
jetAii: 230-1717







ID

jetBii: 1717-2883







NO:

jetCii: 2883-6992







18

jetDii: 6985-8280



Wadjet
61
Strain
yes
SEQ
yes
jetDiii: 444-1700





obtained

ID

jetAiii: 1676-3070





from BGSC

NO:

jetBiii: 3030-3713





(4B4)

19

jetCiii: 3710-6931


Controls



yes

yes


Type III

63
Strain
yes

yes


RM system


obtained


(BceSI)


from





ATCC





(53103)


Type III

64
Strain
yes

yes


TA system


obtained


(ToxIN)


from BGSC





(4D1)


Type II RM

65
Strain
yes

yes


system


obtained


(BamHI)


from





DSMZ





(DSM 7)


Abi system

66
Strain
yes

yes


(AbiH)


obtained





from





DSMZ





(DSM





9378)


Type I RM

67
Strain
yes

yes


system


obtained


(BliDi)


from BGSC





(51A1)


DISARM

68
Ofir et al.
yes

yes





2017


Negative

69

yes

yes


Control









In one case (the Type I Wadjet system) the DNA was synthesized by Gen9 (Boston, Mass.) with synonymous modifications to optimize GC content. In case the donor strains were readily available the system was not synthesized but instead was directly amplified from the genomic DNA of the donor strain using KAPA HiFi HotStart ReadyMix (Kapa Biosystems KK2601) with primers as detailed in Table 5.









TABLE 5







Primers










SEQ ID





NO
Primer
Sequence (5′-3′)
Description










pSG1










SEQ ID
OGO309
aaaGGATCCCTCTAGAGTTAACAAGAGTT
Amplification of plasmid backbone containing amyE


NO: 20

TGTAG
integration cassette with SpecR selection in B. subtilis, and





p15a ori with ampR selection for E. coli. With OGO310





SEQ ID
OGO310
aaaGGCGCGCCATAAAAAACGCCCGGCG
Amplification of plasmid backbone containing amyE


NO: 21

GCAACCGAGCGTTCTGAATCGATCAGA
integration cassette with SpecR selection in B. subtilis, and




CCAGTTTTTAATTTG
p15a on with ampR selection for E. coli, adding





terminator and AscI site upstream to the multiple cloning





site. With OGO309





SEQ ID
OGO311
CTGATCGGATCCTAGAAG
Amplification of the biobrick MCS from pBSC1, use with


NO: 22


OGO312





SEQ ID
OGO312
aaaGGCGCGCCCCCTTTTTTGCCGG
Amplification of the biobrick MCS from pBSC1, adding a


NO: 23


AscI site, use with OGO311





SEQ ID
OSM315
GGCGCGCCATAAAAAAC
pSG1 backbone used in NEBuilder reactions, use with


NO: 24


OSM316





SEQ ID
OSM316
GCGGCCGCGAATTC



NO: 25













Primers for putative systems










SEQ ID
OSM319
GTTGCCGCCGGGCGTTTTTTATGGCGCG
C.N. 42 to lift from strain, use with OSM320


NO: 26

CCGGGAATGCAAAAAGGAGG






SEQ ID
OSM320
ATCCTAGAAGCTTATCGAATTCGCGGCC



NO: 27

GCATATCATCCCTCGTTTTCGTC






SEQ ID
OSM321
ATCCTAGAAGCTTATCGAATTCGCGGCC
C.N. 44 to lift from strain, use with OSM322


NO: 28

GCAGTGGATACAAAGAGTGAACG






SEQ ID
OSM322
GTTGCCGCCGGGCGTTTTTTATGGCGCG



NO: 29

CCATTCATTCTTATTCCGCTAACTTTG






SEQ ID
OSM325
ATCCTAGAAGCTTATCGAATTCGCGGCC
C.N. 45 to lift from strain, use with OSM326


NO: 30

GCGAGTTTGATCAAAGATTTGCC






SEQ ID
OSM326
GTTGCCGCCGGGCGTTTTTTATGGCGCG



NO: 31

CCATTTAATTCTGCTTATCTCCAAG






SEQ ID
OSM327
ATCCTAGAAGCTTATCGAATTCGCGGCC
C.N. 13 to lift from strain, use with OSM328


NO: 32

GCTGCATATTTATAATTGTGTGTTGAG






SEQ ID
OSM328
GTTGCCGCCGGGCGTTTTTTATGGCGCG



NO: 33

CCAGAATGGAAAGTTGAATCAACTC






SEQ ID
OSM333
ATCCTAGAAGCTTATCGAATTCGCGGCC
C.N. 65 to lift from strain, use with OSM334


NO: 34

GCACGATAAACTCGGTGTATTGAC






SEQ ID
OSM334
GTTGCCGCCGGGCGTTTTTTATGGCGCG



NO: 35

CCAAAAGCTTTCGGCATCAAAG






SEQ ID
OSM323
ATCCTAGAAGCTTATCGAATTCGCGGCC
C.N. 46 to lift from strain, use with OSM324


NO: 36

GCTGACCATTTCCCTTCTTTTTTAC






SEQ ID
OSM324
GTTGCCGCCGGGCGTTTTTTATGGCGCG



NO: 37

CCTATAACCAACTCCCAATATATGG






SEQ ID
OSM331
ATCCTAGAAGCTTATCGAATTCGCGGCC
C.N. 67 to lift from strain, use with OSM332


NO: 38

GCAACTAATAGTTTAAAACTTTACGGAT





G






SEQ ID
OSM332
GTTGCCGCCGGGCGTTTTTTATGGCGCG



NO: 39

CCTATCAAGCCCCCTCATTTCA






SEQ ID
OSM340
atcctagaagcttatcgaattcgcggccgcTTCGTTACTT
C.N. 29 to lift from strain, use with OSM341


NO: 40

CTGGGATGGG






SEQ ID
OSM341
gttgccgccgggcgttttttatggcgcgccTGAAAAAGA



NO: 41

CTCCTCCGTATTTG






SEQ ID
OSM365
atcctagaagcttatcgaattcgcggccgcTAACTGGAC
C.N. 34 to lift from strain, use with OSM366


NO: 42

AGTGCTCTTGG






SEQ ID
OSM366
gttgccgccgggcgttttttatggcgcgccATGCCGATA



NO: 43

GAAGATATTGCG






SEQ ID
OSM342
atcctagaagcttatcgaattcgcggccgcTTCCGATAC
C.N. 61 to lift from strain, use with OSM343a


NO: 44

TCTTTAGCCATAA






SEQ ID
OSM343a
gttgccgccgggcgttttttatggcgcgccACAATCACA



NO: 45

TCCTTATTTTCTT






SEQ ID
OSM343b
atcctagaagcttatcgaattcgcggccgcATCTTTTTGA
C.N. 18 to lift from strain, use with OSM344


NO: 46

ATAGTTTCAATGATG






SEQ ID
OSM344
gttgccgccgggcgttttttatggcgcgccAGTGTGGTA



NO: 47

TGGAGATTAGC






SEQ ID
OSM359
atcctagaagcttatcgaattcgcggccgcGTGCTTAGA
C.N. 57 to lift fragment 1 from Genscript plasmid, use


NO: 48

TACGAAGGG
with OSM360





SEQ ID
OSM360
TAGCTCATTCTCTACAAAATCC



NO: 49








SEQ ID
OSM361
TCGATAGAGGATTTTGTAGAG
C.N. 57 to lift fragment 2 from Genscript plasmid, use


NO: 50


with OSM362





SEQ ID
OSM362
TTTTTGACGACCGTCTGAA



NO: 51








SEQ ID
OSM363
AGTTTTGCTATTTTCAGAC
C.N. 57 to lift fragment 3 from Genscript plasmid, use


NO: 52


with OSM364





SEQ ID
OSM364
gttgccgccgggcgttttttatggcgcgccTGGTTATGG



NO: 53

TTAGTATTATCTAAATT






SEQ ID
OSM402
TAGAGCAAATACCTGATCTGG
C.N. 55 to lift fragment 1 from strain, use with OSM371


NO: 54








SEQ ID
OSM371
GTTGCCGCCGGGCGTTTTTTATGGCGCG



NO: 55

CCAGCGGTAAGTTTTATAGAAAAT






SEQ ID
OSM403
TCTCTTAGATCCAGATCAGG
C.N. 55 to lift fragment 2 from strain, use with OSM370


NO: 56








SEQ ID
OSM370
ATCCTAGAAGCTTATCGAATTCGCGGCC



NO: 57

GCAGGGGGGATATAGATTTATATATAA





T






SEQ ID
OSM335
ATCCTAGAAGCTTATCGAATTCGCGGCC
C.N. 25 to lift from strain, use with OSM336


NO: 58

GCACAAGATACATCACATTGAAGG






SEQ ID
OSM336
GTTGCCGCCGGGCGTTTTTTATGGCGCG



NO: 59

CCCAATATATGCGATATACGCAAAAAC






SEQ ID
OSM329
ATCCTAGAAGCTTATCGAATTCGCGGCC
C.N. 64 to lift from strain, use with OSM330


NO: 60

GCACAAATGGGCAGAGAGAG






SEQ ID
OSM330
GTTGCCGCCGGGCGTTTTTTATGGCGCG



NO: 61

CCGATATTTCATTTTCTTCTTCCTCTCAC






SEQ ID
OSM420
ATCCTAGAAGCTTATCGAATTCGCGGCC
C.N. 66 to lift from strain, use with OSM421


NO: 62

GCGGTGAATGTAAAAATATTGATACAG






SEQ ID
OSM421
GTTGCCGCCGGGCGTTTTTTATGGCGCG



NO: 63

CCAATTTAGTCCTCCTGGGG






SEQ ID
OSM31
tgagttgattgcagtccagttac
C.N. 59 to lift fragment 1 from Gen9 construct, use with


NO: 64


OSM32





SEQ ID
OSM32
GTTACCACCTACTATCTCTTCAGC



NO: 65








SEQ ID
OSM33
TCTTTAGCTGAAGAGATAGTAGGTG
C.N. 59 to lift fragment 2 from Gen9 construct, use with


NO: 66


OSM34





SEQ ID
OSM34
tatggaggtcaggtatgatttaaatg



NO: 67








SEQ ID
0G0242
catcactgaccatttaaatcatacctgacctccataCGAATG
p15-pDR110 backbone for C.N. 59, use with OSM28


NO: 68

GCGATTTTCGTTCGTG






SEQ ID
OSM28
gcttgactccagcgtaactggactgcaatcaactcaCGATC



NO: 69

AGACCAGTTTTTAAT






SEQ ID
OSM386
ATCCTAGAAGCTTATCGAATTC
C.N. 56 to lift fragment 1 from Genscript plasmid, use


NO: 70


with OSM387





SEQ ID
OSM387
ATGTCATTCATAGCCAGAGC



NO: 71








SEQ ID
OSM388
AGATTTTAATGCTCTGGCTA
C.N. 56 to lift fragment 2 from Genscript plasmid, use


NO: 72


with OSM389





SEQ ID
OSM389
CTCATCTTCTGATAATGGTCC



NO: 73








SEQ ID
OSM390
CAGCCGAACGGACCATT
C.N. 56 to lift fragment 3 from Genscript plasmid, use


NO: 74


with OSM391





SEQ ID
OSM391
GTTGCCGCCGGGCGT



NO: 75








SEQ ID
OLA489
ATCCTAGAAGCTTATCGAATTCGCGGCC
C.N. 51 to lift from strain, use with OLA490


NO: 76

GCACCTGCCTTCCTTTGATACAATTC






SEQ ID
OLA490
GTTGCCGCCGGGCGTTTTTTATGGCGCG



NO: 77

CCTCAATTTATTGCTTTATTCATTGTGAC





TG









For long systems (>10000 bases) when the donor strain was not available, the system was commercially synthesized in overlapping fragments (Table 4, “Cloning method” column). Systems amplified from genomic DNA or ordered as overlapping fragments were cloned into pSG1-rfp between the AscI and NotI sites using NEBuilder HiFI DNA Assembly cloning kit (NEB E5520S). The full list of sources used for cloning the systems into our model organisms is found in Table 4, including accessions of all strains ordered.


Transformation to B. subtilis was performed using MC medium as previously described (Wilson G A, Bott K F. (1968) Nutritional factors influencing the development of competence in the Bacillus subtilis transformation system. J Bacteriol. 95: 1439-49). MC medium was composed of 80 mM K2HPO4, 30 mM KH2PO4, 2% Glucose, 30 mM Trisodium citrate, 22 μg/ml Ferric ammonium citrate, 0.1% Casein Hydrolysate (CAA), 0.2% potassium glutamate. From an overnight starter of bacteria, 10 μl were diluted in 1 ml of MC medium supplemented with 10 μl 1M MgSO4. After 3 hours of incubation (37° C., 200 rpm), 300 μl was transferred to a new 15 ml tube and ˜200 ng of plasmid DNA was added. The tube was incubated for another 3 hours (37° C., 200 rpm), and the entire reaction was plated on LB agar plates supplemented with 100 μg/ml spectinomycin and incubated overnight at 30° C.


For systems to be tested on E. coli, the cloned vector was transformed into E. coli MG1655 cells (ATCC 47076), and the resulting transformants were verified by PCR. For systems to be tested in B. subtilis, the cloned vector was transformed into B. subtilis BEST7003 cells. The system was integrated into the amyE locus, and resulting transformants were screened on starch plates for amylase-deficient phenotype. Whole-genome sequencing was then applied to all transformed B. subtilis and E. coli clones as described in (Ofir G, Melamed S, Sberro H, Silverman S, Doron S, Yaakov G, Mukamel Z, Sorek R. (2017) DISARM, a novel bacterial defense system with broad anti-phage activities. ibid) to verify system's integrity and lack of mutations.


As a negative control for transformation into B. subtilis, a transformant with an empty plasmid, containing only the spectinomycin resistance gene in the amyE locus, was used. As a negative control for transformation into E. coli, the wild-type E. coli MG1655 carrying an empty plasmid was used.


For strains with gene deletions and point mutations, plasmids containing systems with these deletions/mutations were commercially synthesized by Genscript. The mutated systems were transformed into B. subtilis and E. coli as described above, and clones used were fully sequenced to verify proper integration and sequence of the mutated systems.


Phage Strains, Cultivation, and Plaque Assay


The following B. subtilis phages were obtained from the Bacillus Genetic Stock Center (BGSC): SPO1 (BGSCID 1P4), phi3T (BGSCID 1L1), SPβ (BGSCID 1L5), SPR (BGSCID 1L56), phi105 (BGSCID 1L11), rho14 (BGSCID 1L15), and SPP1 (BGSCID 1P7). Phage phi29 was obtained from the DSMZ (DSM 5546). Phages SBSphiJ and SBSphiC were isolated by us from mixed soil and leaves samples on B. subtilis BEST7003. For this, soil and leaves samples were added to a log phase B. subtilis BEST7003 culture and incubated overnight to enrich for B. subtilis phages. The enriched sample was centrifuged and filtered through 0.2 μm filters, and the filtered supernatant was used to perform double layer plaque assays as described in Kropinski et al. (Kropinski A M, Mazzocco A, Waddell T E, Lingohr E, Johnson R P. Enumeration of Bacteriophages by Double Agar Overlay Plaque Assay. In: Clokie M R J, Kropinski A M, editors. Bacteriophages: Methods and protocols. NY: Humana Press; 2009. pp. 69-76). Single plaques that appeared after overnight incubation were picked, re-isolated 3 times, and amplified as described below.



E. coli phages (T4, T7, lambda-vir) were kindly provided by U. Qimron. Phages SECphi17, SECphi18 and SECphi27 were isolated as described in Wommack et al. (Wommack K E, Williamson K E, Helton R R, Bench S R, Winget D M. Methods for the Isolation of Viruses from Environmental Samples. In: Clokie M R J, Kropinski A M, editors. Bacteriophages: Methods and protocols. NY: Humana Press; 2009. pp. 3-14) from sewage samples on E. coli MG1655. 0.2 μm filtered concentrated sewage samples were used to perform double layer plaque assays, individual plaques were picked, re-isolated 3 times, and amplified as described below.


All phages isolated by us were Illumina sequenced following a library prep using the Nextera protocol (Baym M, Kryazhimskiy S, Lieberman T D, Chung H, Desai M M, Kishony R. (2015) Inexpensive multiplexed library preparation for megabase-sized genomes. PLoS One. 10: e0128036) and assembled using SPAdes v. 3.10.1 using the -careful and -cov-cutoff auto modifiers (Bankevich et al. (2012) A New Genome Assembly Algorithm and Its Applications to Single-Cell Sequencing. J Comput Biol.; 19: 455-477. doi:10.1089/cmb.2012.0021). Assembled genomes and raw reads were deposited in the European Nucleotide Archive (ENA) under study accession PRJEB23070. Phage classification was done according to sequence homology to the closest known similar phage. Phage SECphi17 (ENA ERS1981053) has a 5,538 bp genome and its closest relative is Coliphage WA3 (GenBank DQ079897.1, 66% coverage, 81% identity), indicating it is an ssDNA phage of the Microviridae family. Phage SECphi18 (ENA ERS1981054) has a 44,798 bp genome and its closest relative is Escherichia phage Gluttony (GenBank KX534336.1, 92% coverage, 93% identity), indicating it is a member of the Siphoviridae family. Phage SECphi27 (ENA ERS1981055) has a 51,811 bp genome, and its closest relative is Escherichia phage vB_Eco_swan01 (GenBank LT841304.1, 91% coverage, 98% identity), indicating it is a member of the Siphoviridae family. Phage SBSphiJ (ENA ERS1981056) has a 156,875 bp genome, and its closest relative is Bacillus phage Grass (GenBank KF669652.1, 91% coverage, 95% identity), indicating it is a member of the family Myoviridae. Phage SBSphiC (ENA ERS1981057) has a 144,651 bp genome, and its closest relative is Bacillus phage SP10 (GenBank AB605730.1, 94% coverage, 90% identity), indicating it is a member of the Myoviridae family. Siphoviridae and Myoviridae phage morphologies were verified by electron microscopy (EM). For the EM experiments, phage lysates were blotted onto copper grids, stained using uranyl acetate 2%, and visualized in FEI Tecnai T12 transmitting electron microscope.


Phages were propagated on either E. coli MG1655 or B. subtilis BEST7003 using the plate lysate method as previously described (Fortier L-C, Moineau S. (2009) Phage production and maintenance of stocks, including expected stock lifetimes. Methods Mol Biol. 501: 203-19). Lysate titer was determined using the small drop plaque assay method as previously described (Mazzocco A, Waddell T E, Lingohr E, Johnson R P. (2009) Enumeration of bacteriophages using the small drop plaque assay system. [Internet]. Methods in molecular biology (Clifton, N.J.). pp. 81-5). Bacteria were mixed with MMB agar (LB+0.1 mM MnCl2+5 mM MgCl2+5 mM CaCl2+0.5% agar), and serial dilutions of phage lysate in MMB were dropped on top of them. After the drops dried up, plates were incubated at room temperature overnight. Efficiency of plating (EOP) was measured by performing small drop plaque assay with the same phage lysate on control bacteria and bacteria containing the candidate defense system, and comparing the ratio of plaque formation.


To determine the number of infective centers during infection with T7 phage of control bacteria and bacteria containing type I or type II Zorya (Defense Systems Ia and Ib, respectively), a modified version of the technique described in (Sing et al., (19909) J. Gen. Microbiol. 136:807-1815) as used. Zorya-lacking E. coli MG1655 or Zorya-containing cells were infected with T7 phage at MOI 0.05 and incubated for 10 min at 37° C. to allow adsorption. Cells with adsorbed phages were then centrifuged (1 min, 14,000 rpm) at 4° C., washed once with ice-cold MMB medium, and resuspended in 200 mlice-cold MMB medium. Then, 100 ml aliquots of 10-fold dilutions of resuspended phage-infected cells were mixed with 100 ml of a Zorya-lacking E. coli MG1655 culture grown to O.D. 0.3. The mixture was plated using the double agar over-lay method and infection centers (plaques) were counted after overnight incubation in room temperature.


For the liquid culture infection with T7 phage, overnight cultures of Zorya-lacking E. coli MG1655 or Zorya-containing cells were diluted 1:100 in MMB medium. 180 ml volumes of the diluted culture were dispersed into wells in a 96-well plate and grown at 37° C. with vigorous shaking until early log phase (O.D.600 0.3). 20 mlofT7 phage lysate were added at multiplicities of infection 0.05, 0.5 and 5 in three replicates. Optical density measurements at a wavelength of 600 nm were taken every 15 min using a TECAN Infinite 200 plate reader in a 96-well plate.


Transformation Efficiency Assay


Transformation was performed using the MC medium as described above. To test plasmid transformation efficiency, the episomal Bacillus plasmid pHCMC05 was used (Titok M., Chapuis J, Selezneva Y., Lagodich A., Prokulevich V., Ehrlich S., Jannière L. (2003) Bacillus subtilis soil isolates: plasmid replicon analysis and construction of a new theta-replicating vector. Plasmid. 49: 53-62). Transformation efficiency was calculated by dividing the number of transformants that grew on LB plates containing 5 μg/ml chloramphenicol by the live count on LB plates.


DNA-Seq and RNA-Seq


DNA was extracted from bacteria using Qiagen DNeasy blood and tissue kit (Qiagen 69504). DNA libraries were constructed using the Nextera library preparation protocol as previously published (Baym M, Kryazhimskiy S, Lieberman T D, Chung H, Desai M M, Kishony R. (2015) Inexpensive multiplexed library preparation for megabase-sized genomes. PLoS One. 10: e0128036). RNA-seq was performed with the NEBNext Ultra Directional RNA Library Prep Kit (NEB, E7420) according to the manufacturer's instructions with modifications as previously described (Dar D, Shamir M, Mellin J R, Koutero M, Stern-Ginossar N, Cossart P, Sorek R. (2016) Term-seq reveals abundant ribo-regulation of antibiotics resistance in bacteria. Science. 352: aad9822-aad9822). Prior to library preparation, equal amounts of extracted RNA from 3-7 strain samples were pooled together and processed as a single library. All libraries were sequenced using the Illumina NextSeq500. The sequencing reads were aligned to the reference genomes of B. subtilis BEST7003 (Genbank: AP012496) and E. coli MG1655 (Genbank: NC_000913), and to the plasmid sequence of each system, using Novoalign 3.02.02 (Novocraft Technologies Sdn Bhd, http://www.novocraft.com) with the default parameters and [-r Random]. The coverage along the reference genomes was calculated, to check if each system exists in the genome (DNA-seq) or expressed (RNA-seq). The pooled RNA library was sequenced to a depth of 5 million reads per sample and later aligned to the reference genomes as described.


Example 1
Identification of New Bacterial Defense Systems

Objective:


To comprehensively identify new defense systems enriched within defense islands, in an attempt to systematically map the arsenal of defense systems that are at the disposal of bacteria and archaea in their fight against phages. Anti-phage defense systems were found to be frequently physically clustered in bacterial and archaeal genomes such that, for example, genes comprising restriction enzymes commonly reside in the vicinity of genes comprising infection systems and other phage resistance systems. The observation that defense systems are clustered in genomic “defense islands” has led to the suggestion that genes of unknown function residing within such defense islands may also participate in anti-phage defense.


Methods:


The first step in this discovery effort was to identify gene families that are enriched near known defense systems in the microbial pan-genome (FIG. 1A). For this, 14,083 protein families (pfams) were analyzed in >45,000 available bacterial and archaeal genomes (overall comprising >120 million genes). Each pfam represents a set of genes sharing a common protein domain. For each pfam, the prevalence of its member genes to reside in the vicinity (10 genes from each side) of one or more known defense genes was calculated (FIG. 1B). Pfams were selected that had at least 65% of their member genes found next to defense genes, and that their member genes appeared in diverse defense contexts in different genomes (at least 10% variability; FIG. 1B). These thresholds were selected as they capture the majority of pfams that comprise known defense systems (FIGS. 1A-1C; Table 1). The resulting set of 277 candidate pfams was supplemented by 58 additional gene families that were previously predicted to be associated with known defense systems (Makarova K S, Wolf Y I, Snir S, Koonin E V. (2011) Defense islands in bacterial and archaeal genomes and prediction of novel defense systems. J Bacteriol. 193: 6039-56), altogether yielding a list of 335 candidate gene families (Table 2).


To check whether the defense-associated pfams belong to multi-gene systems, each such pfam was used as an anchor around which commonly associated genes were searched for (FIG. 1A). For this, all the neighboring genes (10 genes from each side) from all the genomes in which members of the anchor pfam occurred were collected, and these genes were clustered based on sequence homology. Cassettes of gene clusters were then searched for that showed conserved order across multiple different genomes, marking such cassettes as candidate multi-gene systems (FIG. 1A).


Results:


The gene annotations in the resulting candidate systems were manually inspected in order to filter out likely false predictions. It was found that 39% of the cases represented non-defense, mobile genetic elements that are known to co-localize to defense islands (Table 2). Additionally, 30% of the resulting candidate defense systems found represented known defense systems whose pfams were not included in the original set of known defense pfams, and 17% belonged to operons probably performing metabolic functions or other functions not associated with defense (FIGS. 2A and 2B).


The remaining systems possibly represent putative new defense systems. To expand the predictions with new pfams that may be specifically enriched next to the putative new defense systems, a second prediction cycle was performed, this time adding the members of the predicted new systems to the positive defense pfam set (FIG. 1A).


Altogether, 41 candidate single-gene or multi-gene systems were retrieved from this analysis (Table 3). This set of systems was further filtered to remove systems that were largely confined to a specific clade (e.g., systems appearing only in cyanobacteria or only in actinobacteria), resulting in a set of 28 candidate systems that showed broad phylogenetic distribution.


Example 2
Verification of New Bacterial Defense Systems

Objective:


To experimentally verify the candidate defense systems identified in Example 1, as having defense system activity.


Methods:


Two bacteria strains were selected for verification of candidate defense systems, Escherichia coli str. MG1655 and Bacillus subtilis str. BEST7003. These bacteria were utilized as models to experimentally examine whether the predicted systems confer defense against phage (FIG. 3A). None of the candidate new systems are naturally present in the genomes of these two bacteria. For each candidate system, source organisms were selected from which the system was taken and heterologously cloned into one of the model organisms. To increase the probability that the cloned system would be compatible and functionally expressed within the receiving bacterium, systems were selected from mesophilic organisms as close phylogenetically as possible to E. coli or to B. subtilis, and included the upstream and downstream intergenic regions so that promoters, terminators or other regulatory sequences would be preserved. Where possible at least two instances of each system were used (from two different source genomes), to account for the possibility that some systems may not be active in their source organism. The DNA of each system, spanning the predicted genes and the intergenic spaces, was synthesized or amplified from the source genome (donor species) and cloned either to E. coli (on a plasmid) or to B. subtilis (genomically integrated). As a control, the procedure was repeated with 5 known defense systems (instances of types I, II and III R-M systems, type III toxin/antitoxin system and an infection gene of the AbiH family) for which source organisms were similarly selected and cloning was performed into B. subtilis, as well a 6th control comprised of the recently discovered DISARM defense system.


Results:


Altogether, heterologously cloning of 61 representative instances of the 28 candidate new systems was attempted, and successful cloning was verified by whole genome sequencing (Table 4). For 27 of these 28 systems there was at least one candidate locus for which cloning was successful, and RNA-seq of the transformants showed that for 26 of the systems, at least one of the candidates was expressed in the receiving E. coli or B. subtilis strain.


The engineered bacteria were then challenged by an array of phages consisting of 10 B. subtilis and 6 E. coli phages, spanning the three major families of tailed dsDNA phages (myo-, sipho- and podo-phages), as well as one ssDNA phage infecting E. coli (FIGS. 3B, 3C, and 3D). Measuring phage efficiency of plating (EOP) on system-containing bacteria vs. control cells, it was found that 9 of the 26 tested systems (35%) showed protection from infection by at least one phage (FIGS. 3B, 3C, 3D, 3E, and 3F). In comparison, three of the six positive control systems showed defense, with the remaining 3 showing no protection against the 10 B. subtilis phages tested.


The 9 verified new systems were named after protective deities from various world mythologies. These defense systems are comprised of between 1 and 5 genes and span between 2 and 12 kb of genomic DNA (Table 6; Table 7).









TABLE 6







Composition of Defense Systems Reported


















No. (%)







# of
of






instances
genomes






detected
in which






within
system


System
Operon
Associated domains
Domain annotations
microbes
is found
comments
















Thoeris
ThsAB
pfam13289, pfam14519,
SIR2, Macro domain,
2,099
2070
Membrane




pfam08937, pfam13676
TIR domain

(4.0%)
associated








(sometime)


Hachiman
HamAB
pfam08878, COG1204,
Helicase
1,781
1742




pfam00270, pfam0271


(3.4%)


Shedu
SduA
pfam14082
Nuclease
1,246
1191







(2.3%)


Gabija
GajAB
pfam13175, COG3593,
ATPase, helicase,
4,598
4360




pfam13361, pfam00580,
nuclease

(8.5)%




COG0210, pfam13245


Septu
PtuAB
pfam13304, COG3950,
ATPase, HNH nuclease
2,506
2117




pfam13395, pfam01844


(4.1%)


Lamassu
LmuAB
pfam14130, pfam02463
SMC ATPase N-terminal
697
682





domain

(1.3%)


Zorya
ZorABCD
pfam01618, pfam13677,
MotA/ExbB, MotB,
1,173
1055
Membrane


(type I)

pfam00691, COG1360,
helicase, Mrr-like

(2.1%)
associated




pfam15611, pfam00176,
nuclease




pfam00271, COG0553,




pfam04471


Zorya
ZorABE
pfam01618, pfam13677,
MotA/ExbB, MotB,
656
655
Membrane


(type II)

pfam00691, COG1360,
HNH nuclease

(1.3%)
associated




COG3183, pfam01844


Kiwa
KwaAB
pfam16162
No annotated domain
934
924
Membrane







(1.8%)
associated


Druantia
DruABC
pfam14236, pfam00270,
Helicase, methylase
1,342
1321



DE (type
pfam00271, pfam09369,


(2.6%)



I)
pfam00145, COG1205,



DruMFG
COG0270



E (type II)



DruHE



(III)


Wadjet
JetABCD
pfam11855, pfam09660,
MukBEF condensin,
3,173
2880




pfam13835, pfam09661,
topoisomerase VI

(5.6%)




pfam13555, pfam13558,




COG4913, COG1196,




pfam11795, pfam09983,




pfam11796, pfam09664,




COG4924
















TABLE 7







Verified Defense Systems
















Median





Associated

gene size



System
Genes
domains
Domain annotation
(aa)
Comment















Thoeris
ThsA
pfam13289,
Sir2/Macro domain
477
In some cases N-




pfam14519
(NAD binding)

terminal







transmembrane







helices



ThsB
pfam08937
TIR domain
195
Often multiple







ThsB genes in the







locus


Hachiman
HamA
pfam08878
Unknown function
269





(DUF1837)






HamB
COG1204,
Helicase
867





pfam00270,







pfam00271





Shedu
SduA
pfam14082
Endonuclease NucS
367





(DUF4263),







pfam01939





Gabija
GajA
pfam13175,
ATPase domain,
670





COG3593
Predicted ATP-







dependent







endonuclease





GajB
pfam04257,
UvrD helicase
598





pfam00580-







pfam13361





Septu
PtuA
pfam13304,
AAA domain,
452
In some cases has




pfam02463
RecF/RecN/SMC N

N-terminal





terminal domain

predicted HNH







nuclease domain



PtuB
pfam13395,
HNH endonuclease
219





pfam01844





Lamassu
LmuA
pfam14130
Unknown function
361





(DUF4297)






LmuB
pfam02463
RecF/RecN/SMC N
559






terminal domain




Zorya
ZorA
pfam01618
MotA/ExbB/TolQ
550
Predicted


type I




transmembrane







helices



ZorB
pfam13677-
MotB
217
Predicted




pfam00691


transmembrane







helix



ZorC
pfam15611
EH signature
470




ZorD
pfam00176-
SWI2/SNF2 helicase
1080





pfam00271





Zorya
ZorE
COG3183,
HNH endonuclease
367



type II

pfam01844





Kiwa
KwaA
No domain

194
Predicted




annotation


transmembrane







helices



KwaB
pfam16162
Unknown function
315





(DUF4868)





Druantia
DruA
pfam14236
Unknown function
404



type I

(DUF4338)






DruB
No domain

531





annotation






DruC
No domain

627





annotation






DruD
No domain

347





annotation






DruE
pfam00270,
Helicase
2104





pfam00271,







pfam09369







(DUF1998)





Druantia
DruM
pfam00145,
Cytosine methylase
386



type II

COG0270






DruF
No domain

852





annotation






DruG
No domain

711





annotation





Druantia
DruH
No domain

1079



type III

annotation





Wadjet
JetA
pfam11855
Unknown functions
488
MukF-like




(DUF3375)/







pfam09660







(DUF2397)






JetB
pfam13835
Unknown functions
247
MukE-like




(DUF4194)/







pfam09661







(DUF2398)






JetC
pfam13555-
ATP binding domain,
1476
MukB-like




pfam13558
Putative exonuclease







SbcC





JetD
pfam11795
Unknown functions
347
Topoisomerase VI




(DUF3322)-


predicted by




pfam09983


structural




(DUF2220)/


similarities




pfam11796







(DUF3323)-







pfam09664







(DUF2399)









Where possible, system consistency was verified by testing for phage resistance in systems where individual genes were deleted (FIG. 3G). We found between several hundreds and several thousand representations of each of the defense systems in sequenced microbial genomes, usually with broad phylogenetic distribution (FIG. 3H; Tables 8-17). Most systems were detected in >10 taxonomic phyla, and 7 of them appear in archaea (FIG. 3H).


Some of the systems seem to target a specific class of phages (e.g., the Thoeris system appears to specifically protect from myophages), while others, such as the Hachiman system, provide broader defense (FIG. 3B). The genes comprising the new systems encode many protein domains that are commonly present in antiviral systems such as CRISPR-Cas and RNAi, including helicases, nucleases, and nucleic acid binding domains, in addition to many domains of unknown function and also atypical domains as described herein. Three of the systems contain membrane-associated proteins as predicted by the presence of multiple transmembrane helices. Further functional analyses was performed for a selected set of systems.


Example 3
Genomic Identification and Analysis of the ZORYA System

Objective:


Identify the candidate defense system based on the enrichment of the anchor pfam15611.


Method:


ZORYA was one of the systems identified in the first round of prediction. The anchor gene family for ZORYA was pfam15611. This pfam had a defense score of 0.98 and a diversity score of 0.55.


Cloning of ZORYA into E. coli MG1655—A cloning vector for large fragments was constructed by assembling the p15a origin of replication (ori) from pACYCDuet-1 and the amyE integration cassette from plasmid pDR110 (see https://www(dot)ncbi(dot)nlm(dot)nih(dot)gov/pmc/articles/PMC3814332/#pgen.1003892.s005). The p15a ori was amplified using primers OGO174+OGO175 (a list of all primers is provided in Table 5). The amyE integration cassette was amplified using primers OGO176+OGO185. The two fragments were assembled and transformed into E. coli cells using Gibson assembly cloning kit (NEB E5510S), and assembled plasmids were verified by restriction pattern and full sequencing.


The backbone of the above described vector was amplified using primers OGO309+OGO310, adding to it a BamHI restriction site and a terminator site. The multiple cloning site of plasmid pBS1C (received from the BGSC) was amplified using primers OGO311+OGO312. Both fragments were digested using AscI and BamHI, ligated using T4 ligase and transformed into E. coli, resulting in plasmid pSG1-rfp. The plasmid was digestion verified and fully sequenced.


A representative ZORYA operon (locus) from E. coli E24377A (RefSeq accession NC_009801, coordinates 298890-307639 of the reverse strand, SEQ ID NO: XXXX) was commercially synthesized (GenScript) directly into pSG1-rfp between the AscI and NotI sites of the multiple cloning site. The cloned vector was transformed into E. coli MG1655 cells, and the resulting transformants were verified by PCR and whole genome sequencing.


Phage cultivation and plaque assays have been described above.


For analysis in solid cultures, Zorya-containing cells (Defense System Ia or Defense System Ib) were infected with T7 phage at MOI 0.05 and were incubated for 10 min at 37° C. to allow phage adsorption (FIG. 4G). Cells with adsorbed phages were then centrifuged and washed to eliminate unabsorbed phages. These T7-infected cells were mixed together with E. coli MG1655 cells that lacked a Zorya defense system, and the mixture was plated using an agar overlay method. Phage bursts from successful infections were visualized as a single infection center on a lawn from the T7-sensitive E. coli strain, enabling an evaluation of the number of phages that have adsorbed and completed a successful infection cycle. For analysis in liquid cultures, T7 infection in liquid cultures of E. coli cells containing type I (FIG. 4H) and type II (FIG. 4I) Zorya. Bacteria were infected at t=0 at multiplicities of infection (MOI) of 0.05, 0.5 and 5.


Results:


The Zorya system (named after a deity from the Slavic mythology) was identified based on the enrichment of the anchor pfam15611, representing a domain of unknown function, within defense islands. Pfam15611-containing gene clusters were previously reported as genomically associated with tellurium- and stress-resistance genes.


The computational analysis found this pfam to be part of a 4-gene system, zorABCD comprising ZorA, ZorB, ZorC, and ZorD polypeptides. Overall the ZORYA gene system encompasses ˜9 kb of DNA, with pfam15611 being the third gene in the system (zorC; FIG. 3C, and FIGS. 4A and 4B; Table 6). Initially 262 appearances of the ZORYA system were found in the dataset that was used in the automatic prediction.


A representative ZORYA operon from E. coli E24377A was cloned into E. coli MG1655 (FIG. 4C), which does not contain an endogenous ZORYA system. The correct insertion of the system into the E. coli MG1655 genome was verified by whole genome sequencing.


In the next step, the E. coli MG1655 containing the ZORYA system (type I) was challenged with phage from three families of the dsDNA tail phages Caudavirales: T4 of Myoviridae, T7 of the Podoviridae, and Lambda of the Siphoviridae. T4 and T7 are obligatory lytic phages, while Lambda is a temperate phage. In addition to the wild-type Lambda phage (lambda-wt), a mutant that is an obligatory lytic phage was also used (lambda-vir). The results showed that the type I ZORYA system provided protection against T7 phage (2-3 orders of magnitude), and lambda-vir phage (at least 2 orders of magnitude), manifested by reduction in plaque formation on the ZORYA-containing strains (FIG. 3E). Further analysis showed that the type I ZORYA system provided 10-10000-fold protection against infection by T7, SECphi27, and lambda-vir phages (FIGS. 3C and 3F). Further searches based on homologies to the first two genes in the system, zorA and zorB, revealed a second type of ZORYA, comprised of the 3 genes zorABE. (FIGS. 4D and 4E). A Type II Zorya system was cloned from E. coli ATCC8739 into E. coli MG1655 and yielded 10,000-fold defense against T7 and 10-fold against the ssDNA phage SECphi17 (FIG. 3C and FIGS. 4B and 4C).


The first two genes of the Zorya system, zorA and zorB, contain protein domains sharing sequence homology with motA and motB, respectively (FIG. 4B). MotA and MotB are inner membrane proteins that are part of the flagellar motor of bacteria. They assemble into a MotAB complex, which forms the stator of the flagellar motor (the static part within which the flagellar rotor swivels). The MotAB complex also forms the proton channel that provides the energy for flagellar rotation, coupling transport of protons into the cell with the rotation (FIG. 4F). While zorB shares the same size and domain organization with motB (including the pfam13677 and pfam00691 domains), zorA contains, in addition to the MotA domain (pfam01618), also a long C-terminal helical domain that is sometime identified as a “methyl-accepting chemotaxis domain” (COG0840). In addition to these two genes, Type I Zorya contains zorC, a gene of unknown function, and zorD, which is a large gene (encoding a ˜1200aa polypeptide) comprising a helicase domain. Type II Zorya lacks zorC and zorD and instead contains zorE, a smaller gene comprising an HNH-endonuclease domain.


Analysis of the Zorya Defense Systems was performed by performing phage infection of Zorya Defense System-containing bacteria cells (Defense System Ia or Defense System Ib) in solid and liquid cultures. Three replicates of cells containing type I Zorya, type II Zorya or no Zorya defense system are shown in FIGS. 4G-4I; data represent, for each replicate, the number of derived infection centers as a fraction from the average number of infection centers derived from Zorya-lacking (“No Zorya”) cells (see Methods). The results show that in cells containing a type I Zorya defense system, only an average of 17% of infection events lead to successful phage progeny, while in cells containing a type II Zorya defense system, 6% of the infected cells yield successful phage bursts. (FIG. 4G) For liquid culture infection, shown are three replicates for each MOI, with each curve showing an individual replicate. The delayed collapse of Zorya-containing cultures suggests that most of the infected Zorya-containing cells undergo abortive infection, while a minority of cells produces viable phage progeny, which eventually accumulate to a high MOI leading to a culture collapse.


Conclusion:


The Zorya defense system was identified in 1829 instances within 1663 sequenced bacterial genomes belonging to 12 phyla, marking this system as prevalent in at least 3% of sequenced bacteria (Table 8).









TABLE 8





ZORYA Defense System and Components Thereof


This table is presented in landscape orientation. Due to the number of columns, the


table has been split into parts. Part A includes the first set of columns and therefore should be


place to the left of subsequent parts (Part B and where relevant Part C). To avoid any doubt, the


rows of the table in each part line up once the tables are placed together.







(Part A)















A
B
C
D
E
F
G


1
assembly_accession
taxid
species_taxid
organism_name
infraspecific_name
phylum
genomic_accession





2
GCA_000017645.1
78245
280

Xanthobacter autotrophicus Py2
Py2
Proteobacteria
CP000781.1


3
GCA_000761245.1
285
285

Comamonas testosteroni

JL40
Proteobacteria
AWOR01000012.1


4
GCA_000017205.1
381754
287

Pseudomonas aeruginosa PA7
PA7
Proteobacteria
CP000744.1


5
GCA_000259025.1
1134459
287

Pseudomonas aeruginosa PADK2_CF510
PADK2_CF510
Proteobacteria
AJHI01000009.1


6
GCA_000297315.1
1163394
287

Pseudomonas aeruginosa ATCC 700888
ATCC 700888
Proteobacteria
AKZF01000392.1


7
GCA_000297355.1
1163395
287

Pseudomonas aeruginosa E2
E2
Proteobacteria
AKZH01000152.1


8
GCA_000399805.1
1315978
287

Pseudomonas aeruginosa VRFPA02
VRFPA02
Proteobacteria
AQHM01000100.1


9
GCA_000467675.1
1350465
287

Pseudomonas aeruginosa VRFPA03
VRFPA03
Proteobacteria
ATNK01000038.1


10
GCA_000480705.1
1402563
287

Pseudomonas aeruginosa BL22
BL22
Proteobacteria
KI518786.1


11
GCA_000480725.1
1402562
287

Pseudomonas aeruginosa BL21
BL21
Proteobacteria
KI518793.1


12
GCA_000480745.1
1402561
287

Pseudomonas aeruginosa BL20
BL20
Proteobacteria
KI518807.1


13
GCA_000480965.1
1402550
287

Pseudomonas aeruginosa BL09
BL09
Proteobacteria
KI518889.1


14
GCA_000481705.1
1402500
287

Pseudomonas aeruginosa X13273
X13273
Proteobacteria
KI519199.1


15
GCA_000481765.1
1402497
287

Pseudomonas aeruginosa 19660
19660
Proteobacteria
KI519236.1


16
GCA_000481825.1
1402494
287

Pseudomonas aeruginosa S54485
S54485
Proteobacteria
KI519256.1


17
GCA_000482005.1
1163395
287

Pseudomonas aeruginosa E2
E2
Proteobacteria
KI519307.1


18
GCA_000496325.1
1408193
287

Pseudomonas aeruginosa VRFPA05
VRFPA05
Proteobacteria
AXZJ01000095.1


19
GCA_000520195.1
1402581
287

Pseudomonas aeruginosa PS42
PS42
Proteobacteria
KI914449.1


20
GCA_000531435.1
1407059
287

Pseudomonas aeruginosa PA38182
PA38182
Proteobacteria
HG530068.1


21
GCA_000531435.1
1407059
287

Pseudomonas aeruginosa PA38182
PA38182
Proteobacteria
HG530068.1


22
GCA_000558345.1
1441931
287

Pseudomonas aeruginosa VRFPA09
VRFPA09
Proteobacteria
JAAO01000047.1


23
GCA_000611995.2
1437873
287

Pseudomonas aeruginosa PA99
PA99
Proteobacteria
KK111873.1


24
GCA_000629065.1
1447541
287

Pseudomonas aeruginosa BWH033
BWH033
Proteobacteria
KK212100.1


25
GCA_000629285.1
1447530
287

Pseudomonas aeruginosa 3575
3575
Proteobacteria
KK212903.1


26
GCA_000629505.1
1418240
287

Pseudomonas aeruginosa BWH054
BWH054
Proteobacteria
KK213223.1


27
GCA_000689435.1
1336203
287

Pseudomonas aeruginosa MH38
MH38
Proteobacteria
CBTQ010000132.1


28
GCA_000689435.1
1336203
287

Pseudomonas aeruginosa MH38
MH38
Proteobacteria
CBTQ010000056.1


29
GCA_000705175.1
1441459
287

Pseudomonas aeruginosa C2773C
C2773C
Proteobacteria
JGZW01000198.1


30
GCA_000829885.1
287
287

Pseudomonas aeruginosa

FRD1
Proteobacteria
CP010555.1


31
GCA_000981825.1
287
287

Pseudomonas aeruginosa

Carb01 63
Proteobacteria
CP011317.1


32
GCA_000981825.1
287
287

Pseudomonas aeruginosa

Carb01 63
Proteobacteria
CP011317.1


33
GCA_001180345.1
287
287

Pseudomonas aeruginosa

P1_London_28_IMP_1_04_05
Proteobacteria
CVUY01000300.1


34
GCA_001180345.1
287
287

Pseudomonas aeruginosa

P1_London_28_IMP_1_04_05
Proteobacteria
CVUY01000281.1


35
GCA_001180365.1
287
287

Pseudomonas aeruginosa

P2_London_28_IMP_1_06_05
Proteobacteria
CVWC01000358.1


36
GCA_001180365.1
287
287

Pseudomonas aeruginosa

P2_London_28_IMP_1_06_05
Proteobacteria
CVWC01000094.1


37
GCA_001180385.1
287
287

Pseudomonas aeruginosa

P3_North_West_16_VIM_2_07_06
Proteobacteria
CVVV01000260.1


38
GCA_001180385.1
287
287

Pseudomonas aeruginosa

P3_North_West_16_VIM_2_07_06
Proteobacteria
CVVV01000250.1


39
GCA_001180405.1
287
287

Pseudomonas aeruginosa

P4_London_1_VIM_2_10_07
Proteobacteria
CVWA01000298.1


40
GCA_001180405.1
287
287

Pseudomonas aeruginosa

P4_London_1_VIM_2_10_07
Proteobacteria
CVWA01000358.1


41
GCA_001180425.1
287
287

Pseudomonas aeruginosa

P5_London_26_VIM_2_01_09
Proteobacteria
CVWS01000233.1


42
GCA_001180445.1
287
287

Pseudomonas aeruginosa

E1_London_17_VIM_2_02_09
Proteobacteria
CWGH01000216.1


43
GCA_001180445.1
287
287

Pseudomonas aeruginosa

E1_London_17_VIM_2_02_09
Proteobacteria
CWGH01000243.1


44
GCA_001180465.1
287
287

Pseudomonas aeruginosa

E2_London_17_VIM_2_02_09
Proteobacteria
CVUZ01000030.1


45
GCA_001180485.1
287
287

Pseudomonas aeruginosa

E3_London_17_VIM_2_03_09
Proteobacteria
CVVB01000221.1


46
GCA_001180485.1
287
287

Pseudomonas aeruginosa

E3_London_17_VIM_2_03_09
Proteobacteria
CVVB01000215.1


47
GCA_001180505.1
287
287

Pseudomonas aeruginosa

E4_London_17_VIM_2_03_09
Proteobacteria
CVUK01000139.1


48
GCA_001180505.1
287
287

Pseudomonas aeruginosa

E4_London_17_VIM_2_03_09
Proteobacteria
CVUK01000152.1


49
GCA_001180525.1
287
287

Pseudomonas aeruginosa

P6_East_of_England_6_IMP_1_03_09
Proteobacteria
CWFP01000032.1


50
GCA_001180525.1
287
287

Pseudomonas aeruginosa

P6_East_of_England_6_IMP_1_03_09
Proteobacteria
CWFP01000037.1


51
GCA_001180545.1
287
287

Pseudomonas aeruginosa

P7_London_17_VIM_2_06_09
Proteobacteria
CVXP01000253.1


52
GCA_001180545.1
287
287

Pseudomonas aeruginosa

P7_London_17_VIM_2_06_09
Proteobacteria
CVXP01000219.1


53
GCA_001180565.1
287
287

Pseudomonas aeruginosa

P8_1_South_East_10_VIM_2_07_09
Proteobacteria
CWET01000247.1


54
GCA_001180565.1
287
287

Pseudomonas aeruginosa

P8_1_South_East_10_VIM_2_07_09
Proteobacteria
CWET01000222.1


55
GCA_001180585.1
287
287

Pseudomonas aeruginosa

P9_East_of_England_6_IMP_13_08_09
Proteobacteria
CWEU01000015.1


56
GCA_001180585.1
287
287

Pseudomonas aeruginosa

P9_East_of_England_6_IMP_13_08_09
Proteobacteria
CWEU01000241.1


57
GCA_001180605.1
287
287

Pseudomonas aeruginosa

P10_London_6_VIM_2_09_09
Proteobacteria
CVVA01000108.1


58
GCA_001180605.1
287
287

Pseudomonas aeruginosa

P10_London_6_VIM_2_09_09
Proteobacteria
CVVA01000120.1


59
GCA_001180625.1
287
287

Pseudomonas aeruginosa

P11_London_17_VIM_2_10_09
Proteobacteria
CVVH01000136.1


60
GCA_001180625.1
287
287

Pseudomonas aeruginosa

P11_London_17_VIM_2_10_09
Proteobacteria
CVVH01000150.1


61
GCA_001180645.1
287
287

Pseudomonas aeruginosa

P12_London_17_VIM_2_11_09
Proteobacteria
CVUP01000157.1


62
GCA_001180645.1
287
287

Pseudomonas aeruginosa

P12_London_17_VIM_2_11_09
Proteobacteria
CVUP01000141.1


63
GCA_001180665.1
287
287

Pseudomonas aeruginosa

P13_London_14_VIM_2_12_09
Proteobacteria
CVUL01000136.1


64
GCA_001180665.1
287
287

Pseudomonas aeruginosa

P13_London_14_VIM_2_12_09
Proteobacteria
CVUL01000126.1


65
GCA_001180685.1
287
287

Pseudomonas aeruginosa

P14_London_17_VIM_2_01_10
Proteobacteria
CVVT01000217.1


66
GCA_001180685.1
287
287

Pseudomonas aeruginosa

P14_London_17_VIM_2_01_10
Proteobacteria
CVVT01000236.1


67
GCA_001180705.1
287
287

Pseudomonas aeruginosa

P15_London_17_02_10
Proteobacteria
CVVW01000231.1


68
GCA_001180705.1
287
287

Pseudomonas aeruginosa

P15_London_17_02_10
Proteobacteria
CVVW01000262.1


69
GCA_001180725.1
287
287

Pseudomonas aeruginosa

P16_Lonon_17_VIM_2_02_10
Proteobacteria
CVVD01000204.1


70
GCA_001180725.1
287
287

Pseudomonas aeruginosa

P16_Lonon_17_VIM_2_02_10
Proteobacteria
CVVD01000193.1


71
GCA_001180745.1
287
287

Pseudomonas aeruginosa

P17_North_West_14_VIM_2_03_10
Proteobacteria
CVUV01000236.1


72
GCA_001180745.1
287
287

Pseudomonas aeruginosa

P17_North_West_14_VIM_2_03_10
Proteobacteria
CVUV01000189.1


73
GCA_001180765.1
287
287

Pseudomonas aeruginosa

P18_London_17_VIM_2_04_10
Proteobacteria
CVVY01000157.1


74
GCA_001180765.1
287
287

Pseudomonas aeruginosa

P18_London_17_VIM_2_04_10
Proteobacteria
CVVY01000399.1


75
GCA_001180785.1
287
287

Pseudomonas aeruginosa

P19_London_7_VIM_2_05_10
Proteobacteria
CVVU01000221.1


76
GCA_001180785.1
287
287

Pseudomonas aeruginosa

P19_London_7_VIM_2_05_10
Proteobacteria
CVVU01000253.1


77
GCA_001180805.1
287
287

Pseudomonas aeruginosa

P20_London_17_VIM_2_05_10
Proteobacteria
CVUO01000146.1


78
GCA_001180805.1
287
287

Pseudomonas aeruginosa

P20_London_17_VIM_2_05_10
Proteobacteria
CVUO01000165.1


79
GCA_001180825.1
287
287

Pseudomonas aeruginosa

P21_London_17_VIM_2_06_10
Proteobacteria
CVVE01000135.1


80
GCA_001180825.1
287
287

Pseudomonas aeruginosa

P21_London_17_VIM_2_06_10
Proteobacteria
CVVE01000123.1


81
GCA_001180845.1
287
287

Pseudomonas aeruginosa

P22_London_17_VIM_2_06_10
Proteobacteria
CVVI01000141.1


82
GCA_001180845.1
287
287

Pseudomonas aeruginosa

P22_London_17_VIM_2_06_10
Proteobacteria
CVVI01000153.1


83
GCA_001180865.1
287
287

Pseudomonas aeruginosa

P23_East_of_England_6_IMP_13_07_10
Proteobacteria
CVUU01000179.1


84
GCA_001180865.1
287
287

Pseudomonas aeruginosa

P23_East_of_England_6_IMP_13_07_10
Proteobacteria
CVUU01000198.1


85
GCA_001180885.1
287
287

Pseudomonas aeruginosa

P24_London_17_VIM_2_08_10
Proteobacteria
CVUR01000168.1


86
GCA_001180885.1
287
287

Pseudomonas aeruginosa

P24_London_17_VIM_2_08_10
Proteobacteria
CVUR01000157.1


87
GCA_001180905.1
287
287

Pseudomonas aeruginosa

P25_London_12_VIM_2_08_10
Proteobacteria
CVVL01000167.1


88
GCA_001180905.1
287
287

Pseudomonas aeruginosa

P25_London_12_VIM_2_08_10
Proteobacteria
CVVL01000150.1


89
GCA_001180925.1
287
287

Pseudomonas aeruginosa

P26_Wales_1_VIM_2_11_10
Proteobacteria
CVVN01000216.1


90
GCA_001180925.1
287
287

Pseudomonas aeruginosa

P26_Wales_1_VIM_2_11_10
Proteobacteria
CVVN01000169.1


91
GCA_001180945.1
287
287

Pseudomonas aeruginosa

P27_Wales_1_VIM_2_02_11
Proteobacteria
CVVX01000242.1


92
GCA_001180945.1
287
287

Pseudomonas aeruginosa

P27_Wales_1_VIM_2_02_11
Proteobacteria
CVVX01000290.1


93
GCA_001180965.1
287
287

Pseudomonas aeruginosa

P28_London_17_02_11
Proteobacteria
CVUQ01000182.1


94
GCA_001180965.1
287
287

Pseudomonas aeruginosa

P28_London_17_02_11
Proteobacteria
CVUQ01000192.1


95
GCA_001180985.1
287
287

Pseudomonas aeruginosa

P29_London_12_VIM_2_05_11
Proteobacteria
CVVO01000189.1


96
GCA_001180985.1
287
287

Pseudomonas aeruginosa

P29_London_12_VIM_2_05_11
Proteobacteria
CVVO01000175.1


97
GCA_001181005.1
287
287

Pseudomonas aeruginosa

P30_South_East_2_VIM_2_10_11
Proteobacteria
CVVK01000149.1


98
GCA_001181005.1
287
287

Pseudomonas aeruginosa

P30_South_East_2_VIM_2_10_11
Proteobacteria
CVVK01000161.1


99
GCA_001181025.1
287
287

Pseudomonas aeruginosa

P31_Wales_1_VIM_2_11_11
Proteobacteria
CVVS01000268.1


100
GCA_001181025.1
287
287

Pseudomonas aeruginosa

P31_Wales_1_VIM_2_11_11
Proteobacteria
CVVS01000311.1


101
GCA_001181045.1
287
287

Pseudomonas aeruginosa

P32_London_17_VIM_2_10_11
Proteobacteria
CVVJ01000160.1


102
GCA_001181045.1
287
287

Pseudomonas aeruginosa

P32_London_17_VIM_2_10_11
Proteobacteria
CVVJ01000144.1


103
GCA_001181065.1
287
287

Pseudomonas aeruginosa

P33_London_28_VIM_2_02_12
Proteobacteria
CVVG01000131.1


104
GCA_001181065.1
287
287

Pseudomonas aeruginosa

P33_London_28_VIM_2_02_12
Proteobacteria
CVVG01000143.1


105
GCA_001181085.1
287
287

Pseudomonas aeruginosa

P34_London_28_VIM_2_02_12
Proteobacteria
CVVF01000155.1


106
GCA_001181085.1
287
287

Pseudomonas aeruginosa

P34_London_28_VIM_2_02_12
Proteobacteria
CVVF01000134.1


107
GCA_001181105.1
287
287

Pseudomonas aeruginosa

P35_London_26_VIM_2_05_12
Proteobacteria
CVUS01000188.1


108
GCA_001181105.1
287
287

Pseudomonas aeruginosa

P35_London_26_VIM_2_05_12
Proteobacteria
CVUS01000164.1


109
GCA_001181125.1
287
287

Pseudomonas aeruginosa

P36_West_Midlands_5_VIM_2_06_12
Proteobacteria
CVVP01000172.1


110
GCA_001181125.1
287
287

Pseudomonas aeruginosa

P36_West_Midlands_5_VIM_2_06_12
Proteobacteria
CVVP01000215.1


111
GCA_001181145.1
287
287

Pseudomonas aeruginosa

P37_London_28_VIM_2_07_12
Proteobacteria
CVUJ01000135.1


112
GCA_001181145.1
287
287

Pseudomonas aeruginosa

P37_London_28_VIM_2_07_12
Proteobacteria
CVUJ01000152.1


113
GCA_001181165.1
287
287

Pseudomonas aeruginosa

P38_London_12_VIM_2_08_12
Proteobacteria
CVUT01000161.1


114
GCA_001181165.1
287
287

Pseudomonas aeruginosa

P38_London_12_VIM_2_08_12
Proteobacteria
CVUT01000152.1


115
GCA_001181185.1
287
287

Pseudomonas aeruginosa

P39_London_29_08_12
Proteobacteria
CVVC01000121.1


116
GCA_001181185.1
287
287

Pseudomonas aeruginosa

P39_London_29_08_12
Proteobacteria
CVVC01000131.1


117
GCA_001181205.1
287
287

Pseudomonas aeruginosa

P40_Scotland_4_VIM_2_09_12
Proteobacteria
CVUM01000136.1


118
GCA_001181205.1
287
287

Pseudomonas aeruginosa

P40_Scotland_4_VIM_2_09_12
Proteobacteria
CVUM01000124.1


119
GCA_001181225.1
287
287

Pseudomonas aeruginosa

P41_London_28_09_12
Proteobacteria
CVVR01000160.1


120
GCA_001181225.1
287
287

Pseudomonas aeruginosa

P41_London_28_09_12
Proteobacteria
CVVR01000143.1


121
GCA_001181245.1
287
287

Pseudomonas aeruginosa

P42_1_London_26_VIM_2_10_12
Proteobacteria
CVWH01000143.1


122
GCA_001181245.1
287
287

Pseudomonas aeruginosa

P42_1_London_26_VIM_2_10_12
Proteobacteria
CVWH01000149.1


123
GCA_001181265.1
287
287

Pseudomonas aeruginosa

P43_1_London_9_VIM_2_11_12
Proteobacteria
CVWJ01000147.1


124
GCA_001181265.1
287
287

Pseudomonas aeruginosa

P43_1_London_9_VIM_2_11_12
Proteobacteria
CVWJ01000137.1


125
GCA_001181285.1
287
287

Pseudomonas aeruginosa

P42_2_London_28_VIM_2_11_12
Proteobacteria
CVWI01000128.1


126
GCA_001181285.1
287
287

Pseudomonas aeruginosa

P42_2_London_28_VIM_2_11_12
Proteobacteria
CVWI01000133.1


127
GCA_001181305.1
287
287

Pseudomonas aeruginosa

P45_London_17_VIM_2_12_12
Proteobacteria
CVWO01000030.1


128
GCA_001181305.1
287
287

Pseudomonas aeruginosa

P45_London_17_VIM_2_12_12
Proteobacteria
CVWO01000099.1


129
GCA_001181325.1
287
287

Pseudomonas aeruginosa

E5_London_17_VIM_2_12_12
Proteobacteria
CVWE01000133.1


130
GCA_001181325.1
287
287

Pseudomonas aeruginosa

E5_London_17_VIM_2_12_12
Proteobacteria
CVWE01000188.1


131
GCA_001181345.1
287
287

Pseudomonas aeruginosa

E6_London_17_VIM_2_12_12
Proteobacteria
CVWD01000029.1


132
GCA_001181345.1
287
287

Pseudomonas aeruginosa

E6_London_17_VIM_2_12_12
Proteobacteria
CVWD01000443.1


133
GCA_001181365.1
287
287

Pseudomonas aeruginosa

P46_South_East_6_12_12
Proteobacteria
CVWM01000196.1


134
GCA_001181365.1
287
287

Pseudomonas aeruginosa

P46_South_East_6_12_12
Proteobacteria
CVWM01000176.1


135
GCA_001181385.1
287
287

Pseudomonas aeruginosa

P47_London_12_VIM_2_12_12
Proteobacteria
CVWN01000372.1


136
GCA_001181385.1
287
287

Pseudomonas aeruginosa

P47_London_12_VIM_2_12_12
Proteobacteria
CVWN01000371.1


137
GCA_001181405.1
287
287

Pseudomonas aeruginosa

P48_London_17_VIM_2_01_13
Proteobacteria
CVWT01000099.1


138
GCA_001181405.1
287
287

Pseudomonas aeruginosa

P48_London_17_VIM_2_01_13
Proteobacteria
CVWT01000133.1


139
GCA_001181425.1
287
287

Pseudomonas aeruginosa

P49_London_7_VIM_2_01_13
Proteobacteria
CVWQ01000279.1


140
GCA_001181425.1
287
287

Pseudomonas aeruginosa

P49_London_7_VIM_2_01_13
Proteobacteria
CVWQ01000286.1


141
GCA_001181445.1
287
287

Pseudomonas aeruginosa

P50_London_9_VIM_2_01_13
Proteobacteria
CVWP01000147.1


142
GCA_001181445.1
287
287

Pseudomonas aeruginosa

P50_London_9_VIM_2_01_13
Proteobacteria
CVWP01000136.1


143
GCA_001181465.1
287
287

Pseudomonas aeruginosa

P43_2_London_9_VIM_2_11_12
Proteobacteria
CVWK01000146.1


144
GCA_001181465.1
287
287

Pseudomonas aeruginosa

P43_2_London_9_VIM_2_11_12
Proteobacteria
CVWK01000139.1


145
GCA_001181485.1
287
287

Pseudomonas aeruginosa

P51_1_London_9_VIM_2_02_13
Proteobacteria
CVWR01000277.1


146
GCA_001181485.1
287
287

Pseudomonas aeruginosa

P51_1_London_9_VIM_2_02_13
Proteobacteria
CVWR01000249.1


147
GCA_001181505.1
287
287

Pseudomonas aeruginosa

E7_London_9_VIM_2_02_13
Proteobacteria
CVWB01000104.1


148
GCA_001181505.1
287
287

Pseudomonas aeruginosa

E7_London_9_VIM_2_02_13
Proteobacteria
CVWB01000325.1


149
GCA_001181525.1
287
287

Pseudomonas aeruginosa

P52_1_London_26_VIM_2_02_13
Proteobacteria
CVWV01000212.1


150
GCA_001181525.1
287
287

Pseudomonas aeruginosa

P52_1_London_26_VIM_2_02_13
Proteobacteria
CVWV01000231.1


151
GCA_001181545.1
287
287

Pseudomonas aeruginosa

P51_2_London_11_VIM_2_02_13
Proteobacteria
CVWU01000143.1


152
GCA_001181545.1
287
287

Pseudomonas aeruginosa

P51_2_London_11_VIM_2_02_13
Proteobacteria
CVWU01000157.1


153
GCA_001181565.1
287
287

Pseudomonas aeruginosa

P52_2_London_26_VIM_2_02_13
Proteobacteria
CVWW01000197.1


154
GCA_001181565.1
287
287

Pseudomonas aeruginosa

P52_2_London_26_VIM_2_02_13
Proteobacteria
CVWW01000223.1


155
GCA_001181585.1
287
287

Pseudomonas aeruginosa

P53_London_9_VIM_2_02_13
Proteobacteria
CWER01000327.1


156
GCA_001181585.1
287
287

Pseudomonas aeruginosa

P53_London_9_VIM_2_02_13
Proteobacteria
CWER01000323.1


157
GCA_001181605.1
287
287

Pseudomonas aeruginosa

P54_1_London_24_VIM_2_04_13
Proteobacteria
CWFR01000366.1


158
GCA_001181605.1
287
287

Pseudomonas aeruginosa

P54_1_London_24_VIM_2_04_13
Proteobacteria
CWFR01000421.1


159
GCA_001181625.1
287
287

Pseudomonas aeruginosa

E8_London_17_VIM_2_04_13
Proteobacteria
CVUW01000183.1


160
GCA_001181625.1
287
287

Pseudomonas aeruginosa

E8_London_17_VIM_2_04_13
Proteobacteria
CVUW01000203.1


161
GCA_001181645.1
287
287

Pseudomonas aeruginosa

E9_London_17_VIM_2_04_13
Proteobacteria
CVUN01000148.1


162
GCA_001181645.1
287
287

Pseudomonas aeruginosa

E9_London_17_VIM_2_04_13
Proteobacteria
CVUN01000161.1


163
GCA_001181665.1
287
287

Pseudomonas aeruginosa

P54_2_London_24_VIM_2_04_13
Proteobacteria
CVXL01000226.1


164
GCA_001181665.1
287
287

Pseudomonas aeruginosa

P54_2_London_24_VIM_2_04_13
Proteobacteria
CVXL01000242.1


165
GCA_001181685.1
287
287

Pseudomonas aeruginosa

P55_London_26_VIM_2_05_13
Proteobacteria
CVWX01000125.1


166
GCA_001181685.1
287
287

Pseudomonas aeruginosa

P55_London_26_VIM_2_05_13
Proteobacteria
CVWX01000140.1


167
GCA_001181705.1
287
287

Pseudomonas aeruginosa

E10_London_26_VIM_2_06_13
Proteobacteria
CVVZ01000308.1


168
GCA_001181705.1
287
287

Pseudomonas aeruginosa

E10_London_26_VIM_2_06_13
Proteobacteria
CVVZ01000025.1


169
GCA_001181725.1
287
287

Pseudomonas aeruginosa

E11_London_26_VIM_2_06_13
Proteobacteria
CVVM01000142.1


170
GCA_001181725.1
287
287

Pseudomonas aeruginosa

E11_London_26_VIM_2_06_13
Proteobacteria
CVVM01000156.1


171
GCA_001181745.1
287
287

Pseudomonas aeruginosa

E12_London_26_VIM_2_06_13
Proteobacteria
CVUX01000216.1


172
GCA_001181745.1
287
287

Pseudomonas aeruginosa

E12_London_26_VIM_2_06_13
Proteobacteria
CVUX01000199.1


173
GCA_001181765.1
287
287

Pseudomonas aeruginosa

E13_London_26_VIM_2_06_13
Proteobacteria
CVVQ01000190.1


174
GCA_001181765.1
287
287

Pseudomonas aeruginosa

E13_London_26_VIM_2_06_13
Proteobacteria
CVVQ01000177.1


175
GCA_001181785.1
287
287

Pseudomonas aeruginosa

E14_London_26_VIM_2_06_13
Proteobacteria
CWGG01000138.1


176
GCA_001181785.1
287
287

Pseudomonas aeruginosa

E14_London_26_VIM_2_06_13
Proteobacteria
CWGG01000153.1


177
GCA_001181805.1
287
287

Pseudomonas aeruginosa

P56_London_12_VIM_2_07_13
Proteobacteria
CVXC01000168.1


178
GCA_001181805.1
287
287

Pseudomonas aeruginosa

P56_London_12_VIM_2_07_13
Proteobacteria
CVXC01000184.1


179
GCA_001181825.1
287
287

Pseudomonas aeruginosa

P8_2_London_17_VIM_2_07_13
Proteobacteria
CVXH01000145.1


180
GCA_001181825.1
287
287

Pseudomonas aeruginosa

P8_2_London_17_VIM_2_07_13
Proteobacteria
CVXH01000148.1


181
GCA_001181845.1
287
287

Pseudomonas aeruginosa

P57_South_East_3_VIM_2_09_13
Proteobacteria
CVWZ01000144.1


182
GCA_001181845.1
287
287

Pseudomonas aeruginosa

P57_South_East_3_VIM_2_09_13
Proteobacteria
CVWZ01000159.1


183
GCA_001181865.1
287
287

Pseudomonas aeruginosa

P58_London_29_09_13
Proteobacteria
CVXA01000139.1


184
GCA_001181865.1
287
287

Pseudomonas aeruginosa

P58_London_29_09_13
Proteobacteria
CVXA01000156.1


185
GCA_001181885.1
287
287

Pseudomonas aeruginosa

P59_Wales_1_VIM_2_09_13
Proteobacteria
CVXN01000001.1


186
GCA_001181885.1
287
287

Pseudomonas aeruginosa

P59_Wales_1_VIM_2_09_13
Proteobacteria
CVXN01000252.1


187
GCA_001181905.1
287
287

Pseudomonas aeruginosa

P60_London_6_VIM_2_11_13
Proteobacteria
CVXD01000175.1


188
GCA_001181905.1
287
287

Pseudomonas aeruginosa

P60_London_6_VIM_2_11_13
Proteobacteria
CVXD01000153.1


189
GCA_001181925.1
287
287

Pseudomonas aeruginosa

P61_London_9_VIM_2_11_13
Proteobacteria
CVXB01000157.1


190
GCA_001181925.1
287
287

Pseudomonas aeruginosa

P61_London_9_VIM_2_11_13
Proteobacteria
CVXB01000171.1


191
GCA_001181945.1
287
287

Pseudomonas aeruginosa

P64_East_of_England_6_01_14
Proteobacteria
CWFQ01000009.1


192
GCA_001181945.1
287
287

Pseudomonas aeruginosa

P64_East_of_England_6_01_14
Proteobacteria
CWFQ01000391.1


193
GCA_001181965.1
287
287

Pseudomonas aeruginosa

P62_London_9_VIM_2_01_14
Proteobacteria
CWEO01000265.1


194
GCA_001181965.1
287
287

Pseudomonas aeruginosa

P62_London_9_VIM_2_01_14
Proteobacteria
CWEO01000250.1


195
GCA_001181985.1
287
287

Pseudomonas aeruginosa

E15_London_28_01_14
Proteobacteria
CVWF01000732.1


196
GCA_001182005.1
287
287

Pseudomonas aeruginosa

P63_London_25_VIM_2_03_14
Proteobacteria
CWFH01000250.1


197
GCA_001182005.1
287
287

Pseudomonas aeruginosa

P63_London_25_VIM_2_03_14
Proteobacteria
CWFH01000268.1


198
GCA_001182025.1
287
287

Pseudomonas aeruginosa

E16_London_17_VIM_2_04_14
Proteobacteria
CVWG01001003.1


199
GCA_001182025.1
287
287

Pseudomonas aeruginosa

E16_London_17_VIM_2_04_14
Proteobacteria
CVWG01000111.1


200
GCA_001182945.1
287
287

Pseudomonas aeruginosa

P44_Wales_1_VIM_2_11_12
Proteobacteria
CVWL01000374.1


201
GCA_001182945.1
287
287

Pseudomonas aeruginosa

P44_Wales_1_VIM_2_11_12
Proteobacteria
CVWL01000327.1


202
GCA_001420185.1
287
287

Pseudomonas aeruginosa

ATCC 33349
Proteobacteria
LINV01000076.1


203
GCA_001444845.1
287
287

Pseudomonas aeruginosa

ATCC 33361
Proteobacteria
LIZH01000277.1


204
GCA_001444865.1
287
287

Pseudomonas aeruginosa

ATCC 33362
Proteobacteria
LIZI01000121.1


205
GCA_001444975.1
287
287

Pseudomonas aeruginosa

ATCC 33359
Proteobacteria
LIZF01000253.1


206
GCA_001444995.1
287
287

Pseudomonas aeruginosa

ATCC 33360
Proteobacteria
LIZG01000273.1


207
GCA_001449385.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07072
Proteobacteria
LLLP01000007.1


208
GCA_001449465.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07165
Proteobacteria
LLLU01000037.1


209
GCA_001449505.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07167
Proteobacteria
LLLW01000014.1


210
GCA_001449515.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07168
Proteobacteria
LLLX01000036.1


211
GCA_001449515.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07168
Proteobacteria
LLLX01000030.1


212
GCA_001449555.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07171
Proteobacteria
LLMA01000028.1


213
GCA_001449555.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07171
Proteobacteria
LLMA01000003.1


214
GCA_001449605.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07174
Proteobacteria
LLMD01000001.1


215
GCA_001449605.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07174
Proteobacteria
LLMD01000070.1


216
GCA_001449625.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07175
Proteobacteria
LLME01000030.1


217
GCA_001449625.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07175
Proteobacteria
LLME01000022.1


218
GCA_001449675.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07180
Proteobacteria
LLMJ01000031.1


219
GCA_001449705.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07221
Proteobacteria
LLMK01000076.1


220
GCA_001449705.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07221
Proteobacteria
LLMK01000071.1


221
GCA_001450165.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07370
Proteobacteria
LLNU01000057.1


222
GCA_001450275.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07379
Proteobacteria
LLOD01000041.1


223
GCA_001450355.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07055
Proteobacteria
LLKZ01000040.1


224
GCA_001450385.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07065
Proteobacteria
LLLC01000012.1


225
GCA_001450465.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07064
Proteobacteria
LLLN01000006.1


226
GCA_001450525.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07173
Proteobacteria
LLMC01000045.1


227
GCA_001450525.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07173
Proteobacteria
LLMC01000054.1


228
GCA_001450625.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07185
Proteobacteria
LLMP01000039.1


229
GCA_001451065.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07392
Proteobacteria
LLOQ01000102.1


230
GCA_001451075.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07391
Proteobacteria
LLOP01000052.1


231
GCA_001451225.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07415
Proteobacteria
LLPC01000038.1


232
GCA_001451505.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07426
Proteobacteria
LLPN01000122.1


233
GCA_001451705.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07491
Proteobacteria
LLPX01000023.1


234
GCA_001451805.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07497
Proteobacteria
LLQD01000079.1


235
GCA_001451945.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07618
Proteobacteria
LLQP01000102.1


236
GCA_001452185.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07637
Proteobacteria
LLRI01000005.1


237
GCA_001452205.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07640
Proteobacteria
LLRL01000163.1


238
GCA_001452365.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07651
Proteobacteria
LLRW01000066.1


239
GCA_001452365.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07651
Proteobacteria
LLRW01000061.1


240
GCA_001452385.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07652
Proteobacteria
LLRX01000045.1


241
GCA_001452415.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07681
Proteobacteria
LLSB01000007.1


242
GCA_001452465.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07687
Proteobacteria
LLSH01000054.1


243
GCA_001452485.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07688
Proteobacteria
LLSI01000049.1


244
GCA_001452485.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07688
Proteobacteria
LLSI01000001.1


245
GCA_001452565.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07693
Proteobacteria
LLSN01000046.1


246
GCA_001452645.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07700
Proteobacteria
LLSU01000053.1


247
GCA_001452645.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07700
Proteobacteria
LLSU01000046.1


248
GCA_001452665.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07702
Proteobacteria
LLSW01000054.1


249
GCA_001452665.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07702
Proteobacteria
LLSW01000062.1


250
GCA_001452765.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07711
Proteobacteria
LLTF01000239.1


251
GCA_001452905.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07253
Proteobacteria
LLTN01000034.1


252
GCA_001453015.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07263
Proteobacteria
LLTV01000056.1


253
GCA_001453615.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07684
Proteobacteria
LLSE01000089.1


254
GCA_001453755.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07705
Proteobacteria
LLSZ01000120.1


255
GCA_001453855.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07256
Proteobacteria
LLTQ01000112.1


256
GCA_001453855.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07256
Proteobacteria
LLTQ01000118.1


257
GCA_001453885.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07259
Proteobacteria
LLTS01000104.1


258
GCA_001453885.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07259
Proteobacteria
LLTS01000112.1


259
GCA_001454125.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07290
Proteobacteria
LLUN01000012.1


260
GCA_001454145.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07291
Proteobacteria
LLUO01000109.1


261
GCA_001454205.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07295
Proteobacteria
LLUR01000002.1


262
GCA_001454225.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07296
Proteobacteria
LLUS01000044.1


263
GCA_001454225.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07296
Proteobacteria
LLUS01000001.1


264
GCA_001454445.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07322
Proteobacteria
LLVI01000081.1


265
GCA_001454445.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07322
Proteobacteria
LLVI01000088.1


266
GCA_001454485.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07324
Proteobacteria
LLVK01000064.1


267
GCA_001454485.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07324
Proteobacteria
LLVK01000044.1


268
GCA_001454495.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07325
Proteobacteria
LLVL01000090.1


269
GCA_001454495.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07325
Proteobacteria
LLVL01000001.1


270
GCA_001454515.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07328
Proteobacteria
LLVO01000057.1


271
GCA_001454515.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07328
Proteobacteria
LLVO01000082.1


272
GCA_001454545.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07329
Proteobacteria
LLVP01000031.1


273
GCA_001454545.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07329
Proteobacteria
LLVP01000037.1


274
GCA_001454565.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07330
Proteobacteria
LLVQ01000079.1


275
GCA_001454565.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07330
Proteobacteria
LLVQ01000086.1


276
GCA_001454675.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07287
Proteobacteria
LLUM01000045.1


277
GCA_001454805.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07326
Proteobacteria
LLVM01000239.1


278
GCA_001454805.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07326
Proteobacteria
LLVM01000224.1


279
GCA_001454825.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07327
Proteobacteria
LLVN01000114.1


280
GCA_001454825.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07327
Proteobacteria
LLVN01000121.1


281
GCA_001469695.1
287
287

Pseudomonas aeruginosa

AATYA
Proteobacteria
LODN01000001.1


282
GCA_001469695.1
287
287

Pseudomonas aeruginosa

AATYA
Proteobacteria
LODN01000079.1


283
GCA_001471355.1
287
287

Pseudomonas aeruginosa

FDAARGOS_154
Proteobacteria
LORM01000001.1


284
GCA_001516165.1
287
287

Pseudomonas aeruginosa

W16407
Proteobacteria
CP008869.1


285
GCA_001516245.1
287
287

Pseudomonas aeruginosa

F23197
Proteobacteria
CP008856.1


286
GCA_001516265.1
287
287

Pseudomonas aeruginosa

F30658
Proteobacteria
CP008857.1


287
GCA_001516265.1
287
287

Pseudomonas aeruginosa

F30658
Proteobacteria
CP008857.1


288
GCA_001535675.1
287
287

Pseudomonas aeruginosa

SPA01
Proteobacteria
LQBU01000001.1


289
GCA_001547575.1
287
287

Pseudomonas aeruginosa

BH6
Proteobacteria
LGVH01000140.1


290
GCA_001560865.1
287
287

Pseudomonas aeruginosa

105777
Proteobacteria
LODH01000011.1


291
GCA_001601745.1
287
287

Pseudomonas aeruginosa

105819
Proteobacteria
LOHH01000029.1


292
GCA_000877315.1
292
292

Burkholderia cepacia

LMG 16656
Proteobacteria
JTDP01000004.1


293
GCA_001522525.1
292
292

Burkholderia cepacia

INT1-BP277
Proteobacteria
LOTX01000037.1


294
GCA_001523085.1
292
292

Burkholderia cepacia

INT25-BP2
Proteobacteria
LOUT01000007.1


295
GCA_000237065.1
1114970
294

Pseudomonas fluorescens F113
F113
Proteobacteria
CP003150.1


296
GCA_000411675.1
1324332
294

Pseudomonas fluorescens LMG 5329
LMG 5329
Proteobacteria
ASGY01000250.1


297
GCA_001542695.1
294
294

Pseudomonas fluorescens

Ps_20
Proteobacteria
LCYD01000004.1


298
GCA_000016865.1
351746
303

Pseudomonas putida F1
F1
Proteobacteria
CP000712.1


299
GCA_000264665.1
231023
303

Pseudomonas putida ND6
ND6
Proteobacteria
CP003588.1


300
GCA_000294445.2
1193146
303

Pseudomonas putida LS46
LS46
Proteobacteria
ALPV02000008.1


301
GCA_000325725.1
1215088
303

Pseudomonas putida HB3267
PC9
Proteobacteria
CP003738.1


302
GCA_001467305.1
303
303

Pseudomonas putida

ABAC8
Proteobacteria
LKGZ01000002.1


303
GCA_000013785.1
379731
316

Pseudomonas stutzeri A1501
A1501
Proteobacteria
CP000304.1


304
GCA_000195105.1
996285
316

Pseudomonas stutzeri DSM 4166
DSM 4166
Proteobacteria
CP002622.1


305
GCA_000237885.2
32042
316

Pseudomonas stutzeri ATCC 14405 = CCUG 16156
CCUG16156
Proteobacteria
AGSL01000126.1


306
GCA_000267545.1
1196835
316

Pseudomonas stutzeri CCUG 29243
CCUG 29243
Proteobacteria
CP003677.1


307
GCA_000307775.2
1218352
316

Pseudomonas stutzeri KOS6
KOS6
Proteobacteria
KK020678.1


308
GCA_000416345.1
1212549
316

Pseudomonas stutzeri B1SMN1
B1SMN1
Proteobacteria
AMVM01000007.1


309
GCA_000416545.1
1194422
317

Pseudomonas syringae pv. actinidiae ICMP 19098
ICMP 19098
Proteobacteria
AOKE01000198.1


310
GCA_000416645.2
1194405
317

Pseudomonas syringae pv. actinidiae ICMP 19096
ICMP 19096
Proteobacteria
AOKF01004024.1


311
GCA_000416745.1
1194401
317

Pseudomonas syringae pv. actinidiae ICMP 19094
ICMP 19094
Proteobacteria
AOKJ01000458.1


312
GCA_000416765.1
1194403
317

Pseudomonas syringae pv. actinidiae ICMP 19095
ICMP 19095
Proteobacteria
AOKI01000655.1


313
GCA_000416785.2
1194402
317

Pseudomonas syringae pv. actinidiae ICMP 18883
ICMP 18883
Proteobacteria
AOKH01000282.1


314
GCA_000416805.1
1194421
317

Pseudomonas syringae pv. actinidiae ICMP 19099
ICMP 19099
Proteobacteria
AOKD01000288.1


315
GCA_000416825.2
1194420
317

Pseudomonas syringae pv. actinidiae ICMP 19100
ICMP 19100
Proteobacteria
AOKC01000529.1


316
GCA_000416905.2
1104682
317

Pseudomonas syringae pv. actinidiae ICMP 18804
ICMP 18804
Proteobacteria
AOJU01004126.1


317
GCA_000737235.1
317
317

Pseudomonas syringae

CEB003
Proteobacteria
JPQT01000163.1


318
GCA_001467225.1
1208099
317

Pseudomonas syringae pv. actinidiae ICMP 19497
ICMP 19497
Proteobacteria
LKBQ01000046.1


319
GCA_000007145.1
190485
339

Xanthomonas campestris pv. campestris str. ATCC 33913
ATCC 33913
Proteobacteria
AE008922.1


320
GCA_000012105.1
314565
339

Xanthomonas campestris pv. campestris str. 8004
8004
Proteobacteria
CP000050.1


321
GCA_001186415.1
340
339

Xanthomonas campestris pv. campestris
ICMP 21080
Proteobacteria
CP012145.1


322
GCA_000018545.1
394
380

Sinorhizobium fredii NGR234
NGR234
Proteobacteria
CP001389.1


323
GCA_001510895.1
381
381

Mesorhizobium loti

UFLA 01-765
Proteobacteria
LPWA01000115.1


324
GCA_001510895.1
381
381

Mesorhizobium loti

UFLA 01-765
Proteobacteria
LPWA01000098.1


325
GCA_000985895.1
323655
399

Neorhizobium galegae bv. orientalis

Proteobacteria
CCRN01000010.1


326
GCA_000021845.1
440085
408

Methylobacterium extorquens CM4
CM4
Proteobacteria
CP001298.1


327
GCA_000048665.1
297245
446

Legionella pneumophila str. Lens
Lens
Proteobacteria
CR628337.1


328
GCA_000306865.1
91891
446

Legionella pneumophila subsp. pneumophila
Lorraine
Proteobacteria
FQ958210.1


329
GCA_900048955.1
446
446

Legionella pneumophila

2532STDY5467593
Proteobacteria
FJID01000003.1


330
GCA_900048965.1
446
446

Legionella pneumophila

2532STDY5467557
Proteobacteria
FJJD01000021.1


331
GCA_900049285.1
446
446

Legionella pneumophila

2532STDY5467623
Proteobacteria
FJLD01000023.1


332
GCA_900049295.1
446
446

Legionella pneumophila

2532STDY5467622
Proteobacteria
FJLF01000024.1


333
GCA_900049305.1
446
446

Legionella pneumophila

2532STDY5467621
Proteobacteria
FJLH01000015.1


334
GCA_900049375.1
446
446

Legionella pneumophila

2532STDY5467550
Proteobacteria
FJJA01000022.1


335
GCA_900050245.1
446
446

Legionella pneumophila

2532STDY5467555
Proteobacteria
FJJC01000012.1


336
GCA_900051005.1
446
446

Legionella pneumophila

2532STDY5467663
Proteobacteria
FJLJ01000022.1


337
GCA_900051015.1
446
446

Legionella pneumophila

2531STDY5467451
Proteobacteria
FJLL01000023.1


338
GCA_900051745.1
446
446

Legionella pneumophila

2532STDY5467554
Proteobacteria
FJJB01000022.1


339
GCA_900052325.1
446
446

Legionella pneumophila

2532STDY5467604
Proteobacteria
FJKF01000025.1


340
GCA_900052335.1
446
446

Legionella pneumophila

2532STDY5467588
Proteobacteria
FJKM01000021.1


341
GCA_900052945.1
446
446

Legionella pneumophila

2532STDY5467560
Proteobacteria
FJIL01000023.1


342
GCA_900053425.1
446
446

Legionella pneumophila

2532STDY5467573
Proteobacteria
FJJV01000023.1


343
GCA_900053435.1
446
446

Legionella pneumophila

2532STDY5467568
Proteobacteria
FJJX01000003.1


344
GCA_900053445.1
446
446

Legionella pneumophila

2532STDY5467595
Proteobacteria
FJJZ01000021.1


345
GCA_900054165.1
446
446

Legionella pneumophila

2532STDY5467626
Proteobacteria
FJHY01000004.1


346
GCA_900054385.1
446
446

Legionella pneumophila

2531STDY5467312
Proteobacteria
FJAT01000023.1


347
GCA_900054395.1
446
446

Legionella pneumophila

2531STDY5467310
Proteobacteria
FJBR01000001.1


348
GCA_900054645.1
446
446

Legionella pneumophila

2532STDY5467583
Proteobacteria
FJKP01000024.1


349
GCA_900054655.1
446
446

Legionella pneumophila

2532STDY5467613
Proteobacteria
FJKY01000028.1


350
GCA_900054665.1
446
446

Legionella pneumophila

2532STDY5467610
Proteobacteria
FJLB01000023.1


351
GCA_900054675.1
446
446

Legionella pneumophila

2532STDY5467611
Proteobacteria
FJLA01000022.1


352
GCA_900054685.1
446
446

Legionella pneumophila

2532STDY5467619
Proteobacteria
FJLG01000023.1


353
GCA_900055215.1
446
446

Legionella pneumophila

2532STDY5467582
Proteobacteria
FJKK01000023.1


354
GCA_900055605.1
446
446

Legionella pneumophila

2532STDY5467580
Proteobacteria
FJIF01000024.1


355
GCA_900055615.1
446
446

Legionella pneumophila

2532STDY5467553
Proteobacteria
FJIH01000023.1


356
GCA_900055625.1
446
446

Legionella pneumophila

2532STDY5467571
Proteobacteria
FJJY01000024.1


357
GCA_900055635.1
446
446

Legionella pneumophila

2532STDY5467607
Proteobacteria
FJLC01000024.1


358
GCA_900056195.1
446
446

Legionella pneumophila

2532STDY5467551
Proteobacteria
FJJP01000022.1


359
GCA_900056205.1
446
446

Legionella pneumophila

2532STDY5467617
Proteobacteria
FJKS01000024.1


360
GCA_900056215.1
446
446

Legionella pneumophila

2532STDY5467616
Proteobacteria
FJKT01000023.1


361
GCA_900056935.1
446
446

Legionella pneumophila

2532STDY5467541
Proteobacteria
FJJR01000023.1


362
GCA_900056945.1
446
446

Legionella pneumophila

2532STDY5467540
Proteobacteria
FJJU01000024.1


363
GCA_900057265.1
446
446

Legionella pneumophila

2532STDY5467592
Proteobacteria
FJKR01000024.1


364
GCA_900057575.1
446
446

Legionella pneumophila

2532STDY5467547
Proteobacteria
FJIP01000023.1


365
GCA_900057585.1
446
446

Legionella pneumophila

2532STDY5467543
Proteobacteria
FJJT01000023.1


366
GCA_900057595.1
446
446

Legionella pneumophila

2532STDY5467574
Proteobacteria
FJKC01000003.1


367
GCA_900057605.1
446
446

Legionella pneumophila

2532STDY5467625
Proteobacteria
FJKU01000024.1


368
GCA_900057615.1
446
446

Legionella pneumophila

2531STDY5467449
Proteobacteria
FJLM01000024.1


369
GCA_900057785.1
446
446

Legionella pneumophila

2532STDY5467576
Proteobacteria
FJIA01000024.1


370
GCA_900058605.1
446
446

Legionella pneumophila

2532STDY5467563
Proteobacteria
FJJL01000023.1


371
GCA_900058825.1
446
446

Legionella pneumophila

2532STDY5467600
Proteobacteria
FJIT01000024.1


372
GCA_900058835.1
446
446

Legionella pneumophila

2532STDY5467548
Proteobacteria
FJIZ01000023.1


373
GCA_900059595.1
446
446

Legionella pneumophila

2532STDY5467603
Proteobacteria
FJKE01000023.1


374
GCA_900059605.1
446
446

Legionella pneumophila

2532STDY5467614
Proteobacteria
FJKV01000024.1


375
GCA_900060005.1
446
446

Legionella pneumophila

2532STDY5467535
Proteobacteria
FJIG01000023.1


376
GCA_900060015.1
446
446

Legionella pneumophila

2532STDY5467596
Proteobacteria
FJJG01000023.1


377
GCA_900060415.1
446
446

Legionella pneumophila

2532STDY5467542
Proteobacteria
FJII01000024.1


378
GCA_900060425.1
446
446

Legionella pneumophila

2532STDY5467549
Proteobacteria
FJIJ01000024.1


379
GCA_900060435.1
446
446

Legionella pneumophila

2532STDY5467544
Proteobacteria
FJIK01000023.1


380
GCA_900060445.1
446
446

Legionella pneumophila

2532STDY5467537
Proteobacteria
FJIM01000023.1


381
GCA_900060455.1
446
446

Legionella pneumophila

2532STDY5467584
Proteobacteria
FJKQ01000023.1


382
GCA_900060775.1
446
446

Legionella pneumophila

2532STDY5467627
Proteobacteria
FJIS01000025.1


383
GCA_900060785.1
446
446

Legionella pneumophila

2532STDY5467556
Proteobacteria
FJJF01000024.1


384
GCA_900061535.1
446
446

Legionella pneumophila

2531STDY5467351
Proteobacteria
FJCL01000024.1


385
GCA_900062525.1
446
446

Legionella pneumophila

2531STDY5467450
Proteobacteria
FJHW01000004.1


386
GCA_900062535.1
446
446

Legionella pneumophila

2532STDY5467575
Proteobacteria
FJHX01000023.1


387
GCA_900062545.1
446
446

Legionella pneumophila

2532STDY5467591
Proteobacteria
FJHZ01000023.1


388
GCA_900062555.1
446
446

Legionella pneumophila

2532STDY5467578
Proteobacteria
FJIB01000025.1


389
GCA_900062565.1
446
446

Legionella pneumophila

2532STDY5467581
Proteobacteria
FJIC01000024.1


390
GCA_900062575.1
446
446

Legionella pneumophila

2532STDY5467577
Proteobacteria
FJIE01000004.1


391
GCA_900062585.1
446
446

Legionella pneumophila

2532STDY5467546
Proteobacteria
FJIN01000024.1


392
GCA_900062595.1
446
446

Legionella pneumophila

2532STDY5467565
Proteobacteria
FJIO01000024.1


393
GCA_900062605.1
446
446

Legionella pneumophila

2532STDY5467561
Proteobacteria
FJIR01000021.1


394
GCA_900062615.1
446
446

Legionella pneumophila

2532STDY5467559
Proteobacteria
FJIQ01000021.1


395
GCA_900062625.1
446
446

Legionella pneumophila

2532STDY5467628
Proteobacteria
FJIU01000023.1


396
GCA_900062635.1
446
446

Legionella pneumophila

2532STDY5467538
Proteobacteria
FJIY01000023.1


397
GCA_900062645.1
446
446

Legionella pneumophila

2532STDY5467545
Proteobacteria
FJIX01000022.1


398
GCA_900062655.1
446
446

Legionella pneumophila

2532STDY5467602
Proteobacteria
FJJH01000024.1


399
GCA_900062665.1
446
446

Legionella pneumophila

2532STDY5467562
Proteobacteria
FJJI01000022.1


400
GCA_900062675.1
446
446

Legionella pneumophila

2532STDY5467539
Proteobacteria
FJJJ01000022.1


401
GCA_900062685.1
446
446

Legionella pneumophila

2532STDY5467566
Proteobacteria
FJJK01000024.1


402
GCA_900062695.1
446
446

Legionella pneumophila

2532STDY5467572
Proteobacteria
FJJM01000023.1


403
GCA_900062705.1
446
446

Legionella pneumophila

2532STDY5467608
Proteobacteria
FJJO01000023.1


404
GCA_900062715.1
446
446

Legionella pneumophila

2532STDY5467564
Proteobacteria
FJJN01000023.1


405
GCA_900062725.1
446
446

Legionella pneumophila

2532STDY5467586
Proteobacteria
FJJQ01000024.1


406
GCA_900062735.1
446
446

Legionella pneumophila

2532STDY5467567
Proteobacteria
FJJW01000021.1


407
GCA_900062745.1
446
446

Legionella pneumophila

2532STDY5467598
Proteobacteria
FJKA01000023.1


408
GCA_900062755.1
446
446

Legionella pneumophila

2532STDY5467585
Proteobacteria
FJKB01000023.1


409
GCA_900063115.1
446
446

Legionella pneumophila

2532STDY5467558
Proteobacteria
FJJS01000025.1


410
GCA_900063125.1
446
446

Legionella pneumophila

2532STDY5467615
Proteobacteria
FJKW01000024.1


411
GCA_900063135.1
446
446

Legionella pneumophila

2532STDY5467587
Proteobacteria
FJKZ01000024.1


412
GCA_900063145.1
446
446

Legionella pneumophila

2532STDY5467612
Proteobacteria
FJKX01000024.1


413
GCA_900063835.1
446
446

Legionella pneumophila

2532STDY5467552
Proteobacteria
FJJE01000022.1


414
GCA_900063845.1
446
446

Legionella pneumophila

2532STDY5467605
Proteobacteria
FJKD01000023.1


415
GCA_900063855.1
446
446

Legionella pneumophila

2532STDY5467597
Proteobacteria
FJKG01000023.1


416
GCA_900063865.1
446
446

Legionella pneumophila

2532STDY5467594
Proteobacteria
FJKH01000022.1


417
GCA_900063875.1
446
446

Legionella pneumophila

2532STDY5467589
Proteobacteria
FJKN01000025.1


418
GCA_900063885.1
446
446

Legionella pneumophila

2532STDY5467601
Proteobacteria
FJKO01000022.1


419
GCA_900063895.1
446
446

Legionella pneumophila

2532STDY5467620
Proteobacteria
FJLE01000025.1


420
GCA_900064205.1
446
446

Legionella pneumophila

2532STDY5467618
Proteobacteria
FJLI01000003.1


421
GCA_900064315.1
446
446

Legionella pneumophila

2532STDY5467599
Proteobacteria
FJKJ01000024.1


422
GCA_900064325.1
446
446

Legionella pneumophila

2532STDY5467606
Proteobacteria
FJKL01000024.1


423
GCA_900064495.1
446
446

Legionella pneumophila

2532STDY5467534
Proteobacteria
FJIW01000023.1


424
GCA_900064755.1
446
446

Legionella pneumophila

2532STDY5467579
Proteobacteria
FJIV01000020.1


425
GCA_900064765.1
446
446

Legionella pneumophila

2532STDY5467590
Proteobacteria
FJKI01000024.1


426
GCA_900073005.1
446
446

Legionella pneumophila

LP_617
Proteobacteria
FJOC01000028.1


427
GCA_001467765.1
456
456

Legionella jordanis

BL-540
Proteobacteria
LNYJ01000003.1


428
GCA_000353775.1
1094483
470

Acinetobacter baumannii ABNIH19
ABNIH19
Proteobacteria
APBH01000063.1


429
GCA_000353955.1
1094470
470

Acinetobacter baumannii ABNIH6
ABNIH6
Proteobacteria
APAX01000087.1


430
GCA_000353975.1
1094471
470

Acinetobacter baumannii ABNIH7
ABNIH7
Proteobacteria
APAY01000451.1


431
GCA_000353995.1
1094474
470

Acinetobacter baumannii ABNIH10
ABNIH10
Proteobacteria
APAZ01000253.1


432
GCA_000354015.1
1094475
470

Acinetobacter baumannii ABNIH11
ABNIH11
Proteobacteria
APBA01000112.1


433
GCA_000580595.1
1310619
470

Acinetobacter baumannii 1419130
1419130
Proteobacteria
JEWL01000035.1


434
GCA_000580635.1
1310647
470

Acinetobacter baumannii 1461402
1461402
Proteobacteria
JEWP01000001.1


435
GCA_000580875.1
1310613
470

Acinetobacter baumannii 1295743
1295743
Proteobacteria
JEWH01000023.1


436
GCA_000580995.1
1310611
470

Acinetobacter baumannii 466760
466760
Proteobacteria
JEXB01000001.1


437
GCA_000581195.1
1310651
470

Acinetobacter baumannii 230853
230853
Proteobacteria
JEWW01000002.1


438
GCA_000582235.1
1310680
470

Acinetobacter baumannii 1239920
1239920
Proteobacteria
JEXZ01000002.1


439
GCA_000582255.1
1310683
470

Acinetobacter baumannii 1566109
1566109
Proteobacteria
JEYB01000087.1


440
GCA_000682355.1
1310685
470

Acinetobacter baumannii 72431
72431
Proteobacteria
JMNZ01000050.1


441
GCA_000805365.1
470
470

Acinetobacter baumannii

1
Proteobacteria
JSAO01000006.1


442
GCA_001028315.1
1409926
470

Acinetobacter baumannii MRSN 58
MRSN 58
Proteobacteria
JPHW01000032.1


443
GCA_001432425.1
470
470

Acinetobacter baumannii

ABBL014
Proteobacteria
LLCU01000093.1


444
GCA_001433005.1
470
470

Acinetobacter baumannii

ABBL038
Proteobacteria
LLDS01000053.1


445
GCA_001578145.1
470
470

Acinetobacter baumannii

XH858
Proteobacteria
CP014528.1


446
GCA_000690355.2
1458258
518

Bordetella bronchiseptica B18-5 (C3)
B18-5 (C3)
Proteobacteria
JGWP01000092.1


447
GCA_000690635.1
1331233
518

Bordetella bronchiseptica MBORD762
MBORD762
Proteobacteria
JHBR01000046.1


448
GCA_000024245.1
622759
542

Zymomonas mobilis subsp. mobilis NCIMB 11163
NCIMB 11163
Proteobacteria
CP001723.1


449
GCA_000218875.1
579138
542

Zymomonas mobilis subsp. pomaceae ATCC 29192
ATCC 29192
Proteobacteria
CP002866.1


450
GCA_001472275.1
548
548

Enterobacter aerogenes

SMART_429
Proteobacteria
LPQB01000006.1


451
GCA_001518035.1
548
548

Enterobacter aerogenes

GN02710
Proteobacteria
LRCB01000137.1


452
GCA_000743785.2
549
549

Pantoea agglomerans

4
Proteobacteria
JPOT02000001.1


453
GCA_000286275.1
1211025
550

Enterobacter cloacae subsp. cloacae ENHKU01
ENHKU01
Proteobacteria
CP003737.1


454
GCA_000496775.1
1399146
550

Enterobacter cloacae S611
S611
Proteobacteria
AXOM01000016.1


455
GCA_000534275.1
1400147
550

Enterobacter cloacae UCI 24
UCI 24
Proteobacteria
KI973153.1


456
GCA_000692355.1
1400148
550

Enterobacter cloacae UCI 29
UCI 29
Proteobacteria
KK736271.1


457
GCA_000784865.1
550
550

Enterobacter cloacae

ECNIH4
Proteobacteria
CP009850.1


458
GCA_000965825.1
550
550

Enterobacter cloacae

CIDEIMsCOL5
Proteobacteria
JZKP01000063.1


459
GCA_000966005.1
550
550

Enterobacter cloacae

CIDEIMsCOL4
Proteobacteria
JZKO01000065.1


460
GCA_001317225.1
336306
550

Enterobacter cloacae subsp. cloacae
ST434:953099839
Proteobacteria
LIEW01000028.1


461
GCA_001441705.1
550
550

Enterobacter cloacae

8706
Proteobacteria
LLXN01000108.1


462
GCA_001518525.1
550
550

Enterobacter cloacae

GN02618
Proteobacteria
LRBY01000003.1


463
GCA_000270125.2
932677
553

Pantoea ananatis AJ13355
AJ13355
Proteobacteria
AP012032.2


464
GCA_000283875.1
1123863
553

Pantoea ananatis LMG 5342
LMG 5342
Proteobacteria
HE617160.1


465
GCA_000294535.1
1218933
554

Pectobacterium carotovorum subsp. carotovorum PCC21
PCC21
Proteobacteria
CP003776.1


466
GCA_000808145.1
180957
554

Pectobacterium carotovorum subsp. brasiliense
YC D62
Proteobacteria
JUJD01000008.1


467
GCA_000808295.1
180957
554

Pectobacterium carotovorum subsp. brasiliense
YC T31
Proteobacteria
JUJL01000008.1


468
GCA_000808315.1
180957
554

Pectobacterium carotovorum subsp. brasiliense
YC T3
Proteobacteria
JUJM01000011.1


469
GCA_000017745.1
331111
562

Escherichia coli O139:H28 str. E24377A
E24377A
Proteobacteria
CP000800.1


470
GCA_000267025.1
1005535
562

Escherichia coli EC1738
EC1738
Proteobacteria
AKMN01000044.1


471
GCA_000267865.2
1005494
562

Escherichia coli PA10
PA10
Proteobacteria
JH708741.1


472
GCA_000304875.2
1005452
562

Escherichia coli 5.2239
5.2239
Proteobacteria
JH970984.1


473
GCA_000316885.2
1005408
562

Escherichia coli 95.0943
95.0943
Proteobacteria
KB000904.1


474
GCA_000335135.1
1005439
562

Escherichia coli 99.1781
99.1781
Proteobacteria
AOEQ01000009.1


475
GCA_000335295.2
1005440
562

Escherichia coli 99.1753
99.1753
Proteobacteria
AOED01000081.1


476
GCA_000335315.2
1005438
562

Escherichia coli 99.1775
99.1775
Proteobacteria
AOEE01000071.1


477
GCA_000340455.2
1081887
562

Escherichia coli 09BKT078844
09BKT078844
Proteobacteria
KB452795.1


478
GCA_000351585.1
1182667
562

Escherichia coli KTE60
KTE60
Proteobacteria
KB732732.1


479
GCA_000352105.1
1169329
562

Escherichia coli KTE9
KTE9
Proteobacteria
KB732995.1


480
GCA_000357165.1
1116056
562

Escherichia coli P0299917.10
P0299917.10
Proteobacteria
APYK01000102.1


481
GCA_000357185.2
1116048
562

Escherichia coli P0299917.2
P0299917.2
Proteobacteria
APYL01000006.1


482
GCA_000357205.2
1116049
562

Escherichia coli P0299917.3
P0299917.3
Proteobacteria
APYM01000020.1


483
GCA_000357305.2
1116050
562

Escherichia coli P0299917.4
P0299917.4
Proteobacteria
APYN01000006.1


484
GCA_000357325.1
1116051
562

Escherichia coli P0299917.5
P0299917.5
Proteobacteria
APYO01000007.1


485
GCA_000357345.2
1116052
562

Escherichia coli P0299917.6
P0299917.6
Proteobacteria
APYP01000006.1


486
GCA_000357365.2
1116053
562

Escherichia coli P0299917.7
P0299917.7
Proteobacteria
APYQ01000007.1


487
GCA_000357505.2
1116055
562

Escherichia coli P0299917.9
P0299917.9
Proteobacteria
APYS01000112.1


488
GCA_000357685.2
1125651
562

Escherichia coli P0304799.3
P0304799.3
Proteobacteria
APZX01000274.1


489
GCA_000358795.2
1116054
562

Escherichia coli P0299917.8
P0299917.8
Proteobacteria
APYR01000109.1


490
GCA_000398885.1
1169351
562

Escherichia coli KTE33
KTE33
Proteobacteria
KB976087.1


491
GCA_000459555.1
1281153
562

Escherichia coli KOEGE 3 (4a)
KOEGE 3 (4a)
Proteobacteria
KE701179.1


492
GCA_000459855.1
1281168
562

Escherichia coli KOEGE 71 (186a)
KOEGE 71 (186a)
Proteobacteria
KE701379.1


493
GCA_000459915.1
1281171
562

Escherichia coli KOEGE 118 (317a)
KOEGE 118 (317a)
Proteobacteria
KE701414.1


494
GCA_000460355.1
1281194
562

Escherichia coli UMEA 3151-1
UMEA 3151-1
Proteobacteria
KE701683.1


495
GCA_000461795.1
1281275
562

Escherichia coli UMEA 3899-1
UMEA 3899-1
Proteobacteria
KE702684.1


496
GCA_000461915.2
1151226
562

Escherichia coli B26-2
B26-2
Proteobacteria
AVQV01000011.1


497
GCA_000461955.2
1151213
562

Escherichia coli B102
B102
Proteobacteria
AVQS01000034.1


498
GCA_000461995.2
1151214
562

Escherichia coli B107
B107
Proteobacteria
AVQT01000036.1


499
GCA_000462025.2
1151225
562

Escherichia coli B26-1
B26-1
Proteobacteria
AVQU01000037.1


500
GCA_000462485.2
1151234
562

Escherichia coli B103
B103
Proteobacteria
AVRS01000033.1


501
GCA_000462505.2
1151243
562

Escherichia coli B104
B104
Proteobacteria
AVRT01000033.1


502
GCA_000462525.2
1151247
562

Escherichia coli B105
B105
Proteobacteria
AVRU01000004.1


503
GCA_000462545.2
1151248
562

Escherichia coli B106
B106
Proteobacteria
AVRV01000031.1


504
GCA_000462685.2
1151227
562

Escherichia coli B40-1
B40-1
Proteobacteria
AVSD01000007.1


505
GCA_000462705.2
1151228
562

Escherichia coli B40-2
B40-2
Proteobacteria
AVSE01000035.1


506
GCA_000462725.2
1151246
562

Escherichia coli B49-2
B49-2
Proteobacteria
AVSF01000004.1


507
GCA_000462765.2
1151239
562

Escherichia coli B83
B83
Proteobacteria
AVSH01000033.1


508
GCA_000462785.2
1151240
562

Escherichia coli B84
B84
Proteobacteria
AVSI01000002.1


509
GCA_000462805.2
1151241
562

Escherichia coli B85
B85
Proteobacteria
AVSJ01000006.1


510
GCA_000462825.2
1151242
562

Escherichia coli B86
B86
Proteobacteria
AVSK01000012.1


511
GCA_000599665.1
562
562

Escherichia coli

ST2747
Proteobacteria
CP007392.1


512
GCA_000599685.1
562
562

Escherichia coli

ST2747
Proteobacteria
CP007393.1


513
GCA_000599705.1
562
562

Escherichia coli

ST2747
Proteobacteria
CP007394.1


514
GCA_000601195.1
1444161
562

Escherichia coli 1-176-05_S3_C2
1-176-05_S3_C2
Proteobacteria
JHDF01000008.1


515
GCA_000614255.1
1446644
562

Escherichia coli O157:H7 str. 2011EL-2114
2011EL-2114
Proteobacteria
JHKH01000012.1


516
GCA_000614645.2
1446643
562

Escherichia coli O157:H7 str. 2011EL-2113
2011EL-2113
Proteobacteria
JHKI01000034.1


517
GCA_000614805.2
1446656
562

Escherichia coli O157:H7 str. F7350
F7350
Proteobacteria
JHJN01000063.1


518
GCA_000615745.2
1446634
562

Escherichia coli O157:H7 str. 2011EL-2103
2011EL-2103
Proteobacteria
JHKR01000093.1


519
GCA_000615785.2
1446635
562

Escherichia coli O157:H7 str. 2011EL-2104
2011EL-2104
Proteobacteria
JHKQ01000088.1


520
GCA_000615815.2
1446636
562

Escherichia coli O157:H7 str. 2011EL-2105
2011EL-2105
Proteobacteria
JHKP01000065.1


521
GCA_000615865.2
1446637
562

Escherichia coli O157:H7 str. 2011EL-2106
2011EL-2106
Proteobacteria
JHKO01000118.1


522
GCA_000615925.2
1446638
562

Escherichia coli O157:H7 str. 2011EL-2107
2011EL-2107
Proteobacteria
JHKN01000091.1


523
GCA_000615965.2
1446639
562

Escherichia coli O157:H7 str. 2011EL-2108
2011EL-2108
Proteobacteria
JHKM01000041.1


524
GCA_000616005.2
1446640
562

Escherichia coli O157:H7 str. 2011EL-2109
2011EL-2109
Proteobacteria
JHKL01000081.1


525
GCA_000616035.2
1446641
562

Escherichia coli O157:H7 str. 2011EL-2111
2011EL-2111
Proteobacteria
JHKK01000026.1


526
GCA_000616075.2
1446642
562

Escherichia coli O157:H7 str. 2011EL-2112
2011EL-2112
Proteobacteria
JHKJ01000066.1


527
GCA_000617465.2
1446524
562

Escherichia coli O111:NM str. 2010C-4735
2010C-4735
Proteobacteria
JHMU01000073.1


528
GCA_000618225.2
1446657
562

Escherichia coli O157:H7 str. F7377
F7377
Proteobacteria
JHJM01000101.1


529
GCA_000619325.2
1446580
562

Escherichia coli O123:H11 str. 2009C-3307
2009C-3307
Proteobacteria
JHHB01000001.1


530
GCA_000704985.1
1444084
562

Escherichia coli 3-105-05_S1_C2
3-105-05_S1_C2
Proteobacteria
JNSA01000028.1


531
GCA_000797815.1
562
562

Escherichia coli

CVM N41556PS
Proteobacteria
JUBQ01000063.1


532
GCA_000797915.1
562
562

Escherichia coli

CVM N41498PS
Proteobacteria
JUBR01000061.1


533
GCA_001281885.1
562
562

Escherichia coli

STEC 2257
Proteobacteria
LGBF01000030.1


534
GCA_001281915.1
562
562

Escherichia coli

STEC 2821
Proteobacteria
LGBI01000040.1


535
GCA_001282065.1
562
562

Escherichia coli

STEC 2820
Proteobacteria
LGBQ01000093.1


536
GCA_001284745.1
562
562

Escherichia coli

401709_aEPEC
Proteobacteria
CYCR01000027.1


537
GCA_001285705.1
562
562

Escherichia coli

402767
Proteobacteria
CYET01000020.1


538
GCA_001297965.1
562
562

Escherichia coli

STEC 915
Proteobacteria
LFUH01000095.1


539
GCA_001297985.1
562
562

Escherichia coli

STEC 623
Proteobacteria
LFUB01000081.1


540
GCA_001309565.1
562
562

Escherichia coli

PARC448
Proteobacteria
LDYO01000075.1


541
GCA_001309965.1
562
562

Escherichia coli

CO283
Proteobacteria
LEAI01000125.1


542
GCA_001419785.1
562
562

Escherichia coli

33
Proteobacteria
LIUW01000013.1


543
GCA_001455035.1
562
562

Escherichia coli

22593
Proteobacteria
LMBK01000190.1


544
GCA_001519145.1
562
562

Escherichia coli

GN02606
Proteobacteria
LQUQ01000101.1


545
GCA_001521225.1
562
562

Escherichia coli

GN02350
Proteobacteria
LQTE01000121.1


546
GCA_001572045.1
562
562

Escherichia coli

CFSAN025093
Proteobacteria
LPXY01000033.1


547
GCA_001572205.1
562
562

Escherichia coli

CFSAN025114
Proteobacteria
LPYO01000230.1


548
GCA_001572345.1
562
562

Escherichia coli

CFSAN025116
Proteobacteria
LPYQ01000200.1


549
GCA_001572445.1
562
562

Escherichia coli

CFSAN025127
Proteobacteria
LPYZ01000229.1


550
GCA_001575465.1
562
562

Escherichia coli

G222
Proteobacteria
LOOL01000028.1


551
GCA_001575625.1
562
562

Escherichia coli

G236
Proteobacteria
LOOR01000015.1


552
GCA_001576035.1
562
562

Escherichia coli

G27
Proteobacteria
LOOY01000001.1


553
GCA_001576095.1
562
562

Escherichia coli

G303
Proteobacteria
LOPE01000051.1


554
GCA_001576205.1
562
562

Escherichia coli

G301
Proteobacteria
LOPD01000001.1


555
GCA_001576325.1
562
562

Escherichia coli

G28
Proteobacteria
LOOZ01000025.1


556
GCA_001576455.1
562
562

Escherichia coli

G51
Proteobacteria
LOPO01000094.1


557
GCA_000191665.1
981367
564

Escherichia fergusonii ECD227
ECD227
Proteobacteria
CM001142.1


558
GCA_000248015.2
1115512
565

Escherichia hermannii NBRC 105704
NBRC 105704
Proteobacteria
BAFF01000030.1


559
GCA_000239255.1
1002364
569

Hafnia alvei ATCC 51873
ATCC 51873
Proteobacteria
JH417508.1


560
GCA_000300675.1
1203545
573

Klebsiella pneumoniae subsp. pneumoniae WGLW2
WGLW2
Proteobacteria
JH930419.1


561
GCA_000300675.1
1203545
573

Klebsiella pneumoniae subsp. pneumoniae WGLW2
WGLW2
Proteobacteria
JH930421.1


562
GCA_000316265.2
1236101
573

Klebsiella pneumoniae JHCK1
JHCK1
Proteobacteria
ANGH02000148.1


563
GCA_000316265.2
1236101
573

Klebsiella pneumoniae JHCK1
JHCK1
Proteobacteria
ANGH02000193.1


564
GCA_000409125.1
1284817
573

Klebsiella pneumoniae UHKPC57
UHKPC57
Proteobacteria
ARPR01000165.1


565
GCA_000417465.1
1284818
573

Klebsiella pneumoniae UHKPC179
UHKPC179
Proteobacteria
ARSM01000009.1


566
GCA_000474635.1
1381121
573

Klebsiella pneumoniae 303K
303K
Proteobacteria
AVAN01000015.1


567
GCA_000492775.1
1328378
573

Klebsiella pneumoniae MGH 46
MGH 46
Proteobacteria
KI535585.1


568
GCA_000529945.1
1432553
573

Klebsiella pneumoniae IS46
IS46
Proteobacteria
CBWL010000661.1


569
GCA_000567405.1
1328405
573

Klebsiella pneumoniae BIDMC 11
BIDMC 11
Proteobacteria
KK036861.1


570
GCA_000567405.1
1328405
573

Klebsiella pneumoniae BIDMC 11
BIDMC 11
Proteobacteria
KK036856.1


571
GCA_000688155.1
1438786
573

Klebsiella pneumoniae MGH 63
MGH 63
Proteobacteria
JJNB01000019.1


572
GCA_000688215.1
1438798
573

Klebsiella pneumoniae MGH 75
MGH 75
Proteobacteria
JJNK01000020.1


573
GCA_000694235.1
1438772
573

Klebsiella pneumoniae CHS 66
CHS 66
Proteobacteria
KK737377.1


574
GCA_000694535.1
1438788
573

Klebsiella pneumoniae MGH 65
MGH 65
Proteobacteria
KK737534.1


575
GCA_000707985.1
1329843
573

Klebsiella pneumoniae BIDMC 33B
BIDMC 33B
Proteobacteria
KL407346.1


576
GCA_000733255.1
1406314
573

Klebsiella pneumoniae subsp. pneumoniae PittNDM01
PittNDM01
Proteobacteria
CP006798.1


577
GCA_000764615.1
573
573

Klebsiella pneumoniae

PMK1
Proteobacteria
CP008929.1


578
GCA_000764635.1
573
573

Klebsiella pneumoniae

BAMC 07-18
Proteobacteria
JRQE01000001.1


579
GCA_000788005.1
573
573

Klebsiella pneumoniae

101712
Proteobacteria
JSZI01000009.1


580
GCA_000943095.1
573
573

Klebsiella pneumoniae

ST15 NDM-1
Proteobacteria
CDQG01000025.1


581
GCA_001031325.1
573
573

Klebsiella pneumoniae

CHS112
Proteobacteria
KQ088280.1


582
GCA_001032775.1
573
573

Klebsiella pneumoniae

CHS201
Proteobacteria
KQ088952.1


583
GCA_001033455.1
573
573

Klebsiella pneumoniae

MGH81
Proteobacteria
KQ089253.1


584
GCA_001033725.1
573
573

Klebsiella pneumoniae

MGH101
Proteobacteria
KQ089465.1


585
GCA_001033755.1
573
573

Klebsiella pneumoniae

MGH111
Proteobacteria
KQ089480.1


586
GCA_001033835.1
573
573

Klebsiella pneumoniae

MGH115
Proteobacteria
KQ089541.1


587
GCA_001033885.1
573
573

Klebsiella pneumoniae

MGH117
Proteobacteria
KQ089551.1


588
GCA_001033925.1
573
573

Klebsiella pneumoniae

MGH124
Proteobacteria
KQ089570.1


589
GCA_001033925.1
573
573

Klebsiella pneumoniae

MGH124
Proteobacteria
KQ089573.1


590
GCA_001034065.1
573
573

Klebsiella pneumoniae

BIDMC90
Proteobacteria
KQ089642.1


591
GCA_001034365.1
573
573

Klebsiella pneumoniae

UCI96
Proteobacteria
KQ089764.1


592
GCA_001185865.1
573
573

Klebsiella pneumoniae

CHS175
Proteobacteria
KQ236853.1


593
GCA_001307175.1
573
573

Klebsiella pneumoniae

KP617
Proteobacteria
CP012753.1


594
GCA_001316865.1
72407
573

Klebsiella pneumoniae subsp. pneumoniae
ST14:944535499
Proteobacteria
LIDW01000003.1


595
GCA_001462705.1
573
573

Klebsiella pneumoniae

K57-33
Proteobacteria
LNGX01000156.1


596
GCA_001463165.1
573
573

Klebsiella pneumoniae

U25
Proteobacteria
CP012043.1


597
GCA_001463475.1
573
573

Klebsiella pneumoniae

50884375
Proteobacteria
LNIS01000122.1


598
GCA_001521895.1
72407
573

Klebsiella pneumoniae subsp. pneumoniae
NUHL24835
Proteobacteria
CP014004.1


599
GCA_001574505.1
573
573

Klebsiella pneumoniae

U41
Proteobacteria
LSTN01000108.1


600
GCA_001596905.1
573
573

Klebsiella pneumoniae

KPOII-4
Proteobacteria
JXIW01000052.1


601
GCA_001596915.1
573
573

Klebsiella pneumoniae

KPOII-2
Proteobacteria
JXIV01000036.1


602
GCA_001596925.1
573
573

Klebsiella pneumoniae

KPOII-2
Proteobacteria
JUBO01000066.1


603
GCA_001596935.1
573
573

Klebsiella pneumoniae

KPOII-1
Proteobacteria
JUBN01000046.1


604
GCA_001596985.1
573
573

Klebsiella pneumoniae

KPOII-7
Proteobacteria
JXIY01000037.1


605
GCA_001596995.1
573
573

Klebsiella pneumoniae

KPOII-10
Proteobacteria
JXJB01000058.1


606
GCA_001597015.1
573
573

Klebsiella pneumoniae

KP-33P
Proteobacteria
JXJG01000008.1


607
GCA_001597095.1
573
573

Klebsiella pneumoniae

KPOII-1
Proteobacteria
JXIU01000015.1


608
GCA_001597115.1
573
573

Klebsiella pneumoniae

KPOII-6
Proteobacteria
JXIX01000053.1


609
GCA_001597145.1
573
573

Klebsiella pneumoniae

KPOII-8
Proteobacteria
JXIZ01000056.1


610
GCA_001597165.1
573
573

Klebsiella pneumoniae

KPOII-9
Proteobacteria
JXJA01000044.1


611
GCA_001597175.1
573
573

Klebsiella pneumoniae

KPEII-1
Proteobacteria
JXJC01000056.1


612
GCA_001597195.1
573
573

Klebsiella pneumoniae

KPEII-2
Proteobacteria
JXJD01000059.1


613
GCA_001597225.1
573
573

Klebsiella pneumoniae

KPEII-3
Proteobacteria
JXJE01000058.1


614
GCA_001597245.1
573
573

Klebsiella pneumoniae

KP-10
Proteobacteria
LDOY01000067.1


615
GCA_001219605.1
630
630

Yersinia enterocolitica

YE04/02
Proteobacteria
CTKX01000003.1


616
GCA_001319885.1
633
633

Yersinia pseudotuberculosis

OK6088
Proteobacteria
CGGM01000007.1


617
GCA_001131685.1
634
634

Yersinia bercovieri

127/84
Proteobacteria
CQBU01000002.1


618
GCA_000612075.2
1448139
644

Aeromonas hydrophila YL17
YL17
Proteobacteria
CP007518.2


619
GCA_001270765.1
648
648

Aeromonas caviae

429865
Proteobacteria
LIIX01000004.1


620
GCA_001446895.1
656
656

Aeromonas allosaccharophila

TTU2014-159ASC
Proteobacteria
LKKI01000013.1


621
GCA_000006745.1
243277
666

Vibrio cholerae O1 biovar El Tor str. N16961
N16961
Proteobacteria
AE003852.1


622
GCA_000016245.1
345073
666

Vibrio cholerae O395
O395
Proteobacteria
CP000627.1


623
GCA_000021605.1
579112
666

Vibrio cholerae M66-2
M66-2
Proteobacteria
CP001233.1


624
GCA_000021625.1
345073
666

Vibrio cholerae O395
O395
Proteobacteria
CP001235.1


625
GCA_000022585.1
593588
666

Vibrio cholerae MJ-1236
MJ-1236
Proteobacteria
CP001485.1


626
GCA_000153865.1
412967
666

Vibrio cholerae MAK 757
MAK 757
Proteobacteria
GG774578.1


627
GCA_000153945.1
417399
666

Vibrio cholerae NCTC 8457
NCTC 8457
Proteobacteria
DS178000.1


628
GCA_000153965.1
417400
666

Vibrio cholerae B33
B33
Proteobacteria
DS178064.1


629
GCA_000166455.2
914149
666

Vibrio cholerae O1 str. 2010EL-1786
2010EL-1786
Proteobacteria
CP003069.1


630
GCA_000167935.2
345076
666

Vibrio cholerae V52
V52
Proteobacteria
KQ410498.1


631
GCA_000168915.3
412614
666

Vibrio cholerae 2740-80
2740-80
Proteobacteria
KQ257329.1


632
GCA_000174275.1
593589
666

Vibrio cholerae RC9
RC9
Proteobacteria
ACHX01000011.1


633
GCA_000174315.1
417400
666

Vibrio cholerae B33
B33
Proteobacteria
ACHZ01000017.1


634
GCA_000174335.1
593587
666

Vibrio cholerae BX 330286
BX 330286
Proteobacteria
ACIA01000006.1


635
GCA_000175695.1
661513
666

Vibrio cholerae CIRS101
CIRS 101
Proteobacteria
ACVW01000011.1


636
GCA_000176395.1
675807
666

Vibrio cholerae RC27
RC27
Proteobacteria
ADAI01000041.1


637
GCA_000176435.1
675808
666

Vibrio cholerae INDRE 91/1
INDRE 91/1
Proteobacteria
ADAK01000056.1


638
GCA_000220725.2
991935
666

Vibrio cholerae HC-49A2
HC-49A2
Proteobacteria
AFOM01000018.1


639
GCA_000220745.3
991930
666

Vibrio cholerae HCUF01
HCUF01
Proteobacteria
AFOO01000018.1


640
GCA_000221345.1
991961
666

Vibrio cholerae HC-40A1
HC-40A1
Proteobacteria
GL988221.1


641
GCA_000221365.1
991965
666

Vibrio cholerae HC-48A1
HC-48A1
Proteobacteria
GL988437.1


642
GCA_000221385.1
991984
666

Vibrio cholerae HC-70A1
HC-70A1
Proteobacteria
GL988603.1


643
GCA_000221425.1
991989
666

Vibrio cholerae HFU-02
HFU-02
Proteobacteria
GL988896.1


644
GCA_000221485.1
991959
666

Vibrio cholerae HC-38A1
HC-38A1
Proteobacteria
GL989435.1


645
GCA_000234375.2
991950
666

Vibrio cholerae HC-06A1
HC-06A1
Proteobacteria
AGUI01000118.1


646
GCA_000234395.2
991933
666

Vibrio cholerae HC-23A1
HC-23A1
Proteobacteria
AGUM01000011.1


647
GCA_000234415.2
991955
666

Vibrio cholerae HC-28A1
HC-28A1
Proteobacteria
AGUN01000124.1


648
GCA_000234435.2
991938
666

Vibrio cholerae HC-43A1
HC-43A1
Proteobacteria
AGUQ01000018.1


649
GCA_000234455.3
991942
666

Vibrio cholerae HC-61A1
HC-61A1
Proteobacteria
AGUS01000010.1


650
GCA_000234865.1
991966
666

Vibrio cholerae HC-48B2
HC-48B2
Proteobacteria
JH377577.1


651
GCA_000234885.1
991957
666

Vibrio cholerae HC-33A2
HC-33A2
Proteobacteria
JH377410.1


652
GCA_000234905.1
991956
666

Vibrio cholerae HC-32A1
HC-32A1
Proteobacteria
JH377638.1


653
GCA_000234925.1
991954
666

Vibrio cholerae HC-22A1
HC-22A1
Proteobacteria
JH377759.1


654
GCA_000234945.1
991953
666

Vibrio cholerae HC-21A1
HC-21A1
Proteobacteria
JH377863.1


655
GCA_000234965.1
991952
666

Vibrio cholerae HC-19A1
HC-19A1
Proteobacteria
JH377908.1


656
GCA_000250855.1
1134456
666

Vibrio cholerae IEC224
IEC224
Proteobacteria
CP003330.1


657
GCA_000279185.1
991963
666

Vibrio cholerae HC-42A1
HC-42A1
Proteobacteria
JH724360.1


658
GCA_000279205.1
991974
666

Vibrio cholerae HC-56A2
HC-56A2
Proteobacteria
JH724528.1


659
GCA_000279245.1
991926
666

Vibrio cholerae CP1041(14)
CP1041(14)
Proteobacteria
ALDE01000022.1


660
GCA_000279305.1
991923
666

Vibrio cholerae CP1032(5)
CP1032(5)
Proteobacteria
ALDA01000015.1


661
GCA_000279325.1
991925
666

Vibrio cholerae CP1038(11)
CP1038(11)
Proteobacteria
ALDC01000012.1


662
GCA_000279345.1
991927
666

Vibrio cholerae CP1042(15)
CP1042(15)
Proteobacteria
ALDF01000012.1


663
GCA_000279375.1
991976
666

Vibrio cholerae HC-57A2
HC-57A2
Proteobacteria
JH724633.1


664
GCA_000279395.1
991929
666

Vibrio cholerae CP1048(21)
CP1048(21)
Proteobacteria
ALDJ01000013.1


665
GCA_000279415.1
991932
666

Vibrio cholerae HC-20A2
HC-20A2
Proteobacteria
ALDL01000012.1


666
GCA_000279455.1
991940
666

Vibrio cholerae HC-46A1
HC-46A1
Proteobacteria
ALDQ01000020.1


667
GCA_000279555.1
991990
666

Vibrio cholerae CP1030(3)
CP1030(3)
Proteobacteria
JH724671.1


668
GCA_000279785.1
991995
666

Vibrio cholerae CP1047(20)
CP1047(20)
Proteobacteria
JH724786.1


669
GCA_000279955.1
992003
666

Vibrio cholerae HC-47A1
HC-47A1
Proteobacteria
JH724973.1


670
GCA_000281655.1
991928
666

Vibrio cholerae CP1046(19)
CP1046(19)
Proteobacteria
ALDH01000023.1


671
GCA_000302755.1
991962
666

Vibrio cholerae HC-41A1
HC-41A1
Proteobacteria
JH941098.1


672
GCA_000302775.1
991960
666

Vibrio cholerae HC-39A1
HC-39A1
Proteobacteria
JH942109.1


673
GCA_000302985.1
991993
666

Vibrio cholerae CP1040(13)
CP1040(13)
Proteobacteria
JH942548.1


674
GCA_000303045.1
991994
666

Vibrio cholerae CP1044(17)
CP1044(17)
Proteobacteria
JH942687.1


675
GCA_000303065.1
991996
666

Vibrio cholerae CP1050(23)
CP1050(23)
Proteobacteria
JH941754.1


676
GCA_000303125.1
1000951
666

Vibrio cholerae HC-81A2
HC-81A2
Proteobacteria
JH941263.1


677
GCA_000304755.1
991924
666

Vibrio cholerae CP1033(6)
CP1033(6)
Proteobacteria
AJRL01000031.1


678
GCA_000304935.2
991951
666

Vibrio cholerae HC-17A1
HC-17A1
Proteobacteria
JH966643.1


679
GCA_000304995.1
991968
666

Vibrio cholerae HC-50A2
HC-50A2
Proteobacteria
JH967085.1


680
GCA_000305075.2
992006
666

Vibrio cholerae HC-62A1
HC-62A1
Proteobacteria
JH967577.1


681
GCA_000305095.2
991987
666

Vibrio cholerae HC-77A1
HC-77A1
Proteobacteria
JH967738.1


682
GCA_000305585.2
991958
666

Vibrio cholerae HC-37A1
HC-37A1
Proteobacteria
JH973721.1


683
GCA_000305625.2
992007
666

Vibrio cholerae HC-62B1
HC-62B1
Proteobacteria
JH976192.1


684
GCA_000305675.2
1000952
666

Vibrio cholerae HC-17A2
HC-17A2
Proteobacteria
JH974083.1


685
GCA_000305695.2
992008
666

Vibrio cholerae HC-69A1
HC-69A1
Proteobacteria
JH974129.1


686
GCA_000318485.2
991931
666

Vibrio cholerae HC-7A1
HC-7A1
Proteobacteria
AGVA02000011.1


687
GCA_000318505.2
991936
666

Vibrio cholerae HC-81A1
HC-81A1
Proteobacteria
AGVC02000007.1


688
GCA_000327105.3
991980
666

Vibrio cholerae HC-64A1
HC-64A1
Proteobacteria
KB454193.1


689
GCA_000327125.3
991981
666

Vibrio cholerae HC-65A1
HC-65A1
Proteobacteria
KB454294.1


690
GCA_000327145.3
991982
666

Vibrio cholerae HC-67A1
HC-67A1
Proteobacteria
KB454387.1


691
GCA_000327165.3
991983
666

Vibrio cholerae HC-68A1
HC-68A1
Proteobacteria
KB454110.1


692
GCA_000327185.3
991985
666

Vibrio cholerae HC-71A1
HC-71A1
Proteobacteria
KB454017.1


693
GCA_000327205.3
1000953
666

Vibrio cholerae HC-72A2
HC-72A2
Proteobacteria
KB453970.1


694
GCA_000327245.3
991988
666

Vibrio cholerae HC-80A1
HC-80A1
Proteobacteria
KB453739.1


695
GCA_000338075.1
1224154
666

Vibrio cholerae O1 str. Inaba G4222

Inaba G4222
Proteobacteria
CM001785.1


696
GCA_000348045.2
1095661
666

Vibrio cholerae O1 str. 116059
116059
Proteobacteria
KB661123.1


697
GCA_000348105.2
1095660
666

Vibrio cholerae O1 str. 95412
95412
Proteobacteria
KB662042.1


698
GCA_000348125.2
1095645
666

Vibrio cholerae O1 str. AG-7404
AG-7404
Proteobacteria
KB662659.1


699
GCA_000348145.2
1095644
666

Vibrio cholerae O1 str. AG-8040
AG-8040
Proteobacteria
KB663097.1


700
GCA_000348165.2
1095651
666

Vibrio cholerae O1 str. EC-0009
EC-0009
Proteobacteria
KB663518.1


701
GCA_000348185.2
1095652
666

Vibrio cholerae O1 str. EC-0012
EC-0012
Proteobacteria
KB661760.1


702
GCA_000348205.2
1095653
666

Vibrio cholerae O1 str. EC-0027
EC-0027
Proteobacteria
KB663429.1


703
GCA_000348225.2
1095654
666

Vibrio cholerae O1 str. EC-0051
EC-0051
Proteobacteria
KB661629.1


704
GCA_000348245.2
1095640
666

Vibrio cholerae O1 str. EDC-020
EDC-020
Proteobacteria
KB663379.1


705
GCA_000348265.2
1095641
666

Vibrio cholerae O1 str. EDC-022
EDC-022
Proteobacteria
KB663300.1


706
GCA_000348285.2
1095646
666

Vibrio cholerae O1 str. EM-1536
EM-1536
Proteobacteria
KB662939.1


707
GCA_000348305.2
1095647
666

Vibrio cholerae O1 str. EM-1546
EM-1546
Proteobacteria
KB663192.1


708
GCA_000348325.2
1095648
666

Vibrio cholerae O1 str. EM-1626
EM-1626
Proteobacteria
KB662879.1


709
GCA_000348365.1
1095650
666

Vibrio cholerae O1 str. EM-1727
EM-1727
Proteobacteria
KB662387.1


710
GCA_000348385.2
1095655
666

Vibrio cholerae O1 str. NHCC-004A
NHCC-004A
Proteobacteria
KB662555.1


711
GCA_000348405.2
1095656
666

Vibrio cholerae O1 str. NHCC-006C
NHCC-006C
Proteobacteria
KB662604.1


712
GCA_000348445.2
1095658
666

Vibrio cholerae O1 str. NHCC-010F
NHCC-010F
Proteobacteria
KB662324.1


713
GCA_000348465.2
1095642
666

Vibrio cholerae O1 str. Nep-21106
Nep-21106
Proteobacteria
KB661614.1


714
GCA_000348485.2
1095643
666

Vibrio cholerae O1 str. Nep-21113
Nep-21113
Proteobacteria
KB662142.1


715
GCA_000348505.2
1095639
666

Vibrio cholerae O1 str. PCS-023
PCS-023
Proteobacteria
KB661938.1


716
GCA_000569115.2
1095638
666

Vibrio cholerae O1 str. PCS-022
PCS-022
Proteobacteria
KK037973.1


717
GCA_000705295.1
686
666

Vibrio cholerae O1 biovar El Tor
M-1293
Proteobacteria
JFFW01000006.1


718
GCA_000710155.1
1343738
666

Vibrio cholerae 2012EL-1759
2012EL-1759
Proteobacteria
JNEW01000011.1


719
GCA_000710445.1
686
666

Vibrio cholerae O1 biovar El Tor
Ogawa RND19188
Proteobacteria
JNGU01000059.1


720
GCA_000710455.1
686
666

Vibrio cholerae O1 biovar El Tor
Ogawa RND19191
Proteobacteria
JNGT01000078.1


721
GCA_000736795.1
666
666

Vibrio cholerae

5473-62
Proteobacteria
JIDI01000041.1


722
GCA_000736855.1
666
666

Vibrio cholerae

1311-69
Proteobacteria
JIDJ01000055.1


723
GCA_000736865.1
666
666

Vibrio cholerae

NIH41
Proteobacteria
JIDH01000006.1


724
GCA_000736925.1
666
666

Vibrio cholerae

981-75
Proteobacteria
JIDM01000006.1


725
GCA_000753725.1
686
666

Vibrio cholerae O1 biovar El Tor
MAK676
Proteobacteria
JRBD01000007.1


726
GCA_000765415.1
666
666

Vibrio cholerae

2012EL-2176
Proteobacteria
CP007634.1


727
GCA_000786335.1
666
666

Vibrio cholerae

81
Proteobacteria
JRQM01000007.1


728
GCA_000786345.1
666
666

Vibrio cholerae

3265/80
Proteobacteria
JRQL01000006.1


729
GCA_000829215.1
1420885
666

Vibrio cholerae MS6
MS6
Proteobacteria
AP014524.1


730
GCA_000939665.1
686
666

Vibrio cholerae O1 biovar El Tor
MAK97
Proteobacteria
JZCB01000007.1


731
GCA_000953755.1
666
666

Vibrio cholerae

InDRE 4354
Proteobacteria
JZUA01000014.1


732
GCA_000953775.1
666
666

Vibrio cholerae

InDRE 4262
Proteobacteria
JZUB01000015.1


733
GCA_000960915.1
686
666

Vibrio cholerae O1 biovar El Tor
M1429
Proteobacteria
LAEM01000007.1


734
GCA_000961975.1
666
666

Vibrio cholerae

D-35
Proteobacteria
LAED01000005.1


735
GCA_000963555.1
686
666

Vibrio cholerae O1 biovar El Tor
FJ147
Proteobacteria
CP009042.1


736
GCA_000965285.1
686
666

Vibrio cholerae O1 biovar El Tor
R17644
Proteobacteria
JRTW01000033.1


737
GCA_000966385.1
666
666

Vibrio cholerae

M818
Proteobacteria
LAHM01000006.1


738
GCA_001029975.1
666
666

Vibrio cholerae

YN2011004
Proteobacteria
KQ087383.1


739
GCA_001030015.1
666
666

Vibrio cholerae

YN97083
Proteobacteria
KQ087448.1


740
GCA_001030035.1
666
666

Vibrio cholerae

YN89004
Proteobacteria
KQ087512.1


741
GCA_001045415.1
666
666

Vibrio cholerae

TSY216
Proteobacteria
CP007653.1


742
GCA_001246285.1
666
666

Vibrio cholerae

A346(2)
Proteobacteria
CWQG01000013.1


743
GCA_001247245.1
666
666

Vibrio cholerae

4679
Proteobacteria
CWOC01000002.1


744
GCA_001247525.1
666
666

Vibrio cholerae

A346(1)
Proteobacteria
CWSM01000004.1


745
GCA_001247835.1
666
666

Vibrio cholerae

1627
Proteobacteria
CWNK01000005.1


746
GCA_001247885.1
666
666

Vibrio cholerae

IDHO1_726
Proteobacteria
CWQN01000008.1


747
GCA_001248135.1
666
666

Vibrio cholerae

A186
Proteobacteria
CWPM01000020.1


748
GCA_001248195.1
666
666

Vibrio cholerae

A60
Proteobacteria
CWOY01000004.1


749
GCA_001248235.1
666
666

Vibrio cholerae

A217
Proteobacteria
CWPV01000006.1


750
GCA_001248365.1
666
666

Vibrio cholerae

A397
Proteobacteria
CWQB01000004.1


751
GCA_001248465.1
666
666

Vibrio cholerae

V212-1
Proteobacteria
CWPH01000003.1


752
GCA_001248505.1
666
666

Vibrio cholerae

4519
Proteobacteria
CWRZ01000004.1


753
GCA_001248645.1
666
666

Vibrio cholerae

6214
Proteobacteria
CWQT01000002.1


754
GCA_001248865.1
666
666

Vibrio cholerae

A193
Proteobacteria
CWPN01000010.1


755
GCA_001248905.1
666
666

Vibrio cholerae

A70
Proteobacteria
CWOM01000009.1


756
GCA_001248945.1
666
666

Vibrio cholerae

A213
Proteobacteria
CWPS01000006.1


757
GCA_001249085.1
666
666

Vibrio cholerae

MBRN14
Proteobacteria
CWNR01000004.1


758
GCA_001249315.1
666
666

Vibrio cholerae

4322
Proteobacteria
CWOX01000006.1


759
GCA_001249515.1
666
666

Vibrio cholerae

6191
Proteobacteria
CWQQ01000006.1


760
GCA_001249715.1
666
666

Vibrio cholerae

GP152
Proteobacteria
CWQK01000006.1


761
GCA_001249815.1
666
666

Vibrio cholerae

7682
Proteobacteria
CWNO01000007.1


762
GCA_001249995.1
666
666

Vibrio cholerae

A177
Proteobacteria
CWNQ01000004.1


763
GCA_001250035.1
666
666

Vibrio cholerae

GP145
Proteobacteria
CWQL01000008.1


764
GCA_001250195.1
666
666

Vibrio cholerae

MJ1485
Proteobacteria
CWNZ01000023.1


765
GCA_001250235.1
666
666

Vibrio cholerae

A19
Proteobacteria
CWSH01000005.1


766
GCA_001250435.1
666
666

Vibrio cholerae

4642
Proteobacteria
CWPE01000005.1


767
GCA_001250455.1
666
666

Vibrio cholerae

A32
Proteobacteria
CWNM01000004.1


768
GCA_001250615.1
666
666

Vibrio cholerae

A488(2)
Proteobacteria
CWOA01000007.1


769
GCA_001250795.1
666
666

Vibrio cholerae

MBN17
Proteobacteria
CWNW01000004.1


770
GCA_001250935.1
666
666

Vibrio cholerae

A61
Proteobacteria
CWOS01000008.1


771
GCA_001251155.1
666
666

Vibrio cholerae

A130
Proteobacteria
CWNY01000012.1


772
GCA_001251415.1
666
666

Vibrio cholerae

A487(2)
Proteobacteria
CWQX01000001.1


773
GCA_001251435.1
666
666

Vibrio cholerae

7687
Proteobacteria
CWRG01000008.1


774
GCA_001251495.1
666
666

Vibrio cholerae

GP16
Proteobacteria
CWQE01000007.1


775
GCA_001251595.1
666
666

Vibrio cholerae

A483
Proteobacteria
CWQA01000003.1


776
GCA_001251935.1
666
666

Vibrio cholerae

6194
Proteobacteria
CWQW01000017.1


777
GCA_001251975.1
666
666

Vibrio cholerae

6212
Proteobacteria
CWQV01000004.1


778
GCA_001252055.1
666
666

Vibrio cholerae

4551
Proteobacteria
CWRK01000003.1


779
GCA_001252075.1
666
666

Vibrio cholerae

4121
Proteobacteria
CWRP01000009.1


780
GCA_001252495.1
666
666

Vibrio cholerae

A18
Proteobacteria
CWSJ01000005.1


781
GCA_001252675.1
666
666

Vibrio cholerae

V5
Proteobacteria
CWNT01000007.1


782
GCA_001252775.1
666
666

Vibrio cholerae

6215
Proteobacteria
CWRD01000009.1


783
GCA_001252855.1
666
666

Vibrio cholerae

4111
Proteobacteria
CWOZ01000011.1


784
GCA_001252875.1
666
666

Vibrio cholerae

A152
Proteobacteria
CWOB01000008.1


785
GCA_001252895.1
666
666

Vibrio cholerae

4585
Proteobacteria
CWRS01000004.1


786
GCA_001253035.1
666
666

Vibrio cholerae

1346
Proteobacteria
CWRJ01000005.1


787
GCA_001253055.1
666
666

Vibrio cholerae

4600
Proteobacteria
CWRW01000004.1


788
GCA_001253155.1
666
666

Vibrio cholerae

A154
Proteobacteria
CWNX01000009.1


789
GCA_001253175.1
666
666

Vibrio cholerae

A184
Proteobacteria
CWOO01000008.1


790
GCA_001253235.1
666
666

Vibrio cholerae

A29
Proteobacteria
CWSI01000004.1


791
GCA_001253295.1
666
666

Vibrio cholerae

A185
Proteobacteria
CWOK01000008.1


792
GCA_001253315.1
666
666

Vibrio cholerae

GP140
Proteobacteria
CWRA01000011.1


793
GCA_001253435.1
666
666

Vibrio cholerae

A51
Proteobacteria
CWOW01000014.1


794
GCA_001253495.1
666
666

Vibrio cholerae

A111
Proteobacteria
CWOV01000006.1


795
GCA_001253555.1
666
666

Vibrio cholerae

A279
Proteobacteria
CWQC01000021.1


796
GCA_001253575.1
666
666

Vibrio cholerae

GP8
Proteobacteria
CWNN01000007.1


797
GCA_001253615.1
666
666

Vibrio cholerae

A219
Proteobacteria
CWPQ01000002.1


798
GCA_001253695.1
666
666

Vibrio cholerae

A31
Proteobacteria
CWSK01000004.1


799
GCA_001253755.1
666
666

Vibrio cholerae

VC51
Proteobacteria
CWOI01000007.1


800
GCA_001253835.1
666
666

Vibrio cholerae

A49
Proteobacteria
CWPI01000004.1


801
GCA_001254055.1
666
666

Vibrio cholerae

A4
Proteobacteria
CWSC01000005.1


802
GCA_001254255.1
666
666

Vibrio cholerae

A481
Proteobacteria
CWQD01000029.1


803
GCA_001254335.1
666
666

Vibrio cholerae

4784
Proteobacteria
CWRV01000004.1


804
GCA_001254355.1
666
666

Vibrio cholerae

MG116226
Proteobacteria
CWSQ01000005.1


805
GCA_001254435.1
666
666

Vibrio cholerae

GP160
Proteobacteria
CWSB01000005.1


806
GCA_001254535.1
666
666

Vibrio cholerae

A59
Proteobacteria
CWOG01000006.1


807
GCA_001254575.1
666
666

Vibrio cholerae

A103
Proteobacteria
CWOP01000008.1


808
GCA_001254635.1
666
666

Vibrio cholerae

4623
Proteobacteria
CWRM01000004.1


809
GCA_001254655.1
666
666

Vibrio cholerae

A10
Proteobacteria
CWSF01000005.1


810
GCA_001254675.1
666
666

Vibrio cholerae

A5
Proteobacteria
CWSE01000005.1


811
GCA_001254895.1
666
666

Vibrio cholerae

MG116025
Proteobacteria
CWNS01000006.1


812
GCA_001254915.1
666
666

Vibrio cholerae

A180
Proteobacteria
CWOR01000008.1


813
GCA_001254955.1
666
666

Vibrio cholerae

6197
Proteobacteria
CWRB01000040.1


814
GCA_001255155.1
666
666

Vibrio cholerae

A22
Proteobacteria
CWNL01000007.1


815
GCA_001255295.1
666
666

Vibrio cholerae

A200
Proteobacteria
CWPW01000009.1


816
GCA_001255575.1
666
666

Vibrio cholerae

A6
Proteobacteria
CWSG01000004.1


817
GCA_001255835.1
666
666

Vibrio cholerae

4536
Proteobacteria
CWSA01000001.1


818
GCA_001255915.1
666
666

Vibrio cholerae

7685
Proteobacteria
CWRI01000009.1


819
GCA_001256015.1
666
666

Vibrio cholerae

4663
Proteobacteria
CWOD01000006.1


820
GCA_001256355.1
666
666

Vibrio cholerae

PRL5
Proteobacteria
CWQI01000001.1


821
GCA_001256655.1
666
666

Vibrio cholerae

A209
Proteobacteria
CWPU01000001.1


822
GCA_001256675.1
666
666

Vibrio cholerae

A241
Proteobacteria
CWPX01000008.1


823
GCA_001256835.1
666
666

Vibrio cholerae

A231
Proteobacteria
CWPP01000001.1


824
GCA_001257035.1
666
666

Vibrio cholerae

4110
Proteobacteria
CWOT01000002.1


825
GCA_001257075.1
666
666

Vibrio cholerae

A488(1)
Proteobacteria
CWSN01000007.1


826
GCA_001257255.1
666
666

Vibrio cholerae

V109
Proteobacteria
CWOJ01000008.1


827
GCA_001257835.1
666
666

Vibrio cholerae

6193
Proteobacteria
CWQZ01000004.1


828
GCA_001257895.1
666
666

Vibrio cholerae

4593
Proteobacteria
CWRL01000004.1


829
GCA_001258495.1
666
666

Vibrio cholerae

4656
Proteobacteria
CWOQ01000004.1


830
GCA_001258535.1
666
666

Vibrio cholerae

7686
Proteobacteria
CWRH01000019.1


831
GCA_001258555.1
666
666

Vibrio cholerae

4488
Proteobacteria
CWRU01000004.1


832
GCA_001258995.1
666
666

Vibrio cholerae

4646
Proteobacteria
CWRX01000004.1


833
GCA_001259055.1
666
666

Vibrio cholerae

4113
Proteobacteria
CWRQ01000003.1


834
GCA_001259135.1
666
666

Vibrio cholerae

4605
Proteobacteria
CWON01000005.1


835
GCA_001259235.1
666
666

Vibrio cholerae

4552
Proteobacteria
CWRT01000003.1


836
GCA_001259315.1
666
666

Vibrio cholerae

A131
Proteobacteria
CWOL01000002.1


837
GCA_001259475.1
666
666

Vibrio cholerae

6210
Proteobacteria
CWQO01000008.1


838
GCA_001259495.1
666
666

Vibrio cholerae

A76
Proteobacteria
CWOF01000008.1


839
GCA_001259555.1
666
666

Vibrio cholerae

A46
Proteobacteria
CWOH01000007.1


840
GCA_001259575.1
666
666

Vibrio cholerae

A390
Proteobacteria
CWQF01000001.1


841
GCA_001259635.1
666
666

Vibrio cholerae

A68
Proteobacteria
CWNV01000008.1


842
GCA_001259715.1
666
666

Vibrio cholerae

4538
Proteobacteria
CWRO01000004.1


843
GCA_001259795.1
666
666

Vibrio cholerae

A389
Proteobacteria
CWQH01000016.1


844
GCA_001259915.1
666
666

Vibrio cholerae

A155
Proteobacteria
CWOE01000008.1


845
GCA_001259935.1
666
666

Vibrio cholerae

A109
Proteobacteria
CWPD01000024.1


846
GCA_001260175.1
666
666

Vibrio cholerae

4662
Proteobacteria
CWRY01000001.1


847
GCA_001260295.1
666
666

Vibrio cholerae

1362
Proteobacteria
CWRR01000004.1


848
GCA_001260335.1
666
666

Vibrio cholerae

4339
Proteobacteria
CWRN01000004.1


849
GCA_001260915.1
666
666

Vibrio cholerae

A66
Proteobacteria
CWOU01000006.1


850
GCA_001260995.1
666
666

Vibrio cholerae

A27
Proteobacteria
CWSD01000004.1


851
GCA_001261075.1
666
666

Vibrio cholerae

PRL64
Proteobacteria
CWQM01000006.1


852
GCA_001261095.1
666
666

Vibrio cholerae

A482
Proteobacteria
CWPZ01000016.1


853
GCA_001261135.1
666
666

Vibrio cholerae

A245
Proteobacteria
CWPY01000019.1


854
GCA_001261515.1
666
666

Vibrio cholerae

A201
Proteobacteria
CWPT01000008.1


855
GCA_001261535.1
666
666

Vibrio cholerae

A487(1)
Proteobacteria
CWSP01000004.1


856
GCA_001261555.1
666
666

Vibrio cholerae

6201
Proteobacteria
CWQP01000004.1


857
GCA_001281585.1
686
666

Vibrio cholerae O1 biovar El Tor
31
Proteobacteria
LIFF01000004.1


858
GCA_001281595.1
686
666

Vibrio cholerae O1 biovar El Tor
39
Proteobacteria
LIFG01000007.1


859
GCA_001281615.1
686
666

Vibrio cholerae O1 biovar El Tor
43
Proteobacteria
LIFH01000031.1


860
GCA_001281665.1
686
666

Vibrio cholerae O1 biovar El Tor
56
Proteobacteria
LIFI01000004.1


861
GCA_001282605.1
666
666

Vibrio cholerae

EC-051
Proteobacteria
LFZZ01000030.1


862
GCA_001318185.1
1433144
666

Vibrio cholerae O1 str. KW3
KW3
Proteobacteria
CP006947.1


863
GCA_001471455.1
666
666

Vibrio cholerae

ATCC 11629
Proteobacteria
LOSM01000005.1


864
GCA_001515095.1
666
666

Vibrio cholerae

ME-7
Proteobacteria
LQBW01000005.1


865
GCA_001517845.1
686
666

Vibrio cholerae O1 biovar El Tor
M1275
Proteobacteria
LRAF01000011.1


866
GCA_001517855.1
686
666

Vibrio cholerae O1 biovar El Tor
M1275D
Proteobacteria
LRAG01000003.1


867
GCA_001521835.1
666
666

Vibrio cholerae

M888
Proteobacteria
LRBH01000022.1


868
GCA_001525525.1
666
666

Vibrio cholerae

ATCC 25874
Proteobacteria
LRIK01000002.1


869
GCA_001543465.1
686
666

Vibrio cholerae O1 biovar El Tor
Inaba PIC018
Proteobacteria
LQHM01000074.1


870
GCA_000260675.1
1095743
736

Haemophilus paraphrohaemolyticus HK411
HK411
Proteobacteria
AJMU01000074.1


871
GCA_000771955.1
750
750

Gallibacterium anatis

F0003406
Proteobacteria
JPXV01000009.1


872
GCA_000772275.1
750
750

Gallibacterium anatis

10672/9
Proteobacteria
JPTU01000008.1


873
GCA_000772385.1
1396511
750

Gallibacterium anatis 7990
7990
Proteobacteria
JPJL01000011.1


874
GCA_000024665.1
59374
833

Fibrobacter succinogenes subsp. succinogenes S85
S85
Fibrobacteres
CP001792.1


875
GCA_000146505.1
59374
833

Fibrobacter succinogenes subsp. succinogenes S85
S85
Fibrobacteres
CP002158.1


876
GCA_000158275.2
457405
851

Fusobacterium nucleatum subsp. animalis 7_1
7_1
Fusobacteria
CP007062.1


877
GCA_000234075.2
693991
851

Fusobacterium nucleatum subsp. polymorphum F0401
F0401
Fusobacteria
ADDB02000001.1


878
GCA_000479285.1
1204474
851

Fusobacterium nucleatum CTI-1
CTI-1
Fusobacteria
KI518459.1


879
GCA_000158215.3
469599
860

Fusobacterium periodonticum 2_1_31
2_1_31
Fusobacteria
KN173678.1


880
GCA_000160475.1
546275
860

Fusobacterium periodonticum ATCC 33693
ATCC 33693
Fusobacteria
GG665893.1


881
GCA_000015485.1
391774
881

Desulfovibrio vulgaris DP4
DP4
Proteobacteria
CP000527.1


882
GCA_000025305.1
591001
905

Acidaminococcus fermentans DSM 20731
DSM 20731
Firmicutes
CP001859.1


883
GCA_000021865.1
272942
1061

Rhodobacter capsulatus SB 1003
SB 1003
Proteobacteria
CP001312.1


884
GCA_000505785.1
1415160
1061

Rhodobacter capsulatus DE442
DE442
Proteobacteria
AYPR01000015.1


885
GCA_000506425.2
1415162
1061

Rhodobacter capsulatus B6
B6
Proteobacteria
AYQA01000010.1


886
GCA_000506565.2
1415163
1061

Rhodobacter capsulatus R121
R121
Proteobacteria
AYQC01000013.1


887
GCA_000506965.2
1415161
1061

Rhodobacter capsulatus Y262
Y262
Proteobacteria
AYQB01000018.1


888
GCA_000341585.2
317619
1223

Prochlorothrix hollandica PCC 9006

Cyanobacteria
AJTX02000004.1


889
GCA_000740735.1
1229
1229

Nitrosococcus oceani

AFC132
Proteobacteria
JPFN01000044.1


890
GCA_001183895.1
1422
1422

Geobacillus stearothermophilus

A1
Firmicutes
LDNS01000331.1


891
GCA_001183915.1
1422
1422

Geobacillus stearothermophilus

P3
Firmicutes
LDNT01000009.1


892
GCA_001587395.1
1422
1422

Geobacillus stearothermophilus

B4114
Firmicutes
LQYY01000004.1


893
GCA_000415905.1
1337888
1462

Geobacillus kaustophilus GBlys
GBlys
Firmicutes
BASG01000012.1


894
GCA_000353265.2
1198630
1516

Thermoanaerobacter thermohydrosulfuricus WC1
WC1
Firmicutes
KB731278.1


895
GCA_000219125.2
1009370
2374

Acetonema longum DSM 6540
DSM 6540
Firmicutes
AFGF01000017.1


896
GCA_000300715.1
1161912
2421

Thermosipho africanus H17ap60334
H17ap60334
Thermotogae
AJIP01000035.1


897
GCA_000284255.1
983917
28068

Rubrivivax gelatinosus IL144
IL144
Proteobacteria
AP012320.1


898
GCA_001467525.1
28082
28082

Legionella anisa

WA-316-C3
Proteobacteria
LNXS01000010.1


899
GCA_000178275.1
702443
28116

Bacteroides ovatus SD CMC 3f
SD CMC 3f
Bacteroidetes
ADMO01000148.1


900
GCA_000017665.1
290339
28141

Cronobacter sakazakii ATCC BAA-894
ATCC BAA-894
Proteobacteria
CP000783.1


901
GCA_000214745.2
930780
28141

Cronobacter sakazakii E899
E899
Proteobacteria
AFMO01000120.1


902
GCA_000316155.1
1208664
28141

Cronobacter sakazakii 696
696
Proteobacteria
CALF01000071.1


903
GCA_000319595.1
1208663
28141

Cronobacter sakazakii 701
701
Proteobacteria
CALE01000616.1


904
GCA_000723765.1
1238450
28173

Vibrio nigripulchritudo SOn1
SOn1
Proteobacteria
LK391965.1


905
GCA_000307105.1
651182
28223

Desulfobacula toluolica Tol2
Tol2
Proteobacteria
FO203503.1


906
GCA_000757225.1
28450
28450

Burkholderia pseudomallei

BEC
Proteobacteria
KN150953.1


907
GCA_000773415.1
1435374
28450

Burkholderia pseudomallei MSHR7500
MSHR7500
Proteobacteria
JREN01000128.1


908
GCA_000774635.1
1434195
28450

Burkholderia pseudomallei MSHR4303
MSHR4303
Proteobacteria
KN323039.1


909
GCA_000775025.1
1437004
28450

Burkholderia pseudomallei MSHR3709
MSHR3709
Proteobacteria
KN323107.1


910
GCA_000775045.1
1435993
28450

Burkholderia pseudomallei MSHR2138
MSHR2138
Proteobacteria
KN323181.1


911
GCA_001202135.1
28450
28450

Burkholderia pseudomallei

P166/04
Proteobacteria
CSLD01000016.1


912
GCA_001448845.1
1240693
28901

Salmonella enterica subsp. enterica serovar Rubislaw str.
SA20030553
Proteobacteria
LHTG01000011.1






SA20030553


913
GCA_000189775.3
858215
29329

Thermoanaerobacterium xylanolyticum LX-11
LX-11
Firmicutes
CP002739.1


914
GCA_000369085.1
1217986
29430

Acinetobacter haemolyticus NIPH 261
NIPH 261
Proteobacteria
KB849819.1


915
GCA_000015745.1
420246
33940

Geobacillus thermodenitrificans NG80-2
NG80-2
Firmicutes
CP000557.1


916
GCA_000016185.1
414684
34018

Rhodospirillum centenum SW
SW; ATCC 51521
Proteobacteria
CP000613.2


917
GCA_000023345.1
543728
34073

Variovorax paradoxus S110
S110
Proteobacteria
CP001635.1


918
GCA_000214275.3
686340
39775

Methylomicrobium album BG8
BG8
Proteobacteria
CM001475.1


919
GCA_000175675.1
596318
40216

Acinetobacter radioresistens SK82
SK82
Proteobacteria
ACVR01000061.1


920
GCA_000367985.1
40373
40373

Acinetobacter sp. CIP-A165
CIP A165
Proteobacteria
KB849201.1


921
GCA_001273775.1
42253
42253

Nitrospira moscoviensis

NSP M-1
Nitrospirae
CP011801.1


922
GCA_000328625.1
748449
42422

Halobacteroides halobius DSM 5150
DSM 5150
Firmicutes
CP003359.1


923
GCA_000154785.2
391595
42443

Roseobacter litoralis Och 149
Och 149
Proteobacteria
CP002623.1


924
GCA_000350165.1
1293054
43595

Halanaerobium saccharolyticum subsp. saccharolyticum
type strain:DSM 6643
Firmicutes
CAUI01000005.1






DSM 6643


925
GCA_000238375.3
1117314
43655

Pseudoalteromonas citrea DSM 8771
NCIMB 1889
Proteobacteria
AHBZ02000147.1


926
GCA_001298525.1
45610
45610

Psychrobacter urativorans

R10.10B
Proteobacteria
CP012678.1


927
GCA_000147695.3
697303
46354

Thermoanaerobacter wiegelii Rt8.B1
Rt8.B1
Firmicutes
CP002991.1


928
GCA_000186425.1
887898
47671

Lautropia mirabilis ATCC 51599
ATCC 51599
Proteobacteria
GL636062.1


929
GCA_001432715.1
48296
48296

Acinetobacter pittii

ABBL005
Proteobacteria
LLCL01000049.1


930
GCA_000219855.1
1051632
53633

Sulfobacillus acidophilus TPY
TPY
Firmicutes
CP002901.1


931
GCA_000237975.1
679936
53633

Sulfobacillus acidophilus DSM 10332
DSM 10332
Firmicutes
CP003179.1


932
GCA_000749925.1
55207
55207

Pectobacterium betavasculorum

NCPPB 2793
Proteobacteria
JQHL01000017.1


933
GCA_001005725.1
56193
56193

Sphingobium chungbukense

DJ77
Proteobacteria
LBIC01000001.1


934
GCA_001529365.1
56812
56812

Shewanella frigidimarina

Ag06-30
Proteobacteria
LRDC01000001.1


935
GCA_000958425.1
61645
61645

Enterobacter asburiae

42192
Proteobacteria
JZYJ01000004.1


936
GCA_001011855.1
61645
61645

Enterobacter asburiae

GN02073
Proteobacteria
LDCE01000036.1


937
GCA_001011955.1
61645
61645

Enterobacter asburiae

GN02208
Proteobacteria
LDCK01000037.1


938
GCA_001023015.1
61645
61645

Enterobacter asburiae

GN04222
Proteobacteria
LECX01000031.1


939
GCA_001471995.1
61645
61645

Enterobacter asburiae

SMART_269
Proteobacteria
LPQP01000010.1


940
GCA_001472305.1
61645
61645

Enterobacter asburiae

SMART_454
Proteobacteria
LPPZ01000027.1


941
GCA_001472715.1
61645
61645

Enterobacter asburiae

SMART_763
Proteobacteria
LPPF01000080.1


942
GCA_001022135.1
61648
61648

Kluyvera intermedia

CAV1151
Proteobacteria
CP011602.1


943
GCA_000317635.1
65093
65093

Halothece sp. PCC 7418
PCC 7418
Cyanobacteria
CP003945.1


944
GCA_000021825.1
65393
65393

Cyanothece sp. PCC 7424
PCC 7424
Cyanobacteria
CP001291.1


945
GCA_000832305.1
68895
68895

Cupriavidus basilensis

4G11
Proteobacteria
CP010537.1


946
GCA_000169135.1
313624
70799

Nodularia spumigena CCY9414
CCY9414
Cyanobacteria
AAVW01000117.1


947
GCA_000340565.3
313624
70799

Nodularia spumigena CCY9414
CCY9414
Cyanobacteria
CP007203.2


948
GCA_000818015.1
1123016
74829

Pseudomonas balearica DSM 6083
DSM6083 (=SP1402)
Proteobacteria
CP007511.1


949
GCA_001458455.1
75695
75695

Chrysosporum ovalisporum

UAM-MAO
Cyanobacteria
CDHJ01000123.1


950
GCA_000242075.2
883150
76832

Myroides odoratimimus CCUG 10230
CCUG 10230
Bacteroidetes
KE161015.1


951
GCA_000026985.1
644651
79967

Erwinia pyrifoliae DSM 12163
DSM 12163
Proteobacteria
FN392235.1


952
GCA_000027265.1
634499
79967

Erwinia pyrifoliae Ep1/96
Ep1/96
Proteobacteria
FP236842.1


953
GCA_000327045.1
765912
80679

Thioflavicoccus mobilis 8321
8321
Proteobacteria
CP003051.1


954
GCA_001458195.1
81569
81569

Ruegeria atlantica

CECT 4292
Proteobacteria
CYPU01000011.1


955
GCA_001586165.1
82983
82983

Obesumbacterium proteus

DSM 2777
Proteobacteria
CP014608.1


956
GCA_000438825.1
1348660
82996

Serratia plymuthica S13

Proteobacteria
CP006566.1


957
GCA_000622345.1
1443112
83219

Sulfitobacter mediterraneus KCTC 32188
KCTC 32188
Proteobacteria
JASH01000008.1


958
GCA_001605015.1
83263
83263

Aminobacter aminovorans

KCTC 2477
Proteobacteria
CP015005.1


959
GCA_000203935.1
94122
94122

Shewanella sp. ANA-3
ANA-3
Proteobacteria
CP000469.1


960
GCA_000067205.1
94624
94624

Bordetella petrii

DSM 12804
Proteobacteria
AM902716.1


961
GCA_000333135.2
985077
95486

Burkholderia cenocepacia BC7

Proteobacteria
ALIZ02000089.1


962
GCA_000333155.2
985076
95486

Burkholderia cenocepacia K56-2Valvano
K56-2Valvano
Proteobacteria
ALJA02000012.1


963
GCA_000981305.1
95486
95486

Burkholderia cenocepacia

K56-2
Proteobacteria
LAUA01000017.1


964
GCA_001523855.1
101571
101571

Burkholderia ubonensis

ABCPW-28
Proteobacteria
LOVU01000053.1


965
GCA_001528985.1
101571
101571

Burkholderia ubonensis

MSMB1162WGS
Proteobacteria
LPDS01000057.1


966
GCA_001530375.1
101571
101571

Burkholderia ubonensis

MSMB1473WGS
Proteobacteria
LPFJ01000144.1


967
GCA_000317575.1
111780
102116

Stanieria cyanosphaera PCC 7437
PCC 7437
Cyanobacteria
CP003653.1


968
GCA_000025645.1
580331
108150

Thermoanaerobacter italicus Ab9
Ab9
Firmicutes
CP001936.1


969
GCA_000215105.1
743718
139208

Isoptericola variabilis 225
225
Actinobacteria
CP002810.1


970
GCA_000024825.1
150340
150340

Vibrio antiquarius

EX25
Proteobacteria
CP001805.1


971
GCA_000152485.1
150340
150340

Vibrio antiquarius

EX25
Proteobacteria
DS267811.1


972
GCA_000759535.1
157783
157783

Pseudomonas cremoricolorata

ND07
Proteobacteria
CP009455.1


973
GCA_000012985.1
349521
158327

Hahella chejuensis KCTC 2396
KCTC 2396
Proteobacteria
CP000155.1


974
GCA_001506165.1
158822
158822

Cedecea neteri

ND02
Proteobacteria
CP011427.1


975
GCA_000181515.1
161528
161528

Erythrobacter sp. SD-21
SD-21
Proteobacteria
ABCG01000002.1


976
GCA_000069785.1
977880
164546

Cupriavidus taiwanensis LMG 19424
LMG19424
Proteobacteria
CU633749.1


977
GCA_000010305.1
379066
173480

Gemmatimonas aurantiaca T-27
T-27
Gemmatimonadetes
AP009153.1


978
GCA_000774145.1
1348058
183795

Pseudomonas mediterranea CFBP 5447
CFBP 5447
Proteobacteria
KN322981.1


979
GCA_000255295.1
1144275
184914

Corallococcus coralloides DSM 2259
DSM 2259
Proteobacteria
CP003389.1


980
GCA_000235975.2
1088721
205844

Novosphingobium pentaromativorans US6-1
US6-1
Proteobacteria
AGFM01000037.1


981
GCA_000767465.1
1088721
205844

Novosphingobium pentaromativorans US6-1
US6-1
Proteobacteria
CP009291.1


982
GCA_000091465.1
575788
212663

Vibrio tasmaniensis LGP32
LGP32
Proteobacteria
FM954972.2


983
GCA_000165815.1
215689
215689

Erwinia sp. Ejp617
Ejp617
Proteobacteria
CP002124.1


984
GCA_000015505.1
365044
216465

Polaromonas naphthalenivorans CJ2
CJ2
Proteobacteria
CP000530.1


985
GCA_000264315.1
1163408
219571

Rhodanobacter fulvus Jip2
Jip2
Proteobacteria
AJXU01000037.1


986
GCA_000315055.1
1129793
222814

Paraglaciecola polaris LMG 21857
LMG 21857
Proteobacteria
BAER01000023.1


987
GCA_000317495.1
1173022
241425

Crinalium epipsammum PCC 9333
PCC 9333
Cyanobacteria
CP003620.1


988
GCA_000742915.1
244366
244366

Klebsiella variicola

BZ19
Proteobacteria
JDWA01000007.1


989
GCA_001048495.1
246167
246167

Vibrio crassostreae

J5-19
Proteobacteria
CCJU01000026.1


990
GCA_001368875.1
246167
246167

Vibrio crassostreae

J5-4
Proteobacteria
CCJX01000059.1


991
GCA_001580835.1
257438
257438

Gluconobacter thailandicus

LMG 1741
Proteobacteria
LHZM01000066.1


992
GCA_000168275.1
262489
262489

delta proteobacterium MLMS-1
MLMS-1
Proteobacteria
AAQF01000005.1


993
GCA_001548015.1
270351
270351

Methylobacterium aquaticum

MA-22A
Proteobacteria
AP014704.1


994
GCA_000968535.1
1091494
271065

Methylomicrobium alcaliphilum 20Z
20Z
Proteobacteria
FO082060.1


995
GCA_000825645.1
271420
271420

Pseudomonas xanthomarina

S11
Proteobacteria
CCYE01000007.1


996
GCA_000280495.1
1177180
283686

Kosakonia radicincitans DSM 16656
DSM 16656
Proteobacteria
JH725436.1


997
GCA_000691205.1
1455607
283686

Kosakonia radicincitans UMEnt01/12
UMEnt01/12
Proteobacteria
JDYJ01000004.1


998
GCA_000317615.1
13035
292566

Dactylococcopsis salina PCC 8305
PCC 8305
Cyanobacteria
CP003944.1


999
GCA_000517385.1
1294265
308892

Bacillus boroniphilus JCM 21738
JCM 21738
Firmicutes
BAUW01000042.1


1000
GCA_000152965.1
314262
314262

Roseobacter sp. MED193
MED193
Proteobacteria
CH902583.1


1001
GCA_000171815.1
314289
314289

Vibrio sp. AND4
AND4
Proteobacteria
ABGR01000004.1


1002
GCA_001458175.1
321267
321267

Shimia marina

CECT 7688
Proteobacteria
CYPW01000010.1


1003
GCA_001544495.1
326475
326475

Paraburkholderia telluris


Proteobacteria
FCNZ01000045.1


1004
GCA_000013905.1
335284
330922

Psychrobacter cryohalolentis K5
K5
Proteobacteria
CP000323.1


1005
GCA_000382885.1
1301087
332056

Sphingobium japonicum BiD32
BiD32
Proteobacteria
CAVK010000098.1


1006
GCA_000015285.1
357804
357794

Psychromonas ingrahamii 37
37
Proteobacteria
CP000510.1


1007
GCA_000302535.1
358220
358220

Acidovorax sp. KKS102
KKS102
Proteobacteria
CP003872.1


1008
GCA_000242115.2
1117958
359110

Pseudomonas extremaustralis 14-3 substr. 14-3b
14-3 substr. 14-3b
Proteobacteria
AHIP01000001.1


1009
GCA_000145255.1
395494
370405

Gallionella capsiferriformans ES-2
ES-2
Proteobacteria
CP002159.1


1010
GCA_000241365.2
386428
386428

Pseudoalteromonas sp. BSi20480
BSi20480
Proteobacteria
BADX01000166.1


1011
GCA_001563285.1
407020
407020

Sphingobium sp. MI1205
MI1205
Proteobacteria
CP005188.1


1012
GCA_000166355.1
632292
413888

Caldicellulosiruptor hydrothermalis 108
108
Firmicutes
CP002219.1


1013
GCA_000177355.1
679191
419005

Prevotella amnii CRIS 21A-A
CRIS 21A-A
Bacteroidetes
ADFQ01000093.1


1014
GCA_001553225.1
419005
419005

Prevotella amnii

DNF00307
Bacteroidetes
KQ960543.1


1015
GCA_000421925.1
1346790
420233

Sphingobium chinhatense IP26
IP26
Proteobacteria
AUDA01000024.1


1016
GCA_001043885.1
1295136
427683

Methylobacterium platani JCM 14648
JCM 14648
Proteobacteria
JXOD01000086.1


1017
GCA_000633575.2
1450518
440518

Sphingobium lucknowense F2
F2
Proteobacteria
JANF02000055.1


1018
GCA_000023645.1
443144
443144

Geobacter sp. M21
M21
Proteobacteria
CP001661.1


1019
GCA_000157035.2
457388
457388

Parabacteroides sp. 2_1_7
2_1_7
Bacteroidetes
KQ236092.1


1020
GCA_001517385.1
466044
466044

Pannonibacter indicus

DSM 23407
Proteobacteria
CYHE01000022.1


1021
GCA_000143085.1
105559
473531

Nitrosococcus watsonii C-113
C-113
Proteobacteria
CP002086.1


1022
GCA_000943805.1
484429
484429

Sphingobium sp. YBL2
YBL2
Proteobacteria
CP010954.1


1023
GCA_000943805.1
484429
484429

Sphingobium sp. YBL2
YBL2
Proteobacteria
CP010954.1


1024
GCA_000242435.1
742743
487173

Dialister succinatiphilus YIT 11850
YIT 11850
Firmicutes
JH591187.1


1025
GCA_001527605.1
488732
488732

Burkholderia diffusa

MSMB1544
Proteobacteria
LOZQ01000052.1


1026
GCA_000173035.1
495036
495036

Geobacillus sp. G11MC16
G11MC16
Firmicutes
ABVH01000002.1


1027
GCA_001545155.1
507626
507626

Halomonas chromatireducens

AGD 8-3
Proteobacteria
CP014226.1


1028
GCA_000245735.2
1129374
545533

Alishewanella jeotgali KCTC 22429
KCTC 22429
Proteobacteria
AHTH01000002.1


1029
GCA_000225565.1
598467
598467

Brenneria sp. EniD312
EniD312
Proteobacteria
CM001230.1


1030
GCA_001499735.1
610332
610332

Thiocapsa sp. KS1
KS1
Proteobacteria
LN848258.1


1031
GCA_000188175.1
626939
626940

Phascolarctobacterium succinatutens YIT 12067
YIT 12067
Firmicutes
GL830854.1


1032
GCA_000307475.1
658661
658661

Parabacteroides sp. D25
D25
Bacteroidetes
JH976502.1


1033
GCA_001305515.1
665126
665126

Prosthecomicrobium hirschii

16
Proteobacteria
LIYW01000001.1


1034
GCA_001579845.1
674703
674703

Rhodoplanes sp. Z2-YC6860
YC6860
Proteobacteria
CP007440.1


1035
GCA_001077885.1
680026
680026

Photobacterium swingsii

CAIM 1393
Proteobacteria
LELC01000014.1


1036
GCA_000253255.1
702113
702113

Novosphingobium sp. PP1Y
PP1Y
Proteobacteria
FR856862.1


1037
GCA_000253255.1
702113
702113

Novosphingobium sp. PP1Y
PP1Y
Proteobacteria
FR856862.1


1038
GCA_000024465.1
488538
767892

Candidatus Puniceispirillum marinum IMCC1322
IMCC1322
Proteobacteria
CP001751.1


1039
GCA_000422025.1
886559
886559

Geobacillus sp. WSUCF1
WSUCF1
Firmicutes
ATCO01000102.1


1040
GCA_001580035.1
936474
936474

Sphingobium sp. 22B
22B
Proteobacteria
LTAB01000001.1


1041
GCA_000178975.2
1198114
940615

Granulicella tundricola MP5ACTX9
MP5ACTX9
Acidobacteria
CP002480.1


1042
GCA_000422205.1
941449
941449

Desulfovibrio sp. X2
X2
Proteobacteria
ATHV01000015.1


1043
GCA_000498695.1
977905
977905

Bacillus sp. 17376
17376
Firmicutes
KI547189.1


1044
GCA_000801085.1
1076549
1076549

Pantoea rodasii

ND03
Proteobacteria
JTJJ01000016.1


1045
GCA_000474655.1
1231725
1089444

Dickeya solani D s0432-1
D s0432-1
Proteobacteria
AMWE01000004.1


1046
GCA_000803195.1
1089444
1089444

Dickeya solani

M005
Proteobacteria
JSXD01000001.1


1047
GCA_000972705.2
1637645
1118279

Limnoraphis robusta CS-951
CS-951
Cyanobacteria
LATL02000068.1


1048
GCA_001517305.1
1137284
1137284

Marinomonas fungiae

JCM 18476
Proteobacteria
CYHG01000005.1


1049
GCA_000282175.1
1144323
1144323

Pseudomonas sp. GM17
GM17
Proteobacteria
AKJU01000007.1


1050
GCA_000282315.2
1144708
1144708

Pseudomonas sp. GM41(2012)
GM41(2012)
Proteobacteria
AKJN02000007.1


1051
GCA_000264335.1
1162282
1162282

Rhodanobacter sp. 115
115
Proteobacteria
AJXS01000176.1


1052
GCA_000407765.1
1169321
1169321

Escherichia sp. KTE114
KTE114
Proteobacteria
KE136626.1


1053
GCA_000350705.1
1169331
1169331

Escherichia sp. KTE11
KTE11
Proteobacteria
KB732246.1


1054
GCA_000407925.1
1169349
1169349

Escherichia sp. KTE31
KTE31
Proteobacteria
KE136722.1


1055
GCA_001550165.1
1176302
1176302

Sphingobium sp. AM
AM
Proteobacteria
LRUK01000005.1


1056
GCA_000408325.1
1182659
1182659

Escherichia sp. KTE52
KTE52
Proteobacteria
KE138680.1


1057
GCA_000398905.1
1182695
1182695

Klebsiella sp. KTE92
KTE92
Proteobacteria
KB976100.1


1058
GCA_000408525.1
1182697
1182697

Escherichia sp. KTE96
KTE96
Proteobacteria
KE137149.1


1059
GCA_000408805.1
1182732
1182732

Escherichia sp. KTE159
KTE159
Proteobacteria
KE137292.1


1060
GCA_000316175.1
1207075
1207075

Pseudomonas sp. UW4
UW4
Proteobacteria
CP003880.1


1061
GCA_000801955.1
1217052
1217052

Ralstonia sp. A12
A12
Proteobacteria
JSZO01000004.1


1062
GCA_000369405.1
1217707
1217707

Acinetobacter sp. ANC 3929
ANC 3929
Proteobacteria
KB849994.1


1063
GCA_000342045.1
1244869
1244869

Magnetospirillum caucaseum

SO-1
Proteobacteria
AONQ01000075.1


1064
GCA_000437815.1
1262687
1262687

Acidaminococcus sp. CAG:542

Firmicutes
FR902027.1


1065
GCA_000434475.1
1262870
1262870

Dialister sp. CAG:486

Firmicutes
FR879630.1


1066
GCA_000495795.1
1282360
1282360

Asticcacaulis sp. AC460
AC460
Proteobacteria
AWGD01000018.1


1067
GCA_000495835.1
1282361
1282361

Asticcacaulis sp. AC402
AC402
Proteobacteria
AWGC01000023.1


1068
GCA_000738435.1
666509
1284658

Planktomarina temperata RCA23

RCA23
Proteobacteria
CP003984.1


1069
GCA_001314555.1
1298881
1298881
Idiomarinaceae bacterium HL-53

Proteobacteria
LIHO01000009.1


1070
GCA_001458075.1
1298881
1298881
Idiomarinaceae bacterium HL-53
HL-53
Proteobacteria
LN899469.1


1071
GCA_000493055.1
1329826
1329826

Enterobacter sp. MGH 22
MGH 22
Proteobacteria
KI535662.1


1072
GCA_000416315.1
1330035
1330035

Osedax symbiont Rs2

Proteobacteria
ASZI01000003.1


1073
GCA_000445145.1
1114964
1332080

Sphingobium baderi LL03
LL03
Proteobacteria
ATIB01000079.1


1074
GCA_001046655.1
1114964
1332080

Sphingobium baderi LL03
LL03
Proteobacteria
KQ130471.1


1075
GCA_000445995.2
1345697
1345697

Geobacillus sp. JF8
JF8
Firmicutes
CP006254.2


1076
GCA_000788395.1
1348114
1348114

Pseudoalteromonas sp. OCN003
OCN003
Proteobacteria
CP009888.1


1077
GCA_001581925.1
1356306
1356306

Ferrovum sp. PN-J185
PN-J185
Proteobacteria
LQZA01000004.1


1078
GCA_001263175.1
1391653
1391653

Vulgatibacter incomptus

DSM 27710
Proteobacteria
CP012332.1


1079
GCA_000475355.1
1396859
1396859

Marinobacter sp. C1S70
C1S70
Proteobacteria
AXBW01000091.1


1080
GCA_000475415.1
1397528
1397528

Halomonas sp. PBN3
PBN3
Proteobacteria
AXCA01000185.1


1081
GCA_001580565.1
1399969
1399969

Burkholderia megalochromosomata

JC2949
Proteobacteria
LRBF01000261.1


1082
GCA_001028775.2
1406431
1406431

Massilia sp. WF1
WF1
Proteobacteria
LELH02000007.1


1083
GCA_000524665.1
1435973
1435973

Alcanivorax sp. 97CO-5
97CO-5
Proteobacteria
KI965903.1


1084
GCA_000585055.1
1454003
1454003

Candidatus Accumulibacter sp. BA-92

Proteobacteria
JEMX01000010.1


1085
GCA_000648925.1
1458357
1458357

Burkholderia jiangsuensis

MP-1
Proteobacteria
JFHF01000072.1


1086
GCA_000828915.1
1458426
1458426
Comamonadaceae bacterium B1
B1
Proteobacteria
AP014569.1


1087
GCA_001368815.1
1462524
1462524

Paraliobacillus sp. PM-2
PM-2
Firmicutes
CTEI01000001.1


1088
GCA_000828975.1
1469502
1469502
Burkholderiales bacterium GJ-E10
GJ-E10
Proteobacteria
AP014683.1


1089
GCA_000611145.2
1470558
1470558

Cupriavidus sp. SK-3
SK-3
Proteobacteria
JFJV02000088.1


1090
GCA_001402345.1
1481663
1481663

Vibrio metoecus

YB5B06
Proteobacteria
LBGQ01000030.1


1091
GCA_001402675.1
1481663
1481663

Vibrio metoecus

YB5B04
Proteobacteria
LBGP01000018.1


1092
GCA_000731675.1
1495066
1495066

Pseudomonas sp. WCS358
WCS358
Proteobacteria
JMIT01000003.1


1093
GCA_000732325.1
1499968
1499968

Paenibacillus sp. TCA20
TCA20
Firmicutes
BBIW01000009.1


1094
GCA_001529965.1
1503055
1503055

Burkholderia territorii

MSMB1301WGS
Proteobacteria
LPEQ01000007.1


1095
GCA_001530725.1
1503055
1503055

Burkholderia territorii

MSMB1502WGS
Proteobacteria
LPFQ01000127.1


1096
GCA_001530925.1
1503055
1503055

Burkholderia territorii

MSMB1840WGS
Proteobacteria
LPGS01000070.1


1097
GCA_000734975.2
1504981
1504981

Halomonas sp. KO116
KO116
Proteobacteria
CP011052.1


1098
GCA_000824845.1
1505933
1505933

Mesorhizobium sp. ORS3359

Proteobacteria
CCNC01000071.1


1099
GCA_000824805.1
1505946
1505946

Mesorhizobium sp. SOD10

Proteobacteria
CCNA01000056.1


1100
GCA_000802135.1
1531958
1531958

Desulfosporosinus sp. BICA1-9

Firmicutes
JUEE01000226.1


1101
GCA_000757485.1
1532557
1532557

Achromobacter sp. RTa
RTa
Proteobacteria
JPYO01000042.1


1102
GCA_000764205.1
1535422
1535422

Thalassotalea sp. ND16A
ND16A
Proteobacteria
JQDZ01000100.1


1103
GCA_001267535.1
1560201
1560201

Erwinia iniecta

B120
Proteobacteria
JRXE01000012.1


1104
GCA_001267545.1
1560201
1560201

Erwinia iniecta

B149
Proteobacteria
JRXF01000008.1


1105
GCA_000788125.1
1561068
1561068

Acinetobacter sp. neg1
neg1
Proteobacteria
JSZD01000006.1


1106
GCA_001411475.1
1563157
1563157

Pseudomonas endophytica

BSTT44
Proteobacteria
LLWH01000196.1


1107
GCA_000934545.1
1565605
1565605
Rhodocyclaceae bacterium PG1-Ca6
PG1-Ca6
Proteobacteria
CP010554.1


1108
GCA_000831325.1
1572758
1572758

Thauera sp. SWB20
SWB20
Proteobacteria
JTDM01000020.1


1109
GCA_001455145.1
1307442
1583098

Fusobacterium hwasookii ChDC F174
ChDC F174
Fusobacteria
CP013331.1


1110
GCA_000836735.1
1588629
1588629

Aeromonas sp. L_1B5_3
L_1B5_3
Proteobacteria
JXIR01000008.1


1111
GCA_001439745.1
1615675
1615675

Pseudomonas sp. DSM 28142
DSM 28142
Proteobacteria
JYLP01000005.1


1112
GCA_001548095.1
1615909
1615909

Geminocystis sp. NIES-3708
NIES-3708
Cyanobacteria
AP014815.1


1113
GCA_000802035.2
1619235
1619235

Pseudomonas sp. BICA1-14

Proteobacteria
JUEC02000002.1


1114
GCA_000958445.1
1619246
1619246

Enterobacter sp. 42202
42202
Proteobacteria
JZYH01000003.1


1115
GCA_000955795.1
1619951
1619951
Burkholderiaceae bacterium 26
26
Proteobacteria
JYOB01000010.1


1116
GCA_000960545.1
1620393
1620393

Vibrio sp. S457-15
S457-15
Proteobacteria
JYOQ01000119.1


1117
GCA_000960425.1
1620394
1620394

Vibrio sp. S512-13
S512-13
Proteobacteria
JYOR01000079.1


1118
GCA_001011155.1
1620421
1620421

Hoeflea sp. IMCC20628
IMCC20628
Proteobacteria
CP011479.1


1119
GCA_001044505.1
1628278
1628278

Nitrospina sp. SCGC_AAA799_A02

Nitrospinae
JZKI01000044.1


1120
GCA_000961835.1
1629711
1629711

Pseudomonas sp. BRH_c35

Proteobacteria
LADX01000225.1


1121
GCA_000961805.1
1629714
1629714
Peptococcaceae bacterium BRH_c23

Firmicutes
LADV01000103.1


1122
GCA_001011715.1
1643812
1643812

Enterobacter sp. GN02174
GN02174
Proteobacteria
LDCI01000011.1


1123
GCA_001023195.1
1643814
1643814

Enterobacter sp. GN02204
GN02204
Proteobacteria
LEEQ01000037.1


1124
GCA_001011975.1
1643815
1643815

Enterobacter sp. GN02225
GN02225
Proteobacteria
LDCL01000065.1


1125
GCA_001077815.1
1648404
1648404

Erythrobacter sp. s21-N3
s21-N3
Proteobacteria
CP011310.1


1126
GCA_001023235.1
1659705
1659705

Enterobacter sp. GN02275
GN02275
Proteobacteria
LEEK01000036.1


1127
GCA_001022355.1
1659709
1659709

Enterobacter sp. GN02366
GN02366
Proteobacteria
LEEC01000026.1


1128
GCA_001022445.2
1659710
1659710

Enterobacter sp. GN02454
GN02454
Proteobacteria
LEDW02000013.1


1129
GCA_001022495.2
1659711
1659711

Enterobacter sp. GN02457
GN02457
Proteobacteria
LEDV02000004.1


1130
GCA_001022995.1
1659720
1659720

Enterobacter sp. GN03191
GN03191
Proteobacteria
LECY01000030.1


1131
GCA_001293045.1
1678678
1678678

Burkholderia sp. HB1
HB1
Proteobacteria
CP012192.1


1132
GCA_001412125.1
1699078
1699078

Geobacillus sp. PA-3
PA-3
Firmicutes
LIDX01000059.1


1133
GCA_001593285.1
1699622
1699622

Psychrobacter sp. P2G3
P2G3
Proteobacteria
CP012529.1


1134
GCA_001271345.1
1702325
1702325

Chelatococcus sp. CO-6
CO-6
Proteobacteria
CP012398.1


1135
GCA_001412595.1
1707785
1707785

Massilia sp. WG5
WG5
Proteobacteria
CP012640.1


1136
GCA_001458295.1
1715692
1715692

Ruegeria sp. CECT 5091
CECT 5091
Proteobacteria
CYUD01000002.1


1137
GCA_001458215.1
1715693
1715693

Phaeobacter sp. CECT 7735
CECT 7735
Proteobacteria
CYTW01000001.1


1138
GCA_001458695.1
1715989
1715989

Candidatus Nitrospira inopinata

Nitrospirae
LN885086.1


1139
GCA_001529285.1
1729582
1729582

Pseudomonas sp. TAA207
TAA207
Proteobacteria
LLWJ01000066.1


1140
GCA_001529305.1
1729583
1729583

Pseudomonas sp. TAD18
TAD18
Proteobacteria
LLWI01000076.1


1141
GCA_001516045.1
1734396
1734396

Desulfosporosinus sp. BRH_c37

Firmicutes
LOEW01000087.1


1142
GCA_001421235.1
1735675
1735675

Rhizobium sp. Leaf202
Leaf202
Proteobacteria
LMKD01000014.1


1143
GCA_001421635.1
1735692
1735692

Sphingomonas sp. Leaf25
Leaf25
Proteobacteria
LMKU01000030.1


1144
GCA_001421985.1
1736231
1736231

Rhizobium sp. Leaf68
Leaf68
Proteobacteria
LMLQ01000014.1


1145
GCA_001423405.1
1736264
1736264

Methylobacterium sp. Leaf123
Leaf123
Proteobacteria
LMNS01000004.1


1146
GCA_001424265.1
1736280
1736280

Acidovorax sp. Leaf160
Leaf160
Proteobacteria
LMOV01000023.1


1147
GCA_001423245.1
1736336
1736336

Aureimonas sp. Leaf324
Leaf324
Proteobacteria
LMOH01000012.1


1148
GCA_001424045.1
1736355
1736355

Rhizobium sp. Leaf371
Leaf371
Proteobacteria
LMQB01000026.1


1149
GCA_001424985.1
1736429
1736429

Rhizobium sp. Root1212
Root1212
Proteobacteria
LMDA01000022.1


1150
GCA_001426805.1
1736462
1736462

Brevundimonas sp. Root1423
Root1423
Proteobacteria
LMFL01000003.1


1151
GCA_001429215.1
1736505
1736505

Acidovorax sp. Root267
Root267
Proteobacteria
LMJC01000005.1


1152
GCA_001428925.1
1736506
1736506

Rhizobium sp. Root268
Root268
Proteobacteria
LMJD01000023.1


1153
GCA_001424925.1
1736515
1736515

Pseudomonas sp. Root329
Root329
Proteobacteria
LMCV01000007.1


1154
GCA_001426345.1
1736537
1736537

Devosia sp. Root436
Root436
Proteobacteria
LMEM01000015.1


1155
GCA_001429505.1
1736544
1736544

Bosea sp. Root483D1
Root483D1
Proteobacteria
LMJW01000003.1


1156
GCA_001427465.1
1736566
1736566

Pseudomonas sp. Root569
Root569
Proteobacteria
LMGQ01000003.1


1157
GCA_001427825.1
1736569
1736569

Brevundimonas sp. Root608
Root608
Proteobacteria
LMGT01000001.1


1158
GCA_001429725.1
1736592
1736592

Rhizobium sp. Root708
Root708
Proteobacteria
LMHV01000043.1


1159
GCA_001414205.1
1737624
1737624

Geobacillus sp. Sah69
Sah69
Firmicutes
LLKS01000066.1


1160
GCA_001542405.1
1755240
1755240

Rhizobium sp. BR10423
BR10423
Proteobacteria
LNCD01000088.1


1161
GCA_001506075.1
1761910
1761910

Vibrio sp. MEBiC08052
MEBiC08052
Proteobacteria
KQ947475.1


1162
GCA_001469895.1
1766621
1766621

Pseudoalteromonas sp. XI10
XI10
Proteobacteria
LOPY01000025.1


1163
GCA_001544695.1
1777135
1777135

Burkholderia sp. LMG 29317

Proteobacteria
FCOM01000073.1


1164
GCA_900044055.1
1777138
1777138

Burkholderia sp. LMG 29320

Proteobacteria
FCOX01000009.1


1165
GCA_900044055.1
1777138
1777138

Burkholderia sp. LMG 29320

Proteobacteria
FCOX01000002.1


1166
GCA_900044055.1
1777138
1777138

Burkholderia sp. LMG 29320

Proteobacteria
FCOX01000040.1


1167
GCA_001544915.1
1777141
1777141

Burkholderia sp. LMG 29323

Proteobacteria
FCOE01000003.1


1168
GCA_001545035.1
1777143
1777143

Burkholderia sp. LMG 29325

Proteobacteria
FCOJ01000099.1


1169
GCA_001577625.1
1785949
1785949
Halobacteroidaceae bacterium T328-2

Firmicutes
LSBO01000115.1


1170
GCA_001581915.1
1789004
1789004

Ferrovum sp. Z-31
Z-31
Proteobacteria
LRRD01000049.1


1171
GCA_000286655.1
1216470
1812935

Enterobacter sp. SST3
SST3
Proteobacteria
ALNS01000022.1


1172
GCA_000467655.2
1334630
1812935

Enterobacter cloacae EC_38VIM1
EC_38VIM1
Proteobacteria
ATHX01000012.1


1173
GCA_000534155.1
1400152
1812935

Enterobacter cloacae UCI 39
UCI 39
Proteobacteria
KI973119.1


1174
GCA_001592395.1
1813182
1813182

Geobacillus sp. JS12
JS12
Firmicutes
CP014749.1


1175
GCA_000024525.1
504472
108

Spirosoma linguale DSM 74
DSM 74
Bacteroidetes
CP001770.1


1176
GCA_000253755.2
887281
195

Campylobacter coli 7--1
7--1
Proteobacteria
AIMZ01000005.1


1177
GCA_000253935.2
887284
195

Campylobacter coli 67-8
67-8
Proteobacteria
AINI01000046.1


1178
GCA_000254035.2
887304
195

Campylobacter coli LMG 23341
LMG 23341
Proteobacteria
AINN01000049.1


1179
GCA_000254055.2
887305
195

Campylobacter coli LMG 23342
LMG 23342
Proteobacteria
AIN001000051.1


1180
GCA_001416745.1
195
195

Campylobacter coli

CVM N42205
Proteobacteria
LBEO01000037.1


1181
GCA_001418825.1
1440776
195

Campylobacter coli CVM 41904
CVM 41904
Proteobacteria
JAJL01000029.1


1182
GCA_001419395.1
1440016
195

Campylobacter coli CVM 41963
CVM 41963
Proteobacteria
JAJR01000050.1


1183
GCA_001441815.1
195
195

Campylobacter coli

CVM N3506
Proteobacteria
JOUR01000007.1


1184
GCA_001442405.1
195
195

Campylobacter coli

CVM N14840
Proteobacteria
JOVV01000015.1


1185
GCA_000705275.1
91352
198

Campylobacter hyointestinalis subsp. hyointestinalis
DSM 19053
Proteobacteria
JHQP01000002.1


1186
GCA_000701165.2
1395570
292

Burkholderia cepacia JBK9
JBK9
Proteobacteria
CP013730.1


1187
GCA_001543265.1
296
296

Pseudomonas fragi

P121
Proteobacteria
CP013861.1


1188
GCA_900048915.1
446
446

Legionella pneumophila

2531STDY5467317
Proteobacteria
FJAM01000003.1


1189
GCA_900051685.1
446
446

Legionella pneumophila

2531STDY5467385
Proteobacteria
FJCH01000002.1


1190
GCA_900052085.1
446
446

Legionella pneumophila

2531STDY5467299
Proteobacteria
FJAW01000009.1


1191
GCA_900059955.1
446
446

Legionella pneumophila

2531STDY5467397
Proteobacteria
FJDI01000005.1


1192
GCA_900060365.1
446
446

Legionella pneumophila

2531STDY5467373
Proteobacteria
FJDE01000004.1


1193
GCA_900061515.1
446
446

Legionella pneumophila

2531STDY5467344
Proteobacteria
FJCG01000004.1


1194
GCA_900061575.1
446
446

Legionella pneumophila

2531STDY5467389
Proteobacteria
FJCV01000005.1


1195
GCA_900070165.1
446
446

Legionella pneumophila

2531STDY5467373
Proteobacteria
FJNL01000004.1


1196
GCA_000176095.1
638315
450

Legionella longbeachae D-4968
D-4968
Proteobacteria
ACZG01000001.1


1197
GCA_000092265.1
1236608
480

Moraxella catarrhalis BBH18
BBH18
Proteobacteria
CP002005.1


1198
GCA_000192905.2
857581
480

Moraxella catarrhalis 7169
7169
Proteobacteria
AERC01000010.1


1199
GCA_000192925.2
857579
480

Moraxella catarrhalis 103P14B1
103P14B1
Proteobacteria
AERE01000083.1


1200
GCA_000192945.2
857578
480

Moraxella catarrhalis 46P47B1
46P47B1
Proteobacteria
AERF01000047.1


1201
GCA_000192965.2
857577
480

Moraxella catarrhalis 12P80B1
12P80B1
Proteobacteria
AERG01000021.1


1202
GCA_000192985.2
857576
480

Moraxella catarrhalis BC1
BC1
Proteobacteria
AERH01000031.1


1203
GCA_000193005.2
857575
480

Moraxella catarrhalis BC7
BC7
Proteobacteria
AERI01000026.1


1204
GCA_000193045.2
857573
480

Moraxella catarrhalis CO72
CO72
Proteobacteria
AERK01000003.1


1205
GCA_000193065.2
857572
480

Moraxella catarrhalis 101P30B1
101P30B1
Proteobacteria
AEPC01000015.1


1206
GCA_000302495.1
749219
480

Moraxella catarrhalis RH4
RH4
Proteobacteria
AMSO01000008.1


1207
GCA_000766665.1
480
480

Moraxella catarrhalis

25239
Proteobacteria
CP007669.1


1208
GCA_001281005.1
546
546

Citrobacter freundii

P10159
Proteobacteria
CP012554.1


1209
GCA_000952375.1
550
550

Enterobacter cloacae

MNCRE12
Proteobacteria
JYME01000006.1


1210
GCA_001005095.1
553
553

Pantoea ananatis

MR5
Proteobacteria
LBFU01000095.1


1211
GCA_000738105.1
180957
554

Pectobacterium carotovorum subsp. brasiliense
CFIA1009
Proteobacteria
JPSN01000016.1


1212
GCA_000808235.1
180957
554

Pectobacterium carotovorum subsp. brasiliense
YCD21
Proteobacteria
JUJJ01000006.1


1213
GCA_000006665.1
155864
562

Escherichia coli O157:H7 str. EDL933
EDL933
Proteobacteria
AE005174.2


1214
GCA_000008865.1
386585
562

Escherichia coli O157:H7 str. Sakai
Sakai substr. RIMD 0509952
Proteobacteria
BA000007.2


1215
GCA_000019385.1
481805
562

Escherichia coli ATCC 8739
ATCC 8739
Proteobacteria
CP000946.1


1216
GCA_000019645.1
439855
562

Escherichia coli SMS-3-5
SMS-3-5
Proteobacteria
CP000970.1


1217
GCA_000021125.1
444450
562

Escherichia coli O157:H7 str. EC4115
EC4115
Proteobacteria
CP001164.1


1218
GCA_000022225.1
544404
562

Escherichia coli O157:H7 str. TW14359
TW14359
Proteobacteria
CP001368.1


1219
GCA_000025165.1
701177
562

Escherichia coli O55:H7 str. CB9615
CB9615
Proteobacteria
CP001846.1


1220
GCA_000155125.1
502346
562

Escherichia coli O157:H7 str. TW14588
TW14588
Proteobacteria
CM000662.1


1221
GCA_000164335.1
749547
562

Escherichia coli MS 187-1
MS 187-1
Proteobacteria
GG772497.1


1222
GCA_000171915.1
444451
562

Escherichia coli O157:H7 str. EC4196
EC4196
Proteobacteria
ABHO01000006.1


1223
GCA_000171935.1
444452
562

Escherichia coli O157:H7 str. EC4113
EC4113
Proteobacteria
ABHP01000015.1


1224
GCA_000171955.1
444453
562

Escherichia coli O157:H7 str. EC4076
EC4076
Proteobacteria
ABHQ01000017.1


1225
GCA_000171975.1
478004
562

Escherichia coli O157:H7 str. EC4401
EC4401
Proteobacteria
ABHR01000005.1


1226
GCA_000171995.1
478005
562

Escherichia coli O157:H7 str. EC4486
EC4486
Proteobacteria
ABHS01000002.1


1227
GCA_000172015.1
478006
562

Escherichia coli O157:H7 str. EC4501
EC4501
Proteobacteria
ABHT01000004.1


1228
GCA_000172035.1
478008
562

Escherichia coli O157:H7 str. EC869
EC869
Proteobacteria
ABHU01000001.1


1229
GCA_000172055.1
478007
562

Escherichia coli O157:H7 str. EC508
EC508
Proteobacteria
ABHW01000003.1


1230
GCA_000176615.2
656437
562

Escherichia coli TA143
TA143
Proteobacteria
GL884236.1


1231
GCA_000181735.1
444447
562

Escherichia coli O157:H7 str. EC4206
EC4206
Proteobacteria
ABHK02000001.1


1232
GCA_000181755.1
444448
562

Escherichia coli O157:H7 str. EC4045
EC4045
Proteobacteria
ABHL02000001.1


1233
GCA_000181775.1
444449
562

Escherichia coli O157:H7 str. EC4042
EC4042
Proteobacteria
ABHM02000001.1


1234
GCA_000187285.4
926026
562

Escherichia coli O157:H7 str. G5101
G5101
Proteobacteria
AETX01000114.1


1235
GCA_000187305.2
926027
562

Escherichia coli O157:H-str. 493-89
493-89
Proteobacteria
AETY01000104.1


1236
GCA_000187325.2
926028
562

Escherichia coli O157:H-str. H 2687
H 2687
Proteobacteria
AETZ01000110.1


1237
GCA_000187365.2
926030
562

Escherichia coli O55:H7 str. USDA 5905
USDA 5905
Proteobacteria
AEUB01000059.1


1238
GCA_000187385.2
926032
562

Escherichia coli O157:H7 str. LSU-61
LSU-61
Proteobacteria
AEUC01000091.1


1239
GCA_000192665.2
997824
562

Escherichia coli O157:H7 str. 1044
1044
Proteobacteria
AERP01000018.1


1240
GCA_000192685.2
997825
562

Escherichia coli O157:H7 str. 1125
1125
Proteobacteria
AERR01000012.1


1241
GCA_000193955.2
941435
562

Escherichia coli O157:H7 str. EC1212
EC1212
Proteobacteria
AERQ01000011.1


1242
GCA_000245515.1
1048689
562

Escherichia coli O55:H7 str. RM12579
RM12579
Proteobacteria
CP003109.1


1243
GCA_000249375.2
868149
562

Escherichia coli DEC4A
DEC4A
Proteobacteria
AIFK01000052.1


1244
GCA_000249395.2
868150
562

Escherichia coli DEC4B
DEC4B
Proteobacteria
AIFL01000076.1


1245
GCA_000249495.2
868155
562

Escherichia coli DEC5A
DEC5A
Proteobacteria
AIFQ01000037.1


1246
GCA_000249535.2
868157
562

Escherichia coli DEC5C
DEC5C
Proteobacteria
AIFS01000052.1


1247
GCA_000249555.2
868158
562

Escherichia coli DEC5D
DEC5D
Proteobacteria
AIFT01000001.1


1248
GCA_000261145.1
656421
562

Escherichia coli M919
M919
Proteobacteria
JH659569.1


1249
GCA_000262125.1
741093
562

Escherichia coli Xuzhou21
Xuzhou21
Proteobacteria
CP001925.1


1250
GCA_000267005.2
1005471
562

Escherichia coli FDA505
FDA505
Proteobacteria
JH692596.1


1251
GCA_000267025.1
1005535
562

Escherichia coli EC1738
EC1738
Proteobacteria
AKMN01000003.1


1252
GCA_000267045.1
1005536
562

Escherichia coli EC1734
EC1734
Proteobacteria
AKMO01000001.1


1253
GCA_000267065.1
1005520
562

Escherichia coli TW09109
TW09109
Proteobacteria
AKLY01000005.1


1254
GCA_000267085.1
1005497
562

Escherichia coli PA22
PA22
Proteobacteria
AKLI01000001.1


1255
GCA_000267105.1
1005508
562

Escherichia coli PA40
PA40
Proteobacteria
AKLQ01000001.1


1256
GCA_000267125.1
1005515
562

Escherichia coli TW06591
TW06591
Proteobacteria
AKLT01000044.1


1257
GCA_000267145.1
1005517
562

Escherichia coli TW10246
TW10246
Proteobacteria
AKLV01000003.1


1258
GCA_000267165.1
1005518
562

Escherichia coli TW11039
TW11039
Proteobacteria
AKLW01000006.1


1259
GCA_000267185.1
1005522
562

Escherichia coli TW10119
TW10119
Proteobacteria
AKMA01000001.1


1260
GCA_000267205.2
1005548
562

Escherichia coli EC1863
EC1863
Proteobacteria
JH692972.1


1261
GCA_000267225.2
1005540
562

Escherichia coli EC1845
EC1845
Proteobacteria
JH693448.1


1262
GCA_000267245.2
1005534
562

Escherichia coli EC4448
EC4448
Proteobacteria
JH693935.1


1263
GCA_000267265.2
1005533
562

Escherichia coli EC4437
EC4437
Proteobacteria
JH694340.1


1264
GCA_000267285.2
1005532
562

Escherichia coli EC4436
EC4436
Proteobacteria
JH694746.1


1265
GCA_000267305.2
1005531
562

Escherichia coli EC4439
EC4439
Proteobacteria
JH697080.1


1266
GCA_000267325.1
1005530
562

Escherichia coli EC4402
EC4402
Proteobacteria
JH697727.1


1267
GCA_000267345.2
1005529
562

Escherichia coli EC4013
EC4013
Proteobacteria
JH698305.1


1268
GCA_000267365.2
1005528
562

Escherichia coli EC4422
EC4422
Proteobacteria
JH695870.1


1269
GCA_000267385.2
1005527
562

Escherichia coli EC4421
EC4421
Proteobacteria
JH696600.1


1270
GCA_000267405.2
1005526
562

Escherichia coli TW14301
TW14301
Proteobacteria
JH695863.1


1271
GCA_000267425.2
1005525
562

Escherichia coli TW14313
TW14313
Proteobacteria
JH695399.1


1272
GCA_000267445.2
1005524
562

Escherichia coli EC4196
EC4196
Proteobacteria
JH699193.1


1273
GCA_000267465.2
1005523
562

Escherichia coli EC4203
EC4203
Proteobacteria
JH699677.1


1274
GCA_000267485.2
1005473
562

Escherichia coli FDA517
FDA517
Proteobacteria
JH701994.1


1275
GCA_000267505.2
1005475
562

Escherichia coli FRIK1996
FRIK1996
Proteobacteria
JH698283.1


1276
GCA_000267525.2
1005476
562

Escherichia coli FRIK1985
FRIK1985
Proteobacteria
JH701532.1


1277
GCA_000267585.2
1005521
562

Escherichia coli TW09195
TW09195
Proteobacteria
JH700736.1


1278
GCA_000267605.2
1005519
562

Escherichia coli TW09098
TW09098
Proteobacteria
JH702452.1


1279
GCA_000267625.2
1005516
562

Escherichia coli TW07945
TW07945
Proteobacteria
JH702467.1


1280
GCA_000267645.2
1005510
562

Escherichia coli PA42
PA42
Proteobacteria
JH702836.1


1281
GCA_000267665.2
1005509
562

Escherichia coli PA41
PA41
Proteobacteria
JH703744.1


1282
GCA_000267685.2
1005507
562

Escherichia coli PA39
PA39
Proteobacteria
JH704563.1


1283
GCA_000267705.2
1005504
562

Escherichia coli PA33
PA33
Proteobacteria
JH705112.1


1284
GCA_000267725.2
1005503
562

Escherichia coli PA32
PA32
Proteobacteria
JH705678.1


1285
GCA_000267745.2
1005502
562

Escherichia coli PA31
PA31
Proteobacteria
JH707077.1


1286
GCA_000267765.2
1005501
562

Escherichia coli PA28
PA28
Proteobacteria
JH705685.1


1287
GCA_000267785.2
1005500
562

Escherichia coli PA25
PA25
Proteobacteria
JH706538.1


1288
GCA_000267805.2
1005499
562

Escherichia coli PA24
PA24
Proteobacteria
JH707528.1


1289
GCA_000267825.2
1005496
562

Escherichia coli PA15
PA15
Proteobacteria
JH707559.1


1290
GCA_000267845.2
1005495
562

Escherichia coli PA14
PA14
Proteobacteria
JH708600.1


1291
GCA_000267865.2
1005494
562

Escherichia coli PA10
PA10
Proteobacteria
JH709066.1


1292
GCA_000267885.2
1005493
562

Escherichia coli PA9
PA9
Proteobacteria
JH709102.1


1293
GCA_000267905.2
1005490
562

Escherichia coli PA5
PA5
Proteobacteria
JH709975.1


1294
GCA_000267925.2
1005488
562

Escherichia coli PA3
PA3
Proteobacteria
JH711390.1


1295
GCA_000267945.2
1005481
562

Escherichia coli 93-001
93-001
Proteobacteria
JH710997.1


1296
GCA_000267965.2
1005478
562

Escherichia coli FRIK1990
FRIK1990
Proteobacteria
JH710503.1


1297
GCA_000302715.1
1005483
562

Escherichia coli FRIK920
FRIK920
Proteobacteria
AMTP01000126.1


1298
GCA_000302735.1
1005491
562

Escherichia coli PA7
PA7
Proteobacteria
AMTQ01000008.1


1299
GCA_000303235.2
1005441
562

Escherichia coli 0.1304
0.1304
Proteobacteria
JH943332.1


1300
GCA_000303275.2
1005482
562

Escherichia coli FRIK523
FRIK523
Proteobacteria
JH943936.1


1301
GCA_000303295.2
1005486
562

Escherichia coli NE098
NE098
Proteobacteria
JH946265.1


1302
GCA_000303315.2
1005554
562

Escherichia coli EC1870
EC1870
Proteobacteria
JH945214.1


1303
GCA_000303335.2
1005553
562

Escherichia coli EC1869
EC1869
Proteobacteria
JH946714.1


1304
GCA_000303355.2
1005552
562

Escherichia coli EC1868
EC1868
Proteobacteria
JH944350.1


1305
GCA_000303375.2
1005551
562

Escherichia coli EC1866
EC1866
Proteobacteria
JH944315.1


1306
GCA_000303415.2
1005549
562

Escherichia coli EC1864
EC1864
Proteobacteria
JH945870.1


1307
GCA_000303435.2
1005547
562

Escherichia coli EC1862
EC1862
Proteobacteria
JH952466.1


1308
GCA_000303455.2
1005546
562

Escherichia coli EC1856
EC1856
Proteobacteria
JH952880.1


1309
GCA_000303475.2
1005545
562

Escherichia coli EC1850
EC1850
Proteobacteria
JH952886.1


1310
GCA_000303495.2
1005544
562

Escherichia coli EC1849
EC1849
Proteobacteria
JH953696.1


1311
GCA_000303515.2
1005543
562

Escherichia coli EC1848
EC1848
Proteobacteria
JH955442.1


1312
GCA_000303535.2
1005542
562

Escherichia coli EC1847
EC1847
Proteobacteria
JH963080.1


1313
GCA_000303555.2
1005541
562

Escherichia coli EC1846
EC1846
Proteobacteria
JH956315.1


1314
GCA_000303575.2
1005539
562

Escherichia coli EC1737
EC1737
Proteobacteria
JH963529.1


1315
GCA_000303595.2
1005538
562

Escherichia coli EC1736
EC1736
Proteobacteria
JH965238.1


1316
GCA_000303615.2
1005537
562

Escherichia coli EC1735
EC1735
Proteobacteria
JH958312.1


1317
GCA_000303675.2
1005506
562

Escherichia coli PA38
PA38
Proteobacteria
JH966117.1


1318
GCA_000303695.2
1005505
562

Escherichia coli PA34
PA34
Proteobacteria
JH963946.1


1319
GCA_000303715.2
1005474
562

Escherichia coli FDA506
FDA506
Proteobacteria
JH964536.1


1320
GCA_000303735.2
1005472
562

Escherichia coli FDA507
FDA507
Proteobacteria
JH963945.1


1321
GCA_000303755.2
1005470
562

Escherichia coli FDA504
FDA504
Proteobacteria
JH961871.1


1322
GCA_000303775.2
1005477
562

Escherichia coli FRIK1999
FRIK1999
Proteobacteria
JH962623.1


1323
GCA_000303795.2
1005480
562

Escherichia coli FRIK1997
FRIK1997
Proteobacteria
JH961362.1


1324
GCA_000303815.2
1005485
562

Escherichia coli NE1487
NE1487
Proteobacteria
JH957512.1


1325
GCA_000303835.2
1005484
562

Escherichia coli NE037
NE037
Proteobacteria
JH960043.1


1326
GCA_000303855.2
1005479
562

Escherichia coli FRIK2001
FRIK2001
Proteobacteria
JH960978.1


1327
GCA_000303875.2
1005489
562

Escherichia coli PA4
PA4
Proteobacteria
JH960549.1


1328
GCA_000303895.2
1005498
562

Escherichia coli PA23
PA23
Proteobacteria
JH959990.1


1329
GCA_000303915.2
1005514
562

Escherichia coli PA49
PA49
Proteobacteria
JH959133.1


1330
GCA_000303935.2
1005511
562

Escherichia coli PA45
PA45
Proteobacteria
JH958691.1


1331
GCA_000303955.2
1005555
562

Escherichia coli TT12B
TT12B
Proteobacteria
JH957216.1


1332
GCA_000303975.2
1005557
562

Escherichia coli MA6
MA6
Proteobacteria
JH956821.1


1333
GCA_000303995.2
1005558
562

Escherichia coli 5905
5905
Proteobacteria
JH958373.1


1334
GCA_000304015.2
1005559
562

Escherichia coli CB7326
CB7326
Proteobacteria
JH956766.1


1335
GCA_000304035.2
1005560
562

Escherichia coli EC96038
EC96038
Proteobacteria
JH955436.1


1336
GCA_000304055.2
1005561
562

Escherichia coli 5412
5412
Proteobacteria
JH954949.1


1337
GCA_000304815.2
1005450
562

Escherichia coli 3.4870
3.4870
Proteobacteria
JH970627.1


1338
GCA_000304835.2
1005463
562

Escherichia coli 8.0416
8.0416
Proteobacteria
AMTN01000133.1


1339
GCA_000304855.2
1005469
562

Escherichia coli 10.0821
10.0821
Proteobacteria
AMTO01000004.1


1340
GCA_000304875.2
1005452
562

Escherichia coli 5.2239
5.2239
Proteobacteria
JH970990.1


1341
GCA_000305155.2
1005455
562

Escherichia coli 6.0172
6.0172
Proteobacteria
JH970109.1


1342
GCA_000305375.2
1005461
562

Escherichia coli 8.0586
8.0586
Proteobacteria
JH969648.1


1343
GCA_000305395.2
1005460
562

Escherichia coli 8.2524
8.2524
Proteobacteria
JH969044.1


1344
GCA_000305415.2
1005466
562

Escherichia coli 10.0833
10.0833
Proteobacteria
JH969098.1


1345
GCA_000305435.2
1005467
562

Escherichia coli 10.0869
10.0869
Proteobacteria
JH968727.1


1346
GCA_000305455.2
1005397
562

Escherichia coli 88.0221
88.0221
Proteobacteria
JH968005.1


1347
GCA_000316325.2
1005396
562

Escherichia coli 88.1467
88.1467
Proteobacteria
KB000019.1


1348
GCA_000316345.2
1005398
562

Escherichia coli 88.1042
88.1042
Proteobacteria
KB006081.1


1349
GCA_000316365.2
1005399
562

Escherichia coli 89.0511
89.0511
Proteobacteria
KB007266.1


1350
GCA_000316385.2
1005400
562

Escherichia coli 90.0091
90.0091
Proteobacteria
KB007294.1


1351
GCA_000316405.2
1005401
562

Escherichia coli 90.0039
90.0039
Proteobacteria
KB006791.1


1352
GCA_000316425.2
1005402
562

Escherichia coli 90.2281
90.2281
Proteobacteria
KB005715.1


1353
GCA_000316445.2
1005403
562

Escherichia coli 93.0055
93.0055
Proteobacteria
KB004131.1


1354
GCA_000316465.1
1005404
562

Escherichia coli 93.0056
93.0056
Proteobacteria
KB004997.1


1355
GCA_000316485.1
1005405
562

Escherichia coli 94.0618
94.0618
Proteobacteria
KB005707.1


1356
GCA_000316505.2
1005420
562

Escherichia coli 97.0007
97.0007
Proteobacteria
ANMC01000275.1


1357
GCA_000316545.2
1005422
562

Escherichia coli 99.0678
99.0678
Proteobacteria
ANME01000013.1


1358
GCA_000316565.2
1005424
562

Escherichia coli 99.0713
99.0713
Proteobacteria
ANMF01000001.1


1359
GCA_000316705.2
1005421
562

Escherichia coli 99.0672
99.0672
Proteobacteria
KB004968.1


1360
GCA_000316725.2
1005418
562

Escherichia coli 97.1742
97.1742
Proteobacteria
KB004341.1


1361
GCA_000316745.2
1005416
562

Escherichia coli 97.0003
97.0003
Proteobacteria
JH999738.1


1362
GCA_000316765.2
1005415
562

Escherichia coli 96.0107
96.0107
Proteobacteria
KB003449.1


1363
GCA_000316785.2
1005412
562

Escherichia coli 96.0939
96.0939
Proteobacteria
KB003084.1


1364
GCA_000316805.2
1005413
562

Escherichia coli 96.0932
96.0932
Proteobacteria
KB003092.1


1365
GCA_000316825.2
1005411
562

Escherichia coli 96.0427
96.0427
Proteobacteria
KB002687.1


1366
GCA_000316845.2
1005406
562

Escherichia coli 95.0183
95.0183
Proteobacteria
KB002150.1


1367
GCA_000316865.2
1005407
562

Escherichia coli 95.1288
95.1288
Proteobacteria
KB001319.1


1368
GCA_000316885.2
1005408
562

Escherichia coli 95.0943
95.0943
Proteobacteria
KB000789.1


1369
GCA_000316905.2
1005410
562

Escherichia coli 96.0428
96.0428
Proteobacteria
KB000504.1


1370
GCA_000318425.2
1005414
562

Escherichia coli 96.0109
96.0109
Proteobacteria
KB009454.1


1371
GCA_000318445.2
1005419
562

Escherichia coli 97.0010
97.0010
Proteobacteria
KB008877.1


1372
GCA_000326965.1
1169382
562

Escherichia coli KTE125
KTE125
Proteobacteria
KB732191.1


1373
GCA_000334975.2
1005433
562

Escherichia coli 99.0815
99.0815
Proteobacteria
AODZ01000274.1


1374
GCA_000334995.2
1005430
562

Escherichia coli 99.0816
99.0816
Proteobacteria
AOEA01000217.1


1375
GCA_000335015.2
1005437
562

Escherichia coli 99.1793
99.1793
Proteobacteria
AOEF01000014.1


1376
GCA_000335035.2
1005436
562

Escherichia coli 99.1805
99.1805
Proteobacteria
AOEG01000281.1


1377
GCA_000335055.2
1051353
562

Escherichia coli ATCC 700728
ATCC 700728
Proteobacteria
AOEH01000126.1


1378
GCA_000335075.2
1005512
562

Escherichia coli PA47
PA47
Proteobacteria
AOEM01000157.1


1379
GCA_000335095.2
1005513
562

Escherichia coli PA48
PA48
Proteobacteria
AOEN01000122.1


1380
GCA_000335115.1
1051348
562

Escherichia coli 7.1982
7.1982
Proteobacteria
AOEP01000011.1


1381
GCA_000335135.1
1005439
562

Escherichia coli 99.1781
99.1781
Proteobacteria
AOEQ01000012.1


1382
GCA_000335155.2
1005435
562

Escherichia coli 99.1762
99.1762
Proteobacteria
AOER01000006.1


1383
GCA_000335175.2
1051352
562

Escherichia coli PA35
PA35
Proteobacteria
AOES01000151.1


1384
GCA_000335195.2
1051347
562

Escherichia coli 3.4880
3.4880
Proteobacteria
AOET01000122.1


1385
GCA_000335215.2
1005423
562

Escherichia coli 99.0670
99.0670
Proteobacteria
AOEV01000013.1


1386
GCA_000335235.2
1005434
562

Escherichia coli 99.0814
99.0814
Proteobacteria
AODY01000209.1


1387
GCA_000335255.2
1005432
562

Escherichia coli 99.0839
99.0839
Proteobacteria
AOEB01000180.1


1388
GCA_000335275.2
1005431
562

Escherichia coli 99.0848
99.0848
Proteobacteria
AOEC01000227.1


1389
GCA_000335295.2
1005440
562

Escherichia coli 99.1753
99.1753
Proteobacteria
AOED01000247.1


1390
GCA_000335315.2
1005438
562

Escherichia coli 99.1775
99.1775
Proteobacteria
AOEE01000251.1


1391
GCA_000335335.2
1051351
562

Escherichia coli PA19
PA19
Proteobacteria
AOEJ01000133.1


1392
GCA_000335355.2
1005487
562

Escherichia coli PA2
PA2
Proteobacteria
AOEL01000002.1


1393
GCA_000335415.2
1051349
562

Escherichia coli PA11
PA11
Proteobacteria
AOEI01000002.1


1394
GCA_000335435.2
1051350
562

Escherichia coli PA13
PA13
Proteobacteria
AOEK01000001.1


1395
GCA_000335455.2
1005492
562

Escherichia coli PA8
PA8
Proteobacteria
AOEO01000008.1


1396
GCA_000340455.2
1081887
562

Escherichia coli 09BKT078844
09BKT078844
Proteobacteria
KB453231.1


1397
GCA_000350025.2
1090930
562

Escherichia coli ONT:H33 str. C48/93
C48/93
Proteobacteria
AHAX01000074.1


1398
GCA_000350045.2
1090929
562

Escherichia coli O127:H27 str. C43/90
C43/90
Proteobacteria
AHAW01000071.1


1399
GCA_000351625.1
1182673
562

Escherichia coli KTE66
KTE66
Proteobacteria
KB732762.1


1400
GCA_000351985.1
1182733
562

Escherichia coli KTE161
KTE161
Proteobacteria
KB732934.1


1401
GCA_000352325.1
1182657
562

Escherichia coli KTE50
KTE50
Proteobacteria
KB733431.1


1402
GCA_000352965.1
1181748
562

Escherichia coli KTE202
KTE202
Proteobacteria
KB733186.1


1403
GCA_000357685.2
1125651
562

Escherichia coli P0304799.3
P0304799.3
Proteobacteria
APZX01000029.1


1404
GCA_000456685.1
1280993
562

Escherichia coli HVH 43 (4-2173468)
HVH 43 (4-2173468)
Proteobacteria
KE699249.1


1405
GCA_000456705.1
1280994
562

Escherichia coli HVH 44 (4-2298570)
HVH 44 (4-2298570)
Proteobacteria
KE699258.1


1406
GCA_000458705.1
1281109
562

Escherichia coli HVH 182 (4-0985554)
HVH 182 (4-0985554)
Proteobacteria
KE700608.1


1407
GCA_000458915.1
1281120
562

Escherichia coli HVH 193 (4-3331423)
HVH 193 (4-3331423)
Proteobacteria
KE700785.1


1408
GCA_000460315.1
1281191
562

Escherichia coli UMEA 3144-1
UMEA 3144-1
Proteobacteria
KE701670.1


1409
GCA_000460355.1
1281194
562

Escherichia coli UMEA 3151-1
UMEA 3151-1
Proteobacteria
KE701689.1


1410
GCA_000461915.2
1151226
562

Escherichia coli B26-2
B26-2
Proteobacteria
AVQV01000001.1


1411
GCA_000461935.2
1081889
562

Escherichia coli 09BKT076207
09BKT076207
Proteobacteria
AVQR01000067.1


1412
GCA_000461955.2
1151213
562

Escherichia coli B102
B102
Proteobacteria
AVQS01000008.1


1413
GCA_000461975.2
1151219
562

Escherichia coli B29-1
B29-1
Proteobacteria
AVQY01000001.1


1414
GCA_000461995.2
1151214
562

Escherichia coli B107
B107
Proteobacteria
AVQT01000005.1


1415
GCA_000462025.2
1151225
562

Escherichia coli B26-1
B26-1
Proteobacteria
AVQU01000001.1


1416
GCA_000462045.2
1151217
562

Escherichia coli B28-1
B28-1
Proteobacteria
AVQW01000010.1


1417
GCA_000462065.2
1151222
562

Escherichia coli B36-2
B36-2
Proteobacteria
AVRB01000001.1


1418
GCA_000462085.2
1151215
562

Escherichia coli B7-1
B7-1
Proteobacteria
AVRC01000049.1


1419
GCA_000462105.2
1151220
562

Escherichia coli B29-2
B29-2
Proteobacteria
AVQZ01000120.1


1420
GCA_000462125.2
1151221
562

Escherichia coli B36-1
B36-1
Proteobacteria
AVRA01000107.1


1421
GCA_000462145.2
1081891
562

Escherichia coli T1282_01
T1282_01
Proteobacteria
AVRM01000132.1


1422
GCA_000462165.2
1081893
562

Escherichia coli T924_01
T924_01
Proteobacteria
AVRP01000002.1


1423
GCA_000462185.2
1151237
562

Escherichia coli B15
B15
Proteobacteria
AVSB01000112.1


1424
GCA_000462225.2
1207035
562

Escherichia coli 14A
14A
Proteobacteria
AVRQ01000005.1


1425
GCA_000462245.2
1207038
562

Escherichia coli 2886-75
2886-75
Proteobacteria
AVRR01000001.1


1426
GCA_000462265.2
1081896
562

Escherichia coli T1840_97
T1840_97
Proteobacteria
AVRN01000121.1


1427
GCA_000462305.2
1081888
562

Escherichia coli 08BKT055439
08BKT055439
Proteobacteria
AVRI01000134.1


1428
GCA_000462325.2
1081895
562

Escherichia coli 08BKT77219
08BKT77219
Proteobacteria
AVRJ01000125.1


1429
GCA_000462345.2
1081894
562

Escherichia coli 09BKT024447
09BKT024447
Proteobacteria
AVRK01000010.1


1430
GCA_000462365.2
1081890
562

Escherichia coli Bd5610_99
Bd5610_99
Proteobacteria
AVRL01000137.1


1431
GCA_000462385.2
1081892
562

Escherichia coli T234_00
T234_00
Proteobacteria
AVRO01000124.1


1432
GCA_000462405.2
1151216
562

Escherichia coli B7-2
B7-2
Proteobacteria
AVRD01000050.1


1433
GCA_000462425.2
1151231
562

Escherichia coli B93
B93
Proteobacteria
AVRE01000046.1


1434
GCA_000462445.2
1151232
562

Escherichia coli B94
B94
Proteobacteria
AVRF01000052.1


1435
GCA_000462465.2
1151233
562

Escherichia coli B95
B95
Proteobacteria
AVRG01000053.1


1436
GCA_000462485.2
1151234
562

Escherichia coli B103
B103
Proteobacteria
AVRS01000001.1


1437
GCA_000462505.2
1151243
562

Escherichia coli B104
B104
Proteobacteria
AVRT01000005.1


1438
GCA_000462525.2
1151247
562

Escherichia coli B105
B105
Proteobacteria
AVRU01000005.1


1439
GCA_000462545.2
1151248
562

Escherichia coli B106
B106
Proteobacteria
AVRV01000001.1


1440
GCA_000462565.2
550673
562

Escherichia coli B108
B108
Proteobacteria
AVRW01000007.1


1441
GCA_000462585.2
1151244
562

Escherichia coli B109
B109
Proteobacteria
AVRX01000001.1


1442
GCA_000462605.2
1151249
562

Escherichia coli B112
B112
Proteobacteria
AVRY01000010.1


1443
GCA_000462625.2
1151250
562

Escherichia coli B113
B113
Proteobacteria
AVRZ01000133.1


1444
GCA_000462645.2
1151251
562

Escherichia coli B114
B114
Proteobacteria
AVSA01000001.1


1445
GCA_000462665.2
1151238
562

Escherichia coli B17
B17
Proteobacteria
AVSC01000121.1


1446
GCA_000462685.2
1151227
562

Escherichia coli B40-1
B40-1
Proteobacteria
AVSD01000010.1


1447
GCA_000462705.2
1151228
562

Escherichia coli B40-2
B40-2
Proteobacteria
AVSE01000003.1


1448
GCA_000462725.2
1151246
562

Escherichia coli B49-2
B49-2
Proteobacteria
AVSF01000006.1


1449
GCA_000462745.2
1151224
562

Escherichia coli B5-2
B5-2
Proteobacteria
AVSG01000001.1


1450
GCA_000462765.2
1151239
562

Escherichia coli B83
B83
Proteobacteria
AVSH01000001.1


1451
GCA_000462785.2
1151240
562

Escherichia coli B84
B84
Proteobacteria
AVSI01000012.1


1452
GCA_000462805.2
1151241
562

Escherichia coli B85
B85
Proteobacteria
AVSJ01000007.1


1453
GCA_000462825.2
1151242
562

Escherichia coli B86
B86
Proteobacteria
AVSK01000136.1


1454
GCA_000462845.2
1151235
562

Escherichia coli B89
B89
Proteobacteria
AVSL01000001.1


1455
GCA_000462865.2
1151236
562

Escherichia coli B90
B90
Proteobacteria
AVSM01000129.1


1456
GCA_000462885.2
1207037
562

Escherichia coli Tx1686
Tx1686
Proteobacteria
AVSN01000001.1


1457
GCA_000462905.2
1207036
562

Escherichia coli Tx3800
Tx3800
Proteobacteria
AVSO01000014.1


1458
GCA_000473725.2
1389955
562

Escherichia coli ATCC 35150
ATCC 35150
Proteobacteria
AWXM02000046.1


1459
GCA_000477495.2
1151218
562

Escherichia coli B28-2
B28-2
Proteobacteria
AVQX01000012.1


1460
GCA_000488355.1
1268982
562

Escherichia coli 907672
907672
Proteobacteria
KI531258.1


1461
GCA_000492235.1
1328450
562

Escherichia coli BIDMC 39
BIDMC 39
Proteobacteria
KI535383.1


1462
GCA_000494995.1
1281069
562

Escherichia coli HVH 136 (4-5970458)
HVH 136 (4-5970458)
Proteobacteria
KI538714.1


1463
GCA_000496345.2
1404261
562

Escherichia coli ATCC BAA-2192
ATCC BAA-2192
Proteobacteria
AYGW02000190.1


1464
GCA_000498255.1
1097579
562

Escherichia coli P4-96
P4-96
Proteobacteria
AHHO01000034.1


1465
GCA_000498275.1
1117111
562

Escherichia coli P4-NR
P4-NR
Proteobacteria
AHHP01000046.1


1466
GCA_000520035.1
1248902
562

Escherichia coli O145:H28 str. RM13514
RM13514
Proteobacteria
CP006027.1


1467
GCA_000601155.1
1444132
562

Escherichia coli 1-110-08_S3_C1
1-110-08_S3_C1
Proteobacteria
JHDN01000003.1


1468
GCA_000601175.1
1444160
562

Escherichia coli 1-110-08_S3_C2
1-110-08_S3_C2
Proteobacteria
JHDM01000091.1


1469
GCA_000601335.1
1444190
562

Escherichia coli 1-110-08_S3_C3
1-110-08_S3_C3
Proteobacteria
JHDL01000001.1


1470
GCA_000614085.2
1446647
562

Escherichia coli O157:H7 str. 2011EL-2288
2011EL-2288
Proteobacteria
JHKE01000007.1


1471
GCA_000614255.1
1446644
562

Escherichia coli O157:H7 str. 2011EL-2114
2011EL-2114
Proteobacteria
JHKH01000002.1


1472
GCA_000614305.2
1446645
562

Escherichia coli O157:H7 str. 2011EL-2286
2011EL-2286
Proteobacteria
JHKG01000013.1


1473
GCA_000614345.2
1446650
562

Escherichia coli O157:H7 str. 2011EL-2312
2011EL-2312
Proteobacteria
JHKB01000003.1


1474
GCA_000614405.2
1446646
562

Escherichia coli O157:H7 str. 2011EL-2287
2011EL-2287
Proteobacteria
JHKF01000001.1


1475
GCA_000614645.2
1446643
562

Escherichia coli O157:H7 str. 2011EL-2113
2011EL-2113
Proteobacteria
JHKI01000015.1


1476
GCA_000614685.2
1446648
562

Escherichia coli O157:H7 str. 2011EL-2289
2011EL-2289
Proteobacteria
JHKD01000001.1


1477
GCA_000614805.2
1446656
562

Escherichia coli O157:H7 str. F7350
F7350
Proteobacteria
JHJN01000036.1


1478
GCA_000614885.2
1446622
562

Escherichia coli O157:H7 str. 2010C-4979C1
2010C-4979C1
Proteobacteria
JHMK01000017.1


1479
GCA_000614965.1
1446619
562

Escherichia coli O157:H7 str. 2009EL1705
2009EL1705
Proteobacteria
JHGE01000007.1


1480
GCA_000615015.1
1446621
562

Escherichia coli O157:H7 str. 2009EL2109
2009EL2109
Proteobacteria
JHGC01000001.1


1481
GCA_000615085.1
1446587
562

Escherichia coli O145:NM str. 2010C-3507
2010C-3507
Proteobacteria
JHFW01000006.1


1482
GCA_000615145.1
1446589
562

Escherichia coli O145:NM str. 2010C-3509
2010C-3509
Proteobacteria
JHFU01000107.1


1483
GCA_000615175.1
1446590
562

Escherichia coli O145:NM str. 2010C-3510
2010C-3510
Proteobacteria
JHFT01000001.1


1484
GCA_000615225.2
1446591
562

Escherichia coli O145:NM str. 2010C-3511
2010C-3511
Proteobacteria
JHFS01000035.1


1485
GCA_000615265.1
1446592
562

Escherichia coli O145:NM str. 2010C-3516
2010C-3516
Proteobacteria
JHFR01000094.1


1486
GCA_000615305.1
1446593
562

Escherichia coli O145:NM str. 2010C-3517
2010C-3517
Proteobacteria
JHFQ01000117.1


1487
GCA_000615345.1
1446594
562

Escherichia coli O145:NM str. 2010C-3518
2010C-3518
Proteobacteria
JHFP01000105.1


1488
GCA_000615385.1
1446595
562

Escherichia coli O145:NM str. 2010C-3521
2010C-3521
Proteobacteria
JHFO01000022.1


1489
GCA_000615415.2
1446596
562

Escherichia coli O145:NM str. 2010C-3526
2010C-3526
Proteobacteria
JHFN01000018.1


1490
GCA_000615695.1
1446633
562

Escherichia coli O157:H7 str. 2011EL-2101
2011EL-2101
Proteobacteria
JHKS01000001.1


1491
GCA_000615745.2
1446634
562

Escherichia coli O157:H7 str. 2011EL-2103
2011EL-2103
Proteobacteria
JHKR01000031.1


1492
GCA_000615785.2
1446635
562

Escherichia coli O157:H7 str. 2011EL-2104
2011EL-2104
Proteobacteria
JHKQ01000016.1


1493
GCA_000615815.2
1446636
562

Escherichia coli O157:H7 str. 2011EL-2105
2011EL-2105
Proteobacteria
JHKP01000014.1


1494
GCA_000615865.2
1446637
562

Escherichia coli O157:H7 str. 2011EL-2106
2011EL-2106
Proteobacteria
JHKO01000009.1


1495
GCA_000615925.2
1446638
562

Escherichia coli O157:H7 str. 2011EL-2107
2011EL-2107
Proteobacteria
JHKN01000006.1


1496
GCA_000615965.2
1446639
562

Escherichia coli O157:H7 str. 2011EL-2108
2011EL-2108
Proteobacteria
JHKM01000031.1


1497
GCA_000616005.2
1446640
562

Escherichia coli O157:H7 str. 2011EL-2109
2011EL-2109
Proteobacteria
JHKL01000015.1


1498
GCA_000616035.2
1446641
562

Escherichia coli O157:H7 str. 2011EL-2111
2011EL-2111
Proteobacteria
JHKK01000003.1


1499
GCA_000616075.2
1446642
562

Escherichia coli O157:H7 str. 2011EL-2112
2011EL-2112
Proteobacteria
JHKJ01000005.1


1500
GCA_000616365.1
1446623
562

Escherichia coli O157:H7 str. 2011EL-1107
2011EL-1107
Proteobacteria
JHLK01000001.1


1501
GCA_000616405.2
1446624
562

Escherichia coli O157:H7 str. 2011EL-2090
2011EL-2090
Proteobacteria
JHLI01000033.1


1502
GCA_000616425.2
1446625
562

Escherichia coli O157:H7 str. 2011EL-2091
2011EL-2091
Proteobacteria
JHLH01000026.1


1503
GCA_000616445.2
1446626
562

Escherichia coli O157:H7 str. 2011EL-2092
2011EL-2092
Proteobacteria
JHLG01000030.1


1504
GCA_000616465.2
1446627
562

Escherichia coli O157:H7 str. 2011EL-2093
2011EL-2093
Proteobacteria
JHLF01000012.1


1505
GCA_000616485.2
1446628
562

Escherichia coli O157:H7 str. 2011EL-2094
2011EL-2094
Proteobacteria
JHLE01000001.1


1506
GCA_000616505.2
1446629
562

Escherichia coli O157:H7 str. 2011EL-2096
2011EL-2096
Proteobacteria
JHLD01000033.1


1507
GCA_000616525.2
1446630
562

Escherichia coli O157:H7 str. 2011EL-2097
2011EL-2097
Proteobacteria
JHLC01000005.1


1508
GCA_000616545.2
1446631
562

Escherichia coli O157:H7 str. 2011EL-2098
2011EL-2098
Proteobacteria
JHLB01000003.1


1509
GCA_000616585.2
1446613
562

Escherichia coli O157:H7 str. 08-3037
08-3037
Proteobacteria
JHKZ01000011.1


1510
GCA_000616605.2
1446614
562

Escherichia coli O157:H7 str. 08-3527
08-3527
Proteobacteria
JHKY01000032.1


1511
GCA_000616645.2
1446615
562

Escherichia coli O157:H7 str. 08-4169
08-4169
Proteobacteria
JHKW01000004.1


1512
GCA_000616665.2
1446586
562

Escherichia coli O145:NM str. 08-4270
08-4270
Proteobacteria
JHKV01000030.1


1513
GCA_000616705.2
1446632
562

Escherichia coli O157:H7 str. 2011EL-2099
2011EL-2099
Proteobacteria
JHKT01000015.1


1514
GCA_000616745.1
1446692
562

Escherichia coli O157:H7 str. K5806
K5806
Proteobacteria
JHHZ01000001.1


1515
GCA_000617345.1
1446585
562

Escherichia coli O145:NM str. 06-3484
06-3484
Proteobacteria
JHNN01000002.1


1516
GCA_000617385.1
1446745
562

Escherichia coli O55:H7 str. 06-3555
06-3555
Proteobacteria
JHNL01000009.1


1517
GCA_000617445.2
1446609
562

Escherichia coli O157:H7 str. 06-3745
06-3745
Proteobacteria
JHNI01000020.1


1518
GCA_000617665.2
1446611
562

Escherichia coli O157:H7 str. 07-3091
07-3091
Proteobacteria
JHNF01000007.1


1519
GCA_000617705.2
1446610
562

Escherichia coli O157:H7 str. 06-4039
06-4039
Proteobacteria
JHNG01000005.1


1520
GCA_000617725.2
1446612
562

Escherichia coli O157:H7 str. 07-3391
07-3391
Proteobacteria
JHNE01000001.1


1521
GCA_000617765.2
1446597
562

Escherichia coli O145:NM str. 2010C-4557C2
2010C-4557C2
Proteobacteria
JHNA01000067.1


1522
GCA_000617965.1
1446680
562

Escherichia coli O157:H7 str. K4405
K4405
Proteobacteria
JHIN01000100.1


1523
GCA_000618025.1
1446663
562

Escherichia coli O157:H7 str. K1420
K1420
Proteobacteria
JHJF01000008.1


1524
GCA_000618045.1
1446653
562

Escherichia coli O157:H7 str. F6749
F6749
Proteobacteria
JHJQ01000001.1


1525
GCA_000618065.2
1446658
562

Escherichia coli O157:H7 str. F7384
F7384
Proteobacteria
JHJL01000002.1


1526
GCA_000618105.2
1446652
562

Escherichia coli O157:H7 str. F6142
F6142
Proteobacteria
JHJT01000009.1


1527
GCA_000618185.1
1446660
562

Escherichia coli O157:H7 str. G5303
G5303
Proteobacteria
JHJI01000027.1


1528
GCA_000618225.2
1446657
562

Escherichia coli O157:H7 str. F7377
F7377
Proteobacteria
JHJM01000002.1


1529
GCA_000618245.1
1446661
562

Escherichia coli O157:H7 str. H2495
H2495
Proteobacteria
JHJH01000020.1


1530
GCA_000618265.2
1446655
562

Escherichia coli O157:H7 str. F6751
F6751
Proteobacteria
JHJO01000004.1


1531
GCA_000618285.2
1446662
562

Escherichia coli O157:H7 str. H2498
H2498
Proteobacteria
JHJG01000003.1


1532
GCA_000618305.2
1446654
562

Escherichia coli O157:H7 str. F6750
F6750
Proteobacteria
JHJP01000010.1


1533
GCA_000618325.1
1446667
562

Escherichia coli O157:H7 str. K1796
K1796
Proteobacteria
JHJA01000003.1


1534
GCA_000618345.1
1446668
562

Escherichia coli O157:H7 str. K1845
K1845
Proteobacteria
JHIZ01000038.1


1535
GCA_000618385.1
1446666
562

Escherichia coli O157:H7 str. K1795
K1795
Proteobacteria
JHJB01000012.1


1536
GCA_000618445.1
1446669
562

Escherichia coli O157:H7 str. K1921
K1921
Proteobacteria
JHIY01000012.1


1537
GCA_000618465.1
1446670
562

Escherichia coli O157:H7 str. K1927
K1927
Proteobacteria
JHIX01000108.1


1538
GCA_000618485.1
1446671
562

Escherichia coli O157:H7 str. K2188
K2188
Proteobacteria
JHIW01000103.1


1539
GCA_000618505.1
1446672
562

Escherichia coli O157:H7 str. K2191
K2191
Proteobacteria
JHIV01000063.1


1540
GCA_000618525.1
1446675
562

Escherichia coli O157:H7 str. K2581
K2581
Proteobacteria
JHIS01000013.1


1541
GCA_000618545.1
1446676
562

Escherichia coli O157:H7 str. K2622
K2622
Proteobacteria
JHIR01000010.1


1542
GCA_000618565.1
1446677
562

Escherichia coli O157:H7 str. K2845
K2845
Proteobacteria
JHIQ01000033.1


1543
GCA_000618585.1
1446678
562

Escherichia coli O157:H7 str. K2854
K2854
Proteobacteria
JHIP01000003.1


1544
GCA_000618605.1
1446679
562

Escherichia coli O157:H7 str. K4396
K4396
Proteobacteria
JHIO01000002.1


1545
GCA_000618625.1
1446681
562

Escherichia coli O157:H7 str. K4406
K4406
Proteobacteria
JHIM01000001.1


1546
GCA_000618665.1
1446674
562

Escherichia coli O157:H7 str. K2324
K2324
Proteobacteria
JHIT01000105.1


1547
GCA_000618685.1
1446682
562

Escherichia coli O157:H7 str. K4527
K4527
Proteobacteria
JHIL01000001.1


1548
GCA_000618745.1
1446683
562

Escherichia coli O157:H7 str. K5418
K5418
Proteobacteria
JHII01000001.1


1549
GCA_000618765.1
1446684
562

Escherichia coli O157:H7 str. K5448
K5448
Proteobacteria
JHIH01000007.1


1550
GCA_000618785.1
1446685
562

Escherichia coli O157:H7 str. K5449
K5449
Proteobacteria
JHIG01000002.1


1551
GCA_000618805.1
1446686
562

Escherichia coli O157:H7 str. K5453
K5453
Proteobacteria
JHIF01000066.1


1552
GCA_000618825.1
1446688
562

Escherichia coli O157:H7 str. K5467
K5467
Proteobacteria
JHID01000001.1


1553
GCA_000618845.1
1446689
562

Escherichia coli O157:H7 str. K5602
K5602
Proteobacteria
JHIC01000015.1


1554
GCA_000618865.1
1446690
562

Escherichia coli O157:H7 str. K5607
K5607
Proteobacteria
JHIB01000088.1


1555
GCA_000618885.1
1446687
562

Escherichia coli O157:H7 str. K5460
K5460
Proteobacteria
JHIE01000002.1


1556
GCA_000618925.2
1446697
562

Escherichia coli O157:H7 str. K7140
K7140
Proteobacteria
JHHK01000016.1


1557
GCA_000618945.2
1446649
562

Escherichia coli O157:H7 str. 2011EL-2290
2011EL-2290
Proteobacteria
JHKC01000008.1


1558
GCA_000618985.2
1446651
562

Escherichia coli O157:H7 str. 2011EL-2313
2011EL-2313
Proteobacteria
JHKA01000028.1


1559
GCA_000619045.2
1446617
562

Escherichia coli O157:H7 str. 2009C-4258
2009C-4258
Proteobacteria
JHGQ01000007.1


1560
GCA_000619145.1
1446618
562

Escherichia coli O157:H7 str. 2009EL1449
2009EL1449
Proteobacteria
JHGF01000005.1


1561
GCA_000619165.1
1446620
562

Escherichia coli O157:H7 str. 2009EL1913
2009EL1913
Proteobacteria
JHGD01000001.1


1562
GCA_000619185.1
1446588
562

Escherichia coli O145:NM str. 2010C-3508
2010C-3508
Proteobacteria
JHFV01000110.1


1563
GCA_000619365.1
1446693
562

Escherichia coli O157:H7 str. K5852
K5852
Proteobacteria
JHHY01000003.1


1564
GCA_000619385.1
1446694
562

Escherichia coli O157:H7 str. K6590
K6590
Proteobacteria
JHHX01000008.1


1565
GCA_000619405.1
1446695
562

Escherichia coli O157:H7 str. K6676
K6676
Proteobacteria
JHHW01000001.1


1566
GCA_000619425.1
1446696
562

Escherichia coli O157:H7 str. K6687
K6687
Proteobacteria
JHHV01000121.1


1567
GCA_000619445.1
1446691
562

Escherichia coli O157:H7 str. K5609
K5609
Proteobacteria
JHIA01000021.1


1568
GCA_000619665.1
1446616
562

Escherichia coli O157:H7 str. 08-4529
08-4529
Proteobacteria
JHHI01000009.1


1569
GCA_000619685.2
1446698
562

Escherichia coli O157:NM str. 08-4540
08-4540
Proteobacteria
JHHH01000020.1


1570
GCA_000627435.1
1444135
562

Escherichia coli 1-250-04_S3_C1
1-250-04_S3_C1
Proteobacteria
JJLU01000053.1


1571
GCA_000627455.1
1444162
562

Escherichia coli 1-182-04_S3_C2
1-182-04_S3_C2
Proteobacteria
JJLT01000250.1


1572
GCA_000627475.1
1444191
562

Escherichia coli 1-182-04_S3_C3
1-182-04_S3_C3
Proteobacteria
JJLS01000230.1


1573
GCA_000627965.1
1444134
562

Escherichia coli 1-182-04_S3_C1
1-182-04_S3_C1
Proteobacteria
JJLV01000176.1


1574
GCA_000632555.1
1446606
562

Escherichia coli O157: str. 2010EL-2044
2010EL-2044
Proteobacteria
JHME01000103.1


1575
GCA_000632655.1
1446607
562

Escherichia coli O157: str. 2010EL-2045
2010EL-2045
Proteobacteria
JHMD01000001.1


1576
GCA_000671295.1
1248823
562

Escherichia coli O145:H28 str. RM12581
RM12581
Proteobacteria
CP007136.1


1577
GCA_000687105.1
1444147
562

Escherichia coli 2-005-03_S3_C2
2-005-03_S3_C2
Proteobacteria
JMGT01000075.1


1578
GCA_000687125.1
1444037
562

Escherichia coli 2-011-08_S1_C1
2-011-08_S1_C1
Proteobacteria
JMGQ01000091.1


1579
GCA_000695155.1
1078035
562

Escherichia coli O145:H28 str. 4865/96
4865/96
Proteobacteria
JHEY01000012.1


1580
GCA_000695175.1
562
562

Escherichia coli

MI10-01
Proteobacteria
JHEZ01000002.1


1581
GCA_000700285.1
1444059
562

Escherichia coli 3-475-03_S1_C1
3-475-03_S1_C1
Proteobacteria
JNMJ01000048.1


1582
GCA_000704005.1
1444151
562

Escherichia coli 2-177-06_S3_C2
2-177-06_S3_C2
Proteobacteria
JNQF01000030.1


1583
GCA_000711415.1
1444071
562

Escherichia coli 2-316-03_S1_C2
2-316-03_S1_C2
Proteobacteria
JOMX01000159.1


1584
GCA_000711475.1
1444042
562

Escherichia coli 2-316-03_S1_C1
2-316-03_S1_C1
Proteobacteria
JOMW01000194.1


1585
GCA_000713175.1
1444281
562

Escherichia coli 6-175-07_S4_C3
6-175-07_S4_C3
Proteobacteria
JORK01000060.1


1586
GCA_000713255.1
1444227
562

Escherichia coli 6-537-08_S4_C1
6-537-08_S4_C1
Proteobacteria
JORS01000112.1


1587
GCA_000713605.1
1444257
562

Escherichia coli 6-537-08_S4_C2
6-537-08_S4_C2
Proteobacteria
JOSG01000027.1


1588
GCA_000713745.1
1444179
562

Escherichia coli 2-177-06_S3_C3
2-177-06_S3_C3
Proteobacteria
JOSO01000008.1


1589
GCA_000713815.1
1444163
562

Escherichia coli 1-250-04_S3_C2
1-250-04_S3_C2
Proteobacteria
JOSR01000197.1


1590
GCA_000713905.1
1444087
562

Escherichia coli 3-475-03_S1_C2
3-475-03_S1_C2
Proteobacteria
JOQC01000025.1


1591
GCA_000713985.1
1444196
562

Escherichia coli 4-203-08_S3_C3
4-203-08_S3_C3
Proteobacteria
JOQH01000040.1


1592
GCA_000714055.1
1444171
562

Escherichia coli 4-203-08_S3_C2
4-203-08_S3_C2
Proteobacteria
JOQK01000042.1


1593
GCA_000714385.1
1444226
562

Escherichia coli 6-175-07_S4_C1
6-175-07_S4_C1
Proteobacteria
JORB01000108.1


1594
GCA_000714415.1
1444255
562

Escherichia coli 6-175-07_S4_C2
6-175-07_S4_C2
Proteobacteria
JORC01000054.1


1595
GCA_000730345.1
1328859
562

Escherichia coli O157:H7 str. SS17
SS17
Proteobacteria
CP008805.1


1596
GCA_000732965.1
155864
562

Escherichia coli O157:H7 str. EDL933
EDL933
Proteobacteria
CP008957.1


1597
GCA_000797775.1
562
562

Escherichia coli

CVM N34322PS
Proteobacteria
JUCY01000038.1


1598
GCA_000798235.1
562
562

Escherichia coli

CVM N36834PS
Proteobacteria
JUCF01000078.1


1599
GCA_000798415.1
562
562

Escherichia coli

CVM N34557PS
Proteobacteria
JUCU01000037.1


1600
GCA_000803705.1
1330457
562

Escherichia coli O157:H7 str. SS52
SS52
Proteobacteria
CP010304.1


1601
GCA_000819265.1
562
562

Escherichia coli

CVM N38428PS
Proteobacteria
JWYX01000074.1


1602
GCA_000934865.1
562
562

Escherichia coli

ATCC 35150
Proteobacteria
JXUS01000117.1


1603
GCA_000935075.1
562
562

Escherichia coli

ATCC 35150 NalR
Proteobacteria
JYIO01000082.1


1604
GCA_000953765.1
562
562

Escherichia coli

MCI_507
Proteobacteria
JZSD01000085.1


1605
GCA_000965565.1
562
562

Escherichia coli

St. Olav172
Proteobacteria
JZDY01000017.1


1606
GCA_000965655.1
562
562

Escherichia coli

St. Olav173
Proteobacteria
JZDZ01000061.1


1607
GCA_000978815.1
83334
562

Escherichia coli O157:H7
7.1_Anguil
Proteobacteria
LAZD01000130.1


1608
GCA_000978845.1
83334
562

Escherichia coli O157:H7
Rafaela_II
Proteobacteria
LAYW01000314.1


1609
GCA_000986635.1
562
562

Escherichia coli

C1-057
Proteobacteria
LAZO01000001.1


1610
GCA_001006425.1
83334
562

Escherichia coli O157:H7
HB74
Proteobacteria
LCWU01000234.1


1611
GCA_001012075.1
562
562

Escherichia coli

CFSAN026805
Proteobacteria
LDCU01000029.1


1612
GCA_001191125.1
562
562

Escherichia coli

CFSAN026804
Proteobacteria
LGZD01000035.1


1613
GCA_001191185.1
562
562

Escherichia coli

CFSAN026847
Proteobacteria
LGZE01000020.1


1614
GCA_001191195.1
562
562

Escherichia coli

CFSAN026846
Proteobacteria
LGZI01000146.1


1615
GCA_001191525.1
562
562

Escherichia coli

CFSAN026848
Proteobacteria
LHAB01000019.1


1616
GCA_001277695.1
562
562

Escherichia coli

503225_aEPEC
Proteobacteria
CYAV01000099.1


1617
GCA_001281685.1
562
562

Escherichia coli

STEC 771
Proteobacteria
LGAZ01000005.1


1618
GCA_001281725.1
562
562

Escherichia coli

STEC 2868
Proteobacteria
LGBJ01000009.1


1619
GCA_001281755.1
562
562

Escherichia coli

E09/224
Proteobacteria
LGBP01000024.1


1620
GCA_001281775.1
562
562

Escherichia coli

STEC 989
Proteobacteria
LGBA01000013.1


1621
GCA_001281795.1
562
562

Escherichia coli

STEC 994
Proteobacteria
LGBB01000045.1


1622
GCA_001281815.1
562
562

Escherichia coli

STEC 1109
Proteobacteria
LGBC01000012.1


1623
GCA_001281845.1
562
562

Escherichia coli

STEC 2075
Proteobacteria
LGBD01000011.1


1624
GCA_001281855.1
562
562

Escherichia coli

STEC 2112
Proteobacteria
LGBE01000001.1


1625
GCA_001281885.1
562
562

Escherichia coli

STEC 2257
Proteobacteria
LGBF01000023.1


1626
GCA_001281905.1
562
562

Escherichia coli

STEC 2410
Proteobacteria
LGBG01000006.1


1627
GCA_001281915.1
562
562

Escherichia coli

STEC 2821
Proteobacteria
LGBI01000140.1


1628
GCA_001281925.1
562
562

Escherichia coli

STEC 2667
Proteobacteria
LGBH01000007.1


1629
GCA_001281965.1
562
562

Escherichia coli

E09/10
Proteobacteria
LGBK01000008.1


1630
GCA_001281985.1
562
562

Escherichia coli

EPEC 287
Proteobacteria
LGBL01000025.1


1631
GCA_001281995.1
562
562

Escherichia coli

EPEC 393
Proteobacteria
LGBM01000019.1


1632
GCA_001282025.1
562
562

Escherichia coli

EPEC 1572
Proteobacteria
LGBN01000001.1


1633
GCA_001282035.1
562
562

Escherichia coli

EPEC 1669
Proteobacteria
LGBO01000067.1


1634
GCA_001282065.1
562
562

Escherichia coli

STEC 2820
Proteobacteria
LGBQ01000003.1


1635
GCA_001297975.1
562
562

Escherichia coli

STEC 343
Proteobacteria
LDOZ01000007.1


1636
GCA_001297985.1
562
562

Escherichia coli

STEC 623
Proteobacteria
LFUB01000011.1


1637
GCA_001297995.1
562
562

Escherichia coli

STEC 605
Proteobacteria
LFUA01000020.1


1638
GCA_001307215.1
83334
562

Escherichia coli O157:H7
WS4202
Proteobacteria
CP012802.1


1639
GCA_001309715.1
562
562

Escherichia coli

PARC447
Proteobacteria
LECJ01000192.1


1640
GCA_001309815.1
562
562

Escherichia coli

03-6430
Proteobacteria
LEAB01000117.1


1641
GCA_001309835.1
562
562

Escherichia coli

PARC449
Proteobacteria
LEAC01000125.1


1642
GCA_001309885.1
562
562

Escherichia coli

CO6CE900
Proteobacteria
LEAE01000148.1


1643
GCA_001309895.1
562
562

Escherichia coli

CO6CE1353
Proteobacteria
LEAF01000141.1


1644
GCA_001309905.1
562
562

Escherichia coli

CO6CE1943
Proteobacteria
LEAG01000046.1


1645
GCA_001309925.1
562
562

Escherichia coli

CO6CE2940
Proteobacteria
LEAH01000084.1


1646
GCA_001309965.1
562
562

Escherichia coli

CO283
Proteobacteria
LEAI01000013.1


1647
GCA_001309985.1
562
562

Escherichia coli

1935
Proteobacteria
LEAD01000163.1


1648
GCA_001309995.1
562
562

Escherichia coli

E0122
Proteobacteria
LEAJ01000145.1


1649
GCA_001310005.1
562
562

Escherichia coli

LCDC7236
Proteobacteria
LEAK01000079.1


1650
GCA_001440045.1
83334
562

Escherichia coli O157:H7
G10
Proteobacteria
LMXL01000097.1


1651
GCA_001484305.1
562
562

Escherichia coli

AY63
Proteobacteria
LLYF01000048.1


1652
GCA_001484355.1
562
562

Escherichia coli

AY71
Proteobacteria
LLYJ01000063.1


1653
GCA_001519775.1
562
562

Escherichia coli

GN02140
Proteobacteria
LQSF01000099.1


1654
GCA_001519815.1
562
562

Escherichia coli

GN02298
Proteobacteria
LQSX01000125.1


1655
GCA_001519835.1
562
562

Escherichia coli

GN02290
Proteobacteria
LQSW01000169.1


1656
GCA_001520115.1
562
562

Escherichia coli

GN02343
Proteobacteria
LQTC01000029.1


1657
GCA_001520235.1
562
562

Escherichia coli

GN02514
Proteobacteria
LQUF01000146.1


1658
GCA_001520275.1
562
562

Escherichia coli

GN02359
Proteobacteria
LQTG01000260.1


1659
GCA_001520435.1
562
562

Escherichia coli

GN02430
Proteobacteria
LQTU01000172.1


1660
GCA_001520495.1
562
562

Escherichia coli

GN02426
Proteobacteria
LQTS01000163.1


1661
GCA_001520575.1
562
562

Escherichia coli

GN02674
Proteobacteria
LQVA01000248.1


1662
GCA_001520835.1
562
562

Escherichia coli

GN02707
Proteobacteria
LQVE01000001.1


1663
GCA_001520935.1
562
562

Escherichia coli

GN03218
Proteobacteria
LQVQ01000300.1


1664
GCA_001520995.1
562
562

Escherichia coli

GN02953
Proteobacteria
LQVM01000164.1


1665
GCA_001558995.1
562
562

Escherichia coli

JEONG-1266
Proteobacteria
CP014314.1


1666
GCA_001571675.1
562
562

Escherichia coli

UC5
Proteobacteria
LRXT01000038.1


1667
GCA_001575305.1
562
562

Escherichia coli

G19
Proteobacteria
LONY01000024.1


1668
GCA_001576035.1
562
562

Escherichia coli

G27
Proteobacteria
LOOY01000033.1


1669
GCA_001576325.1
562
562

Escherichia coli

G28
Proteobacteria
LOOZ01000046.1


1670
GCA_000607265.1
1409787
571

Klebsiella oxytoca G54
G54
Proteobacteria
KK097710.1


1671
GCA_001078255.1
883124
571

Klebsiella oxytoca 10-5249
10-5249
Proteobacteria
KQ235791.1


1672
GCA_000493135.1
1328363
573

Klebsiella pneumoniae MGH 18
MGH 18
Proteobacteria
KI535680.1


1673
GCA_000694715.1
1438797
573

Klebsiella pneumoniae MGH 74
MGH 74
Proteobacteria
KK737643.1


1674
GCA_001033505.1
573
573

Klebsiella pneumoniae

MGH84
Proteobacteria
KQ089360.1


1675
GCA_001441285.1
573
573

Klebsiella pneumoniae

B86
Proteobacteria
UCD01000021.1


1676
GCA_001536385.1
615
615

Serratia marcescens

2880STDY5682927
Proteobacteria
FCJI01000002.1


1677
GCA_001536405.1
615
615

Serratia marcescens

2880STDY5682928
Proteobacteria
FCJJ01000003.1


1678
GCA_001536505.1
615
615

Serratia marcescens

2880STDY5682857
Proteobacteria
FCHL01000002.1


1679
GCA_001536765.1
615
615

Serratia marcescens

2880STDY5682859
Proteobacteria
FCHI01000002.1


1680
GCA_001536965.1
615
615

Serratia marcescens

2880STDY5682942
Proteobacteria
FCJX01000002.1


1681
GCA_001537105.1
615
615

Serratia marcescens

2880STDY5683024
Proteobacteria
FCGC01000003.1


1682
GCA_001537305.1
615
615

Serratia marcescens

2880STDY5682930
Proteobacteria
FCML01000002.1


1683
GCA_001538765.1
615
615

Serratia marcescens

2880STDY5682826
Proteobacteria
FCGQ01000002.1


1684
GCA_001538825.1
615
615

Serratia marcescens

2880STDY5682883
Proteobacteria
FCIK01000002.1


1685
GCA_001539245.1
615
615

Serratia marcescens

2880STDY5682921
Proteobacteria
FCJF01000002.1


1686
GCA_001539385.1
615
615

Serratia marcescens

2880STDY5682913
Proteobacteria
FCIZ01000003.1


1687
GCA_001539425.1
615
615

Serratia marcescens

2880STDY5682877
Proteobacteria
FCIC01000003.1


1688
GCA_001539605.1
615
615

Serratia marcescens

2880STDY5682984
Proteobacteria
FCLJ01000003.1


1689
GCA_001539765.1
615
615

Serratia marcescens

2880STDY5682858
Proteobacteria
FCHM01000002.1


1690
GCA_001539905.1
615
615

Serratia marcescens

2880STDY5682961
Proteobacteria
FCKL01000002.1


1691
GCA_001540085.1
615
615

Serratia marcescens

2880STDY5682925
Proteobacteria
FCMJ01000002.1


1692
GCA_001540185.1
615
615

Serratia marcescens

2880STDY5682832
Proteobacteria
FCGT01000003.1


1693
GCA_001220145.1
630
630

Yersinia enterocolitica

YE38/03
Proteobacteria
CTKL01000007.1


1694
GCA_001116865.1
631
631

Yersinia intermedia

58735
Proteobacteria
CQER01000002.1


1695
GCA_001010935.1
663
663

Vibrio alginolyticus

V2
Proteobacteria
LCSG01000013.1


1696
GCA_001262735.1
669
669

Vibrio harveyi

VH2
Proteobacteria
LGYS01000041.1


1697
GCA_001471575.1
669
669

Vibrio harveyi

LMG 4044
Proteobacteria
LOSK01000001.1


1698
GCA_000707125.1
670
670

Vibrio parahaemolyticus

CFSAN007445
Proteobacteria
JNTC01000018.1


1699
GCA_000786865.1
670
670

Vibrio parahaemolyticus

09.5357
Proteobacteria
JTGT01000603.1


1700
GCA_000877715.1
1288794
670

Vibrio parahaemolyticus EN9701072
EN9701072
Proteobacteria
AOPI01000067.1


1701
GCA_000877755.1
1288789
670

Vibrio parahaemolyticus 3644
3644
Proteobacteria
AOPD01000386.1


1702
GCA_000960655.1
670
670

Vibrio parahaemolyticus

09-3217
Proteobacteria
JZAQ01000061.1


1703
GCA_001006195.1
670
670

Vibrio parahaemolyticus

10-4255
Proteobacteria
JYJT01000016.1


1704
GCA_001268045.1
670
670

Vibrio parahaemolyticus

S456-5
Proteobacteria
LFWN01000091.1


1705
GCA_001270155.1
670
670

Vibrio parahaemolyticus

S439-9
Proteobacteria
LFZA01000015.1


1706
GCA_001273575.1
670
670

Vibrio parahaemolyticus

ISF-29-3
Proteobacteria
LFYM01000016.1


1707
GCA_001559805.1
670
670

Vibrio parahaemolyticus

A4EZ700
Proteobacteria
LOBT01000012.1


1708
GCA_001595575.1
670
670

Vibrio parahaemolyticus

A4EZ724
Proteobacteria
LOHO01000038.1


1709
GCA_000338875.1
1259812
674

Vibrio mimicus CAIM 602
CAIM 602
Proteobacteria
AOMO01000034.1


1710
GCA_000154025.1
410291
680

Vibrio campbellii HY01
HY01
Proteobacteria
DS179487.1


1711
GCA_000178495.1
228399
715

Actinobacillus pleuropneumoniae serovar 1 str. 4074
4074
Proteobacteria
ADOD01000018.1


1712
GCA_000178575.1
754258
715

Actinobacillus pleuropneumoniae serovar 9 str. CVJ13261
CVJ13261
Proteobacteria
ADOI01000037.1


1713
GCA_000178615.1
754260
715

Actinobacillus pleuropneumoniae serovar 11 str. 56153
56153
Proteobacteria
ADOK01000019.1


1714
GCA_000011785.1
205914
731

Haemophilus somnus 129PT
129PT
Proteobacteria
CP000436.1


1715
GCA_000598725.1
1339306
817

Bacteroides fragilis str. 3719 T6
3719 T6
Bacteroidetes
JGEH01000041.1


1716
GCA_000598745.1
1339324
817

Bacteroides fragilis str. S24L26
S24L26
Bacteroidetes
JGEN01000046.1


1717
GCA_000599005.1
1339323
817

Bacteroides fragilis str. S24L15
S24L15
Bacteroidetes
JGEM01000110.1


1718
GCA_000599325.1
1339325
817

Bacteroides fragilis str. S24L34
S24L34
Bacteroidetes
JGEO01000038.1


1719
GCA_001286525.1
817
817

Bacteroides fragilis

BE1
Bacteroidetes
LN877293.1


1720
GCA_000699745.1
1339341
823

Parabacteroides distasonis str. 3776 Po2 i
3776 Po2 i
Bacteroidetes
JNHL01000154.1


1721
GCA_000699785.1
1339342
823

Parabacteroides distasonis str. 3776 D15 i
3776 D15 i
Bacteroidetes
JNHK01000087.1


1722
GCA_000699805.1
1339343
823

Parabacteroides distasonis str. 3776 D15 iv
3776 D15 iv
Bacteroidetes
JNHU01000002.1


1723
GCA_001296085.1
76859
851

Fusobacterium nucleatum subsp. animalis
KCOM 1279
Fusobacteria
CP012713.1


1724
GCA_001546435.1
851
851

Fusobacterium nucleatum

MJR7757B
Fusobacteria
KQ956653.1


1725
GCA_000163935.1
469621
860

Fusobacterium periodonticum 1_1_41FAA
1_1_41FAA
Fusobacteria
GG770381.1


1726
GCA_000143225.1
757424
964

Herbaspirillum seropedicae SmR1
SmR1
Proteobacteria
CP002039.1


1727
GCA_001467505.1
28083
28083

Legionella birminghamensis

CDC#1407-AL-14
Proteobacteria
LNXT01000030.1


1728
GCA_000300175.1
1004787
28108

Alteromonas macleodii str. ‘Balearic Sea AD45’
Balearic Sea AD45
Proteobacteria
CP003873.1


1729
GCA_000176155.1
675813
28172

Vibrio metschnikovii CIP 69.14
CIP 69.14
Proteobacteria
ACZO01000003.1


1730
GCA_000723805.1
1238449
28173

Vibrio nigripulchritudo SO65
SO65
Proteobacteria
LK391963.1


1731
GCA_001050595.1
1238430
28173

Vibrio nigripulchritudo AM115
AM115
Proteobacteria
CANT01000061.1


1732
GCA_001050655.1
1238441
28173

Vibrio nigripulchritudo FTn2
FTn2
Proteobacteria
CANW01000040.1


1733
GCA_001050675.1
1238445
28173

Vibrio nigripulchritudo Pon4
Pon4
Proteobacteria
CAOA01000095.1


1734
GCA_000764185.1
28229
28229

Colwellia psychrerythraea

GAB14E
Proteobacteria
JQEC01000001.1


1735
GCA_000182585.2
536230
28450

Burkholderia pseudomallei MSHR346
MSHR346
Proteobacteria
ACOJ01000001.1


1736
GCA_000756105.1
28450
28450

Burkholderia pseudomallei

MSHR346
Proteobacteria
CP008763.1


1737
GCA_000757105.1
28450
28450

Burkholderia pseudomallei

BDT
Proteobacteria
KN150939.1


1738
GCA_000770435.1
1437000
28450

Burkholderia pseudomallei MSHR1153
MSHR1153
Proteobacteria
CP009272.1


1739
GCA_000774165.1
1435990
28450

Burkholderia pseudomallei MSHR543
MSHR543
Proteobacteria
KN322990.1


1740
GCA_000774325.1
1434206
28450

Burkholderia pseudomallei MSHR4503
MSHR4503
Proteobacteria
KN323005.1


1741
GCA_000774385.1
1434192
28450

Burkholderia pseudomallei MSHR3951
MSHR3951
Proteobacteria
KN323013.1


1742
GCA_000774475.1
1434927
28450

Burkholderia pseudomallei MSHR3964
MSHR3964
Proteobacteria
KN323023.1


1743
GCA_000774575.1
1434203
28450

Burkholderia pseudomallei MSHR3960
MSHR3960
Proteobacteria
KN323029.1


1744
GCA_000775095.1
1439861
28450

Burkholderia pseudomallei TSV5
TSV5
Proteobacteria
JQGY01000129.1


1745
GCA_000775105.1
1439859
28450

Burkholderia pseudomallei TSV32
TSV32
Proteobacteria
JQHT01000033.1


1746
GCA_000959185.1
1249475
28450

Burkholderia pseudomallei MSHR840
MSHR840
Proteobacteria
CP009474.1


1747
GCA_000696465.1
29471
29471

Pectobacterium atrosepticum

JG10-08
Proteobacteria
CP007744.1


1748
GCA_000740965.1
29471
29471

Pectobacterium atrosepticum

21A
Proteobacteria
CP009125.1


1749
GCA_001038685.1
1076138
29471

Pectobacterium atrosepticum ICMP 1526
ICMP 1526
Proteobacteria
ALIV01000021.1


1750
GCA_000764325.1
29495
29495

Vibrio navarrensis

ATCC 51183
Proteobacteria
JMCG01000001.1


1751
GCA_000153205.1
314278
35797

Nitrococcus mobilis Nb-231
Nb-231
Proteobacteria
CH672427.1


1752
GCA_000238375.3
1117314
43655

Pseudoalteromonas citrea DSM 8771
NCIMB 1889
Proteobacteria
AHBZ02000108.1


1753
GCA_000238375.3
1117314
43655

Pseudoalteromonas citrea DSM 8771
NCIMB 1889
Proteobacteria
AHBZ02000100.1


1754
GCA_000238315.3
1117317
43662

Pseudoalteromonas piscicida JCM 20779
JCM 20779
Proteobacteria
AHCC02000002.1


1755
GCA_001467795.1
45067
45067

Legionella lansingensis

ATCC 49751
Proteobacteria
LNYI01000004.1


1756
GCA_000175195.1
637911
51047

Actinobacillus minor NM305
NM305
Proteobacteria
ACQL01000154.1


1757
GCA_000807415.4
61645
61645

Enterobacter asburiae

35734
Proteobacteria
CP012162.1


1758
GCA_000956965.1
61645
61645

Enterobacter asburiae

35618
Proteobacteria
JZZI01000011.1


1759
GCA_001022755.1
61645
61645

Enterobacter asburiae

GN02692
Proteobacteria
LEDI01000011.1


1760
GCA_000786255.1
66269
66269

Pantoea stewartii

M009
Proteobacteria
JRWI01000007.1


1761
GCA_000803205.1
66269
66269

Pantoea stewartii

M073a
Proteobacteria
JSXF01000009.1


1762
GCA_000023545.1
579405
69223

Dickeya paradisiaca Ech703
Ech703
Proteobacteria
CP001654.1


1763
GCA_000153425.1
314280
74109

Photobacterium profundum 3TCK
3TCK
Proteobacteria
CH724134.1


1764
GCA_001449005.1
75105
75105

Paraburkholderia caribensis

MWAP64
Proteobacteria
CP013103.1


1765
GCA_000755725.1
95486
95486

Burkholderia cenocepacia

DDS 22E-1
Proteobacteria
CP007784.1


1766
GCA_001467585.1
1212489
96228

Legionella drozanskii LLAP-1
ATCC 700990
Proteobacteria
LNXY01000001.1


1767
GCA_001527015.1
101571
101571

Burkholderia ubonensis

MSMB1806WGS
Proteobacteria
LPBH01000095.1


1768
GCA_001527185.1
101571
101571

Burkholderia ubonensis

MSMB1800WGS
Proteobacteria
LPBC01000010.1


1769
GCA_001528025.1
101571
101571

Burkholderia ubonensis

MSMB2007WGS
Proteobacteria
LPBW01000043.1


1770
GCA_001528325.1
101571
101571

Burkholderia ubonensis

MSMB2013WGS
Proteobacteria
LPCC01000068.1


1771
GCA_001528445.1
101571
101571

Burkholderia ubonensis

MSMB2024WGS
Proteobacteria
LPCJ01000090.1


1772
GCA_001529565.1
101571
101571

Burkholderia ubonensis

MSMB2022WGS
Proteobacteria
LPCI01000021.1


1773
GCA_001531605.1
101571
101571

Burkholderia ubonensis

MSMB2104WGS
Proteobacteria
LPHJ01000073.1


1774
GCA_001532205.1
101571
101571

Burkholderia ubonensis

MSMB2110WGS
Proteobacteria
LPHP01000067.1


1775
GCA_001532445.1
101571
101571

Burkholderia ubonensis

MSMB2192WGS
Proteobacteria
LPIO01000050.1


1776
GCA_001532455.1
101571
101571

Burkholderia ubonensis

MSMB2191WGS
Proteobacteria
LPIN01000075.1


1777
GCA_001532465.1
101571
101571

Burkholderia ubonensis

MSMB2193WGS
Proteobacteria
LPIP01000082.1


1778
GCA_001534475.1
101571
101571

Burkholderia ubonensis

MSMB2019WGS
Proteobacteria
LPND01000106.1


1779
GCA_001539165.1
101571
101571

Burkholderia ubonensis

MSMB1490WGS
Proteobacteria
LPFP01000003.1


1780
GCA_000769475.1
111105
111105

Porphyromonas gulae

COT-052 OH3498
Bacteroidetes
KN300394.1


1781
GCA_000024725.1
472759
133539

Nitrosococcus halophilus Nc 4
Nc 4
Proteobacteria
CP001798.1


1782
GCA_000183725.1
709032
148813

Sulfuricurvum kujiense DSM 16994
DSM 16994
Proteobacteria
CP002355.1


1783
GCA_000412335.2
566551
158484

Cedecea davisae DSM 4568
DSM 4568
Proteobacteria
KE161030.1


1784
GCA_001596815.1
162157
162157

Pseudoalteromonas spiralis

DSM 16099
Proteobacteria
LVCN01000040.1


1785
GCA_001465295.1
1315283
166935

Pseudoalteromonas translucida KMM 520
KMM 520
Proteobacteria
CP011035.1


1786
GCA_001274855.1
170661
170661

Vibrio xuii

DSM 17185
Proteobacteria
LHPK01000025.1


1787
GCA_000755505.1
178606
178606

Leptospirillum ferriphilum

DSM 14647
Nitrospirae
JPGK01000006.1


1788
GCA_000967895.1
698738
188908

Oleispira antarctica RB-8

Proteobacteria
FO203512.1


1789
GCA_000091465.1
575788
212663

Vibrio tasmaniensis LGP32
LGP32
Proteobacteria
FM954972.2


1790
GCA_001298715.1
235205
235205

Bathymodiolus azoricus thioautotrophic gill symbiont
BazSymA
Proteobacteria
CDSC01000438.1


1791
GCA_001048515.1
246167
246167

Vibrio crassostreae

J5-20
Proteobacteria
CCKB01000061.1


1792
GCA_001368855.1
246167
246167

Vibrio crassostreae

J2-9
Proteobacteria
LK934305.1


1793
GCA_000273235.1
997887
291644

Bacteroides salyersiae CL02T12C01
CL02T12C01
Bacteroidetes
JH724309.1


1794
GCA_000422245.1
1121439
293256

Desulfovibrio alkalitolerans DSM 16529
DSM 16529
Proteobacteria
ATHI01000027.1


1795
GCA_000310145.2
303682
303682

Thauera sp. 28
28
Proteobacteria
AMXA01000025.1


1796
GCA_000153005.1
314290
314290

Vibrio sp. MED222
MED222
Proteobacteria
CH902607.1


1797
GCA_000241185.2
386429
386429

Pseudoalteromonas sp. BSi20495
BSi20495
Proteobacteria
BADY01000203.1


1798
GCA_000156355.1
637616
392484

Methylophaga thiooxydans DMS010
DMS010
Proteobacteria
GG657892.1


1799
GCA_001525985.1
488446
488446

Burkholderia latens

RF32-BP12
Proteobacteria
LOTQ01000014.1


1800
GCA_000467165.1
1219077
512649

Vibrio azureus NBRC 104587
NBRC 104587
Proteobacteria
BATL01000040.1


1801
GCA_000179655.1
517433
517433

Pantoea sp. aB
aB
Proteobacteria
AEDL01000002.1


1802
GCA_000950415.1
553611
553611

Photobacterium leiognathi

ATCC 25521
Proteobacteria
JZSK01000008.1


1803
GCA_000969825.1
1203610
574930

Parabacteroides gordonii MS-1
MS-1
Bacteroidetes
KQ033921.1


1804
GCA_000265075.1
1189621
590849

Nitritalea halalkaliphila LW7
LW7
Bacteroidetes
AJYA01000079.1


1805
GCA_000176215.1
675810
675810

Vibrio sp. RC341
RC341
Proteobacteria
ACZT01000026.1


1806
GCA_000176715.1
675815
675815

Vibrio sp. RC586
RC586
Proteobacteria
ADBD01000008.1


1807
GCA_000224655.1
693988
693988

Bilophila sp. 4_1_30
4_1_30
Proteobacteria
JH114231.1


1808
GCA_000785575.1
701175
701175

Vibrio caribbeanicus

T14
Proteobacteria
JRWR01000004.1


1809
GCA_000755345.1
754436
754436

Photobacterium aphoticum

JCM 19237
Proteobacteria
BBMN01000003.1


1810
GCA_000320365.1
1230338
765840

Moraxella macacae 0408225
0408225
Proteobacteria
ANIN01000001.1


1811
GCA_000211855.3
983544
983544

Lacinutrix sp. 5H-3-7-4
5H-3-7-4
Bacteroidetes
CP002825.1


1812
GCA_000305755.2
992012
992012

Vibrio sp. HENC-03
HENC-03
Proteobacteria
JH976122.1


1813
GCA_000333895.2
1056512
1056512

Grimontia indica

AK16
Proteobacteria
ANFM02000072.1


1814
GCA_000722635.1
1137799
1137799

Endozoicomonas numazuensis

DSM 25634
Proteobacteria
JOKH01000001.1


1815
GCA_000276965.1
1177931
1177931

Thiovulum sp. ES
ES
Proteobacteria
AKKQ01000015.1


1816
GCA_001541335.1
1194427
1194427

Vibrio toranzoniae

Vb 10.8
Proteobacteria
LMXU01000011.1


1817
GCA_000802255.1
1348852
1348852

Mumia flava

MUSC 201
Actinobacteria
JTDJ01000134.1


1818
GCA_000743945.1
1072685
1472345

Basilea psittacipulmonis DSM 24701
DSM 24701
Proteobacteria
CP009238.1


1819
GCA_000830185.1
1539064
1539064

Sulfurovum sp. FS06-10

Proteobacteria
JQIR01000120.1


1820
GCA_000830175.1
1539065
1539065

Sulfurovum sp. FS08-3

Proteobacteria
JQIS01000009.1


1821
GCA_000292935.1
1216362
1583098

Fusobacterium hwasookii ChDC F128
ChDC F128
Fusobacteria
ALVD01000001.1


1822
GCA_000807225.1
1583100
1583100

Myroides sp. A21
A21
Bacteroidetes
CP010327.1


1823
GCA_001431295.1
1590043
1590043

Coxiellaceae bacterium HT99
HT99
Proteobacteria
LKAJ01000001.1


1824
GCA_001188205.1
1647102
1647102

Vibrio sp. VPAP30
VPAP30
Proteobacteria
LBLS01000036.1


1825
GCA_000695255.1
1654360
1654360

Photobacterium galatheae

S2753
Proteobacteria
JMIB01000002.1


1826
GCA_001011075.1
1656220
1656220

Serratia sp. TEL
TEL
Proteobacteria
LDEG01000006.1


1827
GCA_001401805.1
1723758
1723758

Pseudoalteromonas sp. P1-25
P1-25
Proteobacteria
LKDW01000016.1


1828
GCA_001421885.1
1736221
1736221

Pseudomonas sp. Leaf48
Leaf48
Proteobacteria
LMLH01000030.1


1829
GCA_001544875.1
1777139
1777139

Burkholderia sp. LMG 29321

Proteobacteria
FCOA01000023.1


1830
GCA_001537265.1
1805637
1805637

Serratia sp. 2880STDY5682895
2880STDY5682895
Proteobacteria
FCJL01000002.1










(Part B)



























M



Q



U








ZorA



ZorB



ZorC




I
J
K
L
protein
N
O
P
protein
R
S
T
protein



H
#genes
ZorA
PRT SEQ
DNA SEQ
length
ZorB
PRT SEQ
DNA SEQ
length
ZorC
PRT SEQ
DNA SEQ
length


1
Type
identified
protein_accession
ID NO:
ID NO:
(aa)
protein_accession
ID NO:
ID NO:
(aa)
protein_accession
ID NO:
ID NO:
(aa)





2
I
3
ABS66238.1
78
6649
704
ABS66239.1
79
6650
296
ABS66240.1
80
6651
469


3
I
4
KGH31560.1
81
6652
705
KGH31559.1
82
6653
248
KGH31558.1
83
6654
575


4
I
4
ABR84348.1
85
6656
708
ABR81630.1
86
6657
254
ABR85988.1
87
6658
648


5
I
4
EIE46557.1
89
6660
708
EIE46558.1
90
6661
254
EIE46559.1
91
6662
670


6
I
4
EKA35841.1
93
6664
731
EKA35840.1
94
6665
245
EKA35839.1
95
6666
528


7
I
4
EKA51673.1
97
6668
731
EKA51672.1
98
6669
245
EKA51671.1
99
6670
528


8
I
4
EOQ78914.1
101
6672
714
EOQ78913.1
102
6673
245
EOQ78912.1
103
6674
547


9
I
3
EQL43276.1
105
6676
708
EQL43277.1
106
6677
254
EQL43278.1
107
6678
417


10
I
4
ERY08923.1
108
6679
708
ERY08922.1
109
6680
254
ERY08921.1
110
6681
670


11
I
4
ERY16790.1
112
6683
731
ERY16789.1
113
6684
245
ERY16788.1
114
6685
558


12
I
4
ERY21334.1
116
6687
708
ERY21333.1
117
6688
254
ERY21332.1
118
6689
670


13
I
4
ERV56557.1
120
6691
708
ERV56556.1
121
6692
254
ERV56555.1
122
6693
670


14
I
4
ERX20611.1
124
6695
731
ERX20610.1
125
6696
245
ERX20609.1
126
6697
558


15
I
4
ERX27344.1
128
6699
731
ERX27343.1
129
6700
245
ERX27342.1
130
6701
558


16
I
4
ERZ22541.1
132
6703
731
ERZ22540.1
133
6704
245
ERZ22539.1
134
6705
558


17
I
4
ERX75596.1
136
6707
731
ERX75595.1
137
6708
245
ERX75594.1
138
6709
558


18
I
4
ESR70192.1
140
6711
731
ESR70191.1
141
6712
245
ESR70190.1
142
6713
558


19
I
4
ETU86359.1
144
6715
708
ETU86358.1
145
6716
254
ETU86357.1
146
6717
670


20
I
4
CDI94249.1
148
6719
708
CDI94248.1
149
6720
254
CDI94247.1
150
6721
255


21
I
4
CDI95166.1
152
6723
731
CDI95167.1
153
6724
245
CDI95168.1
154
6725
547


22
I
4
EVT82482.1
156
6727
708
EVT82481.1
157
6728
254
EVT82480.1
158
6729
663


23
I
4
EYU03497.1
160
6731
731
EYU03498.1
161
6732
245
EYU03499.1
162
6733
558


24
I
4
EZN45278.1
164
6735
781
EZN45279.1
165
6736
247
EZN45280.1
166
6737
723


25
I
4
EZO27044.1
168
6739
708
EZO27045.1
169
6740
254
EZO27046.1
170
6741
640


26
I
4
EZP05708.1
172
6743
708
EZP05709.1
173
6744
254
EZP05710.1
174
6745
640


27
I
4
CDH74042.1
176
6747
708
CDH74041.1
177
6748
254
CDH74040.1
178
6749
670


28
I
4
CDH70661.1
180
6751
731
CDH70662.1
181
6752
245
CDH70663.1
182
6753
547


29
I
4
KEA10735.1
184
6755
708
KEA10736.1
185
6756
254
KEA10737.1
186
6757
670


30
I
4
AJF50277.1
188
6759
731
AJF50276.1
189
6760
245
AJF50275.1
190
6761
547


31
I
4
AKE69360.1
192
6763
731
AKE69361.1
193
6764
245
AKE69362.1
194
6765
547


32
I
4
AKE72978.1
196
6767
708
AKE72977.1
197
6768
254
AKE72976.1
198
6769
670


33
I
4
CRQ30662.1
200
6771
708
CRQ30646.1
201
6772
254
CRQ30630.1
202
6773
670


34
I
4
CRQ14001.1
204
6775
731
CRQ14037.1
205
6776
245
CRQ14055.1
206
6777
547


35
I
4
CRQ20930.1
208
6779
708
CRQ20903.1
209
6780
254
CRQ20878.1
210
6781
670


36
I
4
CRP04583.1
212
6783
731
CRP04548.1
213
6784
245
CRP04515.1
214
6785
547


37
I
4
CRQ05457.1
216
6787
731
CRQ05470.1
217
6788
245
CRQ05489.1
218
6789
547


38
I
4
CRP94057.1
220
6791
708
CRP94029.1
221
6792
254
CRP94009.1
222
6793
670


39
I
4
CRP94866.1
224
6795
708
CRP94849.1
225
6796
254
CRP94824.1
226
6797
670


40
I
4
CRQ51053.1
228
6799
731
CRQ51040.1
229
6800
245
CRQ51031.1
230
6801
547


41
I
4
CRS01042.1
232
6803
708
CRS01058.1
233
6804
254
CRS01074.1
234
6805
670


42
I
4
CRX34600.1
236
6807
708
CRX34599.1
237
6808
254
CRX34598.1
238
6809
670


43
I
4
CRX35811.1
240
6811
731
CRX35810.1
241
6812
245
CRX35809.1
242
6813
547


44
I
4
CRN87107.1
244
6815
731
CRN87087.1
245
6816
245
CRN87069.1
246
6817
547


45
I
4
CRQ28236.1
248
6819
731
CRQ28254.1
249
6820
245
CRQ28266.1
250
6821
547


46
I
4
CRQ21539.1
252
6823
708
CRQ21557.1
253
6824
254
CRQ21576.1
254
6825
670


47
I
4
CRN79596.1
256
6827
708
CRN79621.1
257
6828
254
CRN79649.1
258
6829
670


48
I
4
CRO17466.1
260
6831
731
CRO17426.1
261
6832
245
CRO17380.1
262
6833
547


49
I
4
CRW80533.1
264
6835
708
CRW80527.1
265
6836
254
CRW80520.1
266
6837
670


50
I
4
CRW81746.1
268
6839
731
CRW81753.1
269
6840
245
CRW81763.1
270
6841
547


51
I
4
CRS64348.1
272
6843
731
CRS64342.1
273
6844
245
CRS64337.1
274
6845
547


52
I
4
CRS61289.1
276
6847
708
CRS61288.1
277
6848
254
CRS61287.1
278
6849
670


53
I
4
CRX10287.1
280
6851
731
CRX10279.1
281
6852
245
CRX10272.1
282
6853
547


54
I
4
CRX00557.1
284
6855
708
CRX00549.1
285
6856
254
CRX00541.1
286
6857
670


55
I
4
CRW55933.1
288
6859
731
CRW55913.1
289
6860
245
CRW55893.1
290
6861
547


56
I
4
CRX16431.1
292
6863
708
CRX16423.1
293
6864
254
CRX16416.1
294
6865
670


57
I
4
CRP10808.1
296
6867
708
CRP10838.1
297
6868
254
CRP10876.1
298
6869
670


58
I
4
CRP41275.1
300
6871
731
CRP41308.1
301
6872
245
CRP41345.1
302
6873
547


59
I
4
CRP14749.1
304
6875
708
CRP14725.1
305
6876
254
CRP14706.1
306
6877
670


60
I
4
CRP47753.1
308
6879
731
CRP47733.1
309
6880
245
CRP47704.1
310
6881
547


61
I
4
CRO88348.1
312
6883
731
CRO88299.1
313
6884
245
CRO88247.1
314
6885
547


62
I
4
CRO42842.1
316
6887
708
CRO42772.1
317
6888
254
CRO42732.1
318
6889
670


63
I
4
CRN87606.1
320
6891
731
CRN87577.1
321
6892
245
CRN87556.1
322
6893
547


64
I
4
CRN66199.1
324
6895
708
CRN66218.1
325
6896
254
CRN66246.1
326
6897
670


65
I
4
CRP41066.1
328
6899
708
CRP41088.1
329
6900
254
CRP41112.1
330
6901
670


66
I
4
CRP68499.1
332
6903
731
CRP68477.1
333
6904
245
CRP68458.1
334
6905
547


67
I
4
CRP76330.1
336
6907
708
CRP76294.1
337
6908
254
CRP76259.1
338
6909
670


68
I
4
CRQ24549.1
340
6911
731
CRQ24529.1
341
6912
245
CRQ24511.1
342
6913
547


69
I
4
CRP82373.1
344
6915
731
CRP82350.1
345
6916
245
CRP82329.1
346
6917
547


70
I
4
CRP61046.1
348
6919
708
CRP61016.1
349
6920
254
CRP60987.1
350
6921
670


71
I
4
CRP29707.1
352
6923
731
CRP29680.1
353
6924
245
CRP29649.1
354
6925
547


72
I
4
CRO50770.1
356
6927
708
CRO50854.1
357
6928
254
CRO50880.1
358
6929
670


73
I
3
CRP19911.1
360
6931
731
CRP19885.1
361
6932
245
CRP19855.1
362
6933
547


74
I
4
CRP88471.1
363
6934
708
CRP88447.1
364
6935
254
CRP88424.1
365
6936
670


75
I
4
CRP42118.1
367
6938
708
CRP42092.1
368
6939
254
CRP42069.1
369
6940
670


76
I
4
CRP91193.1
371
6942
731
CRP91170.1
372
6943
245
CRP91145.1
373
6944
547


77
I
4
CRN61579.1
375
6946
708
CRN61562.1
376
6947
254
CRN61546.1
377
6948
670


78
I
4
CRN91417.1
379
6950
731
CRN91437.1
380
6951
245
CRN91483.1
381
6952
547


79
I
4
CRP44694.1
383
6954
731
CRP44734.1
384
6955
245
CRP44770.1
385
6956
547


80
I
4
CRP16339.1
387
6958
708
CRP16291.1
388
6959
254
CRP16258.1
389
6960
670


81
I
4
CRP57045.1
391
6962
708
CRP57076.1
392
6963
254
CRP57102.1
393
6964
670


82
I
4
CRP83731.1
395
6966
731
CRP83754.1
396
6967
245
CRP83780.1
397
6968
547


83
I
4
CRO13767.1
399
6970
708
CRO13733.1
400
6971
254
CRO13695.1
401
6972
670


84
I
4
CRO55633.1
403
6974
731
CRO55573.1
404
6975
245
CRO55551.1
405
6976
547


85
I
4
CRO41585.1
407
6978
731
CRO41607.1
408
6979
245
CRO41618.1
409
6980
547


86
I
4
CRO12578.1
411
6982
708
CRO12630.1
412
6983
254
CRO12724.1
413
6984
670


87
I
4
CRP86193.1
415
6986
731
CRP86228.1
416
6987
245
CRP86261.1
417
6988
547


88
I
4
CRP43660.1
419
6990
708
CRP43627.1
420
6991
254
CRP43600.1
421
6992
670


89
I
4
CRP83380.1
423
6994
731
CRP83353.1
424
6995
245
CRP83330.1
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126
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127
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128
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129
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130
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133
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134
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137
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138
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139
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140
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141
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142
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143
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144
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145
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146
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147
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148
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149
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150
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151
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152
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153
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154
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155
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156
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157
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158
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159
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160
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161
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162
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163
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164
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165
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166
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167
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168
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169
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170
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172
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173
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174
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175
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176
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177
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178
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179
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180
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181
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182
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183
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184
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185
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186
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187
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188
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189
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190
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191
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192
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193
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194
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195
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196
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197
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198
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199
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200
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201
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202
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203
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204
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205
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206
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207
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208
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209
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210
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211
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212
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213
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214
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215
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216
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217
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218
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219
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731
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942
7513
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220
I
4
KSE22789.1
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708
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945
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254
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946
7517
670


221
I
4
KSG55970.1
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708
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949
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254
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670


222
I
4
KSH11345.1
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708
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223
I
4
KSC39038.1
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731
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224
I
4
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225
I
4
KSC92702.1
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708
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965
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254
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966
7537
670


226
I
4
KSD59501.1
968
7539
708
KSD59502.1
969
7540
254
KSD59503.1
970
7541
670


227
I
4
KSD58176.1
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7543
731
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973
7544
245
KSD58174.1
974
7545
547


228
I
4
KSE83336.1
976
7547
708
KSE83337.1
977
7548
254
KSE83338.1
978
7549
670


229
I
4
KSI47359.1
980
7551
731
KSI47360.1
981
7552
245
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982
7553
547


230
I
4
KSI07558.1
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7555
731
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985
7556
245
KSI07556.1
986
7557
547


231
I
4
KSJ10824.1
988
7559
708
KSJ10823.1
989
7560
254
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7561
670


232
I
4
KSJ26235.1
992
7563
708
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993
7564
254
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994
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670


233
I
4
KSJ98813.1
996
7567
731
KSJ98814.1
997
7568
245
KSJ98815.1
998
7569
558


234
I
4
KSK91641.1
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7571
731
KSK91642.1
1001
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245
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7573
547


235
I
4
KSL06910.1
1004
7575
731
KSL06911.1
1005
7576
245
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1006
7577
558


236
I
4
KSM47321.1
1008
7579
731
KSM47320.1
1009
7580
245
KSM47319.1
1010
7581
558


237
I
4
KSM41525.1
1012
7583
708
KSM41524.1
1013
7584
254
KSM41523.1
1014
7585
721


238
I
4
KSN32759.1
1016
7587
731
KSN32760.1
1017
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245
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1018
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547


239
I
4
KSN33320.1
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7591
708
KSN33321.1
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254
KSN33322.1
1022
7593
670


240
I
4
KSN27912.1
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7595
731
KSN27911.1
1025
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245
KSN27910.1
1026
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547


241
I
4
KSN02517.1
1028
7599
708
KSN02518.1
1029
7600
254
KSN02519.1
1030
7601
640


242
I
4
KSN94642.1
1032
7603
731
KSN94643.1
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245
KSN94644.1
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558


243
I
4
KSN59773.1
1036
7607
708
KSN59774.1
1037
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254
KSN59775.1
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7609
670


244
I
4
KSN68235.1
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7611
731
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245
I
4
KSO78871.1
1044
7615
731
KSO78872.1
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245
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1046
7617
558


246
I
4
KSO73926.1
1048
7619
731
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1049
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245
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1050
7621
547


247
I
4
KSO74314.1
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7623
708
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7624
254
KSO74312.1
1054
7625
670


248
I
4
KSO93081.1
1056
7627
708
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1057
7628
254
KSO93083.1
1058
7629
670


249
I
4
KSO91845.1
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7631
731
KSO91844.1
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245
KSO91843.1
1062
7633
547


250
I
4
KSP60331.1
1064
7635
708
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1065
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254
KSP60333.1
1066
7637
670


251
I
4
KSP82596.1
1068
7639
782
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1069
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247
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7641
723


252
I
4
KSQ11856.1
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731
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1074
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558


253
I
4
KSN68769.1
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7647
731
KSN68770.1
1077
7648
245
KSN68771.1
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558


254
I
4
KSO40824.1
1080
7651
708
KSO40825.1
1081
7652
254
KSO40826.1
1082
7653
721


255
I
4
KSQ48400.1
1084
7655
708
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1085
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254
KSQ48398.1
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670


256
I
4
KSQ47084.1
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731
KSQ47083.1
1089
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KSQ47082.1
1090
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547


257
I
4
KSQ03908.1
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708
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1093
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254
KSQ03906.1
1094
7665
670


258
I
4
KSQ01968.1
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7667
731
KSQ01967.1
1097
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245
KSQ01966.1
1098
7669
547


259
I
4
KSR61594.1
1100
7671
708
KSR61593.1
1101
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254
KSR61592.1
1102
7673
721


260
I
4
KSR90896.1
1104
7675
708
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1105
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254
KSR90898.1
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7677
670


261
I
4
KSR87673.1
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7679
731
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1109
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245
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558


262
I
4
KSR56106.1
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731
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245
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7685
547


263
I
4
KSR68843.1
1116
7687
708
KSR68842.1
1117
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254
KSR68841.1
1118
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670


264
I
4
KSS83648.1
1120
7691
708
KSS83647.1
1121
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254
KSS83646.1
1122
7693
670


265
I
4
KSS82297.1
1124
7695
731
KSS82296.1
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245
KSS82295.1
1126
7697
547


266
I
4
KSS65852.1
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731
KSS65851.1
1129
7700
245
KSS65850.1
1130
7701
547


267
I
4
KSS71074.1
1132
7703
708
KSS71073.1
1133
7704
254
KSS71072.1
1134
7705
670


268
I
4
KSS83671.1
1136
7707
731
KSS83670.1
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7708
245
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1138
7709
547


269
I
4
KSS97189.1
1140
7711
708
KSS97188.1
1141
7712
254
KSS97187.1
1142
7713
670


270
I
4
KSS68542.1
1144
7715
731
KSS68541.1
1145
7716
245
KSS68540.1
1146
7717
547


271
I
4
KSS64139.1
1148
7719
708
KSS64138.1
1149
7720
254
KSS64137.1
1150
7721
670


272
I
4
KST02401.1
1152
7723
708
KST02402.1
1153
7724
254
KST02403.1
1154
7725
670


273
I
4
KST01506.1
1156
7727
731
KST01505.1
1157
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245
KST01504.1
1158
7729
547


274
I
4
KST09053.1
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7731
708
KST09052.1
1161
7732
254
KST09051.1
1162
7733
670


275
I
4
KST07356.1
1164
7735
731
KST07355.1
1165
7736
245
KST07354.1
1166
7737
547


276
I
4
KSR39888.1
1168
7739
708
KSR39889.1
1169
7740
254
KSR39890.1
1170
7741
670


277
I
4
KST03849.1
1172
7743
731
KST03848.1
1173
7744
245
KST03847.1
1174
7745
547


278
I
4
KST05251.1
1176
7747
708
KST05250.1
1177
7748
254
KST05249.1
1178
7749
670


279
I
4
KSS85815.1
1180
7751
708
KSS85816.1
1181
7752
254
KSS85817.1
1182
7753
670


280
I
4
KSS83938.1
1184
7755
731
KSS83937.1
1185
7756
245
KSS83936.1
1186
7757
547


281
I
4
KTF54396.1
1188
7759
708
KTF54397.1
1189
7760
254
KTF54398.1
1190
7761
670


282
I
4
KTF49811.1
1192
7763
731
KTF49810.1
1193
7764
245
KTF49809.1
1194
7765
547


283
I
4
KTK55766.1
1196
7767
782
KTK55767.1
1197
7768
247
KTK55768.1
1198
7769
723


284
I
4
ALZ13984.1
1200
7771
782
ALZ13983.1
1201
7772
247
ALZ13982.1
1202
7773
723


285
I
4
ALY33856.1
1204
7775
731
ALY33855.1
1205
7776
245
ALY33854.1
1206
7777
558


286
I
4
ALY39460.1
1208
7779
731
ALY39461.1
1209
7780
245
ALY39462.1
1210
7781
547


287
I
4
ALY43157.1
1212
7783
708
ALY43156.1
1213
7784
254
ALY43155.1
1214
7785
670


288
I
3
KWR99692.1
1216
7787
731
KWR99691.1
1217
7788
245
KWR99690.1
1218
7789
547


289
I
3
KWZ69450.1
1219
7790
708
KWZ69449.1
1220
7791
254


290
I
4
KXG16565.1
1222
7793
708
KXG16566.1
1223
7794
254
KXG16567.1
1224
7795
670


291
I
4
KYO75360.1
1226
7797
708
KYO75361.1
1227
7798
254
KYO75362.1
1228
7799
670


292
I
3
KIS47213.1
1230
7801
670
KIS48415.1
1231
7802
131


293
I
4
KVA56588.1
1233
7804
670
KVA56589.1
1234
7805
241
KVA56590.1
1235
7806
545


294
I
4
KVC33765.1
1237
7808
670
KVC33766.1
1238
7809
241
KVC33767.1
1239
7810
545


295
I
4
AEV65174.1
1241
7812
608
AEV65173.1
1242
7813
247
AEV65172.1
1243
7814
542


296
I
4
KGE64068.1
1245
7816
730
KGE64069.1
1246
7817
247
KGE64070.1
1247
7818
542


297
I
4
KWV80506.1
1249
7820
781
KWV80505.1
1250
7821
248
KWV80504.1
1251
7822
704


298
I
4
ABQ80738.1
1253
7824
730
ABQ80737.1
1254
7825
247
ABQ80736.1
1255
7826
541


299
I
4
AFK68697.1
1257
7828
730
AFK68696.1
1258
7829
247
AFK68695.1
1259
7830
541


300
I
4
EMR48530.1
1261
7832
781
EMR48531.1
1262
7833
254
EMR48532.1
1263
7834
681


301
I
4
AGA73017.1
1265
7836
730
AGA73018.1
1266
7837
247
AGA73019.1
1267
7838
542


302
I
4
KTC24575.1
1269
7840
782
KTC24464.1
1270
7841
247
KTC24463.1
1271
7842
626


303
I
4
ABP79163.1
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7844
783
ABP79164.1
1274
7845
254
ABP79165.1
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7846
210


304
I
4
AEA83397.1
1277
7848
781
AEA83398.1
1278
7849
254
AEA83399.1
1279
7850
751


305
I
4
EHY79730.1
1281
7852
781
EHY79731.1
1282
7853
254
EHY79732.1
1283
7854
751


306
I
4
AFM32806.1
1285
7856
781
AFM32807.1
1286
7857
254
AFM32808.1
1287
7858
752


307
I
4
EWC39447.1
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7860
682
EWC39446.1
1290
7861
245
EWC39445.1
1291
7862
558


308
I
3
EPL62183.1
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7864
781
EPL62184.1
1294
7865
254


309
I
4
EPM44374.1
1296
7867
659
EPM44375.1
1297
7868
247
EPM44377.1
1298
7869
378


310
I
4
EPN29003.1
1300
7871
659
EPN29004.1
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247
EPN29005.1
1302
7873
518


311
I
4
EPN47277.1
1304
7875
659
EPN47278.1
1305
7876
247
EPN47280.1
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7877
378


312
I
4
EPN38583.1
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7879
659
EPN38584.1
1309
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247
EPN38585.1
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545


313
I
4
EPN31613.1
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7883
659
EPN31614.1
1313
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247
EPN31616.1
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7885
378


314
I
4
EPN22775.1
1316
7887
659
EPN22776.1
1317
7888
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EPN22777.1
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7889
545


315
I
4
EPN13939.1
1320
7891
659
EPN13938.1
1321
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247
EPN13936.1
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7893
378


316
I
4
EPM64842.1
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7895
659
EPM64843.1
1325
7896
247
EPM64844.1
1326
7897
545


317
I
4
KFE44523.1
1328
7899
730
KFE44522.1
1329
7900
247
KFE44521.1
1330
7901
542


318
I
4
KTC49637.1
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7903
730
KTC49636.1
1333
7904
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KTC49752.1
1334
7905
545


319
I
4
AAM40747.1
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7907
629
AAM40748.1
1337
7908
238
AAM40749.1
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7909
491


320
I
4
AAY49837.1
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7911
629
AAY49836.1
1341
7912
238
AAY49835.1
1342
7913
491


321
I
4
AKS16757.1
1344
7915
629
AKS16756.1
1345
7916
238
AKS18353.1
1346
7917
491


322
I
4
ACP24372.1
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7919
481
ACP24373.1
1349
7920
309
ACP24374.1
1350
7921
437


323
I
3
KUM25652.1
1352
7923
675
KUM25651.1
1353
7924
323
KUM25650.1
1354
7925
413


324
I
4
KUM27288.1
1355
7926
723
KUM27287.1
1356
7927
302
KUM27286.1
1357
7928
460


325
I
4
CDZ72588.1
1359
7930
677
CDZ72587.1
1360
7931
326
CDZ72586.1
1361
7932
389


326
I
4
ACK84139.1
1363
7934
685
ACK84140.1
1364
7935
296
ACK84141.1
1365
7936
438


327
I
4
CAH15308.1
1367
7938
657
CAH15307.1
1368
7939
234
CAH15306.1
1369
7940
482


328
I
4
CCD05132.1
1371
7942
636
CCD05131.1
1372
7943
234
CCD05130.1
1373
7944
482


329
I
4
CZL99121.1
1375
7946
636
CZL99087.1
1376
7947
234
CZL99058.1
1377
7948
482


330
I
4
CZN28597.1
1379
7950
636
CZN28565.1
1380
7951
234
CZN28532.1
1381
7952
482


331
I
4
CZP40404.1
1383
7954
636
CZP40292.1
1384
7955
234
CZP40266.1
1385
7956
482


332
I
4
CZP31110.1
1387
7958
636
CZP31151.1
1388
7959
234
CZP31189.1
1389
7960
482


333
I
4
CZP19884.1
1391
7962
636
CZP19847.1
1392
7963
234
CZP19810.1
1393
7964
482


334
I
4
CZN56655.1
1395
7966
636
CZN56617.1
1396
7967
234
CZN56586.1
1397
7968
482


335
I
4
CZN22035.1
1399
7970
636
CZN21995.1
1400
7971
234
CZN21949.1
1401
7972
482


336
I
4
CZP49453.1
1403
7974
636
CZP49417.1
1404
7975
234
CZP49379.1
1405
7976
482


337
I
4
CZP60974.1
1407
7978
636
CZP61042.1
1408
7979
234
CZP61132.1
1409
7980
482


338
I
4
CZN58239.1
1411
7982
636
CZN58276.1
1412
7983
234
CZN58324.1
1413
7984
482


339
I
4
CZO62381.1
1415
7986
636
CZO62416.1
1416
7987
234
CZO62452.1
1417
7988
482


340
I
4
CZO85409.1
1419
7990
636
CZO85444.1
1420
7991
234
CZO85483.1
1421
7992
482


341
I
4
CZN18702.1
1423
7994
636
CZN18741.1
1424
7995
234
CZN18776.1
1425
7996
482


342
I
4
CZO33191.1
1427
7998
636
CZO33228.1
1428
7999
234
CZO33267.1
1429
8000
482


343
I
4
CZN48685.1
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344
I
4
CZO35301.1
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345
I
4
CZL93468.1
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346
I
4
CZH31955.1
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347
I
4
CZG09013.1
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8020
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348
I
4
CZO58196.1
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349
I
4
CZP31281.1
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CZP31240.1
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CZP31204.1
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8028
482


350
I
4
CZP25054.1
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CZP25088.1
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CZP25128.1
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351
I
4
CZO87032.1
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636
CZO87064.1
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CZO87079.1
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482


352
I
4
CZP12610.1
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636
CZP12634.1
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CZP12658.1
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8040
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353
I
4
CZO76824.1
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636
CZO76768.1
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CZO76725.1
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354
I
4
CZM76075.1
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355
I
4
CZM80398.1
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CZM80434.1
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CZM80464.1
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356
I
4
CZO03095.1
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482


357
I
4
CZO99703.1
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CZO99644.1
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358
I
4
CZN78011.1
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636
CZN77981.1
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CZN77962.1
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359
I
4
CZO69823.1
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636
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360
I
4
CZO98643.1
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CZO98681.1
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361
I
4
CZN87164.1
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362
I
4
CZO29078.1
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482


363
I
4
CZO58157.1
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364
I
4
CZM99522.1
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CZM99482.1
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365
I
4
CZN97533.1
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CZN97560.1
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CZN97585.1
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366
I
4
CZN56114.1
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8094
636
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CZN56241.1
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367
I
4
CZP07429.1
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636
CZP07390.1
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CZP07358.1
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8100
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368
I
4
CZP63511.1
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636
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CZP63581.1
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8104
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369
I
4
CZM58627.1
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636
CZM58593.1
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CZM58562.1
1537
8108
482


370
I
4
CZN95768.1
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8110
636
CZN95715.1
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CZN95664.1
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8112
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371
I
4
CZN53092.1
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636
CZN53126.1
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CZN53175.1
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482


372
I
4
CZN21729.1
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636
CZN21768.1
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CZN21791.1
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8120
482


373
I
4
CZO54055.1
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636
CZO54008.1
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CZO53982.1
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482


374
I
4
CZO83037.1
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636
CZO83063.1
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8128
482


375
I
4
CZM80662.1
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636
CZM80631.1
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CZM80598.1
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376
I
4
CZN76327.1
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CZN76305.1
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CZN76257.1
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377
I
4
CZN17181.1
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636
CZN17217.1
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CZN17250.1
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378
I
4
CZN08820.1
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636
CZN08778.1
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CZN08740.1
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379
I
4
CZN07776.1
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636
CZN07744.1
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CZN07717.1
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380
I
4
CZN26973.1
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CZN27020.1
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CZN27059.1
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381
I
4
CZO91605.1
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8154
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CZO91570.1
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CZO91532.1
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382
I
4
CZN16140.1
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CZN16106.1
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CZN16089.1
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383
I
4
CZN39081.1
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636
CZN39046.1
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CZN38988.1
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384
I
4
CZI18710.1
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8166
636
CZI18679.1
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CZI18647.1
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8168
482


385
I
4
CZL86382.1
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8170
636
CZL86343.1
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CZL86298.1
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482


386
I
4
CZM41589.1
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636
CZM41618.1
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CZM41656.1
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8176
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387
I
4
CZM78595.1
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636
CZM78547.1
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CZM78507.1
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8180
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388
I
4
CZM56824.1
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636
CZM56782.1
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CZM56749.1
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8184
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389
I
4
CZM61973.1
1615
8186
636
CZM62010.1
1616
8187
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CZM62034.1
1617
8188
482


390
I
4
CZM06139.1
1619
8190
636
CZM06106.1
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CZM06061.1
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8192
482


391
I
4
CZM97949.1
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636
CZM97974.1
1624
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CZM97996.1
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8196
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392
I
4
CZN32008.1
1627
8198
636
CZN32037.1
1628
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CZN32065.1
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8200
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393
I
4
CZN27707.1
1631
8202
636
CZN27733.1
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CZN27771.1
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8204
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394
I
4
CZM96765.1
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636
CZM96741.1
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CZM96707.1
1637
8208
482


395
I
4
CZN17300.1
1639
8210
636
CZN17329.1
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8211
234
CZN17356.1
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8212
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396
I
4
CZN17894.1
1643
8214
636
CZN17862.1
1644
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CZN17835.1
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8216
482


397
I
4
CZN51335.1
1647
8218
636
CZN51299.1
1648
8219
234
CZN51263.1
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8220
482


398
I
4
CZN80164.1
1651
8222
636
CZN80114.1
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CZN80081.1
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8224
482


399
I
4
CZN83467.1
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8226
636
CZN83507.1
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CZN83551.1
1657
8228
482


400
I
4
CZN87990.1
1659
8230
636
CZN87946.1
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234
CZN87903.1
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8232
482


401
I
4
CZN93946.1
1663
8234
636
CZN93993.1
1664
8235
234
CZN94035.1
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8236
482


402
I
4
CZO07075.1
1667
8238
636
CZO07110.1
1668
8239
234
CZO07154.1
1669
8240
482


403
I
4
CZO12027.1
1671
8242
636
CZO11987.1
1672
8243
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CZO11952.1
1673
8244
482


404
I
4
CZO09452.1
1675
8246
636
CZO09406.1
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8247
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CZO09365.1
1677
8248
482


405
I
4
CZN88093.1
1679
8250
636
CZN88057.1
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CZN88014.1
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8252
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406
I
4
CZO32095.1
1683
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636
CZO32135.1
1684
8255
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CZO32185.1
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482


407
I
4
CZO07325.1
1687
8258
636
CZO07290.1
1688
8259
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CZO07266.1
1689
8260
482


408
I
4
CZO04199.1
1691
8262
636
CZO04172.1
1692
8263
234
CZO04137.1
1693
8264
482


409
I
4
CZN90628.1
1695
8266
636
CZN90659.1
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234
CZN90697.1
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8268
482


410
I
4
CZP18446.1
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636
CZP18413.1
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CZP18376.1
1701
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482


411
I
4
CZP26391.1
1703
8274
636
CZP26289.1
1704
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CZP26260.1
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482


412
I
4
CZP25516.1
1707
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636
CZP25483.1
1708
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CZP25450.1
1709
8280
482


413
I
4
CZN32104.1
1711
8282
636
CZN32073.1
1712
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CZN32054.1
1713
8284
482


414
I
4
CZO49179.1
1715
8286
636
CZO49222.1
1716
8287
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CZO49269.1
1717
8288
482


415
I
4
CZO32890.1
1719
8290
636
CZO32855.1
1720
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CZO32827.1
1721
8292
482


416
I
4
CZO62310.1
1723
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636
CZO62353.1
1724
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CZO62389.1
1725
8296
482


417
I
4
CZO58294.1
1727
8298
636
CZO58318.1
1728
8299
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CZO58349.1
1729
8300
482


418
I
4
CZO85873.1
1731
8302
636
CZO85828.1
1732
8303
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CZO85797.1
1733
8304
482


419
I
4
CZP51088.1
1735
8306
636
CZP51125.1
1736
8307
234
CZP51157.1
1737
8308
482


420
I
4
CZO57150.1
1739
8310
636
CZO57187.1
1740
8311
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CZO57213.1
1741
8312
482


421
I
4
CZO45304.1
1743
8314
636
CZO45268.1
1744
8315
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CZO45218.1
1745
8316
482


422
I
4
CZO91199.1
1747
8318
636
CZO91233.1
1748
8319
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CZO91266.1
1749
8320
482


423
I
4
CZN53802.1
1751
8322
636
CZN53843.1
1752
8323
234
CZN53877.1
1753
8324
482


424
I
4
CZN51375.1
1755
8326
636
CZN51423.1
1756
8327
234
CZN51467.1
1757
8328
482


425
I
4
CZO76010.1
1759
8330
636
CZO76045.1
1760
8331
234
CZO76083.1
1761
8332
482


426
I
4
CZR30116.1
1763
8334
636
CZR30113.1
1764
8335
234
CZR30109.1
1765
8336
482


427
I
4
KTD18860.1
1767
8338
634
KTD18861.1
1768
8339
234
KTD18862.1
1769
8340
482


428
I
3
EMU26880.1
1771
8342
686
EMU26879.1
1772
8343
243
EMU26878.1
1773
8344
456


429
I
3
EMT95386.1
1774
8345
686
EMT95385.1
1775
8346
243
EMT95384.1
1776
8347
456


430
I
4
EMT94539.1
1777
8348
686
EMT94538.1
1778
8349
243
EMT94537.1
1779
8350
456


431
I
3
EMU11117.1
1781
8352
686
EMU11116.1
1782
8353
243
EMU11115.1
1783
8354
387


432
I
4
EMU02182.1
1784
8355
686
EMU02181.1
1785
8356
243
EMU02180.1
1786
8357
456


433
I
4
EXB30082.1
1788
8359
686
EXB30083.1
1789
8360
243
EXB30084.1
1790
8361
466


434
I
4
EXB35593.1
1792
8363
686
EXB35594.1
1793
8364
243
EXB35595.1
1794
8365
466


435
I
4
EXB05632.1
1796
8367
686
EXB05631.1
1797
8368
243
EXB05630.1
1798
8369
466


436
I
4
EXB92756.1
1800
8371
686
EXB92873.1
1801
8372
243
EXB92651.1
1802
8373
466


437
I
4
EXB73471.1
1804
8375
686
EXB73472.1
1805
8376
243
EXB73473.1
1806
8377
466


438
I
4
EXE59934.1
1808
8379
686
EXE59933.1
1809
8380
243
EXE59932.1
1810
8381
471


439
I
4
EXE71111.1
1812
8383
688
EXE71113.1
1813
8384
200
EXE71114.1
1814
8385
466


440
I
4
KCX96450.1
1816
8387
686
KCX96449.1
1817
8388
243
KCX96448.1
1818
8389
466


441
I
4
KHO17164.1
1820
8391
686
KHO17163.1
1821
8392
243
KHO17162.1
1822
8393
456


442
I
4
KLT90624.1
1824
8395
686
KLT90642.1
1825
8396
243
KLT90662.1
1826
8397
456


443
I
4
KRI43455.1
1828
8399
688
KRI43456.1
1829
8400
243
KRI43503.1
1830
8401
457


444
I
4
KRJ35152.1
1832
8403
686
KRJ35151.1
1833
8404
243
KRJ35150.1
1834
8405
466


445
I
4
AMN00863.1
1836
8407
686
AMN00864.1
1837
8408
243
AMN00865.1
1838
8409
466


446
I
4
KDB58749.1
1840
8411
662
KDB58628.1
1841
8412
234
KDB58574.1
1842
8413
570


447
I
4
KDD86366.1
1844
8415
669
KDD86358.1
1845
8416
234
KDD86345.1
1846
8417
570


448
I
4
ACV76373.1
1848
8419
675
ACV76374.1
1849
8420
273
ACV76375.1
1850
8421
433


449
I
4
AEI38596.1
1852
8423
675
AEI38595.1
1853
8424
273
AEI38594.1
1854
8425
433


450
I
4
KTJ39354.1
1856
8427
729
KTJ39355.1
1857
8428
246
KTJ39356.1
1858
8429
559


451
I
4
KUQ09076.1
1860
8431
851
KUQ09077.1
1861
8432
245
KUQ09078.1
1862
8433
597


452
I
4
KYN64186.1
1864
8435
678
KYN64185.1
1865
8436
287
KYN64184.1
1866
8437
441


453
I
4
AFP68831.1
1868
8439
729
AFP68830.1
1869
8440
245
AFP68829.1
1870
8441
70


454
I
4
ESS59441.1
1872
8443
729
ESS59449.1
1873
8444
208
ESS59443.1
1874
8445
560


455
I
4
EUL88641.1
1876
8447
711
EUL88642.1
1877
8448
245
EUL88643.1
1878
8449
560


456
I
4
KDF77544.1
1880
8451
711
KDF77543.1
1881
8452
245
KDF77542.1
1882
8453
560


457
I
4
AIX56040.1
1884
8455
729
AIX56041.1
1885
8456
245
AIX56042.1
1886
8457
504


458
I
4
KJW77580.1
1888
8459
851
KJW77579.1
1889
8460
245
KJW77578.1
1890
8461
597


459
I
4
KJX05616.1
1892
8463
851
KJX05615.1
1893
8464
245
KJX05614.1
1894
8465
597


460
I
3




KPS87963.1
1896
8467
245
KPS87962.1
1897
8468
560


461
I
3




KRS24832.1
1899
8470
245
KRS24833.1
1900
8471
560


462
I
4
KUQ03195.1
1902
8473
729
KUQ03194.1
1903
8474
245
KUQ03193.1
1904
8475
560


463
I
4
BAK13750.1
1906
8477
678
BAK13749.1
1907
8478
287
BAK13748.1
1908
8479
441


464
I
4
CCF11168.1
1910
8481
678
CCF11169.1
1911
8482
287
CCF11170.1
1912
8483
356


465
I
4
AFR04653.1
1914
8485
729
AFR04654.1
1915
8486
246
AFR04655.1
1916
8487
560


466
I
4
KHS69362.1
1918
8489
729
KHS69298.1
1919
8490
246
KHS69299.1
1920
8491
560


467
I
4
KHT02545.1
1922
8493
729
KHT02546.1
1923
8494
246
KHT02547.1
1924
8495
560


468
I
4
KHT03993.1
1926
8497
729
KHT03964.1
1927
8498
246
KHT03965.1
1928
8499
560


469
I
4
ABV17222.1
1930
8501
739
ABV17786.1
1931
8502
246
ABV16709.1
1932
8503
567


470
I
4
EIP59422.1
1934
8505
729
EIP59419.1
1935
8506
246
EIP59433.1
1936
8507
483


471
I
4
EIN79902.1
1938
8509
729
EIN79901.1
1939
8510
246
EIN79900.1
1940
8511
504


472
I
4
EKK37352.1
1942
8513
729
EKK37353.1
1943
8514
246
EKK37354.1
1944
8515
504


473
I
4
EKW33219.1
1946
8517
729
EKW33218.1
1947
8518
246
EKW33217.1
1948
8519
402


474
I
4
ELW24564.1
1950
8521
729
ELW24563.1
1951
8522
246
ELW24562.1
1952
8523
483


475
I
4
ELV55444.1
1954
8525
704
ELV55443.1
1955
8526
246
ELV55442.1
1956
8527
391


476
I
4
ELV58670.1
1958
8529
729
ELV58672.1
1959
8530
246
ELV58675.1
1960
8531
483


477
I
4
ELV27737.1
1962
8533
729
ELV27736.1
1963
8534
246
ELV27735.1
1964
8535
504


478
I
4
ELE34850.1
1966
8537
729
ELE34849.1
1967
8538
246
ELE34848.1
1968
8539
560


479
I
4
ELF60007.1
1970
8541
729
ELF60008.1
1971
8542
246
ELF60009.1
1972
8543
560


480
I
4
ENC42752.1
1974
8545
729
ENC42751.1
1975
8546
246
ENC42750.1
1976
8547
504


481
I
4
ENC49345.1
1978
8549
729
ENC49344.1
1979
8550
246
ENC49343.1
1980
8551
504


482
I
4
ENC65372.1
1982
8553
665
ENC65371.1
1983
8554
246
ENC65370.1
1984
8555
504


483
I
4
ENC60227.1
1986
8557
729
ENC60226.1
1987
8558
246
ENC60225.1
1988
8559
504


484
I
4
ENC64694.1
1990
8561
729
ENC64693.1
1991
8562
246
ENC64692.1
1992
8563
504


485
I
4
ENC77391.1
1994
8565
729
ENC77390.1
1995
8566
246
ENC77389.1
1996
8567
504


486
I
4
ENC83691.1
1998
8569
729
ENC83703.1
1999
8570
246
ENC83675.1
2000
8571
504


487
I
4
ENC86715.1
2002
8573
729
ENC86714.1
2003
8574
246
ENC86713.1
2004
8575
504


488
I
4
ENE16651.1
2006
8577
729
ENE16656.1
2007
8578
246
ENE16652.1
2008
8579
560


489
I
4
ENC77075.1
2010
8581
729
ENC77074.1
2011
8582
246
ENC77073.1
2012
8583
504


490
I
4
EOQ56570.1
2014
8585
851
EOQ56569.1
2015
8586
244
EOQ56568.1
2016
8587
595


491
I
4
ERB06047.1
2018
8589
729
ERB06046.1
2019
8590
246
ERB06045.1
2020
8591
560


492
I
4
EQV94532.1
2022
8593
851
EQV94533.1
2023
8594
244
EQV94534.1
2024
8595
595


493
I
4
EQV96721.1
2026
8597
729
EQV96722.1
2027
8598
246
EQV96723.1
2028
8599
560


494
I
4
ERB23472.1
2030
8601
729
ERB23473.1
2031
8602
246
ERB23474.1
2032
8603
560


495
I
4
ERA25533.1
2034
8605
729
ERA25534.1
2035
8606
246
ERA25535.1
2036
8607
560


496
I
4
ERB97875.1
2038
8609
729
ERB97874.1
2039
8610
246
ERB97873.1
2040
8611
483


497
I
4
ERB87466.1
2042
8613
729
ERB87465.1
2043
8614
246
ERB87464.1
2044
8615
483


498
I
4
ERB73282.1
2046
8617
729
ERB73281.1
2047
8618
246
ERB73280.1
2048
8619
483


499
I
4
ERB84327.1
2050
8621
729
ERB84433.1
2051
8622
246
ERB84435.1
2052
8623
483


500
I
4
ERD03133.1
2054
8625
729
ERD03126.1
2055
8626
246
ERD03124.1
2056
8627
504


501
I
3




ERD02933.1
2058
8629
175
ERD02932.1
2059
8630
307


502
I
4
ERD21118.1
2061
8632
729
ERD21117.1
2062
8633
246
ERD21116.1
2063
8634
483


503
I
4
ERD19184.1
2065
8636
729
ERD19183.1
2066
8637
246
ERD19182.1
2067
8638
483


504
I
4
ERD72949.1
2069
8640
729
ERD72951.1
2070
8641
246
ERD72947.1
2071
8642
483


505
I
4
ERD66562.1
2073
8644
729
ERD66561.1
2074
8645
246
ERD66560.1
2075
8646
504


506
I
4
ERD75978.1
2077
8648
729
ERD75977.1
2078
8649
246
ERD75976.1
2079
8650
483


507
I
4
ERD83534.1
2081
8652
729
ERD83533.1
2082
8653
246
ERD83532.1
2083
8654
483


508
I
4
ERD92971.1
2085
8656
729
ERD92973.1
2086
8657
246
ERD92974.1
2087
8658
483


509
I
4
ERD99050.1
2089
8660
729
ERD99051.1
2090
8661
246
ERD99052.1
2091
8662
483


510
I
4
ERD98127.1
2093
8664
729
ERD98126.1
2094
8665
246
ERD98125.1
2095
8666
504


511
I
4
AHM42039.1
2097
8668
729
AHM42040.1
2098
8669
246
AHM42041.1
2099
8670
560


512
I
4
AHM46674.1
2101
8672
729
AHM46675.1
2102
8673
246
AHM46676.1
2103
8674
560


513
I
4
AHM51229.1
2105
8676
729
AHM51230.1
2106
8677
246
AHM51231.1
2107
8678
560


514
I
4
EYD87612.1
2109
8680
698
EYD87621.1
2110
8681
245
EYD87618.1
2111
8682
595


515
I
4
EYW22456.1
2113
8684
729
EYW22455.1
2114
8685
246
EYW22454.1
2115
8686
560


516
I
4
EYW31324.1
2117
8688
729
EYW31323.1
2118
8689
246
EYW31322.1
2119
8690
560


517
I
4
EYV86555.1
2121
8692
729
EYV86554.1
2122
8693
246
EYV86553.1
2123
8694
560


518
I
4
EYW71956.1
2125
8696
729
EYW71957.1
2126
8697
246
EYW71958.1
2127
8698
560


519
I
4
EYW62757.1
2129
8700
729
EYW62758.1
2130
8701
246
EYW62759.1
2131
8702
560


520
I
4
EYW60244.1
2133
8704
729
EYW60243.1
2134
8705
246
EYW60242.1
2135
8706
560


521
I
4
EYW56544.1
2137
8708
729
EYW56543.1
2138
8709
246
EYW56542.1
2139
8710
560


522
I
4
EYW47186.1
2141
8712
729
EYW47185.1
2142
8713
246
EYW47184.1
2143
8714
560


523
I
4
EYW47506.1
2145
8716
729
EYW47505.1
2146
8717
246
EYW47504.1
2147
8718
560


524
I
4
EYW43756.1
2149
8720
729
EYW43757.1
2150
8721
246
EYW43758.1
2151
8722
560


525
I
4
EYW40414.1
2153
8724
729
EYW40415.1
2154
8725
246
EYW40416.1
2155
8726
560


526
I
4
EYW30112.1
2157
8728
729
EYW30111.1
2158
8729
246
EYW30110.1
2159
8730
560


527
I
4
EYY79851.1
2161
8732
729
EYY79852.1
2162
8733
246
EYY79853.1
2163
8734
560


528
I
4
EZB10673.1
2165
8736
729
EZB10672.1
2166
8737
246
EZB10671.1
2167
8738
560


529
I
4
EZE32940.1
2169
8740
729
EZE32941.1
2170
8741
246
EZE32942.1
2171
8742
560


530
I
4
KDZ82638.1
2173
8744
729
KDZ82652.1
2174
8745
246
KDZ82648.1
2175
8746
560


531
I
4
KHG75769.1
2177
8748
729
KHG75768.1
2178
8749
246
KHG75767.1
2179
8750
560


532
I
4
KHG79503.1
2181
8752
729
KHG79502.1
2182
8753
246
KHG79501.1
2183
8754
560


533
I
4
KOZ37432.1
2185
8756
729
KOZ37431.1
2186
8757
246
KOZ37430.1
2187
8758
560


534
I
4
KOZ53466.1
2189
8760
729
KOZ53465.1
2190
8761
246
KOZ53464.1
2191
8762
560


535
I
4
KOZ92709.1
2193
8764
729
KOZ92708.1
2194
8765
246
KOZ92707.1
2195
8766
560


536
I
4
CTV73490.1
2197
8768
729
CTV73519.1
2198
8769
246
CTV73555.1
2199
8770
560


537
I
4
CTY75965.1
2201
8772
729
CTY75938.1
2202
8773
246
CTY75914.1
2203
8774
560


538
I
4
KPH47568.1
2205
8776
729
KPH47567.1
2206
8777
246
KPH47566.1
2207
8778
560


539
I
4
KPH29388.1
2209
8780
729
KPH29389.1
2210
8781
246
KPH29390.1
2211
8782
560


540
I
4
KPO40054.1
2213
8784
729
KPO40055.1
2214
8785
246
KPO40056.1
2215
8786
560


541
I
4
KPP40484.1
2217
8788
729
KPP40485.1
2218
8789
246
KPP40486.1
2219
8790
560


542
I
4
KQI75364.1
2221
8792
729
KQI75363.1
2222
8793
246
KQI75362.1
2223
8794
560


543
I
4
KST33199.1
2225
8796
729
KST33200.1
2226
8797
246
KST33201.1
2227
8798
560


544
I
4
KUV50206.1
2229
8800
729
KUV50205.1
2230
8801
246
KUV50204.1
2231
8802
560


545
I
4
KUT58773.1
2233
8804
729
KUT58774.1
2234
8805
246
KUT58775.1
2235
8806
560


546
I
4
KXL70397.1
2237
8808
729
KXL70398.1
2238
8809
246
KXL70399.1
2239
8810
560


547
I
4
KXM39825.1
2241
8812
729
KXM39826.1
2242
8813
246
KXM39827.1
2243
8814
560


548
I
4
KXM53390.1
2245
8816
729
KXM53391.1
2246
8817
246
KXM53392.1
2247
8818
560


549
I
4
KXN00948.1
2249
8820
729
KXN00949.1
2250
8821
246
KXN00950.1
2251
8822
560


550
I
4
KXQ06776.1
2253
8824
729
KXQ06777.1
2254
8825
246
KXQ06778.1
2255
8826
560


551
I
4
KXQ54353.1
2257
8828
729
KXQ54354.1
2258
8829
246
KXQ54355.1
2259
8830
560


552
I
4
KXR15706.1
2261
8832
729
KXR15705.1
2262
8833
246
KXR15704.1
2263
8834
560


553
I
4
KXQ76400.1
2265
8836
729
KXQ76401.1
2266
8837
246
KXQ76402.1
2267
8838
560


554
I
4
KXQ99883.1
2269
8840
729
KXQ99884.1
2270
8841
246
KXQ99885.1
2271
8842
560


555
I
4
KXR88728.1
2273
8844
729
KXR88729.1
2274
8845
246
KXR88730.1
2275
8846
560


556
I
4
KXR78157.1
2277
8848
729
KXR78156.1
2278
8849
246
KXR78155.1
2279
8850
560


557
I
4
EGC96566.1
2281
8852
716
EGC96565.1
2282
8853
246
EGC96564.1
2283
8854
560


558
I
4
GAB54113.1
2285
8856
729
GAB54114.1
2286
8857
246
GAB54115.1
2287
8858
560


559
I
4
EHM44110.1
2289
8860
729
EHM44109.1
2290
8861
246
EHM44108.1
2291
8862
560


560
I
4
EKB79928.1
2293
8864
729
EKB79929.1
2294
8865
247
EKB79930.1
2295
8866
560


561
I
4
EKB69927.1
2297
8868
729
EKB69926.1
2298
8869
246
EKB69925.1
2299
8870
560


562
I
4
EMH92817.1
2301
8872
711
EMH92791.1
2302
8873
246
EMH92827.1
2303
8874
483


563
I
4
EMH90435.1
2305
8876
729
EMH90438.1
2306
8877
246
EMH90437.1
2307
8878
560


564
I
4
EPA89068.1
2309
8880
701
EPA89053.1
2310
8881
247
EPA89066.1
2311
8882
560


565
I
4
EPO98337.1
2313
8884
701
EPO98352.1
2314
8885
246
EPO98313.1
2315
8886
560


566
I
4
ERN60891.1
2317
8888
711
ERN60892.1
2318
8889
247
ERN60893.1
2319
8890
560


567
I
4
ESM66670.1
2321
8892
729
ESM66669.1
2322
8893
247
ESM66668.1
2323
8894
560


568
I
3
CDL16831.1
2325
8896
497
CDL16832.1
2326
8897
247
CDL16833.1
2327
8898
560


569
I
4
EWE84467.1
2328
8899
729
EWE84468.1
2329
8900
246
EWE84469.1
2330
8901
560


570
I
4
EWE89858.1
2332
8903
729
EWE89859.1
2333
8904
247
EWE89860.1
2334
8905
560


571
I
4
EZQ78636.1
2336
8907
729
EZQ78637.1
2337
8908
247
EZQ78638.1
2338
8909
560


572
I
4
EZR23958.1
2340
8911
729
EZR23959.1
2341
8912
247
EZR23960.1
2342
8913
560


573
I
4
KDK71110.1
2344
8915
729
KDK71111.1
2345
8916
247
KDK71112.1
2346
8917
560


574
I
4
KDL50055.1
2348
8919
729
KDL50056.1
2349
8920
247
KDL50057.1
2350
8921
560


575
I
4
KEF24231.1
2352
8923
729
KEF24232.1
2353
8924
247
KEF24233.1
2354
8925
560


576
I
4
AIG86121.1
2356
8927
711
AIG86120.1
2357
8928
247
AIG86119.1
2358
8929
521


577
I
4
AIT02041.1
2360
8931
729
AIT02042.1
2361
8932
247
AIT02043.1
2362
8933
560


578
I
4
KGK55644.1
2364
8935
729
KGK55905.1
2365
8936
246
KGK55643.1
2366
8937
560


579
I
4
KHF56285.1
2368
8939
729
KHF56286.1
2369
8940
247
KHF56287.1
2370
8941
560


580
I
4
CEO84459.1
2372
8943
729
CEO84460.1
2373
8944
247
CEO84461.1
2374
8945
560


581
I
4
KLZ85284.1
2376
8947
729
KLZ85285.1
2377
8948
247
KLZ85286.1
2378
8949
560


582
I
4
KME72626.1
2380
8951
729
KME72627.1
2381
8952
246
KME72628.1
2382
8953
560


583
I
4
KMG80267.1
2384
8955
729
KMG80268.1
2385
8956
247
KMG80269.1
2386
8957
560


584
I
4
KMH33138.1
2388
8959
729
KMH33139.1
2389
8960
247
KMH33140.1
2390
8961
560


585
I
4
KMH45006.1
2392
8963
729
KMH45007.1
2393
8964
247
KMH45008.1
2394
8965
560


586
I
4
KMH61874.1
2396
8967
729
KMH61875.1
2397
8968
247
KMH61876.1
2398
8969
560


587
I
4
KMH74805.1
2400
8971
729
KMH74806.1
2401
8972
247
KMH74807.1
2402
8973
560


588
I
4
KMH92291.1
2404
8975
729
KMH92292.1
2405
8976
247
KMH92293.1
2406
8977
560


589
I
4
KMH82199.1
2408
8979
729
KMH82198.1
2409
8980
246
KMH82197.1
2410
8981
560


590
I
4
KMI35044.1
2412
8983
729
KMI35043.1
2413
8984
246
KMI35042.1
2414
8985
560


591
I
4
KMJ00751.1
2416
8987
729
KMJ00752.1
2417
8988
247
KMJ00753.1
2418
8989
560


592
I
4
KMX47009.1
2420
8991
729
KMX47010.1
2421
8992
247
KMX47011.1
2422
8993
560


593
I
4
ALH85688.1
2424
8995
729
ALH88375.1
2425
8996
246
ALH85687.1
2426
8997
560


594
I
4
KPR26030.1
2428
8999
729
KPR26088.1
2429
9000
246
KPR26029.1
2430
9001
560


595
I
4
KSW78890.1
2432
9003
851
KSW78889.1
2433
9004
245
KSW78888.1
2434
9005
627


596
I
4
ALP77147.1
2436
9007
729
ALP81045.1
2437
9008
246
ALP77148.1
2438
9009
560


597
I
4
KSZ25786.1
2440
9011
729
KSZ25847.1
2441
9012
246
KSZ25785.1
2442
9013
560


598
I
4
AMA16471.1
2444
9015
729
AMA19153.1
2445
9016
246
AMA16470.1
2446
9017
560


599
I
4
KXO21002.1
2448
9019
729
KXO21035.1
2449
9020
246
KXO21003.1
2450
9021
560


600
I
4
KYL54018.1
2452
9023
729
KYL54030.1
2453
9024
246
KYL54017.1
2454
9025
560


601
I
4
KYM08970.1
2456
9027
729
KYM08978.1
2457
9028
246
KYM08971.1
2458
9029
560


602
I
4
KYL42995.1
2460
9031
729
KYL43003.1
2461
9032
246
KYL42996.1
2462
9033
560


603
I
4
KYL42676.1
2464
9035
729
KYL42684.1
2465
9036
246
KYL42677.1
2466
9037
560


604
I
4
KYL71102.1
2468
9039
729
KYL71114.1
2469
9040
246
KYL71101.1
2470
9041
560


605
I
4
KYL53998.1
2472
9043
729
KYL54010.1
2473
9044
246
KYL53997.1
2474
9045
560


606
I
4
KYM33518.1
2476
9047
729
KYM33585.1
2477
9048
246
KYM33517.1
2478
9049
560


607
I
4
KYL73344.1
2480
9051
729
KYL73352.1
2481
9052
246
KYL73345.1
2482
9053
560


608
I
4
KYL53874.1
2484
9055
729
KYL53882.1
2485
9056
246
KYL53875.1
2486
9057
560


609
I
4
KYM21786.1
2488
9059
729
KYM21794.1
2489
9060
246
KYM21787.1
2490
9061
560


610
I
4
KYM07148.1
2492
9063
729
KYM07160.1
2493
9064
246
KYM07147.1
2494
9065
560


611
I
4
KYM09278.1
2496
9067
729
KYM09290.1
2497
9068
246
KYM09277.1
2498
9069
560


612
I
4
KYL81720.1
2500
9071
729
KYL81728.1
2501
9072
246
KYL81721.1
2502
9073
560


613
I
4
KYL90348.1
2504
9075
729
KYL90356.1
2505
9076
246
KYL90349.1
2506
9077
560


614
I
4
KYM24956.1
2508
9079
729
KYM24969.1
2509
9080
246
KYM24955.1
2510
9081
560


615
I
4
CQJ58381.1
2512
9083
678
CQJ58386.1
2513
9084
287
CQJ58391.1
2514
9085
442


616
I
4
CFV22988.1
2516
9087
678
CFV22985.1
2517
9088
287
CFV22982.1
2518
9089
442


617
I
4
CNI05577.1
2520
9091
678
CNI05611.1
2521
9092
287
CNI05642.1
2522
9093
442


618
I
4
AHV33806.1
2524
9095
686
AHV33807.1
2525
9096
255
AHV33808.1
2526
9097
686


619
I
4
KOG92701.1
2528
9099
686
KOG92700.1
2529
9100
255
KOG92699.1
2530
9101
686


620
I
4
KRW58412.1
2532
9103
682
KRW58411.1
2533
9104
236
KRW58410.1
2534
9105
567


621
I
4
AAF94913.1
2536
9107
706
AAF94912.1
2537
9108
244
AAF94911.1
2538
9109
483


622
I
4
ABQ21745.1
2540
9111
706
ABQ19942.1
2541
9112
244
ABQ20511.1
2542
9113
483


623
I
4
ACP06009.1
2544
9115
706
ACP06008.1
2545
9116
244
ACP06007.1
2546
9117
483


624
I
4
ACP09874.1
2548
9119
706
ACP09873.1
2549
9120
244
ACP09872.1
2550
9121
483


625
I
3
ACQ60772.1
2552
9123
706
ACQ60773.1
2553
9124
244
ACQ60774.1
2554
9125
483


626
I
4
EFH78549.1
2555
9126
706
EFH78550.1
2556
9127
244
EFH78551.1
2557
9128
483


627
I
3




EAZ72428.1
2559
9130
244
EAZ72422.1
2560
9131
483


628
I
4
EAZ78581.1
2562
9133
706
EAZ78546.1
2563
9134
244
EAZ78565.1
2564
9135
483


629
I
4
AET26859.1
2566
9137
706
AET26858.1
2567
9138
244
AET26857.1
2568
9139
483


630
I
4
KNH51113.1
2570
9141
706
KNH51114.1
2571
9142
244
KNH51115.1
2572
9143
483


631
I
4
KNA61358.1
2574
9145
706
KNA61359.1
2575
9146
244
KNA61360.1
2576
9147
483


632
I
4
EEO08431.1
2578
9149
706
EEO08430.1
2579
9150
244
EEO08429.1
2580
9151
483


633
I
4
EEO16534.1
2582
9153
706
EEO16533.1
2583
9154
244
EEO16532.1
2584
9155
483


634
I
4
EEO20559.1
2586
9157
706
EEO20560.1
2587
9158
244
EEO20561.1
2588
9159
483


635
I
4
EET92687.1
2590
9161
706
EET92688.1
2591
9162
244
EET92689.1
2592
9163
483


636
I
4
EEY40708.1
2594
9165
706
EEY40707.1
2595
9166
244
EEY40706.1
2596
9167
483


637
I
4
EEY47283.1
2598
9169
687
EEY47282.1
2599
9170
244
EEY47281.1
2600
9171
483


638
I
4
EGQ97277.1
2602
9173
687
EGQ97276.1
2603
9174
244
EGQ97275.1
2604
9175
483


639
I
4
EGQ98251.1
2606
9177
706
EGQ98250.1
2607
9178
244
EGQ98249.1
2608
9179
483


640
I
4
EGS48435.1
2610
9181
706
EGS48434.1
2611
9182
244
EGS48433.1
2612
9183
483


641
I
4
EGS47646.1
2614
9185
706
EGS47645.1
2615
9186
244
EGS47644.1
2616
9187
483


642
I
4
EGS47807.1
2618
9189
706
EGS47806.1
2619
9190
244
EGS47805.1
2620
9191
483


643
I
4
EGS62508.1
2622
9193
687
EGS62507.1
2623
9194
244
EGS62506.1
2624
9195
483


644
I
4
EGS70775.1
2626
9197
706
EGS70774.1
2627
9198
244
EGS70773.1
2628
9199
483


645
I
4
EHH71591.1
2630
9201
706
EHH71590.1
2631
9202
244
EHH71589.1
2632
9203
483


646
I
4
EHH83258.1
2634
9205
706
EHH83257.1
2635
9206
244
EHH83256.1
2636
9207
483


647
I
4
EHH87250.1
2638
9209
706
EHH87249.1
2639
9210
244
EHH87248.1
2640
9211
483


648
I
4
EHH97392.1
2642
9213
706
EHH97391.1
2643
9214
244
EHH97390.1
2644
9215
483


649
I
4
EHI04662.1
2646
9217
706
EHI05345.1
2647
9218
218
EHI05392.1
2648
9219
483


650
I
4
EHI04020.1
2650
9221
706
EHI04019.1
2651
9222
244
EHI04018.1
2652
9223
214


651
I
4
EHH99557.1
2654
9225
706
EHH99556.1
2655
9226
244
EHH99555.1
2656
9227
472


652
I
4
EHH93201.1
2658
9229
706
EHH93200.1
2659
9230
244
EHH93199.1
2660
9231
483


653
I
4
EHH82145.1
2662
9233
706
EHH82144.1
2663
9234
244
EHH82143.1
2664
9235
483


654
I
4
EHH72367.1
2666
9237
706
EHH72366.1
2667
9238
244
EHH72365.1
2668
9239
483


655
I
4
EHH76760.1
2670
9241
706
EHH76759.1
2671
9242
244
EHH76758.1
2672
9243
483


656
I
4
AFC58582.1
2674
9245
706
AFC58581.1
2675
9246
244
AFC58580.1
2676
9247
483


657
I
4
EJH73152.1
2678
9249
706
EJH73151.1
2679
9250
244
EJH73150.1
2680
9251
483


658
I
4
EJH69792.1
2682
9253
706
EJH69791.1
2683
9254
244
EJH69790.1
2684
9255
483


659
I
4
EJH28006.1
2686
9257
706
EJH28005.1
2687
9258
218
EJH28004.1
2688
9259
483


660
I
4
EJH27267.1
2690
9261
706
EJH27423.1
2691
9262
244
EJH27099.1
2692
9263
483


661
I
4
EJH29363.1
2694
9265
706
EJH29362.1
2695
9266
218
EJH29361.1
2696
9267
451


662
I
4
EJH38300.1
2698
9269
706
EJH38299.1
2699
9270
244
EJH38298.1
2700
9271
483


663
I
4
EJH70293.1
2702
9273
706
EJH70292.1
2703
9274
244
EJH70291.1
2704
9275
483


664
I
4
EJH44250.1
2706
9277
706
EJH44249.1
2707
9278
218
EJH44248.1
2708
9279
483


665
I
4
EJH55113.1
2710
9281
706
EJH55112.1
2711
9282
244
EJH55111.1
2712
9283
483


666
I
4
EJH55194.1
2714
9285
706
EJH55227.1
2715
9286
218
EJH55313.1
2716
9287
483


667
I
4
EJH83358.1
2718
9289
706
EJH83357.1
2719
9290
244
EJH83356.1
2720
9291
483


668
I
4
EJH85693.1
2722
9293
706
EJH85692.1
2723
9294
244
EJH85691.1
2724
9295
483


669
I
4
EJH80829.1
2726
9297
706
EJH80828.1
2727
9298
244
EJH80827.1
2728
9299
483


670
I
4
EJH40245.1
2730
9301
706
EJH40244.1
2731
9302
244
EJH40243.1
2732
9303
483


671
I
4
EKG51169.1
2734
9305
706
EKG51168.1
2735
9306
244
EKG51167.1
2736
9307
483


672
I
4
EKG45548.1
2738
9309
706
EKG45547.1
2739
9310
244
EKG45546.1
2740
9311
483


673
I
4
EKG69364.1
2742
9313
706
EKG69363.1
2743
9314
244
EKG69362.1
2744
9315
483


674
I
4
EKG78207.1
2746
9317
706
EKG78206.1
2747
9318
244
EKG78205.1
2748
9319
483


675
I
4
EKG79527.1
2750
9321
687
EKG79526.1
2751
9322
244
EKG79525.1
2752
9323
483


676
I
4
EKG89065.1
2754
9325
687
EKG89064.1
2755
9326
218
EKG89063.1
2756
9327
483


677
I
4
EKK80943.1
2758
9329
706
EKK80942.1
2759
9330
244
EKK80941.1
2760
9331
483


678
I
4
EKK97423.1
2762
9333
687
EKK97422.1
2763
9334
244
EKK97421.1
2764
9335
483


679
I
4
EKL07579.1
2766
9337
318
EKL07578.1
2767
9338
244
EKL07615.1
2768
9339
265


680
I
4
EKL26689.1
2770
9341
706
EKL26688.1
2771
9342
244
EKL26687.1
2772
9343
483


681
I
4
EKL25950.1
2774
9345
706
EKL25949.1
2775
9346
244
EKL25948.1
2776
9347
483


682
I
4
EKL86050.1
2778
9349
706
EKL86049.1
2779
9350
244
EKL86048.1
2780
9351
483


683
I
4
EKM09914.1
2782
9353
706
EKM09901.1
2783
9354
244
EKM09801.1
2784
9355
483


684
I
4
EKL86446.1
2786
9357
687
EKL86445.1
2787
9358
244
EKL86444.1
2788
9359
483


685
I
4
EKM18416.1
2790
9361
687
EKM18415.1
2791
9362
244
EKM18414.1
2792
9363
483


686
I
4
ELT24501.1
2794
9365
687
ELT24500.1
2795
9366
218
ELT24499.1
2796
9367
451


687
I
4
ELT39817.1
2798
9369
706
ELT39816.1
2799
9370
244
ELT39815.1
2800
9371
483


688
I
4
ELS74167.1
2802
9373
706
ELS74166.1
2803
9374
244
ELS74165.1
2804
9375
483


689
I
4
ELS81598.1
2806
9377
687
ELS81597.1
2807
9378
244
ELS81596.1
2808
9379
483


690
I
4
ELS88997.1
2810
9381
706
ELS88996.1
2811
9382
244
ELS88995.1
2812
9383
483


691
I
4
ELS96628.1
2814
9385
706
ELS96627.1
2815
9386
244
ELS96626.1
2816
9387
483


692
I
4
ELT03894.1
2818
9389
706
ELT03893.1
2819
9390
244
ELT03892.1
2820
9391
483


693
I
4
ELT10277.1
2822
9393
687
ELT10276.1
2823
9394
244
ELT10275.1
2824
9395
483


694
I
4
ELT32501.1
2826
9397
706
ELT32500.1
2827
9398
244
ELT32499.1
2828
9399
483


695
I
4
EMB02074.1
2830
9401
706
EMB02075.1
2831
9402
244
EMB02076.1
2832
9403
483


696
I
4
EMP84497.1
2834
9405
706
EMP84506.1
2835
9406
244
EMP84573.1
2836
9407
483


697
I
4
EMP97717.1
2838
9409
687
EMP97716.1
2839
9410
244
EMP97715.1
2840
9411
483


698
I
4
EMP95638.1
2842
9413
706
EMP95637.1
2843
9414
244
EMP95636.1
2844
9415
483


699
I
4
EMQ03274.1
2846
9417
706
EMQ03273.1
2847
9418
244
EMQ03272.1
2848
9419
483


700
I
4
EMQ04749.1
2850
9421
687
EMQ04748.1
2851
9422
244
EMQ04747.1
2852
9423
483


701
I
4
EMQ11843.1
2854
9425
687
EMQ11842.1
2855
9426
244
EMQ11841.1
2856
9427
483


702
I
4
EMQ11497.1
2858
9429
706
EMQ11496.1
2859
9430
244
EMQ11495.1
2860
9431
483


703
I
4
EMQ16257.1
2862
9433
687
EMQ16256.1
2863
9434
244
EMQ16255.1
2864
9435
483


704
I
4
EMQ22003.1
2866
9437
706
EMQ22002.1
2867
9438
244
EMQ22001.1
2868
9439
483


705
I
4
EMQ27293.1
2870
9441
706
EMQ27292.1
2871
9442
244
EMQ27291.1
2872
9443
483


706
I
4
EMQ26220.1
2874
9445
706
EMQ26219.1
2875
9446
244
EMQ26218.1
2876
9447
483


707
I
4
EMQ32320.1
2878
9449
706
EMQ32319.1
2879
9450
244
EMQ32318.1
2880
9451
483


708
I
4
EMQ37900.1
2882
9453
706
EMQ37899.1
2883
9454
218
EMQ37898.1
2884
9455
483


709
I
4
EMQ51395.1
2886
9457
706
EMQ51394.1
2887
9458
244
EMQ51393.1
2888
9459
483


710
I
4
EMQ53996.1
2890
9461
706
EMQ53995.1
2891
9462
244
EMQ53994.1
2892
9463
483


711
I
4
EMQ39198.1
2894
9465
687
EMQ39197.1
2895
9466
244
EMQ39196.1
2896
9467
483


712
I
4
EMQ68296.1
2898
9469
687
EMQ68295.1
2899
9470
244
EMQ68294.1
2900
9471
483


713
I
4
EMQ62929.1
2902
9473
687
EMQ62928.1
2903
9474
244
EMQ62927.1
2904
9475
483


714
I
4
EMQ43439.1
2906
9477
706
EMQ43438.1
2907
9478
244
EMQ43437.1
2908
9479
483


715
I
4
EMQ47715.1
2910
9481
706
EMQ47714.1
2911
9482
244
EMQ47713.1
2912
9483
483


716
I
4
EWM32711.1
2914
9485
706
EWM32710.1
2915
9486
244
EWM32709.1
2916
9487
483


717
I
4
KEA49020.1
2918
9489
706
KEA49019.1
2919
9490
244
KEA49018.1
2920
9491
483


718
I
3
KEH05440.1
2922
9493
706
KEH05439.1
2923
9494
244
KEH05438.1
2924
9495
483


719
I
4
KEH80152.1
2925
9496
706
KEH80153.1
2926
9497
244
KEH80154.1
2927
9498
483


720
I
4
KEH82623.1
2929
9500
706
KEH82624.1
2930
9501
244
KEH82625.1
2931
9502
483


721
I
3
KFE04003.1
2933
9504
569
KFE04002.1
2934
9505
244
KFE04000.1
2935
9506
483


722
I
3
KFE07491.1
2936
9507
569
KFE07489.1
2937
9508
244
KFE07492.1
2938
9509
483


723
I
4
KFE03707.1
2939
9510
687
KFE03742.1
2940
9511
244
KFE03727.1
2941
9512
483


724
I
4
KFE20316.1
2943
9514
687
KFE20291.1
2944
9515
244
KFE20317.1
2945
9516
483


725
I
4
KFZ34215.1
2947
9518
706
KFZ34214.1
2948
9519
244
KFZ34213.1
2949
9520
483


726
I
4
AIT29756.1
2951
9522
706
AIT29755.1
2952
9523
244
AIT29754.1
2953
9524
483


727
I
4
KHE18844.1
2955
9526
706
KHE18843.1
2956
9527
244
KHE18842.1
2957
9528
483


728
I
4
KHE21916.1
2959
9530
706
KHE21917.1
2960
9531
244
KHE21918.1
2961
9532
483


729
I
4
BAP03192.1
2963
9534
706
BAP03191.1
2964
9535
244
BAP03190.1
2965
9536
483


730
I
4
KJD16371.1
2967
9538
706
KJD16372.1
2968
9539
244
KJD16373.1
2969
9540
483


731
I
4
KJJ52420.1
2971
9542
706
KJJ52419.1
2972
9543
244
KJJ52418.1
2973
9544
483


732
I
4
KJJ54929.1
2975
9546
706
KJJ54928.1
2976
9547
244
KJJ54927.1
2977
9548
483


733
I
4
KJR76013.1
2979
9550
706
KJR76012.1
2980
9551
244
KJR76011.1
2981
9552
483


734
I
4
KJS92997.1
2983
9554
706
KJS92996.1
2984
9555
244
KJS92995.1
2985
9556
483


735
I
4
AKA00225.1
2987
9558
706
AKA00224.1
2988
9559
244
AKA00223.1
2989
9560
483


736
I
4
KJW14527.1
2991
9562
706
KJW14526.1
2992
9563
244
KJW14525.1
2993
9564
483


737
I
4
KJX83381.1
2995
9566
706
KJX83382.1
2996
9567
244
KJX83383.1
2997
9568
483


738
I
4
KKP13603.1
2999
9570
687
KKP13602.1
3000
9571
218
KKP13601.1
3001
9572
483


739
I
4
KKP11543.1
3003
9574
706
KKP11542.1
3004
9575
244
KKP11541.1
3005
9576
472


740
I
4
KKP10397.1
3007
9578
706
KKP10398.1
3008
9579
218
KKP10399.1
3009
9580
472


741
I
4
AKO75286.1
3011
9582
706
AKO75285.1
3012
9583
244
AKO75284.1
3013
9584
483


742
I
3




CSC37237.1
3015
9586
244
CSC37265.1
3016
9587
492


743
I
4
CRZ83881.1
3018
9589
687
CRZ83843.1
3019
9590
244
CRZ83797.1
3020
9591
166


744
I
4
CSE02212.1
3022
9593
687
CSE02198.1
3023
9594
244
CSE02182.1
3024
9595
483


745
I
4
CRZ49596.1
3026
9597
687
CRZ49592.1
3027
9598
244
CRZ49589.1
3028
9599
483


746
I
4
CSC16355.1
3030
9601
687
CSC16391.1
3031
9602
244
CSC16431.1
3032
9603
483


747
I
4
CSB69082.1
3034
9605
584
CSB69144.1
3035
9606
244
CSB69175.1
3036
9607
483


748
I
4
CSA28373.1
3038
9609
687
CSA28411.1
3039
9610
244
CSA28460.1
3040
9611
483


749
I
4
CSB84212.1
3042
9613
683
CSB84179.1
3043
9614
244
CSB84126.1
3044
9615
166


750
I
4
CSB63035.1
3046
9617
706
CSB63063.1
3047
9618
244
CSB63093.1
3048
9619
483


751
I
4
CSA19108.1
3050
9621
687
CSA19143.1
3051
9622
244
CSA19174.1
3052
9623
483


752
I
4
CSD58035.1
3054
9625
687
CSD58068.1
3055
9626
244
CSD58113.1
3056
9627
483


753
I
3
CSB77636.1
3058
9629
706
CSB77620.1
3059
9630
244
CSB77591.1
3060
9631
265


754
I
4
CSB47699.1
3061
9632
706
CSB47717.1
3062
9633
244
CSB47737.1
3063
9634
483


755
I
4
CSA30864.1
3065
9636
687
CSA30887.1
3066
9637
244
CSA30916.1
3067
9638
483


756
I
4
CSB56036.1
3069
9640
687
CSB56072.1
3070
9641
244
CSB56096.1
3071
9642
483


757
I
4
CRZ98430.1
3073
9644
687
CRZ98405.1
3074
9645
244
CRZ98377.1
3075
9646
483


758
I
4
CSA01223.1
3077
9648
521
CSA01278.1
3078
9649
244
CSA01305.1
3079
9650
174


759
I
4
CSB97601.1
3081
9652
687
CSB97580.1
3082
9653
244
CSB97551.1
3083
9654
307


760
I
4
CSC01831.1
3085
9656
687
CSC01791.1
3086
9657
244
CSC01763.1
3087
9658
483


761
I
4
CRZ46095.1
3089
9660
706
CRZ46097.1
3090
9661
244
CRZ46104.1
3091
9662
93


762
I
4
CSA07930.1
3093
9664
687
CSA07897.1
3094
9665
244
CSA07877.1
3095
9666
483


763
I
4
CSC23820.1
3097
9668
687
CSC23781.1
3098
9669
244
CSC23752.1
3099
9670
483


764
I
3
CSB05145.1
3101
9672
687
CSB05176.1
3102
9673
244
CSB05201.1
3103
9674
483


765
I
4
CSE01515.1
3104
9675
687
CSE01529.1
3105
9676
244
CSE01548.1
3106
9677
483


766
I
3
CSA08484.1
3108
9679
687
CSA08454.1
3109
9680
244


767
I
4
CRZ45176.1
3111
9682
687
CRZ45172.1
3112
9683
244
CRZ45168.1
3113
9684
483


768
I
4
CSA06942.1
3115
9686
687
CSA06965.1
3116
9687
244
CSA06996.1
3117
9688
483


769
I
4
CSA08863.1
3119
9690
687
CSA08826.1
3120
9691
244
CSA08791.1
3121
9692
483


770
I
4
CSA15692.1
3123
9694
687
CSA15667.1
3124
9695
244
CSA15641.1
3125
9696
265


771
I
4
CSA74473.1
3127
9698
706
CSA74503.1
3128
9699
244
CSA74529.1
3129
9700
166


772
I
3




CSB88670.1
3131
9702
244
CSB88619.1
3132
9703
333


773
I
4
CSC80217.1
3134
9705
687
CSC80194.1
3135
9706
244
CSC80172.1
3136
9707
483


774
I
4
CSB83682.1
3138
9709
687
CSB83710.1
3139
9710
244
CSB83780.1
3140
9711
483


775
I
3




CSB56503.1
3142
9713
244
CSB56524.1
3143
9714
483


776
I
4
CSC85490.1
3145
9716
687
CSC85465.1
3146
9717
244
CSC85445.1
3147
9718
483


777
I
4
CSB86358.1
3149
9720
706
CSB86328.1
3150
9721
244
CSB86302.1
3151
9722
265


778
I
4
CSD13052.1
3153
9724
687
CSD13079.1
3154
9725
244
CSD13105.1
3155
9726
483


779
I
4
CSD79475.1
3157
9728
687
CSD79446.1
3158
9729
244
CSD79419.1
3159
9730
483


780
I
4
CSD86966.1
3161
9732
687
CSD86944.1
3162
9733
244
CSD86920.1
3163
9734
483


781
I
4
CSA39609.1
3165
9736
687
CSA39643.1
3166
9737
244
CSA39681.1
3167
9738
483


782
I
4
CSC76746.1
3169
9740
687
CSC76722.1
3170
9741
244
CSC76697.1
3171
9742
483


783
I
4
CSA42744.1
3173
9744
687
CSA42770.1
3174
9745
244
CSA42798.1
3175
9746
483


784
I
4
CSA52054.1
3177
9748
687
CSA52090.1
3178
9749
244
CSA52135.1
3179
9750
483


785
I
4
CSD31909.1
3181
9752
687
CSD31884.1
3182
9753
244
CSD31863.1
3183
9754
483


786
I
4
CSD17795.1
3185
9756
687
CSD17820.1
3186
9757
244
CSD17844.1
3187
9758
483


787
I
4
CSD38760.1
3189
9760
687
CSD38739.1
3190
9761
244
CSD38713.1
3191
9762
483


788
I
4
CSA26418.1
3193
9764
687
CSA26383.1
3194
9765
244
CSA26354.1
3195
9766
483


789
I
4
CSA45804.1
3197
9768
706
CSA45841.1
3198
9769
244
CSA45878.1
3199
9770
483


790
I
4
CSD96243.1
3201
9772
687
CSD96273.1
3202
9773
244
CSD96300.1
3203
9774
483


791
I
4
CSA54123.1
3205
9776
687
CSA54080.1
3206
9777
244
CSA54039.1
3207
9778
483


792
I
3
CSC37722.1
3209
9780
443
CSC37773.1
3210
9781
244


793
I
4
CSA88061.1
3212
9783
443
CSA88093.1
3213
9784
244
CSA88149.1
3214
9785
350


794
I
4
CSA15119.1
3216
9787
706
CSA15151.1
3217
9788
244
CSA15173.1
3218
9789
107


795
I
3




CSC98411.1
3220
9791
218
CSC98455.1
3221
9792
199


796
I
4
CRZ48558.1
3223
9794
687
CRZ48557.1
3224
9795
244
CRZ48553.1
3225
9796
307


797
I
3




CSB25008.1
3227
9798
244
CSB25021.1
3228
9799
360


798
I
4
CSD98728.1
3230
9801
687
CSD98712.1
3231
9802
244
CSD98693.1
3232
9803
483


799
I
3




CSA36905.1
3234
9805
244
CSA36950.1
3235
9806
231


800
I
3
CSA30693.1
3237
9808
706
CSA30747.1
3238
9809
244
CSA30798.1
3239
9810
483


801
I
4
CSD70399.1
3240
9811
687
CSD70430.1
3241
9812
244
CSD70457.1
3242
9813
483


802
I
3




CSD13971.1
3244
9815
244
CSD13924.1
3245
9816
483


803
I
4
CSD31814.1
3247
9818
687
CSD31841.1
3248
9819
244
CSD31862.1
3249
9820
483


804
I
4
CSE18852.1
3251
9822
687
CSE18836.1
3252
9823
244
CSE18821.1
3253
9824
483


805
I
4
CSD93125.1
3255
9826
687
CSD93151.1
3256
9827
244
CSD93175.1
3257
9828
483


806
I
4
CSA21244.1
3259
9830
687
CSA21199.1
3260
9831
244
CSA21173.1
3261
9832
483


807
I
4
CSA44863.1
3263
9834
715
CSA44812.1
3264
9835
244
CSA44762.1
3265
9836
265


808
I
4
CSD30711.1
3267
9838
687
CSD30681.1
3268
9839
244
CSD30657.1
3269
9840
483


809
I
4
CSD92444.1
3271
9842
687
CSD92423.1
3272
9843
244
CSD92407.1
3273
9844
483


810
I
4
CSD99240.1
3275
9846
687
CSD99267.1
3276
9847
244
CSD99291.1
3277
9848
483


811
I
4
CSA23088.1
3279
9850
687
CSA23044.1
3280
9851
244
CSA23002.1
3281
9852
483


812
I
4
CSA49073.1
3283
9854
706
CSA49123.1
3284
9855
244
CSA49171.1
3285
9856
483


813
I
4
CSC63545.1
3287
9858
478
CSC63565.1
3288
9859
244
CSC63589.1
3289
9860
134


814
I
4
CRZ49242.1
3291
9862
687
CRZ49246.1
3292
9863
244
CRZ49252.1
3293
9864
483


815
I
4
CSC03222.1
3295
9866
706
CSC03177.1
3296
9867
244
CSC03135.1
3297
9868
483


816
I
4
CSD87325.1
3299
9870
687
CSD87301.1
3300
9871
244
CSD87274.1
3301
9872
483


817
I
4
CSD21169.1
3303
9874
687
CSD21190.1
3304
9875
244
CSD21226.1
3305
9876
483


818
I
3
CSC95321.1
3307
9878
687
CSC95342.1
3308
9879
244
CSC95365.1
3309
9880
492


819
I
4
CSA26886.1
3310
9881
687
CSA26825.1
3311
9882
244
CSA26777.1
3312
9883
166


820
I
4
CSB50406.1
3314
9885
687
CSB50386.1
3315
9886
244
CSB50354.1
3316
9887
483


821
I
4
CSB24741.1
3318
9889
599
CSB24761.1
3319
9890
244
CSB24790.1
3320
9891
166


822
I
4
CSB68001.1
3322
9893
687
CSB68025.1
3323
9894
244
CSB68050.1
3324
9895
483


823
I
4
CSB16341.1
3326
9897
706
CSB16315.1
3327
9898
244
CSB16293.1
3328
9899
483


824
I
4
CRZ89319.1
3330
9901
687
CRZ89282.1
3331
9902
244
CRZ89245.1
3332
9903
483


825
I
4
CSD99897.1
3334
9905
687
CSD99912.1
3335
9906
244
CSD99928.1
3336
9907
483


826
I
4
CSA40795.1
3338
9909
687
CSA40831.1
3339
9910
244
CSA40854.1
3340
9911
483


827
I
4
CSC19419.1
3342
9913
687
CSC19396.1
3343
9914
244
CSC19370.1
3344
9915
483


828
I
4
CSD27220.1
3346
9917
687
CSD27192.1
3347
9918
244
CSD27166.1
3348
9919
483


829
I
4
CSA25112.1
3350
9921
687
CSA25084.1
3351
9922
244
CSA25048.1
3352
9923
483


830
I
4
CSD33112.1
3354
9925
531
CSD33079.1
3355
9926
244
CSD33047.1
3356
9927
483


831
I
4
CSD26002.1
3358
9929
687
CSD25975.1
3359
9930
244
CSD25966.1
3360
9931
483


832
I
4
CSD38021.1
3362
9933
687
CSD37998.1
3363
9934
244
CSD37970.1
3364
9935
483


833
I
4
CSD14687.1
3366
9937
687
CSD14704.1
3367
9938
244
CSD14728.1
3368
9939
483


834
I
3
CSA18679.1
3370
9941
687
CSA18640.1
3371
9942
244
CSA18601.1
3372
9943
483


835
I
4
CSD46955.1
3373
9944
687
CSD46995.1
3374
9945
244
CSD47023.1
3375
9946
483


836
I
4
CRZ80473.1
3377
9948
716
CRZ80451.1
3378
9949
244
CRZ80418.1
3379
9950
483


837
I
4
CSC19266.1
3381
9952
687
CSC19248.1
3382
9953
244
CSC19228.1
3383
9954
483


838
I
4
CSA24075.1
3385
9956
687
CSA24040.1
3386
9957
244
CSA24013.1
3387
9958
483


839
I
4
CSA07992.1
3389
9960
687
CSA08026.1
3390
9961
244
CSA08045.1
3391
9962
483


840
I
4
CSB55819.1
3393
9964
578
CSB55765.1
3394
9965
244
CSB55741.1
3395
9966
483


841
I
4
CSA25748.1
3397
9968
687
CSA25793.1
3398
9969
244
CSA25829.1
3399
9970
483


842
I
4
CSD34768.1
3401
9972
687
CSD34731.1
3402
9973
244
CSD34701.1
3403
9974
483


843
I
4
CSC58199.1
3405
9976
571
CSC58139.1
3406
9977
244
CSC58133.1
3407
9978
483


844
I
4
CSA23793.1
3409
9980
706
CSA23829.1
3410
9981
244
CSA23867.1
3411
9982
483


845
I
4
CSB25867.1
3413
9984
605
CSB25856.1
3414
9985
244
CSB25844.1
3415
9986
307


846
I
4
CSD08489.1
3417
9988
687
CSD08470.1
3418
9989
244
CSD08448.1
3419
9990
483


847
I
4
CSD25549.1
3421
9992
687
CSD25570.1
3422
9993
244
CSD25590.1
3423
9994
483


848
I
4
CSD28514.1
3425
9996
687
CSD28543.1
3426
9997
244
CSD28572.1
3427
9998
483


849
I
4
CSA45340.1
3429
10000
687
CSA45303.1
3430
10001
244
CSA45263.1
3431
10002
483


850
I
4
CSD82595.1
3433
10004
687
CSD82566.1
3434
10005
244
CSD82541.1
3435
10006
483


851
I
4
CSC20854.1
3437
10008
687
CSC20817.1
3438
10009
244
CSC20782.1
3439
10010
483


852
I
4
CSC43426.1
3441
10012
712
CSC43406.1
3442
10013
244
CSC43375.1
3443
10014
483


853
I
4
CSC06846.1
3445
10016
706
CSC06871.1
3446
10017
244
CSC06894.1
3447
10018
483


854
I
4
CSB50546.1
3449
10020
706
CSB50514.1
3450
10021
244
CSB50503.1
3451
10022
483


855
I
4
CSE01188.1
3453
10024
687
CSE01165.1
3454
10025
244
CSE01149.1
3455
10026
483


856
I
4
CSB99258.1
3457
10028
687
CSB99303.1
3458
10029
244
CSB99336.1
3459
10030
483


857
I
3




KOY92951.1
3461
10032
244
KOY92950.1
3462
10033
483


858
I
4
KOY92344.1
3464
10035
706
KOY92343.1
3465
10036
244
KOY92342.1
3466
10037
483


859
I
4
KOY97240.1
3468
10039
706
KOY97239.1
3469
10040
244
KOY97238.1
3470
10041
483


860
I
4
KOZ01032.1
3472
10043
706
KOZ01031.1
3473
10044
244
KOZ01030.1
3474
10045
483


861
I
4
KPA03327.1
3476
10047
706
KPA03326.1
3477
10048
244
KPA03325.1
3478
10049
483


862
I
4
ALJ63816.1
3480
10051
706
ALJ63817.1
3481
10052
244
ALJ63818.1
3482
10053
483


863
I
4
KTL56325.1
3484
10055
706
KTL56324.1
3485
10056
244
KTL56323.1
3486
10057
483


864
I
3




KUO35497.1
3488
10059
244
KUO35496.1
3489
10060
483


865
I
3
KUP87193.1
3491
10062
706
KUP87194.1
3492
10063
244
KUP87195.1
3493
10064
483


866
I
4
KUP86906.1
3494
10065
706
KUP86907.1
3495
10066
244
KUP86908.1
3496
10067
483


867
I
4
KUY44285.1
3498
10069
706
KUY44286.1
3499
10070
244
KUY44287.1
3500
10071
483


868
I
4
KVI44905.1
3502
10073
706
KVI44904.1
3503
10074
244
KVI44903.1
3504
10075
483


869
I
4
KWW48033.1
3506
10077
706
KWW48034.1
3507
10078
244
KWW48035.1
3508
10079
483


870
I
4
EIG23809.1
3510
10081
728
EIG23861.1
3511
10082
263
EIG23836.1
3512
10083
507


871
I
4
KGQ46272.1
3514
10085
677
KGQ46273.1
3515
10086
298
KGQ46274.1
3516
10087
479


872
I
4
KGQ51096.1
3518
10089
677
KGQ51097.1
3519
10090
298
KGQ51098.1
3520
10091
479


873
I
4
KGQ65037.1
3522
10093
677
KGQ65036.1
3523
10094
298
KGQ65035.1
3524
10095
479


874
I
4
ACX76639.1
3526
10097
584
ACX76638.1
3527
10098
243
ACX76637.1
3528
10099
455


875
I
4
ADL24842.1
3530
10101
584
ADL27028.1
3531
10102
243
ADL26078.1
3532
10103
455


876
I
4
EEO43106.1
3534
10105
535
EEO43107.2
3535
10106
207
EEO43108.1
3536
10107
402


877
I
4
EPC08247.1
3538
10109
535
EPC08246.1
3539
10110
207
EPC08245.1
3540
10111
402


878
I
4
ERT42791.1
3542
10113
583
ERT42790.1
3543
10114
207
ERT42789.1
3544
10115
402


879
I
4
KGE62641.1
3546
10117
583
KGE62642.1
3547
10118
232
KGE62643.1
3548
10119
401


880
I
4
EFE87094.1
3550
10121
583
EFE87095.1
3551
10122
232
EFE87096.1
3552
10123
402


881
I
4
ABM29947.1
3554
10125
677
ABM29948.1
3555
10126
259
ABM29949.1
3556
10127
455


882
I
4
ADB47624.1
3558
10129
616
ADB47623.1
3559
10130
235
ADB47622.1
3560
10131
467


883
I
4
ADE85046.1
3562
10133
681
ADE85047.1
3563
10134
334
ADE85048.1
3564
10135
444


884
I
4
ETD02074.1
3566
10137
681
ETD02075.1
3567
10138
334
ETD02172.1
3568
10139
431


885
I
4
ETD86671.1
3570
10141
681
ETD86670.1
3571
10142
334
ETD86702.1
3572
10143
444


886
I
4
ETD77748.1
3574
10145
681
ETD77749.1
3575
10146
334
ETD77862.1
3576
10147
431


887
I
4
ETE54106.1
3578
10149
681
ETE54107.1
3579
10150
334
ETE54205.1
3580
10151
431


888
I
3
KKI99610.1
3582
10153
673
KKI99609.1
3583
10154
248
KKI99608.1
3584
10155
488


889
I
4
KFI23089.1
3585
10156
701
KFI23090.1
3586
10157
250
KFI23091.1
3587
10158
476


890
I
4
KMY56660.1
3589
10160
648
KMY56661.1
3590
10161
223
KMY56662.1
3591
10162
426


891
I
4
KMY64903.1
3593
10164
648
KMY64904.1
3594
10165
223
KMY64905.1
3595
10166
426


892
I
4
KYD35338.1
3597
10168
648
KYD35337.1
3598
10169
223
KYD35336.1
3599
10170
426


893
I
4
GAD13408.1
3601
10172
460
GAD13407.1
3602
10173
211
GAD13406.1
3603
10174
426


894
I
3
EMT39963.1
3605
10176
540
EMT40032.1
3606
10177
230


895
I
3
EGO65557.1
3608
10179
743
EGO65558.1
3609
10180
232
EGO65559.1
3610
10181
476


896
I
3
EKF49049.1
3611
10182
411
EKF49048.1
3612
10183
218


897
I
4
BAL95138.1
3614
10185
667
BAL95139.1
3615
10186
208
BAL95140.1
3616
10187
565


898
I
4
KTC75261.1
3618
10189
636
KTC75262.1
3619
10190
234
KTC75263.1
3620
10191
482


899
I
4
EFF49971.1
3622
10193
667
EFF49970.1
3623
10194
231
EFF49969.1
3624
10195
616


900
I
4
ABU75897.1
3626
10197
729
ABU75896.1
3627
10198
246
ABU75895.1
3628
10199
562


901
I
3




EGL73326.1
3630
10201
246
EGL73325.1
3631
10202
523


902
I
3
CCK08186.1
3633
10204
259
CCK08187.1
3634
10205
246
CCK08188.1
3635
10206
562


903
I
4
CCK02754.1
3636
10207
656
CCK02755.1
3637
10208
246
CCK02756.1
3638
10209
523


904
I
4
CCO48375.1
3640
10211
706
CCO48376.1
3641
10212
244
CCO48377.1
3642
10213
482


905
I
4
CCK80596.1
3644
10215
641
CCK80597.1
3645
10216
250
CCK80598.1
3646
10217
485


906
I
4
KGD34430.1
3648
10219
667
KGD34483.1
3649
10220
234
KGD34420.1
3650
10221
573


907
I
4
KGS74771.1
3652
10223
670
KGS74845.1
3653
10224
241
KGS74775.1
3654
10225
546


908
I
4
KGW09067.1
3656
10227
667
KGW09406.1
3657
10228
239
KGW09097.1
3658
10229
454


909
I
4
KGX47863.1
3660
10231
555
KGX47852.1
3661
10232
234
KGX47883.1
3662
10233
478


910
I
4
KGX39518.1
3664
10235
667
KGX39502.1
3665
10236
234
KGX39650.1
3666
10237
573


911
I
4
CPH56696.1
3668
10239
780
CPH56659.1
3669
10240
241
CPH56628.1
3670
10241
605


912
I
4
KSB52477.1
3672
10243
729
KSB52476.1
3673
10244
246
KSB52475.1
3674
10245
560


913
I
3
AEF17805.1
3676
10247
540
AEF17804.1
3677
10248
230


914
I
4
ENW17902.1
3679
10250
146
ENW17901.1
3680
10251
243
ENW17900.1
3681
10252
474


915
I
4
ABO66647.1
3683
10254
626
ABO66648.1
3684
10255
223
ABO66649.1
3685
10256
426


916
I
3
ACI99727.1
3687
10258
763
ACI99728.1
3688
10259
314
ACI99729.1
3689
10260
484


917
I
4
ACS21194.1
3690
10261
667
ACS21193.1
3691
10262
234
ACS21192.1
3692
10263
574


918
I
3
EIC29071.1
3694
10265
605
EIC29072.1
3695
10266
231
EIC29073.1
3696
10267
527


919
I
4
EET81943.1
3697
10268
686
EET81942.1
3698
10269
243
EET81941.1
3699
10270
471


920
I
4
ENU31377.1
3701
10272
300
ENU31376.1
3702
10273
243
ENU31375.1
3703
10274
456


921
I
4
ALA59739.1
3705
10276
656
ALA59738.1
3706
10277
240
ALA59737.1
3707
10278
548


922
I
4
AGB41055.1
3709
10280
652
AGB41056.1
3710
10281
228
AGB41057.1
3711
10282
417


923
I
4
AEI93759.1
3713
10284
462
AEI93760.1
3714
10285
323
AEI93761.1
3715
10286
437


924
I
4
CCU78667.1
3717
10288
654
CCU78668.1
3718
10289
262
CCU78669.1
3719
10290
398


925
I
4
ERG17892.1
3721
10292
691
ERG17893.1
3722
10293
247
ERG17894.1
3723
10294
480


926
I
4
ALF60586.1
3725
10296
688
ALF60587.1
3726
10297
243
ALF60588.1
3727
10298
457


927
I
3
AEM78245.1
3729
10300
540
AEM78246.1
3730
10301
230


928
I
4
EFV93687.1
3732
10303
690
EFV93688.1
3733
10304
236
EFV93689.1
3734
10305
565


929
I
4
KRI14520.1
3736
10307
688
KRI14521.1
3737
10308
243
KRI14522.1
3738
10309
457


930
I
4
AEJ38288.1
3740
10311
647
AEJ38287.1
3741
10312
210
AEJ38286.1
3742
10313
398


931
I
4
AEW03630.1
3744
10315
647
AEW03629.1
3745
10316
229
AEW03628.1
3746
10317
398


932
I
4
KFX14697.1
3748
10319
729
KFX14696.1
3749
10320
245
KFX14695.1
3750
10321
560


933
I
4
KKW93255.1
3752
10323
641
KKW93256.1
3753
10324
242
KKW94108.1
3754
10325
426


934
I
4
KVX03061.1
3756
10327
723
KVX03060.1
3757
10328
252
KVX03059.1
3758
10329
565


935
I
4
KJM54480.1
3760
10331
851
KJM54479.1
3761
10332
245
KJM54478.1
3762
10333
597


936
I
4
KLF88330.1
3764
10335
729
KLF88329.1
3765
10336
246
KLF88328.1
3766
10337
560


937
I
4
KLG16016.1
3768
10339
729
KLG16015.1
3769
10340
246
KLG16014.1
3770
10341
560


938
I
4
KLP43536.1
3772
10343
729
KLP43535.1
3773
10344
246
KLP43534.1
3774
10345
560


939
I
4
KTK05050.1
3776
10347
851
KTK05049.1
3777
10348
245
KTK05048.1
3778
10349
597


940
I
4
KTJ30242.1
3780
10351
729
KTJ30243.1
3781
10352
246
KTJ30244.1
3782
10353
560


941
I
4
KTI23428.1
3784
10355
851
KTI23427.1
3785
10356
245
KTI23426.1
3786
10357
597


942
I
4
AKL12331.1
3788
10359
729
AKL12332.1
3789
10360
246
AKL12333.1
3790
10361
560


943
I
3
AFZ43911.1
3792
10363
746
AFZ43910.1
3793
10364
236
AFZ43909.1
3794
10365
507


944
I
3
ACK72258.1
3795
10366
456
ACK72256.1
3796
10367
222
ACK72255.1
3797
10368
501


945
I
4
AJG24952.1
3798
10369
667
AJG24951.1
3799
10370
53
AJG24950.1
3800
10371
556


946
I
3
EAW43011.1
3802
10373
656
EAW43010.1
3803
10374
216
EAW43009.1
3804
10375
464


947
I
3
AHJ30056.1
3805
10376
635
AHJ30057.1
3806
10377
216
AHJ30058.1
3807
10378
464


948
I
4
AJE15429.1
3808
10379
731
AJE15428.1
3809
10380
245
AJE15427.1
3810
10381
558


949
I
3
CEJ44798.1
3812
10383
627
CEJ44797.1
3813
10384
214
CEJ44796.1
3814
10385
459


950
I
4
EHO11882.1
3815
10386
509
EHO11881.1
3816
10387
238
EHO11883.1
3817
10388
475


951
I
4
CAY72975.1
3819
10390
729
CAY72976.1
3820
10391
245
CAY72978.1
3821
10392
566


952
I
4
CAX54367.1
3823
10394
729
CAX54368.1
3824
10395
245
CAX54369.1
3825
10396
566


953
I
4
AGA90547.1
3827
10398
586
AGA90548.1
3828
10399
283
AGA90549.1
3829
10400
425


954
I
4
CUH46419.1
3831
10402
681
CUH46420.1
3832
10403
372
CUH46421.1
3833
10404
449


955
I
4
AMO80628.1
3835
10406
729
AMO80629.1
3836
10407
247
AMO80630.1
3837
10408
563


956
I
4
AGP47378.1
3839
10410
572
AGP47379.1
3840
10411
263
AGP47380.1
3841
10412
443


957
I
4
KIN78156.1
3843
10414
680
KIN78155.1
3844
10415
367
KIN78154.1
3845
10416
738


958
I
4
AMS40143.1
3847
10418
651
AMS40142.1
3848
10419
302
AMS40141.1
3849
10420
461


959
I
4
ABK50003.1
3851
10422
696
ABK50004.1
3852
10423
243
ABK50005.1
3853
10424
475


960
I
4
CAP40556.1
3855
10426
680
CAP40555.1
3856
10427
237
CAP40554.1
3857
10428
558


961
I
4
ERI29961.1
3859
10430
670
ERI29880.1
3860
10431
241
ERI29995.1
3861
10432
546


962
I
4
EPZ86961.1
3863
10434
670
EPZ86615.1
3864
10435
241
EPZ86681.1
3865
10436
546


963
I
4
KKI79474.1
3867
10438
670
KKI79473.1
3868
10439
241
KKI79472.1
3869
10440
546


964
I
4
KVD94073.1
3871
10442
674
KVD94072.1
3872
10443
236
KVD94070.1
3873
10444
261


965
I
4
KVT83333.1
3875
10446
667
KVT83334.1
3876
10447
234
KVT83335.1
3877
10448
576


966
I
4
KVW62590.1
3879
10450
667
KVW62589.1
3880
10451
234
KVW62588.1
3881
10452
576


967
I
3
AFZ37310.1
3883
10454
781
AFZ37311.1
3884
10455
264
AFZ37312.1
3885
10456
502


968
I
3
ADD01957.1
3886
10457
540
ADD01958.1
3887
10458
230


969
I
4
AEG43650.1
3889
10460
541
AEG43649.1
3890
10461
277
AEG43648.1
3891
10462
514


970
I
4
ACY51399.1
3893
10464
706
ACY51400.1
3894
10465
244
ACY51401.1
3895
10466
483


971
I
4
EDN58079.1
3897
10468
706
EDN58080.1
3898
10469
244
EDN58081.1
3899
10470
483


972
I
4
AIR88232.1
3901
10472
730
AIR88231.1
3902
10473
247
AIR88230.1
3903
10474
542


973
I
4
ABC30363.1
3905
10476
666
ABC30364.1
3906
10477
263
ABC30365.1
3907
10478
493


974
I
4
ALV90959.1
3909
10480
729
ALV90958.1
3910
10481
245
ALV90957.1
3911
10482
560


975
I
4
EDL49433.1
3913
10484
641
EDL49432.1
3914
10485
242
EDL49431.1
3915
10486
429


976
I
4
CAQ68802.1
3917
10488
663
CAQ68801.1
3918
10489
252
CAQ68800.1
3919
10490
554


977
I
4
BAH37227.1
3921
10492
669
BAH37228.1
3922
10493
230
BAH37229.1
3923
10494
459


978
I
4
KGU86620.1
3925
10496
730
KGU86621.1
3926
10497
247
KGU86622.1
3927
10498
542


979
I
3
AFE04995.1
3929
10500
644




AFE04997.1
3930
10501
464


980
I
4
EHJ60585.1
3932
10503
641
EHJ60586.1
3933
10504
242
EHJ60587.1
3934
10505
458


981
I
4
AIT79637.1
3936
10507
641
AIT79636.1
3937
10508
242
AIT79635.1
3938
10509
429


982
I
3
CAV18535.1
3940
10511
688
CAV18536.1
3941
10512
218
CAV18537.1
3942
10513
625


983
I
4
ADP10192.1
3943
10514
729
ADP10191.1
3944
10515
245
ADP10190.1
3945
10516
566


984
I
4
ABM39550.1
3947
10518
816
ABM39549.1
3948
10519
235
ABM39548.1
3949
10520
602


985
I
4
EIL89340.1
3951
10522
631
EIL89341.1
3952
10523
236
EIL89342.1
3953
10524
559


986
I
4
GAC31728.1
3955
10526
692
GAC31729.1
3956
10527
243
GAC31730.1
3957
10528
475


987
I
3
AFZ12767.1
3959
10530
726
AFZ12766.1
3960
10531
239
AFZ12765.1
3961
10532
474


988
I
4
KFK00375.1
3962
10533
729
KFK00374.1
3963
10534
246
KFK00373.1
3964
10535
560


989
I
4
CDT04278.1
3966
10537
704
CDT04296.1
3967
10538
243
CDT04305.1
3968
10539
483


990
I
4
CDT11699.1
3970
10541
704
CDT11706.1
3971
10542
243
CDT11714.1
3972
10543
483


991
I
4
KXV35460.1
3974
10545
672
KXV35459.1
3975
10546
287
KXV35477.1
3976
10547
425


992
I
4
EAT06411.1
3978
10549
507
EAT06417.1
3979
10550
272
EAT06418.1
3980
10551
486


993
I
4
BAQ44674.1
3982
10553
679
BAQ44675.1
3983
10554
310
BAQ44676.1
3984
10555
438


994
I
4
CCE22484.1
3986
10557
642
CCE22485.1
3987
10558
252
CCE22486.1
3988
10559
498


995
I
4
CEG51215.1
3990
10561
781
CEG51216.1
3991
10562
254
CEG51217.1
3992
10563
754


996
I
4
EJI89226.1
3994
10565
729
EJI89227.1
3995
10566
247
EJI89228.1
3996
10567
567


997
I
4
KDE37034.1
3998
10569
729
KDE37033.1
3999
10570
247
KDE37032.1
4000
10571
569


998
I
3
AFZ51166.1
4002
10573
481
AFZ51165.1
4003
10574
240
AFZ51164.1
4004
10575
501


999
I
3
GAE46380.1
4005
10576
629
GAE46381.1
4006
10577
223


1000
I
4
EAQ47302.1
4008
10579
680
EAQ47301.1
4009
10580
367
EAQ47300.1
4010
10581
741


1001
I
4
EDP59419.1
4012
10583
706
EDP59418.1
4013
10584
244
EDP59417.1
4014
10585
483


1002
I
4
CUH52012.1
4016
10587
486
CUH52011.1
4017
10588
358
CUH52010.1
4018
10589
436


1003
I
4
CVK01182.1
4020
10591
844
CVK01173.1
4021
10592
240
CVK01163.1
4022
10593
658


1004
I
4
ABE74734.1
4024
10595
688
ABE74735.1
4025
10596
243
ABE74736.1
4026
10597
473


1005
I
3
CCW17770.1
4028
10599
549




CCW17772.1
4029
10600
468


1006
I
3
ABM05098.1
4031
10602
454
ABM05096.1
4032
10603
220
ABM05095.1
4033
10604
541


1007
I
4
AFU46476.1
4034
10605
727
AFU46477.1
4035
10606
255
AFU46478.1
4036
10607
646


1008
I
4
EZI30545.1
4038
10609
730
EZI30546.1
4039
10610
247
EZI30547.1
4040
10611
542


1009
I
3
ADL55134.1
4042
10613
648
ADL55135.1
4043
10614
238
ADL55136.1
4044
10615
527


1010
I
4
GAA77183.1
4045
10616
692
GAA77182.1
4046
10617
243
GAA77181.1
4047
10618
476


1011
I
4
AMK16850.1
4049
10620
660
AMK16851.1
4050
10621
236
AMK16852.1
4051
10622
560


1012
I
3
ADQ06821.1
4053
10624
539
ADQ06820.1
4054
10625
241


1013
I
4
EFN90481.1
4056
10627
460
EFN90483.1
4057
10628
230
EFN90478.1
4058
10629
459


1014
I
3




KXB76242.1
4060
10631
230
KXB76241.1
4061
10632
459


1015
I
4
EPR18405.1
4063
10634
669
EPR18406.1
4064
10635
242
EPR18407.1
4065
10636
466


1016
I
4
KMO18101.1
4067
10638
907
KMO18102.1
4068
10639
260
KMO18103.1
4069
10640
465


1017
I
3
KER36348.1
4071
10642
641
KER36349.1
4072
10643
242
KER36350.1
4073
10644
466


1018
I
4
ACT17070.1
4074
10645
666
ACT17071.1
4075
10646
239
ACT17072.1
4076
10647
556


1019
I
4
KMW37149.1
4078
10649
667
KMW37148.1
4079
10650
231
KMW37147.1
4080
10651
616


1020
I
3




CUB00791.1
4082
10653
322
CUB00793.1
4083
10654
437


1021
I
4
ADJ28737.1
4085
10656
700
ADJ28736.1
4086
10657
250
ADJ28735.1
4087
10658
477


1022
I
3




AJR24432.1
4089
10660
236
AJR24433.1
4090
10661
560


1023
I
4
AJR25287.1
4092
10663
657
AJR25288.1
4093
10664
236
AJR25289.1
4094
10665
557


1024
I
4
EHO63928.1
4096
10667
584
EHO63911.1
4097
10668
222
EHO63912.1
4098
10669
452


1025
I
4
KVM95917.1
4100
10671
674
KVM95916.1
4101
10672
236
KVM95915.1
4102
10673
475


1026
I
4
EDY06977.1
4104
10675
648
EDY06976.1
4105
10676
223
EDY06975.1
4106
10677
426


1027
I
3
AMD01537.1
4108
10679
656
AMD01536.1
4109
10680
254
AMD01535.1
4110
10681
570


1028
I
4
EHR42621.1
4111
10682
745
EHR42622.1
4112
10683
263
EHR42623.1
4113
10684
495


1029
I
4
EHD22817.1
4115
10686
729
EHD22818.1
4116
10687
246
EHD22819.1
4117
10688
560


1030
I
4
CRI66748.1
4119
10690
660
CRI66749.1
4120
10691
242
CRI66750.1
4121
10692
576


1031
I
4
EFY05649.1
4123
10694
706
EFY05648.1
4124
10695
244
EFY05647.1
4125
10696
461


1032
I
4
EKN30947.1
4127
10698
667
EKN30946.1
4128
10699
231
EKN30945.1
4129
10700
616


1033
I
4
KPL51797.1
4131
10702
671
KPL51798.1
4132
10703
288
KPL51799.1
4133
10704
467


1034
I
3
AMN39053.1
4135
10706
688




AMN39055.1
4136
10707
481


1035
I
4
KMV29900.1
4138
10709
605
KMV29899.1
4139
10710
261
KMV29898.1
4140
10711
468


1036
I
4
CCA91254.1
4142
10713
612
CCA91255.1
4143
10714
258
CCA91256.1
4144
10715
433


1037
I
4
CCA92387.1
4146
10717
641
CCA92388.1
4147
10718
242
CCA92389.1
4148
10719
458


1038
I
4
ADE38421.1
4150
10721
656
ADE38422.1
4151
10722
270
ADE38423.1
4152
10723
462


1039
I
4
EPR27897.1
4154
10725
648
EPR27898.1
4155
10726
230
EPR27899.1
4156
10727
426


1040
I
4
KYC33906.1
4158
10729
657
KYC33907.1
4159
10730
236
KYC33908.1
4160
10731
557


1041
I
3
ADW69601.1
4162
10733
650
ADW69602.1
4163
10734
227
ADW69603.1
4164
10735
445


1042
I
4
EPR43451.1
4165
10736
571
EPR43452.1
4166
10737
255
EPR43453.1
4167
10738
454


1043
I
3
ESU31843.1
4169
10740
629
ESU31842.1
4170
10741
223


1044
I
4
KHJ69401.1
4172
10743
729
KHJ69400.1
4173
10744
245
KHJ69399.1
4174
10745
560


1045
I
4
ERO56341.1
4176
10747
729
ERO56340.1
4177
10748
247
ERO56339.1
4178
10749
561


1046
I
4
KHN63194.1
4180
10751
729
KHN63195.1
4181
10752
247
KHN63196.1
4182
10753
561


1047
I
3
KKD39674.1
4184
10755
733
KKD39673.1
4185
10756
238
KMW70735.1
4186
10757
384


1048
I
4
CUB04084.1
4187
10758
621
CUB04083.1
4188
10759
252
CUB04082.1
4189
10760
571


1049
I
4
EJM18419.1
4191
10762
730
EJM18418.1
4192
10763
247
EJM18417.1
4193
10764
541


1050
I
4
EUB73632.1
4195
10766
771
EUB73631.1
4196
10767
247
EUB73630.1
4197
10768
652


1051
I
3
EIL96364.1
4199
10770
625
EIL96363.1
4200
10771
241
EIL96362.1
4201
10772
523


1052
I
4
EOU44970.1
4202
10773
851
EOU44971.1
4203
10774
244
EOU44972.1
4204
10775
595


1053
I
4
ELC22340.1
4206
10777
851
ELC22341.1
4207
10778
245
ELC22342.1
4208
10779
595


1054
I
4
EOU82992.1
4210
10781
851
EOU82993.1
4211
10782
244
EOU82994.1
4212
10783
595


1055
I
4
KXU33094.1
4214
10785
657
KXU33093.1
4215
10786
236
KXU33092.1
4216
10787
550


1056
I
4
EOV44196.1
4218
10789
851
EOV44197.1
4219
10790
245
EOV44198.1
4220
10791
595


1057
I
4
EOQ55527.1
4222
10793
729
EOQ55528.1
4223
10794
247
EOQ55529.1
4224
10795
560


1058
I
4
EOV91297.1
4226
10797
851
EOV91298.1
4227
10798
245
EOV91299.1
4228
10799
595


1059
I
4
EOW68209.1
4230
10801
851
EOW68210.1
4231
10802
245
EOW68211.1
4232
10803
595


1060
I
4
AFY17876.1
4234
10805
800
AFY17877.1
4235
10806
247
AFY17878.1
4236
10807
720


1061
I
4
KHK57292.1
4238
10809
685
KHK57293.1
4239
10810
236
KHK57294.1
4240
10811
558


1062
I
4
ENW78275.1
4242
10813
686
ENW78276.1
4243
10814
243
ENW78277.1
4244
10815
462


1063
I
4
EME68216.1
4246
10817
827
EME68215.1
4247
10818
251
EME68214.1
4248
10819
457


1064
I
4
CDE94534.1
4250
10821
616
CDE94533.1
4251
10822
235
CDE94532.1
4252
10823
467


1065
I
4
CDA50128.1
4254
10825
657
CDA50129.1
4255
10826
228
CDA50130.1
4256
10827
437


1066
I
4
ESQ90328.1
4258
10829
648
ESQ90329.1
4259
10830
251
ESQ90330.1
4260
10831
455


1067
I
4
ESQ74514.1
4262
10833
662
ESQ74515.1
4263
10834
267
ESQ74516.1
4264
10835
464


1068
I
4
AII86799.1
4266
10837
616
AII86800.1
4267
10838
431
AII86801.1
4268
10839
675


1069
I
4
KPQ04149.1
4270
10841
692
KPQ04148.1
4271
10842
243
KPQ04147.1
4272
10843
475


1070
I
4
CUS49192.1
4274
10845
692
CUS49191.1
4275
10846
243
CUS49190.1
4276
10847
475


1071
I
4
ESN27965.1
4278
10849
711
ESN27964.1
4279
10850
245
ESN27963.1
4280
10851
560


1072
I
4
EPJ56201.1
4282
10853
678
EPJ56200.1
4283
10854
350
EPJ56199.1
4284
10855
552


1073
I
4
EQA99142.1
4286
10857
652
EQA99141.1
4287
10858
250
EQA99140.1
4288
10859
476


1074
I
4
KMS61577.1
4290
10861
652
KMS61417.1
4291
10862
250
KMS61578.1
4292
10863
476


1075
I
4
AGT31732.2
4294
10865
650
AGT31733.1
4295
10866
223
AGT31734.1
4296
10867
426


1076
I
4
AIY66372.1
4298
10869
675
AIY65737.1
4299
10870
247
AIY65736.1
4300
10871
480


1077
I
4
KXW55388.1
4302
10873
653
KXW55387.1
4303
10874
249
KXW55386.1
4304
10875
493


1078
I
4
AKU92633.1
4306
10877
529
AKU92632.1
4307
10878
238
AKU92631.1
4308
10879
470


1079
I
3
ERS81916.1
4310
10881
678
ERS81915.1
4311
10882
263
ERS81914.1
4312
10883
246


1080
I
3
ERS83845.1
4313
10884
666




ERS83848.1
4314
10885
578


1081
I
4
KXU87120.1
4316
10887
897
KXU87121.1
4317
10888
241
KXU87122.1
4318
10889
597


1082
I
4
KLU37751.1
4320
10891
667
KLU37750.1
4321
10892
234
KLU37749.1
4322
10893
578


1083
I
4
EUC70211.1
4324
10895
632
EUC70007.1
4325
10896
251
EUC70008.1
4326
10897
508


1084
I
4
EXI82583.1
4328
10899
679
EXI82584.1
4329
10900
236
EXI82585.1
4330
10901
573


1085
I
4
KAK42943.1
4332
10903
785
KAK42944.1
4333
10904
252
KAK42945.1
4334
10905
618


1086
I
4
BAO84440.1
4336
10907
644
BAO84441.1
4337
10908
236
BAO84442.1
4338
10909
609


1087
I
3
CQR46611.1
4340
10911
629
CQR46610.1
4341
10912
236


1088
I
4
BAP87805.1
4343
10914
653
BAP87806.1
4344
10915
237
BAP87807.1
4345
10916
212


1089
I
4
KDP87791.1
4347
10918
663
KDP87792.1
4348
10919
252
KDP87793.1
4349
10920
599


1090
I
4
KQB03823.1
4351
10922
706
KQB03824.1
4352
10923
244
KQB03825.1
4353
10924
483


1091
I
4
KQA99550.1
4355
10926
706
KQA99549.1
4356
10927
244
KQA99548.1
4357
10928
483


1092
I
4
KEY85736.1
4359
10930
730
KEY85735.1
4360
10931
247
KEY85734.1
4361
10932
542


1093
I
4
GAK41823.1
4363
10934
616
GAK41824.1
4364
10935
258
GAK41825.1
4365
10936
424


1094
I
4
KVV58314.1
4367
10938
674
KVV58315.1
4368
10939
236
KVV58316.1
4369
10940
475


1095
I
4
KVX28279.1
4371
10942
674
KVX28280.1
4372
10943
236
KVX28281.1
4373
10944
564


1096
I
4
KVZ97547.1
4375
10946
674
KVZ97546.1
4376
10947
236
KVZ97545.1
4377
10948
475


1097
I
4
AJY51021.1
4379
10950
711
AJY51020.1
4380
10951
254
AJY51019.1
4381
10952
530


1098
I
4
CDX33063.1
4383
10954
723
CDX33066.1
4384
10955
302
CDX33069.1
4385
10956
460


1099
I
4
CDX43778.1
4387
10958
723
CDX43775.1
4388
10959
302
CDX43772.1
4389
10960
460


1100
I
3
KJS80656.1
4391
10962
700
KJS80657.1
4392
10963
242


1101
I
4
KGD90262.1
4394
10965
669
KGD90263.1
4395
10966
234
KGD90264.1
4396
10967
570


1102
I
3
KGJ90758.1
4398
10969
595
KGJ90759.1
4399
10970
261
KGJ90760.1
4400
10971
390


1103
I
4
KOC90088.1
4401
10972
729
KOC90087.1
4402
10973
246
KOC90086.1
4403
10974
560


1104
I
4
KOC94084.1
4405
10976
729
KOC94083.1
4406
10977
246
KOC94082.1
4407
10978
560


1105
I
4
KHF78369.1
4409
10980
687
KHF78368.1
4410
10981
243
KHF78367.1
4411
10982
472


1106
I
4
KQB52476.1
4413
10984
730
KQB52477.1
4414
10985
247
KQB52478.1
4415
10986
549


1107
I
3




AJP47988.1
4417
10988
236
AJP47987.1
4418
10989
553


1108
I
4
KIN89757.1
4420
10991
666
KIN89556.1
4421
10992
235
KIN89775.1
4422
10993
595


1109
I
4
ALQ39732.1
4424
10995
583
ALQ39733.1
4425
10996
232
ALQ39734.1
4426
10997
402


1110
I
4
KIQ83921.1
4428
10999
737
KIQ83920.1
4429
11000
247
KIQ83919.1
4430
11001
586


1111
I
4
KRP95697.1
4432
11003
730
KRP95696.1
4433
11004
247
KRP95695.1
4434
11005
542


1112
I
3
BAQ62924.1
4436
11007
772
BAQ62925.1
4437
11008
222
BAQ62926.1
4438
11009
503


1113
I
3
KJS80968.1
4439
11010
698
KJS80967.1
4440
11011
254
KJS80966.1
4441
11012
752


1114
I
4
KJM39259.1
4442
11013
729
KJM39258.1
4443
11014
245
KJM39257.1
4444
11015
504


1115
I
4
KJJ99150.1
4446
11017
685
KJJ99540.1
4447
11018
235
KJJ99149.1
4448
11019
558


1116
I
4
KJQ91383.1
4450
11021
706
KJQ91384.1
4451
11022
244
KJQ91385.1
4452
11023
483


1117
I
4
KJQ87529.1
4454
11025
706
KJQ87530.1
4455
11026
244
KJQ87531.1
4456
11027
483


1118
I
4
AKI01763.1
4458
11029
720
AKI01764.1
4459
11030
302
AKI01765.1
4460
11031
473


1119
I
3
KMP10823.1
4462
11033
578




KMP10824.1
4463
11034
471


1120
I
4
KJS25182.1
4465
11036
781
KJS25181.1
4466
11037
254
KJS25180.1
4467
11038
754


1121
I
3
KJS49376.1
4469
11040
700
KJS49375.1
4470
11041
242


1122
I
4
KLG11560.1
4472
11043
851
KLG11561.1
4473
11044
245
KLG11562.1
4474
11045
597


1123
I
4
KLP25065.1
4476
11047
729
KLP25066.1
4477
11048
245
KLP25067.1
4478
11049
560


1124
I
4
KLG16385.1
4480
11051
729
KLG16384.1
4481
11052
245
KLG16383.1
4482
11053
504


1125
I
4
AKQ40863.1
4484
11055
641
AKQ40862.1
4485
11056
242
AKQ43011.1
4486
11057
440


1126
I
4
KLR33911.1
4488
11059
729
KLR33910.1
4489
11060
245
KLR33909.1
4490
11061
560


1127
I
4
KLQ90823.1
4492
11063
729
KLQ90824.1
4493
11064
245
KLQ90825.1
4494
11065
560


1128
I
4
KYO07696.1
4496
11067
851
KYO07695.1
4497
11068
245
KYO07694.1
4498
11069
597


1129
I
3




KYO16913.1
4500
11071
245
KYO16912.1
4501
11072
560


1130
I
4
KLP47189.1
4503
11074
729
KLP47188.1
4504
11075
245
KLP47187.1
4505
11076
560


1131
I
4
ALE53304.1
4507
11078
674
ALE53303.1
4508
11079
236
ALE53302.1
4509
11080
564


1132
I
4
KQB93617.1
4511
11082
648
KQB93618.1
4512
11083
223
KQB93619.1
4513
11084
426


1133
I
4
AMN49377.1
4515
11086
688
AMN49378.1
4516
11087
243
AMN49379.1
4517
11088
473


1134
I
3
ALA18584.1
4519
11090
715
ALA18585.1
4520
11091
306
ALA18586.1
4521
11092
432


1135
I
4
ALK96263.1
4522
11093
667
ALK96264.1
4523
11094
234
ALK96265.1
4524
11095
578


1136
I
4
CUJ89804.1
4526
11097
486
CUJ89796.1
4527
11098
358
CUJ89790.1
4528
11099
436


1137
I
4
CUJ83670.1
4530
11101
686
CUJ83678.1
4531
11102
371
CUJ83691.1
4532
11103
447


1138
I
4
CUQ65734.1
4534
11105
605
CUQ65733.1
4535
11106
244
CUQ65732.1
4536
11107
479


1139
I
4
KVV05820.1
4538
11109
730
KVV05821.1
4539
11110
247
KVV05822.1
4540
11111
551


1140
I
4
KVV04346.1
4542
11113
730
KVV04345.1
4543
11114
247
KVV04344.1
4544
11115
551


1141
I
4
KUO77795.1
4546
11117
697
KUO77796.1
4547
11118
242
KUO77797.1
4548
11119
399


1142
I
4
KQM30744.1
4550
11121
483
KQM30743.1
4551
11122
310
KQM30742.1
4552
11123
443


1143
I
4
KQM97531.1
4554
11125
747
KQM97532.1
4555
11126
227
KQM97534.1
4556
11127
409


1144
I
4
KQN80963.1
4558
11129
483
KQN80962.1
4559
11130
310
KQN80961.1
4560
11131
443


1145
I
4
KQQ29436.1
4562
11133
679
KQQ29437.1
4563
11134
296
KQQ29438.1
4564
11135
438


1146
I
4
KQR49970.1
4566
11137
685
KQR49971.1
4567
11138
236
KQR49972.1
4568
11139
445


1147
I
3
KQQ86297.1
4570
11141
679
KQQ86070.1
4571
11142
332
KQQ86071.1
4572
11143
437


1148
I
4
KQS63846.1
4573
11144
677
KQS63847.1
4574
11145
326
KQS63848.1
4575
11146
437


1149
I
4
KQV35757.1
4577
11148
677
KQV35758.1
4578
11149
326
KQV35917.1
4579
11150
437


1150
I
4
KQY95048.1
4581
11152
650
KQY95047.1
4582
11153
249
KQY95046.1
4583
11154
354


1151
I
4
KRD25370.1
4585
11156
725
KRD25371.1
4586
11157
255
KRD25372.1
4587
11158
645


1152
I
4
KRD25864.1
4589
11160
677
KRD25865.1
4590
11161
326
KRD26022.1
4591
11162
437


1153
I
4
KQV20173.1
4593
11164
730
KQV20174.1
4594
11165
247
KQV20175.1
4595
11166
542


1154
I
4
KQX34369.1
4597
11168
654
KQX34248.1
4598
11169
311
KQX34249.1
4599
11170
434


1155
I
4
KRE22550.1
4601
11172
651
KRE22551.1
4602
11173
306
KRE22552.1
4603
11174
455


1156
I
4
KRA26262.1
4605
11176
730
KRA26261.1
4606
11177
247
KRA26260.1
4607
11178
542


1157
I
4
KRA28534.1
4609
11180
650
KRA28533.1
4610
11181
249
KRA28532.1
4611
11182
461


1158
I
4
KRB49806.1
4613
11184
699
KRB49805.1
4614
11185
314
KRB49804.1
4615
11186
470


1159
I
4
KQC46104.1
4617
11188
648
KQC46105.1
4618
11189
223
KQC46106.1
4619
11190
426


1160
I
4
KWV49702.1
4621
11192
676
KWV49701.1
4622
11193
332
KWV49700.1
4623
11194
435


1161
I
4
KUI99562.1
4625
11196
548
KUI99563.1
4626
11197
244
KUI99564.1
4627
11198
484


1162
I
4
KTG21218.1
4629
11200
723
KTG21219.1
4630
11201
252
KTG21220.1
4631
11202
564


1163
I
4
CVJ90686.1
4633
11204
903
CVJ90696.1
4634
11205
236
CVJ90705.1
4635
11206
594


1164
I
4
CVK24348.1
4637
11208
780
CVK24349.1
4638
11209
241
CVK24350.1
4639
11210
630


1165
I
4
CVK22610.1
4641
11212
724
CVK22609.1
4642
11213
252
CVK22608.1
4643
11214
546


1166
I
4
CVK27724.1
4645
11216
785
CVK27723.1
4646
11217
252
CVK27722.1
4647
11218
556


1167
I
4
CVJ14788.1
4649
11220
767
CVJ14762.1
4650
11221
241
CVJ14745.1
4651
11222
746


1168
I
4
CVJ96983.1
4653
11224
844
CVJ96975.1
4654
11225
240
CVJ96968.1
4655
11226
658


1169
I
4
KXS40897.1
4657
11228
657
KXS40896.1
4658
11229
245
KXS40895.1
4659
11230
391


1170
I
4
KXW57569.1
4661
11232
646
KXW57568.1
4662
11233
237
KXW57567.1
4663
11234
499


1171
I
4
EJO46330.1
4665
11236
711
EJO46331.1
4666
11237
246
EJO46332.1
4667
11238
560


1172
I
4
EPY95209.1
4669
11240
851
EPY95208.1
4670
11241
245
EPY95207.1
4671
11242
597


1173
I
4
EUL64248.1
4673
11244
711
EUL64247.1
4674
11245
246
EUL64246.1
4675
11246
560


1174
I
4
AMQ20312.1
4677
11248
648
AMQ20313.1
4678
11249
223
AMQ20314.1
4679
11250
426


1175
II
3
ADB42634.1
4681
11252
472
ADB42633.1
4682
11253
222


1176
II
3
EIA72761.1
4684
11255
432
EIA72760.1
4685
11256
235


1177
II
3
EIA87029.1
4687
11258
432
EIA87028.1
4688
11259
235


1178
II
3
EIA94951.1
4690
11261
432
EIA94950.1
4691
11262
235


1179
II
3
EIA95449.1
4693
11264
432
EIA95448.1
4694
11265
235


1180
II
3
KQH60908.1
4696
11267
432
KQH60907.1
4697
11268
235


1181
II
3
KQI25488.1
4699
11270
432
KQI25489.1
4700
11271
235


1182
II
3
KQI25380.1
4702
11273
432
KQI25381.1
4703
11274
235


1183
II
3
KRS58891.1
4705
11276
432
KRS58892.1
4706
11277
235


1184
II
3
KRS89289.1
4708
11279
432
KRS89290.1
4709
11280
234


1185
II
3
KEA44658.1
4711
11282
480
KEA44659.1
4712
11283
239


1186
II
3
ALX13353.1
4714
11285
427
ALX11999.1
4715
11286
230


1187
II
3
AMB80664.1
4717
11288
547
AMB81837.1
4718
11289
240


1188
II
3
CZG58504.1
4720
11291
498
CZG58452.1
4721
11292
230


1189
II
3
CZH63906.1
4723
11294
498
CZH63878.1
4724
11295
230


1190
II
3
CZG92946.1
4726
11297
498
CZG92895.1
4727
11298
230


1191
II
3
CZI24914.1
4729
11300
498
CZI24954.1
4730
11301
230


1192
II
3
CZI29146.1
4732
11303
498
CZI29107.1
4733
11304
230


1193
II
3
CZH75364.1
4735
11306
498
CZH75396.1
4736
11307
230


1194
II
3
CZI28533.1
4738
11309
498
CZI28487.1
4739
11310
230


1195
II
3
CZQ90586.1
4741
11312
498
CZQ90595.1
4742
11313
230


1196
II
3
EEZ95918.1
4744
11315
455
EEZ95917.1
4745
11316
230


1197
II
3
ADG61932.1
4747
11318
465
ADG61931.1
4748
11319
228


1198
II
3
EGE12537.1
4750
11321
465
EGE12536.1
4751
11322
204


1199
II
3
EGE10945.1
4753
11324
465
EGE10944.1
4754
11325
204


1200
II
3
EGE11787.1
4756
11327
465
EGE11786.1
4757
11328
204


1201
II
3
EGE15771.1
4759
11330
342
EGE15772.1
4760
11331
204


1202
II
3
EGE17285.1
4762
11333
465
EGE17284.1
4763
11334
204


1203
II
3
EGE18525.1
4765
11336
465
EGE18524.1
4766
11337
204


1204
II
3
EGE26180.1
4768
11339
378
EGE26179.1
4769
11340
204


1205
II
3
EGE24867.1
4771
11342
465
EGE24866.1
4772
11343
204


1206
II
3
EKF83143.1
4774
11345
465
EKF83142.1
4775
11346
214


1207
II
3
AIT43974.1
4777
11348
378
AIT43973.1
4778
11349
238


1208
II
3
ALD78152.1
4780
11351
498
ALD78151.1
4781
11352
235


1209
II
3
KJI56238.1
4783
11354
550
KJI56239.1
4784
11355
235


1210
II
3
KKW50395.1
4786
11357
180
KKW50401.1
4787
11358
226


1211
II
3
KFF70136.1
4789
11360
459
KFF70137.1
4790
11361
244


1212
II
3
KHS98349.1
4792
11363
459
KHS98348.1
4793
11364
244


1213
II
3
AAG59482.1
4795
11366
550
AAG59481.1
4796
11367
235


1214
II
3
BAB38681.1
4798
11369
550
BAB38680.1
4799
11370
235


1215
II
3
ACA79490.1
4801
11372
550
ACA79491.1
4802
11373
235


1216
II
3
ACB17340.1
4804
11375
550
ACB16649.1
4805
11376
235


1217
II
3
ACI35160.1
4807
11378
550
ACI35732.1
4808
11379
235


1218
II
3
ACT75062.1
4810
11381
550
ACT75061.1
4811
11382
235


1219
II
3
ADD59517.1
4813
11384
550
ADD59516.1
4814
11385
235


1220
II
3
EEC30753.1
4816
11387
550
EEC30190.1
4817
11388
235


1221
II
3
EFK27048.1
4819
11390
550
EFK27047.1
4820
11391
235


1222
II
3
EDU34174.1
4822
11393
550
EDU34140.1
4823
11394
235


1223
II
3
EDU54291.1
4825
11396
550
EDU54290.1
4826
11397
235


1224
II
3
EDU68759.1
4828
11399
550
EDU68786.1
4829
11400
235


1225
II
3
EDU76183.1
4831
11402
550
EDU76267.1
4832
11403
235


1226
II
3
EDU82627.1
4834
11405
550
EDU82726.1
4835
11406
235


1227
II
3
EDU87443.1
4837
11408
550
EDU87344.1
4838
11409
235


1228
II
3
EDU93482.1
4840
11411
550
EDU93378.1
4841
11412
235


1229
II
3
EDU97879.1
4843
11414
550
EDU97966.1
4844
11415
235


1230
II
3
EGI28993.1
4846
11417
550
EGI28991.1
4847
11418
159


1231
II
3
EDZ75683.1
4849
11420
550
EDZ75201.1
4850
11421
235


1232
II
3
EDZ82225.1
4852
11423
550
EDZ82316.1
4853
11424
235


1233
II
3
EDZ89786.1
4855
11426
550
EDZ89331.1
4856
11427
235


1234
II
3
EFX08673.1
4858
11429
550
EFX08672.1
4859
11430
235


1235
II
3
EFX13462.1
4861
11432
550
EFX13461.1
4862
11433
235


1236
II
3
EFX18239.1
4864
11435
550
EFX18238.1
4865
11436
235


1237
II
3
EFX28078.1
4867
11438
498
EFX28077.1
4868
11439
235


1238
II
3
EFX32591.1
4870
11441
498
EFX32590.1
4871
11442
235


1239
II
3
EGD70493.1
4873
11444
550
EGD70492.1
4874
11445
206


1240
II
3
EGD69129.1
4876
11447
550
EGD69130.1
4877
11448
206


1241
II
3
EFW65234.1
4879
11450
550
EFW65235.1
4880
11451
206


1242
II
3
AEZ43447.1
4882
11453
550
AEZ43446.1
4883
11454
235


1243
II
3
EHU86059.1
4885
11456
550
EHU86058.1
4886
11457
210


1244
II
3
EHU89504.1
4888
11459
498
EHU89503.1
4889
11460
76


1245
II
3
EHV18499.1
4891
11462
498
EHV18498.1
4892
11463
210


1246
II
3
EHV31734.1
4894
11465
550
EHV31797.1
4895
11466
206


1247
II
3
EHV46593.1
4897
11468
498
EHV46592.1
4898
11469
210


1248
II
3
EIF87146.1
4900
11471
550
EIF87145.1
4901
11472
235


1249
II
3
AFJ31993.1
4903
11474
550
AFJ31992.1
4904
11475
235


1250
II
3
EIN15909.1
4906
11477
550
EIN15908.1
4907
11478
210


1251
II
3
EIP63310.1
4909
11480
550
EIP63578.1
4910
11481
206


1252
II
3
EIP71583.1
4912
11483
550
EIP71554.1
4913
11484
202


1253
II
3
EIO79100.1
4915
11486
550
EIO79099.1
4916
11487
210


1254
II
3
EIN94365.1
4918
11489
550
EIN94459.1
4919
11490
202


1255
II
3
EIO32395.1
4921
11492
550
EIO32394.1
4922
11493
210


1256
II
3
EIO45819.1
4924
11495
550
EIO46021.1
4925
11496
210


1257
II
3
EIO63273.1
4927
11498
550
EIO63762.1
4928
11499
210


1258
II
3
EIO69657.1
4930
11501
550
EIO69656.1
4931
11502
210


1259
II
3
EIO86334.1
4933
11504
550
EIO86307.1
4934
11505
206


1260
II
3
EIP72925.1
4936
11507
550
EIP72924.1
4937
11508
210


1261
II
3
EIP72313.1
4939
11510
550
EIP72312.1
4940
11511
210


1262
II
3
EIP50029.1
4942
11513
550
EIP50028.1
4943
11514
206


1263
II
3
EIP48998.1
4945
11516
550
EIP49007.1
4946
11517
205


1264
II
3
EIP40275.1
4948
11519
550
EIP40258.1
4949
11520
235


1265
II
3
EIP35349.1
4951
11522
550
EIP35359.1
4952
11523
210


1266
II
3
EIP27300.1
4954
11525
452
EIP27306.1
4955
11526
210


1267
II
3
EIP38853.1
4957
11528
550
EIP38852.1
4958
11529
210


1268
II
3
EIP33942.1
4960
11531
550
EIP33941.1
4961
11532
210


1269
II
3
EIP10352.1
4963
11534
550
EIP10349.1
4964
11535
210


1270
II
3
EIP05667.1
4966
11537
550
EIP05660.1
4967
11538
210


1271
II
3
EIP03403.1
4969
11540
452
EIP03404.1
4970
11541
210


1272
II
3
EIO92501.1
4972
11543
550
EIO92517.1
4973
11544
210


1273
II
3
EIO87483.1
4975
11546
550
EIO87493.1
4976
11547
202


1274
II
3
EIN16733.1
4978
11549
550
EIN16732.1
4979
11550
210


1275
II
3
EIN15657.1
4981
11552
550
EIN15629.1
4982
11553
210


1276
II
3
EIN33040.1
4984
11555
550
EIN33050.1
4985
11556
210


1277
II
3
EIO86817.1
4987
11558
191
EIO86816.1
4988
11559
202


1278
II
3
EIO65815.1
4990
11561
550
EIO65813.1
4991
11562
210


1279
II
3
EIO79447.1
4993
11564
550
EIO79464.1
4994
11565
210


1280
II
3
EIO49130.1
4996
11567
550
EIO49202.1
4997
11568
202


1281
II
3
EIO29777.1
4999
11570
550
EIO29776.1
5000
11571
206


1282
II
3
EIO24705.1
5002
11573
452
EIO24703.1
5003
11574
210


1283
II
3
EIO11193.1
5005
11576
550
EIO11192.1
5006
11577
210


1284
II
3
EIO07409.1
5008
11579
550
EIO07417.1
5009
11580
210


1285
II
3
EIO07023.1
5011
11582
550
EIO07031.1
5012
11583
210


1286
II
3
EIO09663.1
5014
11585
550
EIO09672.1
5015
11586
206


1287
II
3
EIN89796.1
5017
11588
550
EIN89896.1
5018
11589
210


1288
II
3
EIN88185.1
5020
11591
550
EIN88192.1
5021
11592
210


1289
II
3
EIN85439.1
5023
11594
550
EIN85471.1
5024
11595
210


1290
II
3
EIN69802.1
5026
11597
550
EIN69801.1
5027
11598
210


1291
II
3
EIN65413.1
5029
11600
550
EIN65412.1
5030
11601
202


1292
II
3
EIN68646.1
5032
11603
550
EIN68645.1
5033
11604
210


1293
II
3
EIN52366.1
5035
11606
550
EIN52365.1
5036
11607
210


1294
II
3
EIN49112.1
5038
11609
550
EIN49111.1
5039
11610
210


1295
II
3
EIN33836.1
5041
11612
550
EIN33835.1
5042
11613
210


1296
II
3
EIN35239.1
5044
11615
550
EIN35238.1
5045
11616
202


1297
II
3
EKG95781.1
5047
11618
550
EKG95780.1
5048
11619
205


1298
II
3
EKH07680.1
5050
11621
550
EKH07679.1
5051
11622
206


1299
II
3
EKJ54995.1
5053
11624
550
EKJ54994.1
5054
11625
210


1300
II
3
EKJ48134.1
5056
11627
550
EKJ48188.1
5057
11628
210


1301
II
3
EKJ52904.1
5059
11630
550
EKJ52873.1
5060
11631
210


1302
II
3
EKJ36498.1
5062
11633
550
EKJ36497.1
5063
11634
202


1303
II
3
EKJ47662.1
5065
11636
550
EKJ47661.1
5066
11637
210


1304
II
3
EKJ36051.1
5068
11639
550
EKJ36042.1
5069
11640
210


1305
II
3
EKJ20862.1
5071
11642
498
EKJ20861.1
5072
11643
210


1306
II
3
EKJ19824.1
5074
11645
550
EKJ19823.1
5075
11646
206


1307
II
3
EKJ00851.1
5077
11648
550
EKJ00850.1
5078
11649
210


1308
II
3
EKI92952.1
5080
11651
550
EKI92951.1
5081
11652
210


1309
II
3
EKJ05352.1
5083
11654
550
EKJ05390.1
5084
11655
202


1310
II
3
EKI82675.1
5086
11657
550
EKI82674.1
5087
11658
210


1311
II
3
EKI91870.1
5089
11660
550
EKI91869.1
5090
11661
210


1312
II
3
EKI72763.1
5092
11663
550
EKI72762.1
5093
11664
210


1313
II
3
EKI64838.1
5095
11666
550
EKI64837.1
5096
11667
210


1314
II
3
EKI59123.1
5098
11669
550
EKI59122.1
5099
11670
210


1315
II
3
EKI57117.1
5101
11672
550
EKI57139.1
5102
11673
206


1316
II
3
EKI46667.1
5104
11675
550
EKI46666.1
5105
11676
210


1317
II
3
EKI33386.1
5107
11678
498
EKI33385.1
5108
11679
210


1318
II
3
EKH20917.1
5110
11681
550
EKH20916.1
5111
11682
210


1319
II
3
EKH25286.1
5113
11684
550
EKH25285.1
5114
11685
210


1320
II
3
EKH13352.1
5116
11687
550
EKH13351.1
5117
11688
210


1321
II
3
EKH36315.1
5119
11690
550
EKH36314.1
5120
11691
210


1322
II
3
EKH26863.1
5122
11693
550
EKH26862.1
5123
11694
210


1323
II
3
EKH48829.1
5125
11696
550
EKH48828.1
5126
11697
210


1324
II
3
EKH53678.1
5128
11699
550
EKH53677.1
5129
11700
210


1325
II
3
EKH61580.1
5131
11702
550
EKH61520.1
5132
11703
210


1326
II
3
EKH63165.1
5134
11705
550
EKH63164.1
5135
11706
210


1327
II
3
EKH71847.1
5137
11708
550
EKH71789.1
5138
11709
210


1328
II
3
EKH63848.1
5140
11711
550
EKH63847.1
5141
11712
210


1329
II
3
EKH83439.1
5143
11714
550
EKH83457.1
5144
11715
210


1330
II
3
EKH87900.1
5146
11717
550
EKH87899.1
5147
11718
210


1331
II
3
EKH95565.1
5149
11720
550
EKH95564.1
5150
11721
210


1332
II
3
EKI01262.1
5152
11723
550
EKI01261.1
5153
11724
210


1333
II
3
EKI02731.1
5155
11726
550
EKI02730.1
5156
11727
210


1334
II
3
EKH96738.1
5158
11729
550
EKH96737.1
5159
11730
210


1335
II
3
EKI03040.1
5161
11732
550
EKI03039.1
5162
11733
210


1336
II
3
EKI06059.1
5164
11735
550
EKI06058.1
5165
11736
210


1337
II
3
EKK37394.1
5167
11738
550
EKK37393.1
5168
11739
210


1338
II
3
EKK71766.1
5170
11741
550
EKK71765.1
5171
11742
210


1339
II
3
EKK91183.1
5173
11744
550
EKK91182.1
5174
11745
210


1340
II
3
EKK36994.1
5176
11747
550
EKK36843.1
5177
11748
206


1341
II
3
EKK37977.1
5179
11750
550
EKK37976.1
5180
11751
206


1342
II
3
EKK61089.1
5182
11753
550
EKK61088.1
5183
11754
205


1343
II
3
EKK52332.1
5185
11756
550
EKK52331.1
5186
11757
210


1344
II
3
EKK67939.1
5188
11759
550
EKK67938.1
5189
11760
210


1345
II
3
EKK62291.1
5191
11762
550
EKK62290.1
5192
11763
210


1346
II
3
EKK87667.1
5194
11765
550
EKK87666.1
5195
11766
210


1347
II
3
EKV88765.1
5197
11768
550
EKV88764.1
5198
11769
210


1348
II
3
EKV85098.1
5200
11771
550
EKV85097.1
5201
11772
210


1349
II
3
EKV70652.1
5203
11774
550
EKV70651.1
5204
11775
210


1350
II
3
EKW05771.1
5206
11777
550
EKW05770.1
5207
11778
202


1351
II
3
EKV91529.1
5209
11780
550
EKV91591.1
5210
11781
210


1352
II
3
EKW03290.1
5212
11783
550
EKW03180.1
5213
11784
210


1353
II
3
EKW04243.1
5215
11786
550
EKW04288.1
5216
11787
210


1354
II
3
EKW19024.1
5218
11789
550
EKW19023.1
5219
11790
210


1355
II
3
EKW08487.1
5221
11792
550
EKW08486.1
5222
11793
210


1356
II
3
EKW71371.1
5224
11795
550
EKW71370.1
5225
11796
210


1357
II
3
EKW96655.1
5227
11798
550
EKW96654.1
5228
11799
202


1358
II
3
EKW96260.1
5230
11801
550
EKW96259.1
5231
11802
210


1359
II
3
EKW76356.1
5233
11804
498
EKW76355.1
5234
11805
210


1360
II
3
EKW75842.1
5236
11807
550
EKW75841.1
5237
11808
206


1361
II
3
EKW68012.1
5239
11810
550
EKW68011.1
5240
11811
202


1362
II
3
EKW74793.1
5242
11813
550
EKW74753.1
5243
11814
210


1363
II
3
EKW43906.1
5245
11816
550
EKW43905.1
5246
11817
210


1364
II
3
EKW70675.1
5248
11819
550
EKW70674.1
5249
11820
210


1365
II
3
EKW38124.1
5251
11822
550
EKW38123.1
5252
11823
210


1366
II
3
EKW21071.1
5254
11825
352
EKW21070.1
5255
11826
210


1367
II
3
EKW36043.1
5257
11828
550
EKW36042.1
5258
11829
202


1368
II
3
EKW36718.1
5260
11831
550
EKW36717.1
5261
11832
210


1369
II
3
EKW51278.1
5263
11834
550
EKW51302.1
5264
11835
210


1370
II
3
EKY34591.1
5266
11837
550
EKY34590.1
5267
11838
210


1371
II
3
EKY34729.1
5269
11840
498
EKY34728.1
5270
11841
206


1372
II
3
ELI49200.1
5272
11843
550
ELI49199.1
5273
11844
235


1373
II
3
ELV23654.1
5275
11846
550
ELV23653.1
5276
11847
210


1374
II
3
ELV30876.1
5278
11849
550
ELV30875.1
5279
11850
210


1375
II
3
ELV62885.1
5281
11852
498
ELV62893.1
5282
11853
210


1376
II
3
ELV61722.1
5284
11855
443
ELV61721.1
5285
11856
210


1377
II
3
ELV63259.1
5287
11858
550
ELV63258.1
5288
11859
210


1378
II
3
ELV91642.1
5290
11861
550
ELV91641.1
5291
11862
206


1379
II
3
ELV93149.1
5293
11864
550
ELV93148.1
5294
11865
210


1380
II
3
ELW21805.1
5296
11867
550
ELW21804.1
5297
11868
205


1381
II
3
ELW24262.1
5299
11870
550
ELW24261.1
5300
11871
210


1382
II
3
ELW27707.1
5302
11873
550
ELW27706.1
5303
11874
210


1383
II
3
ELW23231.1
5305
11876
550
ELW23230.1
5306
11877
202


1384
II
3
ELW28316.1
5308
11879
550
ELW28315.1
5309
11880
202


1385
II
3
ELW46370.1
5311
11882
550
ELW46369.1
5312
11883
210


1386
II
3
ELV14533.1
5314
11885
550
ELV14532.1
5315
11886
210


1387
II
3
ELV31270.1
5317
11888
550
ELV31244.1
5318
11889
210


1388
II
3
ELV35522.1
5320
11891
550
ELV35521.1
5321
11892
206


1389
II
3
ELV44403.1
5323
11894
452
ELV44402.1
5324
11895
235


1390
II
3
ELV47175.1
5326
11897
550
ELV47167.1
5327
11898
206


1391
II
3
ELV76553.1
5329
11900
550
ELV76552.1
5330
11901
202


1392
II
3
ELV98805.1
5332
11903
550
ELV98804.1
5333
11904
210


1393
II
3
ELV75967.1
5335
11906
550
ELV75966.1
5336
11907
210


1394
II
3
ELV90962.1
5338
11909
550
ELV90961.1
5339
11910
235


1395
II
3
ELW12424.1
5341
11912
550
ELW12423.1
5342
11913
210


1396
II
3
ELV15308.1
5344
11915
550
ELV15307.1
5345
11916
210


1397
II
3
EMR91942.1
5347
11918
550
EMR91943.1
5348
11919
235


1398
II
3
EMS03600.1
5350
11921
550
EMS03599.1
5351
11922
235


1399
II
3
ELE41780.1
5353
11924
550
ELE41779.1
5354
11925
235


1400
II
3
ELF28432.1
5356
11927
550
ELF28431.1
5357
11928
235


1401
II
3
ELG08155.1
5359
11930
550
ELG08154.1
5360
11931
235


1402
II
3
ELH63190.1
5362
11933
550
ELH63189.1
5363
11934
235


1403
II
3
ENE27218.1
5365
11936
550
ENE27216.1
5366
11937
206


1404
II
3
EQO57392.1
5368
11939
550
EQO57391.1
5369
11940
235


1405
II
3
EQO66403.1
5371
11942
550
EQO66402.1
5372
11943
235


1406
II
3
EQT31739.1
5374
11945
550
EQT31738.1
5375
11946
235


1407
II
3
EQT84558.1
5377
11948
550
EQT84557.1
5378
11949
235


1408
II
3
ERB08804.1
5380
11951
550
ERB08803.1
5381
11952
235


1409
II
3
ERB13352.1
5383
11954
550
ERB13353.1
5384
11955
235


1410
II
3
ERC00102.1
5386
11957
550
ERC00101.1
5387
11958
206


1411
II
3
ERB68141.1
5389
11960
550
ERB68140.1
5390
11961
210


1412
II
3
ERB88973.1
5392
11963
550
ERB88972.1
5393
11964
210


1413
II
3
ERC15358.1
5395
11966
550
ERC15203.1
5396
11967
202


1414
II
3
ERB79215.1
5398
11969
550
ERB79214.1
5399
11970
205


1415
II
3
ERB91962.1
5401
11972
550
ERB92027.1
5402
11973
205


1416
II
3
ERC08311.1
5404
11975
550
ERC08310.1
5405
11976
210


1417
II
3
ERC32305.1
5407
11978
550
ERC32304.1
5408
11979
210


1418
II
3
ERC25309.1
5410
11981
550
ERC25308.1
5411
11982
205


1419
II
3
ERC09303.1
5413
11984
550
ERC09302.1
5414
11985
210


1420
II
3
ERC10658.1
5416
11987
550
ERC10657.1
5417
11988
206


1421
II
3
ERE14327.1
5419
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550
ERE14326.1
5420
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210


1422
II
3
ERC92367.1
5422
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550
ERC92366.1
5423
11994
235


1423
II
3
ERD40230.1
5425
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550
ERD40229.1
5426
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210


1424
II
3
ERC91695.1
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550
ERC91694.1
5429
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206


1425
II
3
ERD09264.1
5431
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550
ERD09263.1
5432
12003
210


1426
II
3
ERC65822.1
5434
12005
550
ERC65821.1
5435
12006
210


1427
II
3
ERC53517.1
5437
12008
550
ERC53516.1
5438
12009
202


1428
II
3
ERE00881.1
5440
12011
550
ERE00880.1
5441
12012
210


1429
II
3
ERE21796.1
5443
12014
550
ERE21795.1
5444
12015
202


1430
II
3
ERC61430.1
5446
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550
ERC61431.1
5447
12018
235


1431
II
3
ERC74185.1
5449
12020
550
ERC74184.1
5450
12021
210


1432
II
3
ERC30060.1
5452
12023
550
ERC30059.1
5453
12024
206


1433
II
3
ERC33933.1
5455
12026
550
ERC33932.1
5456
12027
210


1434
II
3
ERC40340.1
5458
12029
550
ERC40339.1
5459
12030
206


1435
II
3
ERC48257.1
5461
12032
550
ERC48256.1
5462
12033
210


1436
II
3
ERD08504.1
5464
12035
550
ERD08318.1
5465
12036
206


1437
II
3
ERD05019.1
5467
12038
550
ERD05018.1
5468
12039
210


1438
II
3
ERD20746.1
5470
12041
550
ERD20745.1
5471
12042
206


1439
II
3
ERD22950.1
5473
12044
550
ERD22949.1
5474
12045
210


1440
II
3
ERD23990.1
5476
12047
550
ERD23989.1
5477
12048
210


1441
II
3
ERD35106.1
5479
12050
550
ERD35201.1
5480
12051
214


1442
II
3
ERD37183.1
5482
12053
550
ERD37182.1
5483
12054
210


1443
II
3
ERD26787.1
5485
12056
498
ERD26788.1
5486
12057
210


1444
II
3
ERD52929.1
5488
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550
ERD52928.1
5489
12060
210


1445
II
3
ERD45127.1
5491
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550
ERD45126.1
5492
12063
210


1446
II
3
ERD72597.1
5494
12065
550
ERD72596.1
5495
12066
205


1447
II
3
ERD68376.1
5497
12068
550
ERD68375.1
5498
12069
202


1448
II
3
ERD73526.1
5500
12071
498
ERD73510.1
5501
12072
210


1449
II
3
ERD83187.1
5503
12074
550
ERD83186.1
5504
12075
206


1450
II
3
ERD87990.1
5506
12077
550
ERD87989.1
5507
12078
210


1451
II
3
ERD91775.1
5509
12080
550
ERD91774.1
5510
12081
210


1452
II
3
ERD98682.1
5512
12083
550
ERD98681.1
5513
12084
210


1453
II
3
ERD88427.1
5515
12086
498
ERD88426.1
5516
12087
205


1454
II
3
ERE36110.1
5518
12089
550
ERE36109.1
5519
12090
210


1455
II
3
ERE23639.1
5521
12092
550
ERE23638.1
5522
12093
210


1456
II
3
ERE42060.1
5524
12095
550
ERE42059.1
5525
12096
210


1457
II
3
ERE45408.1
5527
12098
550
ERE45407.1
5528
12099
202


1458
II
3
ETJ70764.1
5530
12101
550
ETJ70765.1
5531
12102
235


1459
II
3
ERC07680.1
5533
12104
550
ERC07679.1
5534
12105
206


1460
II
3
ESD10539.1
5536
12107
550
ESD10538.1
5537
12108
235


1461
II
3
ESL20616.1
5539
12110
550
ESL20617.1
5540
12111
235


1462
II
3
ESP12226.1
5542
12113
550
ESP12225.1
5543
12114
235


1463
II
3
ETJ79053.1
5545
12116
550
ETJ79052.1
5546
12117
235


1464
II
3
EST67462.1
5548
12119
550
EST67463.1
5549
12120
55


1465
II
3
EST67376.1
5551
12122
550
EST67377.1
5552
12123
235


1466
II
3
AHG12155.1
5554
12125
498
AHG12154.1
5555
12126
210


1467
II
3
EYE30767.1
5557
12128
550
EYE30766.1
5558
12129
235


1468
II
3
EYE15509.1
5560
12131
550
EYE15508.1
5561
12132
235


1469
II
3
EYE15596.1
5563
12134
550
EYE15595.1
5564
12135
210


1470
II
3
EYW09907.1
5566
12137
550
EYW09908.1
5567
12138
210


1471
II
3
EYW25814.1
5569
12140
550
EYW25815.1
5570
12141
210


1472
II
3
EYW27180.1
5572
12143
550
EYW27179.1
5573
12144
210


1473
II
3
EYW07431.1
5575
12146
550
EYW07430.1
5576
12147
210


1474
II
3
EYW24509.1
5578
12149
550
EYW24508.1
5579
12150
210


1475
II
3
EYW34609.1
5581
12152
550
EYW34608.1
5582
12153
210


1476
II
3
EYW13500.1
5584
12155
550
EYW13499.1
5585
12156
210


1477
II
3
EYV89287.1
5587
12158
550
EYV89288.1
5588
12159
210


1478
II
3
EYY46579.1
5590
12161
550
EYY46580.1
5591
12162
210


1479
II
3
EYV70454.1
5593
12164
550
EYV70453.1
5594
12165
210


1480
II
3
EYV67646.1
5596
12167
550
EYV67645.1
5597
12168
210


1481
II
3
EYV59035.1
5599
12170
550
EYV59034.1
5600
12171
210


1482
II
3
EYV37954.1
5602
12173
550
EYV37955.1
5603
12174
210


1483
II
3
EYV46019.1
5605
12176
550
EYV46020.1
5606
12177
210


1484
II
3
EYV44256.1
5608
12179
550
EYV44255.1
5609
12180
210


1485
II
3
EYV24873.1
5611
12182
550
EYV24872.1
5612
12183
210


1486
II
3
EYV22945.1
5614
12185
550
EYV22946.1
5615
12186
210


1487
II
3
EYV18170.1
5617
12188
550
EYV18171.1
5618
12189
210


1488
II
3
EYV20080.1
5620
12191
550
EYV20081.1
5621
12192
210


1489
II
3
EYV16482.1
5623
12194
550
EYV16481.1
5624
12195
210


1490
II
3
EYW83367.1
5626
12197
550
EYW83368.1
5627
12198
210


1491
II
3
EYW75519.1
5629
12200
550
EYW75518.1
5630
12201
210


1492
II
3
EYW71149.1
5632
12203
550
EYW71148.1
5633
12204
210


1493
II
3
EYW67181.1
5635
12206
550
EYW67182.1
5636
12207
210


1494
II
3
EYW64050.1
5638
12209
550
EYW64051.1
5639
12210
210


1495
II
3
EYW57178.1
5641
12212
550
EYW57179.1
5642
12213
210


1496
II
3
EYW49140.1
5644
12215
550
EYW49139.1
5645
12216
210


1497
II
3
EYW49453.1
5647
12218
550
EYW49452.1
5648
12219
210


1498
II
3
EYW43050.1
5650
12221
550
EYW43051.1
5651
12222
210


1499
II
3
EYW39160.1
5653
12224
550
EYW39159.1
5654
12225
210


1500
II
3
EYX70058.1
5656
12227
550
EYX70057.1
5657
12228
210


1501
II
3
EYX57445.1
5659
12230
550
EYX57446.1
5660
12231
210


1502
II
3
EYX54550.1
5662
12233
550
EYX54551.1
5663
12234
210


1503
II
3
EYX48136.1
5665
12236
550
EYX48137.1
5666
12237
210


1504
II
3
EYX44883.1
5668
12239
550
EYX44884.1
5669
12240
210


1505
II
3
EYX43991.1
5671
12242
550
EYX43990.1
5672
12243
210


1506
II
3
EYX33006.1
5674
12245
550
EYX33007.1
5675
12246
210


1507
II
3
EYX30698.1
5677
12248
550
EYX30699.1
5678
12249
210


1508
II
3
EYX27759.1
5680
12251
550
EYX27758.1
5681
12252
210


1509
II
3
EYX13626.1
5683
12254
550
EYX13625.1
5684
12255
210


1510
II
3
EYX12329.1
5686
12257
550
EYX12330.1
5687
12258
210


1511
II
3
EYX02202.1
5689
12260
550
EYX02201.1
5690
12261
210


1512
II
3
EYW98550.1
5692
12263
550
EYW98549.1
5693
12264
210


1513
II
3
EYW85334.1
5695
12266
550
EYW85335.1
5696
12267
210


1514
II
3
EYV84725.1
5698
12269
550
EYV84726.1
5699
12270
210


1515
II
3
EYZ76664.1
5701
12272
550
EYZ76665.1
5702
12273
210


1516
II
3
EYZ63882.1
5704
12275
550
EYZ63883.1
5705
12276
210


1517
II
3
EYZ52260.1
5707
12278
550
EYZ52261.1
5708
12279
210


1518
II
3
EYZ37414.1
5710
12281
550
EYZ37413.1
5711
12282
210


1519
II
3
EYZ38309.1
5713
12284
550
EYZ38310.1
5714
12285
210


1520
II
3
EYZ36219.1
5716
12287
550
EYZ36220.1
5717
12288
210


1521
II
3
EYZ14531.1
5719
12290
550
EYZ14532.1
5720
12291
210


1522
II
3
EZC28522.1
5722
12293
550
EZC28521.1
5723
12294
210


1523
II
3
EZB48636.1
5725
12296
550
EZB48635.1
5726
12297
210


1524
II
3
EZB05976.1
5728
12299
550
EZB05977.1
5729
12300
210


1525
II
3
EZB18141.1
5731
12302
550
EZB18140.1
5732
12303
210


1526
II
3
EZA89753.1
5734
12305
550
EZA89754.1
5735
12306
210


1527
II
3
EZB32013.1
5737
12308
550
EZB32012.1
5738
12309
210


1528
II
3
EZB20622.1
5740
12311
550
EZB20623.1
5741
12312
210


1529
II
3
EZB41522.1
5743
12314
550
EZB41521.1
5744
12315
210


1530
II
3
EZB11567.1
5746
12317
550
EZB11568.1
5747
12318
210


1531
II
3
EZB46983.1
5749
12320
550
EZB46982.1
5750
12321
210


1532
II
3
EZB04405.1
5752
12323
550
EZB04406.1
5753
12324
210


1533
II
3
EZB74688.1
5755
12326
550
EZB74687.1
5756
12327
210


1534
II
3
EZB73672.1
5758
12329
550
EZB73671.1
5759
12330
210


1535
II
3
EZB73224.1
5761
12332
550
EZB73225.1
5762
12333
210


1536
II
3
EZB87909.1
5764
12335
550
EZB87908.1
5765
12336
210


1537
II
3
EZB80137.1
5767
12338
550
EZB80138.1
5768
12339
210


1538
II
3
EZB81693.1
5770
12341
550
EZB81692.1
5771
12342
210


1539
II
3
EZB96172.1
5773
12344
264
EZB96173.1
5774
12345
210


1540
II
3
EZC15365.1
5776
12347
498
EZC15364.1
5777
12348
210


1541
II
3
EZC19641.1
5779
12350
550
EZC19640.1
5780
12351
210


1542
II
3
EZC20554.1
5782
12353
550
EZC20553.1
5783
12354
210


1543
II
3
EZC30166.1
5785
12356
550
EZC30167.1
5786
12357
210


1544
II
3
EZC37647.1
5788
12359
550
EZC37648.1
5789
12360
210


1545
II
3
EZC43981.1
5791
12362
550
EZC43980.1
5792
12363
210


1546
II
3
EZB95444.1
5794
12365
550
EZB95445.1
5795
12366
210


1547
II
3
EZC48750.1
5797
12368
550
EZC48751.1
5798
12369
210


1548
II
3
EZC62957.1
5800
12371
550
EZC62958.1
5801
12372
210


1549
II
3
EZC70420.1
5803
12374
550
EZC70419.1
5804
12375
210


1550
II
3
EZC77660.1
5806
12377
550
EZC77659.1
5807
12378
210


1551
II
3
EZC64797.1
5809
12380
550
EZC64798.1
5810
12381
210


1552
II
3
EZC90331.1
5812
12383
550
EZC90330.1
5813
12384
210


1553
II
3
EZC92769.1
5815
12386
550
EZC92768.1
5816
12387
210


1554
II
3
EZC86951.1
5818
12389
550
EZC86950.1
5819
12390
210


1555
II
3
EZC83412.1
5821
12392
550
EZC83411.1
5822
12393
210


1556
II
3
EZD75267.1
5824
12395
550
EZD75266.1
5825
12396
210


1557
II
3
EZF08562.1
5827
12398
550
EZF08563.1
5828
12399
210


1558
II
3
EZF05483.1
5830
12401
550
EZF05484.1
5831
12402
210


1559
II
3
EZE61419.1
5833
12404
550
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1560
II
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1561
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1562
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1563
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1564
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1565
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1566
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1567
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1568
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1569
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1570
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1571
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1572
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1573
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1574
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1576
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1588
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1596
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1599
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1600
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1601
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1630
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1633
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1636
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1637
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1638
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1639
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1640
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1642
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1643
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1647
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1648
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1649
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1650
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1651
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1652
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1653
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1654
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1655
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1657
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1658
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1659
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1669
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1670
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1671
II
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6170
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1672
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1673
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1674
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1675
II
3
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1676
II
3
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1677
II
3
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1678
II
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1679
II
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CVB67027.1
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1680
II
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1681
II
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1683
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1685
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1687
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1688
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1689
II
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205


1690
II
3
CVE95450.1
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1691
II
3
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12801
205


1692
II
3
CVA05211.1
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550
CVA05242.1
6233
12804
205


1693
II
3
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1694
II
3
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1695
II
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1696
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1699
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1700
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KIT58955.1
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1701
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1702
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1703
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1704
II
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1705
II
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1706
II
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1707
II
3
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1708
II
3
KYJ92316.1
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KYJ92315.1
6281
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1709
II
3
EMB49752.1
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1710
II
3
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EDL69242.1
6287
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1711
II
3
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1712
II
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6293
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1713
II
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1714
II
3
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ABI24729.1
6299
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1715
II
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EYA48172.1
6302
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1716
II
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1717
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1718
II
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6311
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1719
II
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6314
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1720
II
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KDS43042.1
6317
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1721
II
3
KDS37991.1
6319
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12891
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1722
II
3
KDS73983.1
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KDS73984.1
6323
12894
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1723
II
3
ALF18255.1
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ALF18256.1
6326
12897
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1724
II
3
KXA24061.1
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KXA24060.1
6329
12900
234


1725
II
3
EFG28532.1
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EFG28533.1
6332
12903
232


1726
II
3
ADJ62020.1
6334
12905
435
ADJ62019.1
6335
12906
232


1727
II
3
KTC70124.1
6337
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KTC70123.1
6338
12909
230


1728
II
3
AFT94972.1
6340
12911
598
AFT94973.1
6341
12912
235


1729
II
3
EEX38485.1
6343
12914
583
EEX38486.1
6344
12915
235


1730
II
3
CCN78625.1
6346
12917
592
CCN78626.1
6347
12918
236


1731
II
3
CCN34617.1
6349
12920
592
CCN34618.1
6350
12921
236


1732
II
3
CCN40571.1
6352
12923
592
CCN40570.1
6353
12924
236


1733
II
3
CCN66135.1
6355
12926
592
CCN66136.1
6356
12927
236


1734
II
3
KGJ97945.1
6358
12929
598
KGJ97946.1
6359
12930
238


1735
II
3
EEP49046.1
6361
12932
435
EEP51863.1
6362
12933
230


1736
II
3
AIP07406.1
6364
12935
435
AIP07455.1
6365
12936
230


1737
II
3
KGC46655.1
6367
12938
435
KGC46770.1
6368
12939
230


1738
II
3
AIV54526.1
6370
12941
435
AIV54849.1
6371
12942
230


1739
II
3
KGU70585.1
6373
12944
435
KGU70576.1
6374
12945
230


1740
II
3
KGV18629.1
6376
12947
435
KGV17582.1
6377
12948
230


1741
II
3
KGV95069.1
6379
12950
435
KGV94752.1
6380
12951
230


1742
II
3
KGV65245.1
6382
12953
435
KGV65979.1
6383
12954
230


1743
II
3
KGV93341.1
6385
12956
435
KGV92723.1
6386
12957
230


1744
II
3
KGX53114.1
6388
12959
435
KGX53127.1
6389
12960
230


1745
II
3
KGX64948.1
6391
12962
435
KGX64947.1
6392
12963
230


1746
II
3
AJX70756.1
6394
12965
435
AJX71777.1
6395
12966
230


1747
II
3
AIA69103.1
6397
12968
459
AIA69102.1
6398
12969
244


1748
II
3
AIK12008.1
6400
12971
459
AIK12007.1
6401
12972
244


1749
II
3
KMK83438.1
6403
12974
459
KMK83437.1
6404
12975
244


1750
II
3
KGK11299.1
6406
12977
583
KGK11298.1
6407
12978
235


1751
II
3
EAR22192.1
6409
12980
606
EAR22191.1
6410
12981
237


1752
II
3
ERG19017.1
6412
12983
391
ERG19018.1
6413
12984
217


1753
II
3
ERG19053.1
6415
12986
599
ERG19054.1
6416
12987
235


1754
II
3
ERG37343.1
6418
12989
588
ERG37344.1
6419
12990
234


1755
II
3
KTD25444.1
6421
12992
494
KTD25443.1
6422
12993
230


1756
II
3
EER46085.1
6424
12995
586
EER46086.1
6425
12996
229


1757
II
3
AKZ71842.1
6427
12998
550
AKZ71841.1
6428
12999
235


1758
II
3
KJN72848.1
6430
13001
550
KJN72849.1
6431
13002
235


1759
II
3
KLQ05988.1
6433
13004
550
KLQ05987.1
6434
13005
235


1760
II
3
KHE02046.1
6436
13007
433
KHE02111.1
6437
13008
226


1761
II
3
KHN64404.1
6439
13010
433
KHN64740.1
6440
13011
226


1762
II
3
ACS83827.1
6442
13013
520
ACS83826.1
6443
13014
248


1763
II
3
EAS45749.1
6445
13016
585
EAS45750.1
6446
13017
237


1764
II
3
ALP65206.1
6448
13019
435
ALP66609.1
6449
13020
230


1765
II
3
AIO36173.1
6451
13022
445
AIO34939.1
6452
13023
230


1766
II
3
KTC93828.1
6454
13025
494
KTC93827.1
6455
13026
230


1767
II
3
KVP70159.1
6457
13028
435
KVP70160.1
6458
13029
232


1768
II
3
KVP49168.1
6460
13031
435
KVP49169.1
6461
13032
232


1769
II
3
KVQ79696.1
6463
13034
435
KVQ79697.1
6464
13035
232


1770
II
3
KVR10907.1
6466
13037
435
KVR10908.1
6467
13038
232


1771
II
3
KVR50011.1
6469
13040
435
KVR50012.1
6470
13041
232


1772
II
3
KVR54358.1
6472
13043
435
KVR54359.1
6473
13044
232


1773
II
3
KWB45018.1
6475
13046
435
KWB45017.1
6476
13047
232


1774
II
3
KWB78076.1
6478
13049
435
KWB78077.1
6479
13050
232


1775
II
3
KWD39079.1
6481
13052
435
KWD39080.1
6482
13053
232


1776
II
3
KWD33064.1
6484
13055
435
KWD33065.1
6485
13056
232


1777
II
3
KWD38753.1
6487
13058
435
KWD38754.1
6488
13059
232


1778
II
3
KWO93445.1
6490
13061
435
KWO93444.1
6491
13062
232


1779
II
3
KVX24372.1
6493
13064
435
KVX24373.1
6494
13065
232


1780
II
3
KGO04268.1
6496
13067
488
KGO04269.1
6497
13068
233


1781
II
3
ADE14195.1
6499
13070
606
ADE14194.1
6500
13071
237


1782
II
3
ADR35021.1
6502
13073
378
ADR35022.1
6503
13074
238


1783
II
3
EPF16739.1
6505
13076
435
EPF16738.1
6506
13077
226


1784
II
3
KYL32886.1
6508
13079
587
KYL32887.1
6509
13080
234


1785
II
3
ALS34707.1
6511
13082
588
ALS34708.1
6512
13083
232


1786
II
3
KOO13437.1
6514
13085
583
KOO13436.1
6515
13086
235


1787
II
3
KGA93591.1
6517
13088
387
KGA93590.1
6518
13089
238


1788
II
3
CCK76631.1
6520
13091
572
CCK76632.1
6521
13092
234


1789
II
3
CAV18530.1
6523
13094
590
CAV18531.1
6524
13095
236


1790
II
3
CEO93970.1
6526
13097
490
CEO93972.1
6527
13098
196


1791
II
3
CDT36105.1
6529
13100
567
CDT36097.1
6530
13101
233


1792
II
3
CDT66931.1
6532
13103
567
CDT66922.1
6533
13104
233


1793
II
3
EIY57316.1
6535
13106
529
EIY57317.1
6536
13107
233


1794
II
3
EPR32275.1
6538
13109
439
EPR32276.1
6539
13110
235


1795
II
3
ENO91777.1
6541
13112
532
ENO91778.1
6542
13113
243


1796
II
3
EAQ53529.1
6544
13115
519
EAQ53528.1
6545
13116
236


1797
II
3
GAA81805.1
6547
13118
588
GAA81804.1
6548
13119
232


1798
II
3
EEF80486.1
6550
13121
599
EEF80469.1
6551
13122
212


1799
II
3
KVA10031.1
6553
13124
435
KVA10030.1
6554
13125
230


1800
II
3
GAD76289.1
6556
13127
583
GAD76290.1
6557
13128
235


1801
II
3
EFM21230.1
6559
13130
550
EFM21229.1
6560
13131
235


1802
II
3
KJF90748.1
6562
13133
583
KJF90749.1
6563
13134
235


1803
II
3
KKB47519.1
6565
13136
508
KKB47518.1
6566
13137
233


1804
II
3
EIM72585.1
6568
13139
289
EIM72584.1
6569
13140
249


1805
II
3
EEX64653.1
6571
13142
414
EEX64652.1
6572
13143
217


1806
II
3
EEY99587.1
6574
13145
584
EEY99586.1
6575
13146
217


1807
II
3
EGW44491.1
6577
13148
425
EGW44490.1
6578
13149
236


1808
II
3
KHD25429.1
6580
13151
679
KHD25430.1
6581
13152
236


1809
II
3
GAL03971.1
6583
13154
658
GAL03972.1
6584
13155
235


1810
II
3
ELA08940.1
6586
13157
561
ELA08939.1
6587
13158
230


1811
II
3
AEH01975.1
6589
13160
407
AEH01976.1
6590
13161
234


1812
II
3
EKM24778.1
6592
13163
591
EKM24779.1
6593
13164
236


1813
II
3
EOD77073.1
6595
13166
583
EOD77074.1
6596
13167
236


1814
II
3
KEQ18612.1
6598
13169
675
KEQ18611.1
6599
13170
234


1815
II
3
EJF07133.1
6601
13172
511
EJF07137.1
6602
13173
245


1816
II
3
KWU01629.1
6604
13175
677
KWU01630.1
6605
13176
236


1817
II
3
KHL11033.1
6607
13178
435
KHL11032.1
6608
13179
230


1818
II
3
AIL32429.1
6610
13181
506
AIL32428.1
6611
13182
222


1819
II
3
KIM02579.1
6613
13184
399
KIM02580.1
6614
13185
230


1820
II
3
KIM12269.1
6616
13187
440
KIM12268.1
6617
13188
250


1821
II
3
EJU08777.1
6619
13190
659
EJU08778.1
6620
13191
234


1822
II
3
AJA69892.1
6622
13193
463
AJA69893.1
6623
13194
235


1823
II
3
KRG22676.1
6625
13196
497
KRG22677.1
6626
13197
214


1824
II
3
KLN64107.1
6628
13199
550
KLN64108.1
6629
13200
235


1825
II
3
KDM93486.1
6631
13202
560
KDM93485.1
6632
13203
235


1826
II
3
KLE39938.1
6634
13205
550
KLE39937.1
6635
13206
235


1827
II
3
KPZ54442.1
6637
13208
588
KPZ54443.1
6638
13209
232


1828
II
3
KQN43371.1
6640
13211
547
KQN43544.1
6641
13212
240


1829
II
3
CVJ63610.1
6643
13214
435
CVJ63623.1
6644
13215
230


1830
II
3
CVE17086.1
6646
13217
550
CVE17042.1
6647
13218
205










(Part C)






















Y



AC









ZorD



ZorE



V
W
X
protein
Z
AA
AB
protein
AD
AE



ZorD
PRT SEQ
DNA SEQ
length
ZorE
PRT SEQ
DNA SEQ
length
Genomic Start
Genomic End
AF


1
protein_accession
ID NO:
ID NO:
(aa)
protein_accession
ID NO:
ID NO:
(aa)
Point
Point
comments





2








1103024
1107464


3
KGH31557.1
84
6655
1089




109913
117783


4
ABR83422.1
88
6659
1010




6232483
6240424


5
EIE46560.1
92
6663
1013




167614
175555


6
EKA35838.1
96
6667
1083




52101
59974


7
EKA51670.1
100
6671
1083




3200
11072


8
EOQ78911.1
104
6675
1083




9650
17440


9








4597
8758


10
ERY08920.1
111
6682
1013




714819
722760


11
ERY16787.1
115
6686
1083




5165403
5173276


12
ERY21331.1
119
6690
1013




1199237
1207178


13
ERV56554.1
123
6694
1013




739445
747386


14
ERX20608.1
127
6698
1083




1361333
1369206


15
ERX27341.1
131
6702
1083




19893
27765


16
ERZ22538.1
135
6706
1083




2803767
2811640


17
ERX75593.1
139
6710
1083




1559729
1567601


18
ESR70189.1
143
6714
1083




64238
72111


19
ETU86356.1
147
6718
1013




956562
964503


20
CDI94245.1
151
6722
1028




6519543
6527528
Additional ZorC homolog CDI94246.1


21
CDI95169.1
155
6726
1083




7388834
7396675


22
EVT82479.1
159
6730
782




1
7247


23
EYU03500.1
163
6734
1082




54121
61990


24
EZN45281.1
167
6738
1009




8398
16691


25
EZO27047.1
171
6742
1014




504264
512118


26
EZP05711.1
175
6746
1014




1929997
1937851


27
CDH74039.1
179
6750
1028




47360
55346


28
CDH70664.1
183
6754
1083




20547
28388


29
KEA10738.1
187
6758
1013




116482
124423


30
AJF50274.1
191
6762
1083




1683969
1691810


31
AKE69363.1
195
6766
1083




2967762
2975603


32
AKE72975.1
199
6770
1028




7120178
7128164


33
CRQ30613.1
203
6774
1028




10264
18250


34
CRQ14077.1
207
6778
1083




20601
28442


35
CRQ20861.1
211
6782
1028




21948
29934


36
CRP04479.1
215
6786
1083




2221
10062


37
CRQ05508.1
219
6790
1083




20602
28443


38
CRP93982.1
223
6794
1028




14375
22361


39
CRP94802.1
227
6798
1028




21977
29963


40
CRQ51017.1
231
6802
1083




7536
15377


41
CRS01084.1
235
6806
1028




19796
27782


42
CRX34597.1
239
6810
1028




21981
29967


43
CRX35808.1
243
6814
1083




7536
15377


44
CRN87050.1
247
6818
1083




7536
15377


45
CRQ28286.1
251
6822
1083




20602
28443


46
CRQ21590.1
255
6826
1028




19796
27782


47
CRN79674.1
259
6830
1028




19796
27782


48
CRO17354.1
263
6834
1083




7536
15377


49
CRW80513.1
267
6838
1028




1009
8995


50
CRW81768.1
271
6842
1083




3068
10909


51
CRS64331.1
275
6846
1083




7536
15377


52
CRS61286.1
279
6850
1028




21981
29967


53
CRX10264.1
283
6854
1083




7536
15377


54
CRX00531.1
287
6858
1028




21972
29958


55
CRW55874.1
291
6862
1083




7536
15377


56
CRX16408.1
295
6866
1028




10272
18258


57
CRP10908.1
299
6870
1028




19796
27782


58
CRP41378.1
303
6874
1083




20600
28441


59
CRP14671.1
307
6878
1028




21981
29967


60
CRP47678.1
311
6882
1083




7536
15377


61
CRO88182.1
315
6886
1083




7536
15377


62
CRO42689.1
319
6890
1028




21982
29968


63
CRN87527.1
323
6894
1083




7536
15377


64
CRN66270.1
327
6898
1028




19796
27782


65
CRP41135.1
331
6902
1028




19796
27782


66
CRP68434.1
335
6906
1083




7536
15377


67
CRP76218.1
339
6910
1028




21981
29967


68
CRQ24486.1
343
6914
1083




7536
15377


69
CRP82303.1
347
6918
1083




7536
15377


70
CRP60955.1
351
6922
1028




21979
29965


71
CRP29619.1
355
6926
1083




7536
15377


72
CRO50908.1
359
6930
1028




19796
27782


73








2197
6787


74
CRP88395.1
366
6937
1028




15384
23370


75
CRP42036.1
370
6941
1028




21981
29967


76
CRP91116.1
374
6945
1083




7536
15377


77
CRN61529.1
378
6949
1028




21982
29968


78
CRN91506.1
382
6953
1083




20602
28443


79
CRP44801.1
386
6957
1083




20602
28443


80
CRP16211.1
390
6961
1028




21981
29967


81
CRP57132.1
394
6965
1028




19796
27782


82
CRP83812.1
398
6969
1083




20602
28443


83
CRO13657.1
402
6973
1028




28606
36592


84
CRO55518.1
406
6977
1083




7536
15377


85
CRO41650.1
410
6981
1083




20602
28443


86
CRO12755.1
414
6985
1028




19796
27782


87
CRP86290.1
418
6989
1083




20602
28443


88
CRP43574.1
422
6993
1028




21972
29958


89
CRP83305.1
426
6997
1083




7536
15377


90
CRP15159.1
430
7001
1028




19797
27783


91
CRP60560.1
434
7005
1028




21977
29963


92
CRQ10764.1
438
7009
1083




7536
15377


93
CRP54752.1
442
7013
1083




7536
15377


94
CRP76522.1
446
7017
1028




19796
27782


95
CRP46003.1
450
7021
1083




20602
28443


96
CRP23116.1
454
7025
1028




21977
29963


97
CRP65472.1
458
7029
1028




19796
27782


98
CRP93795.1
462
7033
1083




7536
15377


99
CRQ27545.1
466
7037
1028




19797
27783


100
CRQ56549.1
470
7041
1083




7536
15377


101
CRP80501.1
474
7045
1083




20602
28443


102
CRP35990.1
478
7049
1028




21982
29968


103
CRO87201.1
482
7053
1028




19796
27782


104
CRP11419.1
486
7057
1083




7536
15377


105
CRP24877.1
490
7061
1083




7536
15377


106
CRO90725.1
494
7065
1028




19796
27782


107
CRP17797.1
498
7069
1083




7536
15377


108
CRO58922.1
502
7073
1028




19796
27782


109
CRP26962.1
506
7077
1028




21977
29963


110
CRP96154.1
510
7081
1083




5235
13076


111
CRN60218.1
514
7085
1028




19796
27782


112
CRO00192.1
518
7089
1083




7536
15377


113
CRO92517.1
522
7093
1083




7536
15377


114
CRO70260.1
526
7097
1028




19796
27782


115
CRP22828.1
530
7101
1028




21981
29967


116
CRP50508.1
534
7105
1083




7536
15377


117
CRO39287.1
538
7109
1083




20601
28442


118
CRO06853.1
542
7113
1028




19796
27782


119
CRP42088.1
546
7117
1083




20602
28443


120
CRP08999.1
550
7121
1028




21977
29963


121
CRQ56997.1
554
7125
1083




7536
15377


122
CRQ59380.1
558
7129
1028




19796
27782


123
CRQ91375.1
562
7133
1083




7536
15377


124
CRQ84097.1
566
7137
1028




21977
29963


125
CRQ52244.1
570
7141
1083




7536
15377


126
CRQ54306.1
574
7145
1028




19796
27782


127
CRQ62236.1
578
7149
1083




7536
15377


128
CRQ81684.1
582
7153
1028




21977
29963


129
CRQ17181.1
586
7157
1028




19796
27782


130
CRQ37577.1
589
7160
1083




20602
28443


131
CRQ86033.1
593
7164
1083




3165
11006


132
CRQ40649.1
597
7168
1028




21981
29967


133
CRQ91563.1
601
7172
1083




20602
28443


134
CRQ79048.1
605
7176
1028




21981
29967


135
CRR29633.1
609
7180
1083




7536
15377


136
CRR29050.1
613
7184
1028




10273
18259


137
CRR72814.1
617
7188
1028




19796
27782


138
CRR80212.1
621
7192
1083




7536
15377


139
CRR16565.1
625
7196
1083




20602
28443


140
CRR21548.1
629
7200
1028




21979
29965


141
CRQ92439.1
633
7204
1083




7536
15377


142
CRQ86092.1
637
7208
1028




19796
27782


143
CRQ59643.1
641
7212
1083




20602
28443


144
CRQ56267.1
645
7216
1028




19796
27782


145
CRR63880.1
649
7220
1083




20602
28443


146
CRR21712.1
653
7224
1028




21977
29963


147








2348
6938


148
CRP93286.1
660
7231
1028




15000
22986


149
CRR90653.1
664
7235
1028




19796
27782


150
CRS00769.1
668
7239
1083




20650
28491


151
CRR57278.1
672
7243
1028




21981
29967


152
CRR67560.1
676
7247
1083




20600
28441


153
CRR87246.1
680
7251
1028




21981
29967


154
CRS01368.1
684
7255
1083




20650
28491


155
CRX14802.1
688
7259
1083




20571
28412


156
CRX13614.1
692
7263
1028




19796
27782


157
CRX26810.1
696
7267
1028




10207
18193


158








20601
25191


159
CRP16606.1
703
7274
1028




21972
29958


160
CRP62133.1
707
7278
1083




7536
15377


161
CRO03492.1
711
7282
1028




21974
29960


162
CRO33372.1
715
7286
1083




7536
15377


163
CRS11153.1
719
7290
1028




21977
29963


164
CRS17556.1
723
7294
1083




7536
15377


165
CRR97375.1
727
7298
1028




19796
27782


166
CRS12921.1
731
7302
1083




20650
28491


167
CRP70784.1
735
7306
1028




19796
27782


168
CRO21080.1
739
7310
1083




7536
15377


169
CRO99381.1
743
7314
1028




19796
27782


170
CRP25040.1
747
7318
1083




7536
15377


171
CRP38642.1
751
7322
1083




7536
15377


172
CRP11550.1
755
7326
1028




21982
29968


173
CRP98584.1
759
7330
1083




20650
28491


174
CRP72862.1
763
7334
1028




21977
29963


175
CRX06581.1
767
7338
1028




19796
27782


176
CRX13436.1
771
7342
1083




20650
28491


177
CRR85682.1
775
7346
1028




21981
29967


178
CRR95301.1
779
7350
1083




7536
15377


179
CRR86731.1
783
7354
1083




7536
15377


180
CRR89302.1
787
7358
1028




19796
27782


181
CRS01767.1
791
7362
1028




19796
27782


182
CRS11319.1
795
7366
1083




7536
15377


183
CRR80885.1
799
7370
1028




21985
29971


184
CRR92362.1
803
7374
1083




7536
15377


185
CRR30192.1
807
7378
1083




7536
15377


186
CRS13888.1
811
7382
1028




19797
27783


187
CRS13748.1
815
7386
1083




7536
15377


188
CRR98713.1
819
7390
1028




19796
27782


189
CRS06172.1
823
7394
1028




21977
29963


190
CRS13985.1
827
7398
1083




20602
28443


191
CRW73996.1
831
7402
617




9779
16532


192
CRX24341.1
835
7406
1083




20602
28443


193
CRX24406.1
839
7410
1083




7536
15377


194
CRX17822.1
843
7414
1028




15348
23334


195
CRR62878.1
847
7418
1083




7536
15377


196
CRX06818.1
851
7422
1028




21984
29970


197
CRX13750.1
855
7426
1083




20602
28443


198
CRR17545.1
859
7430
1083




6790
14631


199
CRQ30075.1
863
7434
1028




10239
18225


200
CRR51884.1
867
7438
1083




7536
15377


201
CRQ97126.1
871
7442
1028




21982
29968


202
KQJ58849.1
875
7446
1012




96
8034


203
KRU98871.1
879
7450
1083




4551
12425


204
KRV03413.1
883
7454
1083




10551
18423


205
KRU83197.1
887
7458
1083




3589
11464


206
KRU92654.1
891
7462
1083




4551
12425


207
KSD25192.1
895
7466
1013




113233
121174


208
KSD74105.1
899
7470
1013




106671
114764


209
KSD60221.1
903
7474
1028




115376
123362


210
KSD87955.1
907
7478
1083




7720
15561


211
KSD88702.1
911
7482
1028




20150
28136


212
KSD50143.1
915
7486
1083




7720
15561


213
KSD56742.1
919
7490
1028




202494
210480


214
KSE06416.1
923
7494
1028




691615
699601


215
KSD97267.1
927
7498
1083




8459
16300


216
KSE55323.1
931
7502
1083




7720
15561


217
KSE57197.1
935
7506
1028




20032
28018


218
KSE67394.1
939
7510
1083




7720
15561


219
KSE22577.1
943
7514
1083




7720
15561


220
KSE22792.1
947
7518
1028




19980
27966


221
KSG55973.1
951
7522
1013




113233
121174


222
KSH11348.1
955
7526
1013




114765
122706


223
KSC39035.1
959
7530
1083




3729
11602


224
KSC26156.1
963
7534
1083




607382
615223


225
KSC92705.1
967
7538
1013




113233
121174


226
KSD59504.1
971
7542
1028




20152
28138


227
KSD58173.1
975
7546
1083




7720
15561


228
KSE83339.1
979
7550
1013




111993
119934


229
KSI47362.1
983
7554
1083




26399
34240


230
KSI07555.1
987
7558
1083




7720
15561


231
KSJ10821.1
991
7562
1028




28779
36765


232
KSJ26232.1
995
7566
1013




280039
287980


233
KSJ98816.1
999
7570
1083




178760
186632


234
KSK91644.1
1003
7574
1083




44277
52118


235
KSL06913.1
1007
7578
1083




6696
14569


236
KSM47318.1
1011
7582
1083




186153
194025


237
KSM41522.1
1015
7586
1013




174276
182369


238
KSN32762.1
1019
7590
1083




20786
28627


239
KSN33323.1
1023
7594
1028




20152
28138


240
KSN27909.1
1027
7598
1083




5029
12870


241
KSN02520.1
1031
7602
1014




88424
96278


242
KSN94645.1
1035
7606
1083




6822
14695


243
KSN59776.1
1039
7610
1028




19980
27966


244
KSN68238.1
1043
7614
1083




678802
686643


245
KSO78874.1
1047
7618
1083




6821
14694


246
KSO73923.1
1051
7622
1083




7720
15561


247
KSO74311.1
1055
7626
1028




28768
36754


248
KSO93084.1
1059
7630
1028




19851
27837


249
KSO91842.1
1063
7634
1083




7720
15561


250
KSP60334.1
1067
7638
1028




19084
27070


251
KSP82593.1
1071
7642
1009




65229
73525


252
KSQ11853.1
1075
7646
1083




262790
270663


253
KSN68772.1
1079
7650
1083




6822
14695


254
KSO40827.1
1083
7654
1013




176313
184406


255
KSQ48397.1
1087
7658
1028




29036
37022


256
KSQ47081.1
1091
7662
1083




7720
15561


257
KSQ03905.1
1095
7666
1028




29276
37262


258
KSQ01965.1
1099
7670
1083




7720
15561


259
KSR61591.1
1103
7674
1013




101987
110080


260
KSR90899.1
1107
7678
1013




112375
120316


261
KSR87676.1
1111
7682
1083




6822
14695


262
KSR56103.1
1115
7686
1083




7720
15561


263
KSR68840.1
1119
7690
1028




691615
699601


264
KSS83645.1
1123
7694
1028




28814
36800


265
KSS82294.1
1127
7698
1083




7720
15561


266
KSS65849.1
1131
7702
1083




7720
15561


267
KSS71071.1
1135
7706
1028




65766
73752


268
KSS83668.1
1139
7710
1083




7720
15561


269
KSS97186.1
1143
7714
1028




691552
699538


270
KSS68539.1
1147
7718
1083




7720
15561


271
KSS64136.1
1151
7722
1028




303502
311488


272
KST02404.1
1155
7726
1028




20083
28069


273
KST01503.1
1159
7730
1083




7720
15561


274
KST09050.1
1163
7734
1028




28768
36754


275
KST07353.1
1167
7738
1083




7719
15560


276
KSR39891.1
1171
7742
1028




123377
131363


277
KST03846.1
1175
7746
1083




7720
15561


278
KST05248.1
1179
7750
1028




28768
36754


279
KSS85818.1
1183
7754
1028




20152
28138


280
KSS83935.1
1187
7758
1083




7720
15561


281
KTF54399.1
1191
7762
1028




20040
28026


282
KTF49808.1
1195
7766
1083




7726
15567


283
KTK55769.1
1199
7770
964




5885944
5897844


284
ALZ13981.1
1203
7774
1009




3432864
3441160


285
ALY33853.1
1207
7778
1082




398410
406279


286
ALY39463.1
1211
7782
1083




155293
163134


287
ALY43154.1
1215
7786
1013




4323402
4331343


288








3032150
3036740


289
KWZ69448.1
1221
7792
1013




10132
18224


290
KXG16568.1
1225
7796
1013




153843
161784


291
KYO75363.1
1229
7800
1028




19761
27747


292
KIS48445.1
1232
7803
536




2364174
2369453


293
KVA56603.1
1236
7807
1198




199542
207683


294
KVC33768.1
1240
7811
860




118414
125547


295
AEV65171.1
1244
7815
1082




6013571
6021027


296
KGE64071.1
1248
7819
1082




75257
83079


297
KWV80503.1
1252
7823
1009




1368440
1376687


298
ABQ80735.1
1256
7827
1082




5169632
5177451


299
AFK68694.1
1260
7831
1083




1915596
1923415


300
EMR48533.1
1264
7835
1012




523291
531481


301
AGA73020.1
1268
7839
1095




2309435
2317296


302
KTC24574.1
1272
7843
1009




91397
99402


303
ABP79170.1
1276
7847
1012




1580205
1591257
Additional ZorC homolog ABP79169.1


304
AEA83400.1
1280
7851
1012




1567955
1576354


305
EHY79733.1
1284
7855
1012




65479
73878


306
AFM32809.1
1288
7859
1012




1676860
1685262


307
EWC39444.1
1292
7863
1083




336964
344689


308
EPL62185.1
1295
7866
1012




213132
221531


309
EPM44378.1
1299
7870
1082




14136
21754


310
EPN29006.1
1303
7874
177




667
5568


311
EPN47281.1
1307
7878
183




2221
7140


312
EPN38586.1
1311
7882
184




2215
7137


313
EPN31619.1
1315
7886
928




16485
30385
longer system - ZorD annotated manually


314
EPN22778.1
1319
7890
1082




16485
24103


315
EPN13935.1
1323
7894
1082




1746
9364


316
EPM64845.1
1327
7898
1082




677
8295


317
KFE44520.1
1331
7902
1082




131424
139246


318
KTC49635.1
1335
7906
1082




2323
10154


319
AAM40750.1
1339
7910
1065




1688713
1696136


320
AAY49834.1
1343
7914
1065




3347629
3355052


321
AKS18352.1
1347
7918
641




3124168
3131591


322
ACP24375.1
1351
7922
1072




631821
638722


323








41480
45803


324
KUM27285.1
1358
7929
970




191211
198647


325
CDZ72585.1
1362
7933
1033




110001
117427


326
ACK84142.1
1366
7937
1033




3482023
3489384


327
CAH15305.1
1370
7941
1128




1195308
1202768


328
CCD05129.1
1374
7945
1128




1099307
1106704


329
CZL99023.1
1378
7949
1128




8467
15864


330
CZN28496.1
1382
7953
1128




8467
15864


331
CZP40238.1
1386
7957
1128




8467
15864


332
CZP31232.1
1390
7961
1128




37176
44573


333
CZP19776.1
1394
7965
1128




8467
15864


334
CZN56551.1
1398
7969
1128




8467
15864


335
CZN21905.1
1402
7973
1128




8467
15864


336
CZP49331.1
1406
7977
1128




8467
15864


337
CZP61158.1
1410
7981
1128




37472
44869


338
CZN58367.1
1414
7985
1128




37472
44869


339
CZO62490.1
1418
7989
1128




37166
44563


340
CZO85517.1
1422
7993
1128




37472
44869


341
CZN18828.1
1426
7997
1128




37183
44580


342
CZO33299.1
1430
8001
1128




37166
44563


343
CZN48822.1
1434
8005
1128




148086
155483


344
CZO35416.1
1438
8009
1128




37456
44853


345
CZL93564.1
1442
8013
1128




131968
139365


346
CZH31874.1
1446
8017
1128




8467
15864


347
CZG09164.1
1450
8021
1129




167538
174938


348
CZO58072.1
1454
8025
1128




8467
15864


349
CZP31158.1
1458
8029
1128




677
8074


350
CZP25160.1
1462
8033
1128




37183
44580


351
CZO87108.1
1466
8037
1128




37166
44563


352
CZP12686.1
1470
8041
1128




37456
44853


353
CZO76680.1
1474
8045
1128




8438
15835


354
CZM75981.1
1478
8049
1128




8467
15864


355
CZM80502.1
1482
8053
1128




37456
44853


356
CZO03187.1
1486
8057
1128




37166
44563


357
CZO99623.1
1490
8061
1128




8467
15864


358
CZN77929.1
1494
8065
1128




8467
15864


359
CZO69927.1
1498
8069
1128




37456
44853


360
CZO98759.1
1502
8073
1128




37472
44869


361
CZN87263.1
1506
8077
1128




37472
44869


362
CZO28947.1
1510
8081
1128




8467
15864


363
CZO58257.1
1514
8085
1128




37166
44563


364
CZM99444.1
1518
8089
1128




8467
15864


365
CZN97615.1
1522
8093
1128




37183
44580


366
CZN56267.1
1526
8097
1128




148086
155483


367
CZP07331.1
1530
8101
1128




8467
15864


368
CZP63613.1
1534
8105
1128




37440
44837


369
CZM58531.1
1538
8109
1128




8490
15887


370
CZN95629.1
1542
8113
1128




8441
15838


371
CZN53220.1
1546
8117
1128




37166
44563


372
CZN21830.1
1550
8121
1128




37472
44869


373
CZO53942.1
1554
8125
1128




8467
15864


374
CZO83111.1
1558
8129
1128




37472
44869


375
CZM80568.1
1562
8133
1128




8467
15864


376
CZN76211.1
1566
8137
1128




8467
15864


377
CZN17285.1
1570
8141
1128




37472
44869


378
CZN08698.1
1574
8145
1128




8472
15869


379
CZN07686.1
1578
8149
1128




8467
15864


380
CZN27100.1
1582
8153
1128




37456
44853


381
CZO91499.1
1586
8157
1128




8467
15864


382
CZN16051.1
1590
8161
1128




8467
15864


383
CZN38967.1
1594
8165
1128




8467
15864


384
CZI18617.1
1598
8169
1128




8467
15864


385
CZL86257.1
1602
8173
1128




8467
15864


386
CZM41687.1
1606
8177
1128




37166
44563


387
CZM78452.1
1610
8181
1128




8467
15864


388
CZM56718.1
1614
8185
1128




8467
15864


389
CZM62068.1
1618
8189
1128




37472
44869


390
CZM06036.1
1622
8193
1128




8467
15864


391
CZM98015.1
1626
8197
1128




37456
44853


392
CZN32097.1
1630
8201
1128




37183
44580


393
CZN27816.1
1634
8205
1128




37183
44580


394
CZM96679.1
1638
8209
1128




8467
15864


395
CZN17375.1
1642
8213
1128




37166
44563


396
CZN17807.1
1646
8217
1128




8467
15864


397
CZN51221.1
1650
8221
1128




8467
15864


398
CZN80042.1
1654
8225
1128




8467
15864


399
CZN83589.1
1658
8229
1128




37183
44580


400
CZN87872.1
1662
8233
1128




8408
15805


401
CZN94066.1
1666
8237
1128




37183
44580


402
CZO07198.1
1670
8241
1128




37510
44907


403
CZO11915.1
1674
8245
1128




8467
15864


404
CZO09323.1
1678
8249
1128




8467
15864


405
CZN87980.1
1682
8253
1128




8500
15897


406
CZO32215.1
1686
8257
1128




37183
44580


407
CZO07237.1
1690
8261
1128




8467
15864


408
CZO04106.1
1694
8265
1128




8472
15869


409
CZN90727.1
1698
8269
1128




37183
44580


410
CZP18336.1
1702
8273
1128




8467
15864


411
CZP26215.1
1706
8277
1128




8467
15864


412
CZP25407.1
1710
8281
1128




8467
15864


413
CZN32022.1
1714
8285
1128




8467
15864


414
CZO49291.1
1718
8289
1128




37183
44580


415
CZO32798.1
1722
8293
1128




8467
15864


416
CZO62433.1
1726
8297
1128




37166
44563


417
CZO58360.1
1730
8301
1128




37456
44853


418
CZO85770.1
1734
8305
1128




8467
15864


419
CZP51187.1
1738
8309
1128




37440
44837


420
CZO57236.1
1742
8313
1128




148086
155483


421
CZO45203.1
1746
8317
1128




8467
15864


422
CZO91301.1
1750
8321
1128




37472
44869


423
CZN53915.1
1754
8325
1128




37183
44580


424
CZN51502.1
1758
8329
1128




37440
44837


425
CZO76121.1
1762
8333
1128




37183
44580


426
CZR30106.1
1766
8337
1128




435
7832


427
KTD18863.1
1770
8341
1125




828
8210


428








5615
9801


429








2638
6824


430
EMT94536.1
1780
8351
1067




7878
15300


431








1
3978


432
EMU02179.1
1787
8358
1067




2863
10285


433
EXB30085.1
1791
8362
1067




38504
45935


434
EXB35596.1
1795
8366
1067




190269
197700


435
EXB05629.1
1799
8370
1067




29426
36857


436
EXB92792.1
1803
8374
1067




600238
607669


437
EXB73474.1
1807
8378
1067




187080
194511


438
EXE59931.1
1811
8382
1067




198540
205983


439
EXE71115.1
1815
8386
717




5498
11879


440
KCX96447.1
1819
8390
1067




1709
9140


441
KHO17161.1
1823
8394
1067




15406
22828


442
KLT90614.1
1827
8398
1067




4629
12051


443
KRI43457.1
1831
8402
1068




19553
26974


444
KRJ35149.1
1835
8406
1067




9974
17405


445
AMN00866.1
1839
8410
1070




1372997
1380433


446
KDB58589.1
1843
8414
1300




192445
200726


447
KDD86367.1
1847
8418
1293




46614
54916


448
ACV76376.1
1851
8422
1034




19297
26557


449
AEI38593.1
1855
8426
1034




2402
9662


450
KTJ39357.1
1859
8430
1081




145121
152985


451
KUQ09079.1
1863
8434
1079




68203
76536


452
KYN64183.1
1867
8438
1042




702125
709468


453
AFP68827.1
1871
8442
1080




1024953
1032814
Additional ZorC homolog AFP68828.1


454
ESS59418.1
1875
8446
1080




17627
25491


455
EUL88644.1
1879
8450
78




3297579
3302381


456
KDF77541.1
1883
8454
78




65448
70250


457
AIX56043.1
1887
8458
1080




3771498
3779361


458
KJW77577.1
1891
8462
1079




1673
10006


459
KJX05613.1
1895
8466
1079




1673
10006


460
KPS87961.1
1898
8469
1035




1
5522


461
KRS24834.1
1901
8472
1080




6925
12583


462
KUQ03192.1
1905
8476
1080




42478
50340


463
BAK13747.1
1909
8480
1042




4393137
4400480


464
CCF11171.1
1913
8484
1042




3979011
3986353


465
AFR04656.1
1917
8488
1080




3684004
3691868


466
KHS69300.1
1921
8492
1080




46628
54492


467
KHT02548.1
1925
8496
1080




45831
53695


468
KHT03966.1
1929
8500
1080




47097
54961


469
ABV17208.1
1933
8504
1080




299412
307306


470
EIP59430.1
1937
8508
220




26726
32010


471
EIN79899.1
1941
8512
1080




3501
11365


472
EKK37355.1
1945
8516
1080




1607
9471


473
EKW33216.1
1949
8520
1080




2019
9883


474
ELW24561.1
1953
8524
1080




660
8524


475
ELV55441.1
1957
8528
1080




1478
9222


476
ELV58669.1
1961
8532
1080




664
8528


477
ELV27734.1
1965
8536
1080




64453
72317


478
ELE34847.1
1969
8540
1080




52842
60706


479
ELF60010.1
1973
8544
1084




586259
594135


480
ENC42749.1
1977
8548
1080




33688
41552


481
ENC49342.1
1981
8552
1080




27211
35075


482
ENC65369.1
1985
8556
1080




2255
9929


483
ENC60224.1
1989
8560
1080




27020
34884


484
ENC64691.1
1993
8564
1080




26939
34803


485
ENC77388.1
1997
8568
1080




26972
34836


486
ENC83661.1
2001
8572
1080




27153
35017


487
ENC86712.1
2005
8576
1080




27619
35483


488
ENE16671.1
2009
8580
1080




1801
9665


489
ENC77072.1
2013
8584
1080




27211
35075


490
EOQ56567.1
2017
8588
1079




636603
644930


491
ERB06044.1
2021
8592
1080




39898
47762


492
EQV94535.1
2025
8596
1079




962513
970840


493
EQV96724.1
2029
8600
1084




653799
661675


494
ERB23475.1
2033
8604
1080




1404484
1412348


495
ERA25536.1
2037
8608
1080




337494
345358


496
ERB97872.1
2041
8612
1080




2550
10414


497
ERB87463.1
2045
8616
1080




835
8699


498
ERB73279.1
2049
8620
1080




2197
10061


499
ERB84450.1
2053
8624
1080




5599
13463


500
ERD03125.1
2057
8628
1080




834
8698


501
ERD02931.1
2060
8631
111




2176
3966


502
ERD21115.1
2064
8635
1080




1073
8937


503
ERD19181.1
2068
8639
1080




2495
10359


504
ERD72946.1
2072
8643
1080




1149
9013


505
ERD66559.1
2076
8647
1080




600
8464


506
ERD75975.1
2080
8651
1080




945
8809


507
ERD83531.1
2084
8655
1080




658
8522


508
ERD92969.1
2088
8659
1080




1952
9816


509
ERD99053.1
2092
8663
1080




1388
9252


510
ERD98124.1
2096
8667
1080




1079
8943


511
AHM42042.1
2100
8671
1084




488627
496503


512
AHM46677.1
2104
8675
1084




496169
504045


513
AHM51232.1
2108
8679
1084




497566
505442


514
EYD87638.1
2112
8683
1079




41244
49112


515
EYW22453.1
2116
8687
1080




168471
176335


516
EYW31321.1
2120
8691
1080




1923
9787


517
EYV86552.1
2124
8695
1080




1922
9786


518
EYW71959.1
2128
8699
1080




26412
34276


519
EYW62760.1
2132
8703
1080




26412
34276


520
EYW60241.1
2136
8707
1080




1922
9786


521
EYW56541.1
2140
8711
1080




2143
10007


522
EYW47183.1
2144
8715
1080




3218
11082


523
EYW47503.1
2148
8719
1080




3222
11086


524
EYW43759.1
2152
8723
1080




26417
34281


525
EYW40417.1
2156
8727
1080




26412
34276


526
EYW30109.1
2160
8731
1080




1922
9786


527
EYY79854.1
2164
8735
1080




34684
42548


528
EZB10670.1
2168
8739
1080




2019
9883


529
EZE32943.1
2172
8743
1080




26396
34260


530
KDZ82664.1
2176
8747
1080




17465
25329


531
KHG75766.1
2180
8751
1080




581
8445


532
KHG79500.1
2184
8755
1080




921
8785


533
KOZ37429.1
2188
8759
1080




64411
72275


534
KOZ53463.1
2192
8763
1080




4236
12100


535
KOZ92706.1
2196
8767
1080




6079
13943


536
CTV73579.1
2200
8771
1080




14419
22283


537
CTY75874.1
2204
8775
1080




70490
78354


538
KPH47565.1
2208
8779
1080




596
8460


539
KPH29391.1
2212
8783
1080




26567
34431


540
KPO40057.1
2216
8787
1080




26789
34653


541
KPP40487.1
2220
8791
1080




27360
35224


542
KQI75361.1
2224
8795
1080




53820
61684


543
KST33202.1
2228
8799
1080




27013
34877


544
KUV50203.1
2232
8803
1084




16306
24182


545
KUT58776.1
2236
8807
1080




39315
47179


546
KXL70400.1
2240
8811
1080




1546
9410


547
KXM39828.1
2244
8815
1080




6312
14176


548
KXM53393.1
2248
8819
1080




2592
10456


549
KXN00951.1
2252
8823
1080




4479
12343


550
KXQ06779.1
2256
8827
1080




75
7939


551
KXQ54356.1
2260
8831
1080




314
8178


552
KXR15703.1
2264
8835
1080




50549
58413


553
KXQ76403.1
2268
8839
1080




522
8386


554
KXQ99886.1
2272
8843
1080




312
8176


555
KXR88731.1
2276
8847
1080




238975
246839


556
KXR78154.1
2280
8851
1080




8890
16754


557
EGC96563.1
2284
8855
1080




3169949
3177774


558
GAB54116.1
2288
8859
627




9182
15685


559
EHM44107.1
2292
8863
1080




4368
12232


560
EKB79931.1
2296
8867
1080




833707
841571


561
EKB69924.1
2300
8871
1082




141821
149691


562
EMH92795.1
2304
8875
470




56292
64102


563
EMH90434.1
2308
8879
1082




2827
10697


564
EPA89043.1
2312
8883
1080




31904
39684


565
EPO98322.1
2316
8887
1080




3559
11339


566
ERN60894.1
2320
8891
1080




58696
66506


567
ESM66667.1
2324
8895
1080




3031589
3039453


568








7279
11205


569
EWE84470.1
2331
8902
1082




156425
164295


570
EWE89861.1
2335
8906
1080




59506
67370


571
EZQ78639.1
2339
8910
1080




56522
64386


572
EZR23961.1
2343
8914
1080




56535
64399


573
KDK71113.1
2347
8918
1080




56471
64335


574
KDL50058.1
2351
8922
1080




102416
110280


575
KEF24234.1
2355
8926
1080




298318
306182


576
AIG86118.1
2359
8930
1080




2499874
2507684


577
AIT02044.1
2363
8934
1080




2796337
2804201


578
KGK55642.1
2367
8938
1080




4976163
4984027


579
KHF56288.1
2371
8942
1080




56658
64522


580
CEO84462.1
2375
8946
1080




56654
64518


581
KLZ85287.1
2379
8950
1080




299767
307631


582
KME72629.1
2383
8954
1082




341221
349091


583
KMG80270.1
2387
8958
1080




56631
64495


584
KMH33141.1
2391
8962
1080




298484
306348


585
KMH45009.1
2395
8966
1080




298657
306521


586
KMH61877.1
2399
8970
1080




298657
306521


587
KMH74808.1
2403
8974
1080




298345
306209


588
KMH92294.1
2407
8978
1080




298488
306352


589
KMH82196.1
2411
8982
1082




33540
41410


590
KMI35041.1
2415
8986
1082




411073
418943


591
KMJ00754.1
2419
8990
1080




298445
306309


592
KMX47012.1
2423
8994
1080




159517
167381


593
ALH85686.1
2427
8998
1080




2553997
2561861


594
KPR26028.1
2431
9002
1080




257164
265028


595
KSW78887.1
2435
9006
1077




127014
135431


596
ALP77149.1
2439
9010
1080




1308820
1316684


597
KSZ25784.1
2443
9014
1080




284411
292275


598
AMA16469.1
2447
9018
1080




2542623
2550487


599
KXO21004.1
2451
9022
1080




28886
36750


600
KYL54016.1
2455
9026
1080




10919
18783


601
KYM08972.1
2459
9030
1080




14860
22724


602
KYL42997.1
2463
9034
1080




14860
22724


603
KYL42678.1
2467
9038
1080




14870
22734


604
KYL71100.1
2471
9042
1080




10922
18786


605
KYL53996.1
2475
9046
1080




10920
18784


606
KYM33516.1
2479
9050
1080




284951
292815


607
KYL73346.1
2483
9054
1080




14860
22724


608
KYL53876.1
2487
9058
1080




14862
22726


609
KYM21788.1
2491
9062
1080




14861
22725


610
KYM07146.1
2495
9066
1080




10923
18787


611
KYM09276.1
2499
9070
1080




10920
18784


612
KYL81722.1
2503
9074
1080




14861
22725


613
KYL90350.1
2507
9078
1080




14861
22725


614
KYM24954.1
2511
9082
1080




10920
18784


615
CQJ58396.1
2515
9086
1042




442633
449979


616
CFV22979.1
2519
9090
1042




128423
135769


617
CNI05674.1
2523
9094
1042




382852
390198


618
AHV33809.1
2527
9098
1019




445565
453509


619
KOG92698.1
2531
9102
1019




891037
898981


620
KRW58409.1
2535
9106
1254




282454
290695


621
AAF94909.1
2539
9110
940




1898009
1905745


622
ABQ21454.1
2543
9114
1146




1451122
1458848


623
ACP06006.1
2547
9118
1149




1845143
1852878


624
ACP09871.1
2551
9122
1146




1982541
1990267


625








1741763
1746058


626
EFH78552.1
2558
9129
1149




406663
414398


627
EAZ72426.1
2561
9132
1149




102894
108516


628
EAZ78570.1
2565
9136
1149




39155
46890


629
AET26856.1
2569
9140
1149




1369410
1377145


630
KNH51116.1
2573
9144
1149




31898
39633


631
KNA61361.1
2577
9148
1149




426524
434259


632
EEO08428.1
2581
9152
932




320173
327908


633
EEO16531.1
2585
9156
932




1108223
1115958


634
EEO20562.1
2589
9160
932




1025633
1033368


635
EET92690.1
2593
9164
1149




31076
38811


636
EEY40705.1
2597
9168
1149




318366
326101


637
EEY47280.1
2601
9172
1149




293048
300726


638
EGQ97274.1
2605
9176
1149




315513
323191


639
EGQ98248.1
2609
9180
1149




315860
323595


640
EGS48432.1
2613
9184
1149




2498
10233


641
EGS47643.1
2617
9188
1149




159058
166793


642
EGS47804.1
2621
9192
1149




159009
166744


643
EGS62505.1
2625
9196
1149




159057
166735


644
EGS70772.1
2629
9200
1149




159054
166789


645
EHH71588.1
2633
9204
1149




87128
94863


646
EHH83255.1
2637
9208
1149




313471
321206


647
EHH87247.1
2641
9212
1149




159015
166750


648
EHH97389.1
2645
9216
1149




315855
323590


649
EHI04570.1
2649
9220
1149




318768
326503


650
EHI04038.1
2653
9224
1149




1
6847
Additional ZorC homolog EHI04039.1


651
EHH99554.1
2657
9228
1149




159021
166756


652
EHH93198.1
2661
9232
1149




159052
166787


653
EHH82142.1
2665
9236
1149




159011
166746


654
EHH72364.1
2669
9240
1149




159013
166748


655
EHH76757.1
2673
9244
1149




159078
166813


656
AFC58579.1
2677
9248
1149




1944318
1952053


657
EJH73149.1
2681
9252
1149




159078
166813


658
EJH69789.1
2685
9256
1149




159086
166821


659
EJH28003.1
2689
9260
1149




159398
167133


660
EJH27515.1
2693
9264
1149




159452
167187


661
EJH29360.1
2697
9268
1149




314088
321823


662
EJH38297.1
2701
9272
1149




311261
318996


663
EJH70290.1
2705
9276
1149




159175
166910


664
EJH44247.1
2709
9280
1149




313098
320833


665
EJH55110.1
2713
9284
1149




1125543
1133278


666
EJH55326.1
2717
9288
1149




315841
323576


667
EJH83355.1
2721
9292
1149




360461
368196


668
EJH85690.1
2725
9296
1149




159055
166790


669
EJH80826.1
2729
9300
1149




159198
166933


670
EJH40242.1
2733
9304
1149




349947
357682


671
EKG51166.1
2737
9308
1149




159143
166878


672
EKG45545.1
2741
9312
1149




159094
166829


673
EKG69361.1
2745
9316
1149




159020
166755


674
EKG78204.1
2749
9320
1149




360413
368148


675
EKG79524.1
2753
9324
1149




159046
166724


676
EKG89062.1
2757
9328
1149




159114
166792


677
EKK80940.1
2761
9332
1149




152818
160553


678
EKK97420.1
2765
9336
1149




159065
166743


679
EKL07614.1
2769
9340
932




2711
8667


680
EKL26686.1
2773
9344
1149




159013
166748


681
EKL25947.1
2777
9348
1149




159005
166740


682
EKL86047.1
2781
9352
1149




159001
166736


683
EKM09898.1
2785
9356
1149




159050
166785


684
EKL86443.1
2789
9360
1149




159016
166694


685
EKM18413.1
2793
9364
1149




159007
166685


686
ELT24498.1
2797
9368
1149




318101
325779


687
ELT39814.1
2801
9372
1149




318117
325852


688
ELS74164.1
2805
9376
1149




159011
166746


689
ELS81595.1
2809
9380
1149




159013
166691


690
ELS88994.1
2813
9384
1149




159009
166744


691
ELS96625.1
2817
9388
1149




159067
166802


692
ELT03891.1
2821
9392
1149




159007
166742


693
ELT10274.1
2825
9396
1149




159009
166687


694
ELT32498.1
2829
9400
1149




159005
166740


695
EMB02077.1
2833
9404
1149




2023763
2031498


696
EMP84511.1
2837
9408
1149




159020
166755


697
EMP97714.1
2841
9412
1146




159712
167381


698
EMP95635.1
2845
9416
1149




159039
166774


699
EMQ03271.1
2849
9420
1149




159039
166774


700
EMQ04746.1
2853
9424
1149




159015
166693


701
EMQ11840.1
2857
9428
1149




159023
166701


702
EMQ11494.1
2861
9432
1149




159013
166748


703
EMQ16254.1
2865
9436
1149




159021
166699


704
EMQ22000.1
2869
9440
1149




159017
166752


705
EMQ27290.1
2873
9444
1149




130877
138612


706
EMQ26217.1
2877
9448
1149




130881
138616


707
EMQ32317.1
2881
9452
1149




159017
166752


708
EMQ37897.1
2885
9456
1149




159026
166761


709
EMQ51392.1
2889
9460
1149




159021
166756


710
EMQ53993.1
2893
9464
1149




159019
166754


711
EMQ39195.1
2897
9468
1149




159017
166695


712
EMQ68293.1
2901
9472
1149




159017
166695


713
EMQ62926.1
2905
9476
1149




159012
166690


714
EMQ43436.1
2909
9480
1149




159013
166748


715
EMQ47712.1
2913
9484
1149




159021
166756


716
EWM32708.1
2917
9488
1149




130877
138612


717
KEA49017.1
2921
9492
1149




158099
165834


718








327156
331451


719
KEH80155.1
2928
9499
1149




31003
38738


720
KEH82626.1
2932
9503
1149




31003
38738


721








5628
9512


722








1490
5374


723
KFE03686.1
2942
9513
1149




158948
166626


724
KFE20273.1
2946
9517
1149




31824
39502


725
KFZ34212.1
2950
9521
1149




158938
166673


726
AIT29753.1
2954
9525
1149




1367243
1374978


727
KHE18841.1
2958
9529
1149




115674
123409


728
KHE21919.1
2962
9533
1149




30978
38713


729
BAP03189.1
2966
9537
1149




1752968
1760703


730
KJD16374.1
2970
9541
1149




31764
39499


731
KJJ52417.1
2974
9545
1149




311822
319557


732
KJJ54926.1
2978
9549
1149




311849
319584


733
KJR76010.1
2982
9553
1149




158920
166655


734
KJS92994.1
2986
9557
1146




159627
167353


735
AKA00222.1
2990
9561
1149




1981293
1989028


736
KJW14524.1
2994
9565
1149




22906
30641


737
KJX83384.1
2998
9569
1149




30976
38711


738
KKP13600.1
3002
9573
1149




311137
318815


739
KKP11540.1
3006
9577
1149




159049
166784


740
KKP10400.1
3010
9581
1149




31066
38801


741
AKO75283.1
3014
9585
1149




1873149
1880884


742
CSC37318.1
3017
9588
650




33349
39027


743
CRZ83750.1
3021
9592
1149




323105
330857


744
CSE02169.1
3025
9596
1149




310728
318406


745
CRZ49585.1
3029
9600
1149




310734
318412


746
CSC16469.1
3033
9604
1149




31070
38748


747
CSB69205.1
3037
9608
1149




31121
38824


748
CSA28505.1
3041
9612
1146




31851
39520


749
CSB84087.1
3045
9616
657




135830
143726


750
CSB63121.1
3049
9620
1149




16865
24600


751
CSA19206.1
3053
9624
1149




31070
38748


752
CSD58145.1
3057
9628
1149




31082
38760


753








166125
170429


754
CSB47757.1
3064
9635
1149




31012
38747


755
CSA30951.1
3068
9639
1146




31850
39519


756
CSB56119.1
3072
9643
1149




31737
39415


757
CRZ98351.1
3076
9647
1149




365059
372737


758
CSA01334.1
3080
9651
1149




17713
25417


759
CSB97529.1
3084
9655
1149




159188
166980


760
CSC01752.1
3088
9659
1149




159378
167056


761
CRZ46109.1
3092
9663
565




31477
39390


762
CSA07846.1
3096
9667
1149




361547
369225


763
CSC23719.1
3100
9671
1149




159382
167060


764








31152
35390


765
CSE01568.1
3107
9678
1149




31080
38758


766
CSA08428.1
3110
9681
1149




111629
119351


767
CRZ45164.1
3114
9685
1149




360008
367686


768
CSA07018.1
3118
9689
1149




31070
38748


769
CSA08758.1
3122
9693
1149




311375
319053


770
CSA15617.1
3126
9697
1151




118328
126027


771
CSA74554.1
3130
9701
421




31048
38213


772
CSB88604.1
3133
9704
650




202946
208618


773
CSC80153.1
3137
9708
1149




158978
166656


774
CSB83805.1
3141
9712
1146




33081
40750


775
CSB56566.1
3144
9715
902




33322
38967


776
CSC85417.1
3148
9719
1149




49583
57261


777
CSB86278.1
3152
9723
327




79066
86933


778
CSD13130.1
3156
9727
1149




31083
38761


779
CSD79384.1
3160
9731
1149




158961
166639


780
CSD86903.1
3164
9735
1149




311074
318752


781
CSA39718.1
3168
9739
1149




31077
38755


782
CSC76671.1
3172
9743
1149




159318
166996


783
CSA42827.1
3176
9747
1149




17305
24983


784
CSA52168.1
3180
9751
1149




31069
38747


785
CSD31842.1
3184
9755
1149




310993
318671


786
CSD17868.1
3188
9759
1149




31086
38764


787
CSD38685.1
3192
9763
1149




310723
318401


788
CSA26333.1
3196
9767
1149




159373
167051


789
CSA45918.1
3200
9771
1149




31045
38780


790
CSD96324.1
3204
9775
1149




31082
38760


791
CSA54003.1
3208
9779
1149




159718
167396


792
CSC37805.1
3211
9782
233




32052
39355


793
CSA88183.1
3215
9786
413




33049
40215


794
CSA15198.1
3219
9790
496




31993
39834


795
CSC98525.1
3222
9793
327




34368
40014


796
CRZ48549.1
3226
9797
1157




160331
168052


797
CSB25047.1
3229
9800
435




34141
39160
Additional ZorC homolog CSB25035.1


798
CSD98674.1
3233
9804
1149




360011
367689


799
CSA36985.1
3236
9807
650




33493
39175


800








32082
36377


801
CSD70475.1
3243
9814
1149




31083
38761


802
CSD13890.1
3246
9817
657




459
6109


803
CSD31883.1
3250
9821
1149




31084
38762


804
CSE18808.1
3254
9825
1149




158956
166634


805
CSD93195.1
3258
9829
1149




31084
38762


806
CSA21132.1
3262
9833
1149




159994
167672


807
CSA44698.1
3266
9837
1146




160570
168345


808
CSD30628.1
3270
9841
1149




207665
215343


809
CSD92385.1
3274
9845
1149




310736
318414


810
CSD99314.1
3278
9849
1149




31871
39549


811
CSA22955.1
3282
9853
1149




159775
167453


812
CSA49214.1
3286
9857
366




31257
39041


813
CSC63613.1
3290
9861
650




9409
16634


814
CRZ49258.1
3294
9865
1149




33478
41156


815
CSC03090.1
3298
9869
1149




124696
132431


816
CSD87248.1
3302
9873
1149




310735
318413


817
CSD21248.1
3306
9877
1149




388072
395750


818








31912
36177


819
CSA26743.1
3313
9884
1149




159358
167090


820
CSB50330.1
3317
9888
1149




668438
676116


821
CSB24819.1
3321
9892
233




32013
39918


822
CSB68067.1
3325
9896
650




31070
38775


823
CSB16272.1
3329
9900
915




333817
341563


824
CRZ89203.1
3333
9904
1149




310756
318434


825
CSD99947.1
3337
9908
1149




31875
39553


826
CSA40881.1
3341
9912
1149




31156
38834


827
CSC19347.1
3345
9916
1149




310775
318453


828
CSD27143.1
3349
9920
1149




158972
166650


829
CSA25008.1
3353
9924
1149




159300
166978


830
CSD33007.1
3357
9928
1149




26879
34089


831
CSD25943.1
3361
9932
1149




311072
318750


832
CSD37937.1
3365
9936
1149




310737
318415


833
CSD14752.1
3369
9940
1149




31084
38762


834








162427
166665


835
CSD47052.1
3376
9947
1149




31087
38765


836
CRZ80385.1
3380
9951
1149




313075
320840


837
CSC19211.1
3384
9955
1149




168078
175756


838
CSA23993.1
3388
9959
1146




160208
167877


839
CSA08080.1
3392
9963
1149




31862
39540


840
CSB55683.1
3396
9967
797




278315
286089


841
CSA25866.1
3400
9971
1149




31850
39528


842
CSD34664.1
3404
9975
1149




310731
318409


843
CSC58104.1
3408
9979
1146




63231
70982


844
CSA23928.1
3412
9983
817




31012
38784


845
CSB25832.1
3416
9987
239




4488
12028


846
CSD08425.1
3420
9991
1149




310632
318310


847
CSD25614.1
3424
9995
1149




31075
38753


848
CSD28595.1
3428
9999
1149




31079
38757


849
CSA45233.1
3432
10003
1146




160096
167765


850
CSD82509.1
3436
10007
1149




360009
367687


851
CSC20734.1
3440
10011
1149




159381
167059


852
CSC43362.1
3444
10015
902




63491
71271


853
CSC06923.1
3448
10019
1149




31021
38756


854
CSB50482.1
3452
10023
1149




177974
185709


855
CSE01128.1
3456
10027
1149




310979
318657


856
CSB99370.1
3460
10031
1149




31077
38755


857
KOY92949.1
3463
10034
1149




212064
217686


858
KOY92341.1
3467
10038
1149




159277
167012


859
KOY97237.1
3471
10042
1149




12401
20136


860
KOZ01029.1
3475
10046
1149




211986
219721


861
KPA03324.1
3479
10050
1149




360412
368147


862
ALJ63819.1
3483
10054
1149




1178223
1185958


863
KTL56322.1
3487
10058
1146




324982
332708


864
KUO35495.1
3490
10061
1149




158946
164568


865








30980
35275


866
KUP86909.1
3497
10068
1149




30979
38714


867
KUY44288.1
3501
10072
1149




30985
38720


868
KVI44902.1
3505
10076
1149




343662
351397


869
KWW48036.1
3509
10080
1149




31013
38748


870
EIG23745.1
3513
10084
999




100888
108391


871
KGQ46275.1
3517
10088
1033




80629
88171


872
KGQ51099.1
3521
10092
1033




57777
65324


873
KGQ65034.1
3525
10096
1033




22663
30210


874
ACX76636.1
3529
10100
1045




3759682
3766672


875
ADL25841.1
3533
10104
1045




363595
370585


876
EEO43109.1
3537
10108
1163




2128114
2135123


877
EHG17833.2
3541
10112
1163




2126049
2133058


878
ERT42788.1
3545
10116
1163




50872
58025


879
KGE62644.1
3549
10120
1162




397783
404930


880
EFE87097.1
3553
10124
1166




770761
777911


881
ABM29950.1
3557
10128
1131




3435271
3442881


882
ADB47621.1
3561
10132
969




1390210
1397088


883
ADE85049.1
3565
10136
1030




1376580
1384055


884
ETD02076.1
3569
10140
1030




56033
63508


885
ETD86669.1
3573
10144
1029




52380
59851


886
ETD77750.1
3577
10148
1030




226246
233721


887
ETE54108.1
3581
10152
1030




56001
63476


888








130723
134953


889
KFI23092.1
3588
10159
1150




38137
45876


890
KMY56663.1
3592
10163
874




14053
20516


891
KMY64906.1
3596
10167
874




14041
20504


892
KYD35335.1
3600
10171
860




7802
14262


893
GAD13405.1
3604
10175
860




26441
32340


894
EMT39962.1
3607
10178
931




147491
153762


895








189427
193818


896
EKF49052.1
3613
10184
832




59928
66237
Gene EKF49051.1


897
BAL95141.1
3617
10188
1287




1873936
1882199


898
KTC75264.1
3621
10192
574




10108
15843


899
EFF49968.1
3625
10196
221




66300
71522


900
ABU75894.1
3629
10200
1080




573812
581682


901
EGL73324.1
3632
10203
1080




1391
7059


902








3085383
3088601


903
CCK02757.1
3639
10210
1080




1992732
2000383


904
CCO48378.1
3643
10214
1149




351151
358883


905
CCK80599.1
3647
10218
1149




2847791
2855375


906
KGD34413.1
3651
10222
961




604039
612320


907
KGS74755.1
3655
10226
1253




44290
52434


908
KGW09385.1
3659
10230
1257




3032122
3040259


909
KGX47861.1
3663
10234
881




14326
22286


910
KGX39521.1
3667
10238
1290




2107525
2115821


911
CPH56590.1
3671
10242
1258




30629
39310


912
KSB52474.1
3675
10246
1080




185515
193379


913
AEF17802.1
3678
10249
930




1842826
1849094


914
ENW17899.1
3682
10253
1067




59747
65556


915
ABO66650.1
3686
10257
874




1352626
1359020


916








2415017
2419718


917
ACS21191.1
3693
10264
1291




4851523
4859825


918








1418094
1422180


919
EET81940.1
3700
10271
1067




99524
106967


920
ENU31374.1
3704
10275
1067




191572
197836


921
ALA59736.1
3708
10279
1244




3145019
3153095


922
AGB41058.1
3712
10283
1172




1097125
1104635


923
AEI93762.1
3716
10287
1058




1813459
1820361


924
CCU78670.1
3720
10291
939




785072
791847


925
ERG17895.1
3724
10295
1152




22799
30533


926
ALF60589.1
3728
10299
1075




2700909
2708350


927
AEM78248.1
3731
10302
931




840832
847102


928
EFV93690.1
3735
10306
1109




3038718
3046540


929
KRI14523.1
3739
10310
1068




149243
156664


930
AEJ38285.1
3743
10314
908




54168
60713


931
AEW03627.1
3747
10318
908




54408
60953


932
KFX14694.1
3751
10322
1080




19071
26935


933
KKW93257.1
3755
10326
1274




127747
135625


934
KVX03058.1
3759
10330
1007




67700
75395


935
KJM54477.1
3763
10334
1079




76651
84984


936
KLF88327.1
3767
10338
1080




57307
65172


937
KLG16013.1
3771
10342
1079




39524
47386


938
KLP43533.1
3775
10346
1080




57204
65069


939
KTK05047.1
3779
10350
1079




80895
89228


940
KTJ30245.1
3783
10354
1079




10225
18087


941
KTI23425.1
3787
10358
1079




288377
296710


942
AKL12334.1
3791
10362
1080




2215142
2223007


943








1907323
1912534


944








4313226
4317455


945
AJG24949.1
3801
10372
1288




3725247
3733546


946








8581
12602


947








3803428
3807386


948
AJE15426.1
3811
10382
1083




2249957
2257829


949








869
4909


950
EHO11884.1
3818
10389
1089




1267870
1274810


951
CAY72980.1
3822
10393
1081




680846
688730


952
CAX54370.1
3826
10397
1081




680824
688708


953
AGA90550.1
3830
10401
966




1965119
1972029


954
CUH46422.1
3834
10405
1042




70525
78149


955
AMO80631.1
3838
10409
1082




1259869
1267751


956
AGP47381.1
3842
10413
1042




4767443
4774474


957
KIN78153.1
3846
10417
1032




1354
9819


958
AMS40140.1
3850
10421
1000




1255627
1262896


959
ABK50006.1
3854
10425
1148




4544823
4552542


960
CAP40553.1
3858
10429
1246




241480
249729


961
ERI29927.1
3862
10433
501




71963
77851


962
EPZ87097.1
3866
10437
1253




687271
695415


963
KKI79918.1
3870
10441
1221




2182489
2190633


964
KVD94187.1
3874
10445
1253




12091
20284


965
KVT83336.1
3878
10449
1288




78180
86479


966
KVW62587.1
3882
10453
1288




3262
11561


967








4322511
4327158


968
ADD01960.1
3888
10459
931




714604
720875


969
AEG43647.1
3892
10463
1005




936023
943033


970
ACY51402.1
3896
10467
1149




1803262
1810997


971
EDN58082.1
3900
10471
1149




98875
106610


972
AIR88229.1
3904
10475
1082




609086
616908


973
ABC30367.1
3908
10479
1003




3762737
3770015


974
ALV90956.1
3912
10483
1083




367721
375594


975
EDL49430.1
3916
10487
1270




30300
38162


976
CAQ68799.1
3920
10491
1097




858781
866499


977
BAH37230.1
3924
10495
1150




220564
228082


978
KGU86623.1
3928
10499
1082




16946
24768


979
AFE11186.1
3931
10502
858




3778679
3785329


980
EHJ60588.1
3935
10506
1271




82585
90450


981
AIT79634.1
3939
10510
1271




1565213
1573078


982








1479567
1484303


983
ADP10189.1
3946
10517
1081




558724
566608


984
ABM39547.1
3950
10521
1259




145574
154312


985
EIL89343.1
3954
10525
1080




112461
119985


986
GAC31731.1
3958
10529
1156




31246
38984


987








2144456
2148780


988
KFK00372.1
3965
10536
1080




91457
99321


989
CDT04312.1
3969
10540
1148




483924
491657


990
CDT11724.1
3973
10544
1148




106517
114250


991
KXV35458.1
3977
10548
1028




11957
19254


992
EAT06419.1
3981
10552
952




18325
29199


993
BAQ44677.1
3985
10556
1033




1242440
1249828


994
CCE22487.1
3989
10560
1003




864299
871500


995
CEG51219.1
3993
10564
1012




170325
178733


996
EJI89229.1
3997
10568
390




559407
565225


997
KDE37031.1
4001
10572
1081




305795
313692


998








2602720
2606694


999
GAE46383.1
4007
10578
810




27879
34299


1000
EAQ47299.1
4011
10582
1032




3319389
3327854


1001
EDP59416.1
4015
10586
1149




217393
225128


1002
CUH52009.1
4019
10590
1071




33047
40102


1003
CVK01153.1
4023
10594
1256




2323
11357


1004
ABE74737.1
4027
10598
1075




1137832
1145312


1005
CCW17773.1
4030
10601
1251




59
7588


1006








4213818
4218168


1007
AFU46479.1
4037
10608
1093




3031899
3040069


1008
EZI30548.1
4041
10612
1082




320199
328021


1009








1174385
1178645


1010
GAA77180.1
4048
10619
1151




153172
160898


1011
AMK16853.1
4052
10623
1074




479754
487343


1012
ADQ06818.1
4055
10626
939




1109840
1116255


1013
EFN90476.1
4059
10630
1090




8688
15379


1014
KXB76240.1
4062
10633
255




20
2822


1015
EPR18408.1
4066
10637
441




4420
10039


1016
KMO18104.1
4070
10641
968




1639
9617


1017








3802
7852


1018
ACT17073.1
4077
10648
1248




1186285
1194417


1019
KMW37146.1
4081
10652
916




352471
359778


1020
CUB00796.1
4084
10655
1032




1448
6835


1021
ADJ28734.1
4088
10659
1145




2071841
2079565


1022
AJR24434.1
4091
10662
1074




2738468
2744069


1023
AJR25290.1
4095
10666
1073




3840140
3847708


1024
EHO63913.1
4099
10670
1088




191966
200316


1025
KVM95914.1
4103
10674
1250




212451
220642


1026
EDY06974.1
4107
10678
874




313023
319483


1027








2634211
2638780


1028
EHR42624.1
4114
10685
986




67071
74599


1029
EHD22820.1
4118
10689
1083




3735867
3743740


1030
CRI66751.1
4122
10693
1249




5085246
5093439


1031
EFY05646.1
4126
10697
1109




5476
13083


1032
EKN30944.1
4130
10701
916




354487
361794


1033
KPL51800.1
4134
10705
1004




1329326
1336639


1034
AMN39056.1
4137
10708
960




660425
667875


1035
KMV29897.1
4141
10712
927




126899
133697


1036
CCA91257.1
4145
10716
1170




303090
310618


1037
CCA92390.1
4149
10720
1271




1576101
1583966


1038
ADE38424.1
4153
10724
1130




185251
192804


1039
EPR27901.1
4157
10728
666




4547
11006


1040
KYC33909.1
4161
10732
1073




68665
76233


1041








3008592
3012561


1042
EPR43454.1
4168
10739
962




39663
46452


1043
ESU31840.1
4171
10742
886




2112774
2119197


1044
KHJ69398.1
4175
10746
1083




29299
37172


1045
ERO56338.1
4179
10750
1080




712736
720606


1046
KHN63197.1
4183
10754
1081




41108
48981


1047








24422
28518


1048
CUB04081.1
4190
10761
1008




169304
176741


1049
EJM18416.1
4194
10765
1082




19009
26828


1050
EUB73629.1
4198
10769
1009




891473
899518


1051








80
4289


1052
EOU44973.1
4205
10776
1079




2232245
2240572


1053
ELC22343.1
4209
10780
1079




132985
141312


1054
EOU82995.1
4213
10784
1079




1010570
1018897


1055
KXU33091.1
4217
10788
1073




97745
105313


1056
EOV44199.1
4221
10792
1079




2185792
2194119


1057
EOQ55530.1
4225
10796
1080




932985
940849


1058
EOV91300.1
4229
10800
1079




1475831
1484158


1059
EOW68212.1
4233
10804
1079




141883
150210


1060
AFY17879.1
4237
10808
1011




795376
803717


1061
KHK57377.1
4241
10812
1254




222685
230903


1062
ENW78278.1
4245
10816
1067




453952
461376


1063
EME68213.1
4249
10820
1120




587
8575


1064
CDE94531.1
4253
10824
972




1395
8284


1065
CDA50131.1
4257
10828
1097




3567
10917


1066
ESQ90331.1
4261
10832
1186




26132
33751


1067
ESQ74517.1
4265
10836
1252




23941
31878


1068
AII86802.1
4269
10840
1040




1362274
1370579


1069
KPQ04146.1
4273
10844
1149




804600
812315


1070
CUS49189.1
4277
10848
1149




2278030
2285745


1071
ESN27962.1
4281
10852
1080




61729
69537


1072
EPJ56198.1
4285
10856
994




22834
30573


1073
EQA99139.1
4289
10860
1250




233840
241719


1074
KMS61418.1
4293
10864
1250




3101463
3109342


1075
AGT31735.1
4297
10868
865




1327845
1334314


1076
AIY65735.1
4301
10872
1152




2507239
2514925


1077
KXW55385.1
4305
10876
1331




74261
82426


1078
AKU92630.1
4309
10880
920




3541455
3548134


1079








1
3561


1080
ERS83849.1
4315
10886
545




18505
26132


1081
KXU87123.1
4319
10890
1257




16810
25813


1082
KLU37748.1
4323
10894
1284




146865
155158


1083
EUC70009.1
4327
10898
1004




47366
54537


1084
EXI82586.1
4331
10902
1250




64911
73149


1085
KAK42946.1
4335
10906
1102




16857
25146


1086
BAO84443.1
4339
10910
1255




2386040
2394279


1087
CQR46608.1
4342
10913
898




914451
920975


1088
BAP87808.1
4346
10917
1256




715557
723918


1089
KDP87794.1
4350
10921
1097




19414
27256


1090
KQB03826.1
4354
10925
1149




16315
24050


1091
KQA99547.1
4358
10929
1149




159021
166756


1092
KEY85733.1
4362
10933
1082




94535
102357


1093
GAK41826.1
4366
10937
917




154548
161205


1094
KVV58317.1
4370
10941
1263




7829
16059


1095
KVX28282.1
4374
10945
1263




7829
16059


1096
KVZ97544.1
4378
10949
1250




209019
217210


1097
AJY51018.1
4382
10953
1010




2719272
2726819


1098
CDX33072.1
4386
10957
992




46644
54080


1099
CDX43769.1
4390
10961
992




2178
9614


1100
KJS80659.1
4393
10964
1169




21617
29198


1101
KGD90265.1
4397
10968
1293




461343
469645


1102








9785
13551


1103
KOC90085.1
4404
10975
1083




30118
37991


1104
KOC94081.1
4408
10979
1083




18469
26342


1105
KHF78366.1
4412
10983
1069




824611
832051


1106
KQB52479.1
4416
10987
1082




8344
16187


1107
AJP47986.1
4419
10990
1254




1006536
1012681


1108
KIN89384.1
4423
10994
1285




719621
727970


1109
ALQ39735.1
4427
10998
1163




878815
885968


1110
KIQ83918.1
4431
11002
1078




96014
103978


1111
KRP95694.1
4435
11006
1082




120090
127912


1112








3688839
3693414


1113








318
5435


1114
KJM39256.1
4445
11016
1080




95946
103809


1115
KJJ99148.1
4449
11020
1260




335865
344079


1116
KJQ91386.1
4453
11024
1149




23951
31686


1117
KJQ87532.1
4457
11028
1149




23951
31686


1118
AKI01766.1
4461
11032
989




3205142
3212616


1119
KMP10825.1
4464
11035
1132




4141
11432


1120
KJS25179.1
4468
11039
1012




393
8801


1121
KJS49373.1
4471
11042
1169




1742
9323


1122
KLG11563.1
4475
11046
1079




101392
109725


1123
KLP25068.1
4479
11050
1080




12174
20036


1124
KLG16382.1
4483
11054
1080




92870
100733


1125
AKQ40861.1
4487
11058
1243




103859
111640


1126
KLR33908.1
4491
11062
1080




7456
15318


1127
KLQ90826.1
4495
11066
1080




420860
428722


1128
KYO07693.1
4499
11070
1079




361776
370109


1129
KYO16911.1
4502
11073
1080




24041
29699


1130
KLP47186.1
4506
11077
1080




39512
47374


1131
ALE53301.1
4510
11081
1252




36044
44241


1132
KQB93620.1
4514
11085
874




20482
26942


1133
AMN49380.1
4518
11089
1075




1279035
1286515


1134








3339822
3344259


1135
ALK96266.1
4525
11096
1284




1851643
1859936


1136
CUJ89784.1
4529
11100
1071




341420
348475


1137
CUJ83699.1
4533
11104
1039




311766
319390


1138
CUQ65731.1
4537
11108
1151




722567
729986


1139
KVV05823.1
4541
11112
1082




20533
28381


1140
KVV04343.1
4545
11116
1082




212447
220295


1141
KUO77798.1
4549
11120
1163




3229
10766


1142
KQM30741.1
4553
11124
1069




115202
122116


1143
KQM97535.1
4557
11128
1194




10557
18537


1144
KQN80960.1
4561
11132
1069




115205
122119


1145
KQQ29439.1
4565
11136
1033




213672
221015


1146
KQR49973.1
4569
11140
1250




159043
167267


1147








618525
622872


1148
KQS63849.1
4576
11147
1033




214815
222241


1149
KQV35759.1
4580
11151
1033




269085
276511


1150
KQY95045.1
4584
11155
1228




46871
54637


1151
KRD25373.1
4588
11159
1093




92331
100492


1152
KRD25866.1
4592
11163
1033




269071
276497


1153
KQV20176.1
4596
11167
1084




52687
60515


1154
KQX34250.1
4600
11171
1028




21428
28723


1155
KRE22553.1
4604
11175
999




7778
15050


1156
KRA26259.1
4608
11179
1082




142278
150100


1157
KRA28531.1
4612
11183
1228




295879
303645


1158
KRB49803.1
4616
11187
988




113257
120693


1159
KQC46107.1
4620
11191
874




19282
25742


1160
KWV49699.1
4624
11195
1032




46982
54421


1161
KUI99565.1
4628
11199
1156




1381229
1388527


1162
KTG21221.1
4632
11203
1007




2662
10353


1163
CVJ90715.1
4636
11207
1285




15727
24792


1164
CVK24351.1
4640
11211
1264




173387
182161


1165
CVK22607.1
4644
11215
1094




247062
254978


1166
CVK27721.1
4648
11219
1104




11000
19159


1167
CVJ14724.1
4652
11223
1257




373326
382397


1168
CVJ96960.1
4656
11227
1256




4116
13150


1169
KXS40894.1
4660
11231
781




1
6250


1170
KXW57566.1
4664
11235
1236




203
8225


1171
EJO46333.1
4668
11239
1079




3283
11091


1172
EPY95206.1
4672
11243
1079




81138
89471


1173
EUL64245.1
4676
11247
1079




52392
60200


1174
AMQ20315.1
4680
11251
874




858032
864492


1175




ADB42632.1
4683
11254
260
34303
37171


1176




EIA72759.1
4686
11257
272
4981
7798


1177




EIA87027.1
4689
11260
272
587
3404


1178




EIA94949.1
4692
11263
272
4929
7746


1179




EIA95447.1
4695
11266
272
4929
7746


1180




KQH60906.1
4698
11269
272
4977
7794


1181




KQI25490.1
4701
11272
272
6992
9809


1182




KQI25382.1
4704
11275
272
29293
32110


1183




KRS58893.1
4707
11278
272
205116
207933


1184




KRS89291.1
4710
11281
272
37988
40802


1185




KEA44660.1
4713
11284
258
75386
78313


1186




ALX12000.1
4716
11287
282
2362582
2365410


1187




AMB80663.1
4719
11290
171
3818332
3821205


1188




CZG58405.1
4722
11293
288
228584
231634


1189




CZH63846.1
4725
11296
288
299658
302708


1190




CZG92852.1
4728
11299
288
132992
136042


1191




CZI24994.1
4731
11302
288
5076
8126


1192




CZI29056.1
4734
11305
288
236475
239525


1193




CZH75430.1
4737
11308
288
4977
8027


1194




CZI28436.1
4740
11311
288
236475
239525


1195




CZQ90608.1
4743
11314
288
5076
8126


1196




EEZ95916.1
4746
11317
270
1176272
1179193


1197




ADG61930.1
4749
11320
238
1638409
1641357


1198




EGE12535.1
4752
11323
283
142451
145399


1199




EGE10943.1
4755
11326
283
32251
35199


1200




EGE11784.1
4758
11329
238
35082
38030


1201




EGE15773.1
4761
11332
283
36412
38991


1202




EGE17283.1
4764
11335
283
104584
107532


1203




EGE18523.1
4767
11338
283
113565
116513


1204




EGE26178.1
4770
11341
283
113528
116215


1205




EGE24865.1
4773
11344
283
113550
116498


1206




EKF83141.1
4776
11347
283
182847
185795


1207




AIT43972.1
4779
11350
283
1706599
1709286


1208




ALD78150.1
4782
11353
363
3528333
3531638


1209




KJI56240.1
4785
11356
363
155926
159387


1210




KKW50396.1
4788
11359
286
1
2089


1211




KFF70138.1
4791
11362
291
156818
159810


1212




KHS98347.1
4794
11365
291
92311
95303


1213




AAG59480.1
4797
11368
367
5390202
5393675


1214




BAB38679.1
4800
11371
367
5360199
5363672


1215




ACA79492.1
4803
11374
367
4265907
4269380


1216




ACB17260.1
4806
11377
367
4909284
4912757


1217




ACI34823.1
4809
11380
367
5433847
5437320


1218




ACT75060.1
4812
11383
367
5389908
5393381


1219




ADD59515.1
4815
11386
367
5198464
5201937


1220




EEC29617.1
4818
11389
367
1434820
1438293


1221




EFK27046.1
4821
11392
367
3332
6805


1222




EDU34130.1
4824
11395
367
92585
96058


1223




EDU54254.1
4827
11398
367
93693
97166


1224




EDU68785.1
4830
11401
367
71232
74705


1225




EDU76194.1
4833
11404
367
110915
114388


1226




EDU82467.1
4836
11407
367
309575
313048


1227




EDU87384.1
4839
11410
367
111793
115266


1228




EDU93251.1
4842
11413
367
312441
315914


1229




EDU97861.1
4845
11416
367
75960
79433


1230




EGI28990.1
4848
11419
367
292706
296178


1231




EDZ76317.1
4851
11422
367
2709358
2712831


1232




EDZ82369.1
4854
11425
367
2577686
2581159


1233




EDZ88717.1
4857
11428
367
3697436
3700909


1234




EFX08671.1
4860
11431
367
283864
287337


1235




EFX13460.1
4863
11434
367
289307
292780


1236




EFX18237.1
4866
11437
367
289258
292731


1237




EFX28076.1
4869
11440
367
211056
214373


1238




EFX32589.1
4872
11443
367
18337
21654


1239




EGD70491.1
4875
11446
367
274421
277894


1240




EGD69131.1
4878
11449
367
361430
364903


1241




EFW65236.1
4881
11452
367
470631
474104


1242




AEZ43445.1
4884
11455
367
5125498
5128971


1243




EHU86057.1
4887
11458
367
77320
80793


1244




EHU89502.1
4890
11461
367
311953
315268


1245




EHV18497.1
4893
11464
367
37259
40576


1246




EHV31799.1
4896
11467
367
307976
311449


1247




EHV46591.1
4899
11470
367
161927
165244


1248




EIF87144.1
4902
11473
367
447700
451173


1249




AFJ31991.1
4905
11476
367
5247976
5251449


1250




EIN15907.1
4908
11479
367
9700
13173


1251




EIP63614.1
4911
11482
367
76951
80424


1252




EIP71436.1
4914
11485
367
10354
13827


1253




EIO79098.1
4917
11488
351
77077
80550


1254




EIN94506.1
4920
11491
367
76794
80267


1255




EIO32393.1
4923
11494
367
78914
82387


1256




EIO45814.1
4926
11497
367
241456
244929


1257




EIO63773.1
4929
11500
367
250314
253787


1258




EIO69655.1
4932
11503
367
10239
13712


1259




EIO86632.1
4935
11506
367
250688
254161


1260




EIP72923.1
4938
11509
367
9692
13165


1261




EIP72311.1
4941
11512
367
26220
29693


1262




EIP50027.1
4944
11515
367
26239
29712


1263




EIP49011.1
4947
11518
367
9686
13159


1264




EIP40252.1
4950
11521
367
9696
13169


1265




EIP35337.1
4953
11524
367
26235
29708


1266




EIP27296.1
4956
11527
367
23530
26709


1267




EIP38851.1
4959
11530
367
75543
79016


1268




EIP33940.1
4962
11533
367
9690
13163


1269




EIP10351.1
4965
11536
367
9692
13165


1270




EIP05659.1
4968
11539
367
7027
10500


1271




EIP03401.1
4971
11542
367
1558
4737


1272




EIO92489.1
4974
11545
367
26262
29735


1273




EIO87488.1
4977
11548
367
26302
29775


1274




EIN16731.1
4980
11551
367
9693
13166


1275




EIN15643.1
4983
11554
367
3483
6956


1276




EIN33047.1
4986
11557
367
9701
13174


1277




EIO86815.1
4989
11560
39
1
1412


1278




EIO65805.1
4992
11563
367
9691
13164


1279




EIO79511.1
4995
11566
162
3560
6418


1280




EIO49184.1
4998
11569
367
9700
13173


1281




EIO29775.1
5001
11572
367
1758
5231


1282




EIO24810.1
5004
11575
105
9701
12947


1283




EIO11191.1
5007
11578
367
9700
13173


1284




EIO07423.1
5010
11581
367
9694
13167


1285




EIO07038.1
5013
11584
367
9698
13171


1286




EIO09723.1
5016
11587
367
9696
13169


1287




EIN89792.1
5019
11590
367
112339
115812


1288




EIN88208.1
5022
11593
367
26149
29622


1289




EIN85417.1
5025
11596
367
9700
13173


1290




EIN69800.1
5028
11599
367
9696
13169


1291




EIN65411.1
5031
11602
367
9693
13166


1292




EIN68644.1
5034
11605
367
9696
13169


1293




EIN52364.1
5037
11608
367
9696
13169


1294




EIN49110.1
5040
11611
367
26227
29700


1295




EIN33834.1
5043
11614
367
9692
13165


1296




EIN35237.1
5046
11617
367
29162
32635


1297




EKG95779.1
5049
11620
367
3432
6905


1298




EKH07678.1
5052
11623
367
364931
368404


1299




EKJ54993.1
5055
11626
367
9700
13173


1300




EKJ48079.1
5058
11629
367
9705
13178


1301




EKJ52900.1
5061
11632
367
9688
13161


1302




EKJ36496.1
5064
11635
367
9694
13167


1303




EKJ47660.1
5067
11638
367
9700
13173


1304




EKJ36025.1
5070
11641
367
9698
13171


1305




EKJ20860.1
5073
11644
367
9698
13015


1306




EKJ19822.1
5076
11647
367
9694
13167


1307




EKJ00849.1
5079
11650
367
23510
26983


1308




EKJ92950.1
5082
11653
367
112428
115901


1309




EKJ05366.1
5085
11656
367
26146
29619


1310




EKI82673.1
5088
11659
367
26272
29745


1311




EKI91868.1
5091
11662
367
75553
79026


1312




EKI72761.1
5094
11665
351
26220
29693


1313




EKI64836.1
5097
11668
367
26230
29703


1314




EKI59121.1
5100
11671
367
9693
13166


1315




EKI57124.1
5103
11674
351
9695
13168


1316




EKI46664.1
5106
11677
351
9693
13166


1317




EKI33384.1
5109
11680
367
9694
13011


1318




EKH20915.1
5112
11683
367
9699
13172


1319




EKH25284.1
5115
11686
367
328332
331805


1320




EKH13350.1
5118
11689
367
9702
13175


1321




EKH36313.1
5121
11692
367
9704
13177


1322




EKH26861.1
5124
11695
367
115401
118874


1323




EKH48827.1
5127
11698
367
9700
13173


1324




EKH53676.1
5130
11701
367
115476
118949


1325




EKH61521.1
5133
11704
367
9699
13172


1326




EKH63163.1
5136
11707
367
248863
252336


1327




EKH71773.1
5139
11710
367
9699
13172


1328




EKH63846.1
5142
11713
367
9702
13175


1329




EKH83482.1
5145
11716
367
9704
13177


1330




EKH87898.1
5148
11719
367
9702
13175


1331




EKH95563.1
5151
11722
367
9704
13177


1332




EKI01260.1
5154
11725
367
115400
118873


1333




EKI02729.1
5157
11728
367
67397
70870


1334




EKH96736.1
5160
11731
367
9432
12905


1335




EKI03038.1
5163
11734
367
9488
12961


1336




EKI06057.1
5166
11737
367
66831
70304


1337




EKK37392.1
5169
11740
367
9688
13161


1338




EKK71764.1
5172
11743
367
68104
71577


1339




EKK91181.1
5175
11746
367
6240
9713


1340




EKK36880.1
5178
11749
367
9701
13174


1341




EKK37975.1
5181
11752
351
9698
13171


1342




EKK61087.1
5184
11755
367
9682
13155


1343




EKK52330.1
5187
11758
367
9684
13157


1344




EKK67937.1
5190
11761
367
75545
79018


1345




EKK62289.1
5193
11764
367
75520
78993


1346




EKK87665.1
5196
11767
367
77628
81101


1347




EKV88763.1
5199
11770
367
3477
6950


1348




EKV85096.1
5202
11773
367
9696
13169


1349




EKV70650.1
5205
11776
367
9694
13167


1350




EKW05769.1
5208
11779
367
75769
79242


1351




EKV91511.1
5211
11782
367
3479
6952


1352




EKW03278.1
5214
11785
367
9690
13163


1353




EKW04231.1
5217
11788
367
9698
13171


1354




EKW19022.1
5220
11791
367
9700
13173


1355




EKW08485.1
5223
11794
367
9700
13173


1356




EKW71369.1
5226
11797
351
6744
10217


1357




EKW96653.1
5229
11800
367
75179
78652


1358




EKW96258.1
5232
11803
367
9885
13358


1359




EKW76354.1
5235
11806
367
29183
32500


1360




EKW75840.1
5238
11809
367
9851
13324


1361




EKW68010.1
5241
11812
367
9909
13382


1362




EKW74813.1
5244
11815
351
9682
13155


1363




EKW43904.1
5247
11818
367
79656
83129


1364




EKW70673.1
5250
11821
367
75702
79175


1365




EKW38122.1
5253
11824
367
9692
13165


1366




EKW21069.1
5256
11827
367
3479
6358


1367




EKW36076.1
5259
11830
105
26295
29801


1368




EKW36716.1
5262
11833
351
9702
13175


1369




EKW51351.1
5265
11836
367
9684
13157


1370




EKY34589.1
5268
11839
367
9698
13171


1371




EKY34727.1
5271
11842
367
9696
13013


1372




ELI49198.1
5274
11845
367
723
4196


1373




ELV23652.1
5277
11848
367
19030
22503


1374




ELV30874.1
5280
11851
367
3059
6532


1375




ELV62889.1
5283
11854
367
29755
33072


1376




ELV61720.1
5286
11857
367
352
3504


1377




ELV63257.1
5289
11860
367
482
3955


1378




ELV91640.1
5292
11863
367
26114
29587


1379




ELV93147.1
5295
11866
367
2876
6349


1380




ELW21803.1
5298
11869
367
19055
22528


1381




ELW24260.1
5301
11872
367
355
3828


1382




ELW27705.1
5304
11875
367
9838
13311


1383




ELW23229.1
5307
11878
367
342
3815


1384




ELW28314.1
5310
11881
367
9868
13341


1385




ELW46368.1
5313
11884
367
9890
13363


1386




ELV14531.1
5316
11887
367
362
3835


1387




ELV31269.1
5319
11890
367
26209
29682


1388




ELV35520.1
5322
11893
367
26046
29519


1389




ELV44401.1
5325
11896
367
1488
4667


1390




ELV47161.1
5328
11899
367
9825
13298


1391




ELV76551.1
5331
11902
367
18805
22278


1392




ELV98803.1
5334
11905
367
9948
13421


1393




ELV75965.1
5337
11908
367
9795
13268


1394




ELV90960.1
5340
11911
367
351
3824


1395




ELW12422.1
5343
11914
367
9877
13350


1396




ELV15306.1
5346
11917
351
9689
13162


1397




EMR91944.1
5349
11920
367
5144
8617


1398




EMS03598.1
5352
11923
367
7561
11034


1399




ELE41778.1
5355
11926
365
3624619
3628086


1400




ELF28430.1
5358
11929
367
2021904
2025377


1401




ELG08153.1
5361
11932
367
1531417
1534890


1402




ELH63188.1
5364
11935
367
388742
392215


1403




ENE27217.1
5367
11938
172
180
3065


1404




EQO57390.1
5370
11941
367
620369
623842


1405




EQO66401.1
5373
11944
367
1177818
1181291


1406




EQT31737.1
5376
11947
367
348841
352314


1407




EQT84556.1
5379
11950
367
632377
635850


1408




ERB08802.1
5382
11953
367
3407072
3410545


1409




ERB13354.1
5385
11956
367
322637
326110


1410




ERC00100.1
5388
11959
367
77309
80782


1411




ERB68139.1
5391
11962
367
75975
79448


1412




ERB88971.1
5394
11965
367
9811
13284


1413




ERC15172.1
5397
11968
367
9856
13329


1414




ERB79213.1
5400
11971
367
77187
80660


1415




ERB91730.1
5403
11974
367
77192
80665


1416




ERC08309.1
5406
11977
367
9951
13424


1417




ERC32303.1
5409
11980
367
9828
13301


1418




ERC25307.1
5412
11983
367
249232
252705


1419




ERC09301.1
5415
11986
367
9873
13346


1420




ERC10656.1
5418
11989
367
9861
13334


1421




ERE14325.1
5421
11992
367
78160
81633


1422




ERC92365.1
5424
11995
367
503
3976


1423




ERD40228.1
5427
11998
367
9979
13452


1424




ERC91693.1
5430
12001
367
78422
81895


1425




ERD09262.1
5433
12004
367
9938
13411


1426




ERC65820.1
5436
12007
367
76813
80286


1427




ERC53515.1
5439
12010
367
79318
82791


1428




ERE00879.1
5442
12013
367
79822
83295


1429




ERE21794.1
5445
12016
367
77012
80485


1430




ERC61432.1
5448
12019
367
29621
33094


1431




ERC74183.1
5451
12022
367
7928
11401


1432




ERC30058.1
5454
12025
367
249421
252894


1433




ERC33931.1
5457
12028
367
251930
255403


1434




ERC40338.1
5460
12031
367
248447
251920


1435




ERC48255.1
5463
12034
367
313847
317320


1436




ERD08377.1
5466
12037
367
10188
13661


1437




ERD05017.1
5469
12040
367
10008
13481


1438




ERD20744.1
5472
12043
367
10127
13600


1439




ERD22948.1
5475
12046
367
9957
13430


1440




ERD23988.1
5478
12049
367
9873
13346


1441




ERD35067.1
5481
12052
367
10031
13504


1442




ERD37181.1
5484
12055
367
9911
13384


1443




ERD26789.1
5487
12058
367
29789
33106


1444




ERD52927.1
5490
12061
367
9940
13413


1445




ERD45125.1
5493
12064
367
9940
13413


1446




ERD72595.1
5496
12067
367
9928
13401


1447




ERD68374.1
5499
12070
367
9876
13349


1448




ERD73628.1
5502
12073
367
9971
13288


1449




ERD83185.1
5505
12076
367
9864
13337


1450




ERD87988.1
5508
12079
367
9921
13394


1451




ERD91773.1
5511
12082
367
10046
13519


1452




ERD98680.1
5514
12085
367
9963
13436


1453




ERD88425.1
5517
12088
367
9908
13225


1454




ERE36108.1
5520
12091
367
9963
13436


1455




ERE23637.1
5523
12094
367
324
3797


1456




ERE42058.1
5526
12097
367
76380
79853


1457




ERE45406.1
5529
12100
367
76828
80301


1458




ETJ70766.1
5532
12103
367
294
3767


1459




ERC07678.1
5535
12106
367
9843
13316


1460




ESD10537.1
5538
12109
367
455
3928


1461




ESL20618.1
5541
12112
367
2605262
2608735


1462




ESP12224.1
5544
12115
367
347406
350879


1463




ETJ79051.1
5547
12118
367
9638
13111


1464




EST67464.1
5550
12121
367
62231
65703


1465




EST67378.1
5553
12124
367
35969
39442


1466




AHG12153.1
5556
12127
367
5404978
5408295


1467




EYE30765.1
5559
12130
367
13431
16904


1468




EYE15507.1
5562
12133
367
8798
12271


1469




EYE15594.1
5565
12136
367
8718
12191


1470




EYW09909.1
5568
12139
367
361634
365107


1471




EYW25816.1
5571
12142
367
361618
365091


1472




EYW27178.1
5574
12145
367
75562
79035


1473




EYW07429.1
5577
12148
367
9641
13114


1474




EYW24507.1
5580
12151
367
76003
79476


1475




EYW34607.1
5583
12154
367
9641
13114


1476




EYW13498.1
5586
12157
367
76031
79504


1477




EYV89289.1
5589
12160
367
361672
365145


1478




EYY46581.1
5592
12163
367
358618
362091


1479




EYV70452.1
5595
12166
367
125628
129101


1480




EYV67644.1
5598
12169
367
298415
301888


1481




EYV59033.1
5601
12172
367
136307
139780


1482




EYV37956.1
5604
12175
367
6474
9947


1483




EYV46021.1
5607
12178
367
116589
120062


1484




EYV44254.1
5610
12181
367
135140
138613


1485




EYV24871.1
5613
12184
367
136213
139686


1486




EYV22947.1
5616
12187
367
18805
22278


1487




EYV18172.1
5619
12190
367
116382
119855


1488




EYV20082.1
5622
12193
367
17020
20493


1489




EYV16480.1
5625
12196
367
135221
138694


1490




EYW83369.1
5628
12199
367
361672
365145


1491




EYW75517.1
5631
12202
367
9640
13113


1492




EYW71147.1
5634
12205
367
9640
13113


1493




EYW67183.1
5637
12208
367
361537
365010


1494




EYW64052.1
5640
12211
367
361536
365009


1495




EYW57180.1
5643
12214
367
361537
365010


1496




EYW49138.1
5646
12217
367
9640
13113


1497




EYW49451.1
5649
12220
367
9640
13113


1498




EYW43052.1
5652
12223
367
361537
365010


1499




EYW39158.1
5655
12226
367
9640
13113


1500




EYX70056.1
5658
12229
367
246056
249529


1501




EYX57447.1
5661
12232
367
361672
365145


1502




EYX54552.1
5664
12235
367
361672
365145


1503




EYX48138.1
5667
12238
367
361672
365145


1504




EYX44885.1
5670
12241
367
361672
365145


1505




EYX43989.1
5673
12244
367
9641
13114


1506




EYX33008.1
5676
12247
367
361672
365145


1507




EYX30700.1
5679
12250
367
361672
365145


1508




EYX27757.1
5682
12253
367
9641
13114


1509




EYX13624.1
5685
12256
367
9642
13115


1510




EYX12331.1
5688
12259
367
361671
365144


1511




EYX02200.1
5691
12262
367
9639
13112


1512




EYW98548.1
5694
12265
367
135915
139388


1513




EYW85336.1
5697
12268
367
361672
365145


1514




EYV84727.1
5700
12271
367
361904
365377


1515




EYZ76666.1
5703
12274
367
114299
117772


1516




EYZ63884.1
5706
12277
367
22138
25611


1517




EYZ52262.1
5709
12280
367
361630
365103


1518




EYZ37412.1
5712
12283
367
9641
13114


1519




EYZ38311.1
5715
12286
367
361657
365130


1520




EYZ36221.1
5718
12289
367
361632
365105


1521




EYZ14533.1
5721
12292
367
16533
20006


1522




EZC28520.1
5724
12295
367
75292
78765


1523




EZB48634.1
5727
12298
367
10661
14134


1524




EZB05978.1
5730
12301
367
361672
365145


1525




EZB18139.1
5733
12304
367
75494
78967


1526




EZA89755.1
5736
12307
367
361630
365103


1527




EZB32011.1
5739
12310
367
9642
13115


1528




EZB20624.1
5742
12313
367
361672
365145


1529




EZB41520.1
5745
12316
367
9639
13112


1530




EZB11569.1
5748
12319
367
361763
365236


1531




EZB46981.1
5751
12322
367
9639
13112


1532




EZB04407.1
5754
12325
367
361672
365145


1533




EZB74686.1
5757
12328
367
9945
13418


1534




EZB73670.1
5760
12331
367
9018
12491


1535




EZB73226.1
5763
12334
367
1813
5286


1536




EZB87907.1
5766
12337
367
10203
13676


1537




EZB80139.1
5769
12340
367
361406
364879


1538




EZB81691.1
5772
12343
367
9836
13309


1539




EZB96174.1
5775
12346
367
1
2617


1540




EZC15363.1
5778
12349
367
10311
13628


1541




EZC19639.1
5781
12352
367
10014
13487


1542




EZC20552.1
5784
12355
367
9755
13228


1543




EZC30168.1
5787
12358
367
363212
366685


1544




EZC37649.1
5790
12361
367
361839
365312


1545




EZC43979.1
5793
12364
367
247561
251034


1546




EZB95446.1
5796
12367
367
156780
160253


1547




EZC48752.1
5799
12370
367
361737
365210


1548




EZC62959.1
5802
12373
367
73369
76842


1549




EZC70418.1
5805
12376
367
10529
14002


1550




EZC77658.1
5808
12379
367
9929
13402


1551




EZC64799.1
5811
12382
367
361985
365458


1552




EZC90329.1
5814
12385
367
9858
13331


1553




EZC92767.1
5817
12388
367
10327
13800


1554




EZC86949.1
5820
12391
367
9288
12761


1555




EZC83410.1
5823
12394
367
10360
13833


1556




EZD75265.1
5826
12397
367
9641
13114


1557




EZF08564.1
5829
12400
367
361634
365107


1558




EZF05485.1
5832
12403
367
361566
365039


1559




EZE61417.1
5835
12406
367
79039
82512


1560




EZE88802.1
5838
12409
367
10505
13978


1561




EZE89445.1
5841
12412
367
247303
250776


1562




EZE90571.1
5844
12415
367
17451
20924


1563




EZD08972.1
5847
12418
367
361866
365339


1564




EZD16777.1
5850
12421
367
298547
301798


1565




EZD15761.1
5853
12424
367
361275
364748


1566




EZD19492.1
5856
12427
367
361814
365287


1567




EZD00271.1
5859
12430
367
91957
95430


1568




EZD85326.1
5862
12433
367
76047
79520


1569




EZD90120.1
5865
12436
367
9641
13114


1570




EZJ86913.1
5868
12439
367
311
3784


1571




EZJ76225.1
5871
12442
367
2720
6037


1572




EZJ72756.1
5874
12445
367
645
4118


1573




EZK00743.1
5877
12448
367
2714
6187


1574




EZQ47390.1
5880
12451
367
298328
301801


1575




EZQ50286.1
5883
12454
367
361835
365308


1576




AHY73972.1
5886
12457
367
5404976
5408293


1577




KDA71003.1
5889
12460
367
9097
12570


1578




KDA57922.1
5892
12463
365
4997
8308


1579




KDM81017.1
5895
12466
367
152275
155748


1580




KDM84276.1
5898
12469
367
16699
20172


1581




KDT83301.1
5901
12472
367
26840
30313


1582




KDX42981.1
5904
12475
365
42388
45699


1583




KEJ21095.1
5907
12478
367
8693
12166


1584




KEJ20439.1
5910
12481
367
8678
12151


1585




KEM49613.1
5913
12484
367
27031
30504


1586




KEM85728.1
5916
12487
367
26649
30122


1587




KEN65094.1
5919
12490
367
726
4199


1588




KEO16488.1
5922
12493
365
5063
8374


1589




KEO21425.1
5925
12496
367
264
3737


1590




KEK80774.1
5928
12499
367
61240
64713


1591




KEK94611.1
5931
12502
367
26970
30443


1592




KEL07349.1
5934
12505
367
24905
28378


1593




KEL97935.1
5937
12508
367
1475
4948


1594




KEM08523.1
5940
12511
367
26927
30400


1595




AIF96930.1
5943
12514
367
5385621
5389094


1596




AIG71770.1
5946
12517
367
5409083
5412556


1597




KHI41606.1
5949
12520
367
168373
171846


1598




KHH50141.1
5952
12523
365
52610
56077


1599




KHI22223.1
5955
12526
367
1989
5462


1600




AJA29432.1
5958
12529
367
5350388
5353861


1601




KIG29574.1
5961
12532
367
33089
36562


1602




KIY28269.1
5964
12535
367
10372
13845


1603




KIZ09775.1
5967
12538
367
9762
13235


1604




KJJ46590.1
5970
12541
367
66829
70302


1605




KJW55351.1
5973
12544
367
136995
140468


1606




KJW51699.1
5976
12547
367
116958
120431


1607




KKF77969.1
5979
12550
367
10494
13967


1608




KKF80394.1
5982
12553
367
9762
13235


1609




KKK30169.1
5985
12556
367
2135963
2139436


1610




KKY44748.1
5988
12559
149
1
2817


1611




KLG52814.1
5991
12562
367
114307
117780


1612




KNF16833.1
5994
12565
367
1989
5462


1613




KNF20998.1
5997
12568
367
114447
117920


1614




KNF39643.1
6000
12571
367
16655
20128


1615




KNG40955.1
6003
12574
367
146674
150147


1616




CTT73476.1
6006
12577
367
5649
9122


1617




KOZ12762.1
6009
12580
367
78490
81963


1618




KOZ62644.1
6012
12583
367
9646
13119


1619




KOZ92034.1
6015
12586
367
47766
51239


1620




KOZ11133.1
6018
12589
367
9649
13122


1621




KOZ14563.1
6021
12592
367
248571
252044


1622




KOZ32806.1
6024
12595
367
75809
79282


1623




KOZ23194.1
6027
12598
367
361705
365178


1624




KOZ33144.1
6030
12601
367
9646
13119


1625




KOZ37733.1
6033
12604
367
9647
13120


1626




KOZ50075.1
6036
12607
367
361612
365085


1627




KOZ47192.1
6039
12610
367
9644
13117


1628




KOZ49648.1
6042
12613
367
361767
365240


1629




KOZ66198.1
6045
12616
367
67507
70980


1630




KOZ69679.1
6048
12619
367
361543
365016


1631




KOZ74920.1
6051
12622
367
17746
21219


1632




KOZ84732.1
6054
12625
367
66782
70255


1633




KOZ80207.1
6057
12628
367
66781
70254


1634




KOZ97680.1
6060
12631
367
150289
153762


1635




KPH45896.1
6063
12634
367
248360
251833


1636




KPH35133.1
6066
12637
367
361701
365174


1637




KPH38254.1
6069
12640
367
78493
81966


1638




ALH93592.1
6072
12643
367
5193818
5197291


1639




KPO74167.1
6075
12646
367
9683
13156


1640




KPP03704.1
6078
12649
367
114577
118050


1641




KPP08803.1
6081
12652
367
115506
118979


1642




KPP18127.1
6084
12655
367
363358
366831


1643




KPP23764.1
6087
12658
367
9682
13155


1644




KPP34278.1
6090
12661
367
9682
13155


1645




KPP38848.1
6093
12664
367
9682
13155


1646




KPP49036.1
6096
12667
367
9683
13156


1647




KPP10064.1
6099
12670
367
9683
13156


1648




KPP41786.1
6102
12673
367
9681
13154


1649




KPP53633.1
6105
12676
367
363428
366901


1650




KRQ04752.1
6108
12679
367
280602
284075


1651




KUG91602.1
6111
12682
367
545
4018


1652




KUH02055.1
6114
12685
367
27065
30538


1653




KUS40189.1
6117
12688
367
8291
11764


1654




KUT25844.1
6120
12691
367
14510
17983


1655




KUT16912.1
6123
12694
367
2806
6279


1656




KUT50284.1
6126
12697
367
17959
21432


1657




KUU89823.1
6129
12700
367
29590
33063


1658




KUT63219.1
6132
12703
367
9401
12874


1659




KUU32868.1
6135
12706
367
28187
31660


1660




KUU24008.1
6138
12709
367
8294
11767


1661




KUV87989.1
6141
12712
367
8488
11961


1662




KUW19157.1
6144
12715
367
103408
106881


1663




KUW69108.1
6147
12718
367
60641
64114


1664




KUW47133.1
6150
12721
367
28184
31657


1665




AMG80378.1
6153
12724
367
4055455
4058928


1666




KXK90274.1
6156
12727
367
382661
386134


1667




KXP75342.1
6159
12730
367
60834
64307


1668




KXR06381.1
6162
12733
365
17180
20647


1669




KXR86338.1
6165
12736
365
17181
20648


1670




EYT05879.1
6168
12739
363
315579
319040


1671




KMV95470.1
6171
12742
363
1142870
1146331


1672




ESN46749.1
6174
12745
363
356404
359865


1673




KDL89508.1
6177
12748
363
320792
324253


1674




KMG65745.1
6180
12751
363
5112636
5116097


1675




KRR31032.1
6183
12754
363
59524
62985


1676




CVD68076.1
6186
12757
363
361657
365120


1677




CVD62391.1
6189
12760
363
246007
249470


1678




CVA98365.1
6192
12763
363
246132
249595


1679




CVB66940.1
6195
12766
363
245939
249402


1680




CVE07646.1
6198
12769
363
211862
215325


1681




CUZ34247.1
6201
12772
363
363056
366519


1682




CVH03739.1
6204
12775
363
215808
219271


1683




CUZ32693.1
6207
12778
363
361916
365379


1684




CVC01550.1
6210
12781
363
249441
252904


1685




CVC86891.1
6213
12784
363
249294
252757


1686




CVC74523.1
6216
12787
363
212906
216369


1687




CVC09195.1
6219
12790
363
362064
365527


1688




CVG04243.1
6222
12793
363
361779
365242


1689




CVB23944.1
6225
12796
363
362214
365677


1690




CVE95538.1
6228
12799
363
361839
365302


1691




CVG92146.1
6231
12802
363
214249
217712


1692




CVA05266.1
6234
12805
363
364092
367555


1693




COJ21090.1
6237
12808
363
32605
36068


1694




CNK85655.1
6240
12811
363
185197
188660


1695




KLE23457.1
6243
12814
361
207605
211169


1696




KNY42367.1
6246
12817
371
142231
145804


1697




KTL44733.1
6249
12820
378
1320810
1324404


1698




KED68171.1
6252
12823
378
48394
51988


1699




KHF16014.1
6255
12826
361
33571
37114


1700




KIT58954.1
6258
12829
378
63893
67196


1701




KIT38900.1
6261
12832
378
8473
11776


1702




KJR33560.1
6264
12835
378
440782
444376


1703




KKX83989.1
6267
12838
378
440597
444191


1704




KOE91952.1
6270
12841
378
474874
478468


1705




KOF38059.1
6273
12844
361
9424
12967


1706




KON59156.1
6276
12847
279
561224
564323


1707




KXG05867.1
6279
12850
378
440782
444376


1708




KYJ92314.1
6282
12853
378
440782
444376


1709




EMB49754.1
6285
12856
372
6770
9839


1710




EDL69244.1
6288
12859
378
167290
170884


1711




EFM85264.1
6291
12862
269
139662
142821


1712




EFM93936.1
6294
12865
269
112997
116156


1713




EFM98323.1
6297
12868
269
139455
142614


1714




ABI24730.1
6300
12871
269
481084
484348


1715




EYA48171.1
6303
12874
267
60770
63872


1716




EYA76043.1
6306
12877
278
199288
202423


1717




EYA68805.1
6309
12880
278
1
3131


1718




EYA80657.1
6312
12883
278
47013
50148


1719




CUA18410.1
6315
12886
278
2195155
2198290


1720




KDS43043.1
6318
12889
306
21582
24750


1721




KDS37969.1
6321
12892
306
65172
68340


1722




KDS73985.1
6324
12895
306
108116
111284


1723




ALF18257.1
6327
12898
273
1819401
1822845


1724




KXA24059.1
6330
12901
273
105285
108729


1725




EFG28534.1
6333
12904
192
82671
86075


1726




ADJ62018.1
6336
12907
293
542484
545370


1727




KTC70122.1
6339
12910
143
45
2660


1728




AFT94974.1
6342
12913
364
1736318
1739982


1729




EEX38487.1
6345
12916
361
46338
49881


1730




CCN78627.1
6348
12919
361
1996439
2000017


1731




CCN34619.1
6351
12922
361
70222
73800


1732




CCN40569.1
6354
12925
361
26343
29921


1733




CCN66137.1
6357
12928
361
70235
73813


1734




KGJ97947.1
6360
12931
373
43748
47386


1735




EEP52109.1
6363
12934
282
1752487
1755339


1736




AIP08273.1
6366
12937
282
87534
90386


1737




KGC46811.1
6369
12940
282
924785
927637


1738




AIV53984.1
6372
12943
282
1079826
1082678


1739




KGU70602.1
6375
12946
281
1500031
1502880


1740




KGV18647.1
6378
12949
282
3065754
3068606


1741




KGV94868.1
6381
12952
282
2670857
2673709


1742




KGV65995.1
6384
12955
282
197475
200327


1743




KGV92499.1
6387
12958
282
459725
462577


1744




KGX53111.1
6390
12961
282
123203
126055


1745




KGX64950.1
6393
12964
282
2770
5622


1746




AJX71012.1
6396
12967
282
2464517
2467369


1747




AIA69101.1
6399
12970
291
101386
104378


1748




AIK12006.1
6402
12973
291
101407
104399


1749




KMK83436.1
6405
12976
291
83001
85993


1750




KGK11297.1
6408
12979
378
1809125
1812719


1751




EAR22190.1
6411
12982
368
1014237
1017892


1752




ERG19019.1
6414
12985
262
12777
15389


1753




ERG19055.1
6417
12988
382
10170
13838


1754




ERG37345.1
6420
12991
219
39830
42959


1755




KTD25442.1
6423
12994
272
53517
56564


1756




EER46087.1
6426
12997
280
22897
26188


1757




AKZ71840.1
6429
13000
363
570853
574314


1758




KJN72850.1
6432
13003
363
57346
60807


1759




KLQ05986.1
6435
13006
363
77216
80677


1760




KHE02047.1
6438
13009
286
126996
129842


1761




KHN64403.1
6441
13012
286
308711
311557


1762




ACS83825.1
6444
13015
287
7960
11128


1763




EAS45751.1
6447
13018
363
696153
699714


1764




ALP65205.1
6450
13021
282
1243807
1246659


1765




AIO35887.1
6453
13024
282
2947387
2950269


1766




KTC93826.1
6456
13027
270
188880
191921


1767




KVP70161.1
6459
13030
284
94244
97102


1768




KVP49170.1
6462
13033
284
184358
187216


1769




KVQ79698.1
6465
13036
284
191818
194676


1770




KVR10909.1
6468
13039
284
191827
194685


1771




KVR50013.1
6471
13042
284
96265
99123


1772




KVR54360.1
6474
13045
284
94349
97207


1773




KWB45016.1
6477
13048
284
5874
8732


1774




KWB78078.1
6480
13051
284
94316
97174


1775




KWD39081.1
6483
13054
284
184358
187216


1776




KWD33066.1
6486
13057
284
191818
194676


1777




KWD38755.1
6489
13060
284
96265
99123


1778




KWO93443.1
6492
13063
284
28626
31484


1779




KVX24374.1
6495
13066
284
110871
113729


1780




KGO04270.1
6498
13069
259
857
3814


1781




ADE14193.1
6501
13072
377
1007627
1011302


1782




ADR35023.1
6504
13075
172
2375586
2377970


1783




EPF16737.1
6507
13078
281
2485440
2488277


1784




KYL32888.1
6510
13081
379
8157
11763


1785




ALS34709.1
6513
13084
378
195869
199469


1786




KOO13435.1
6516
13087
371
119459
123032


1787




KGA93589.1
6519
13090
195
161290
163757


1788




CCK76633.1
6522
13093
369
2728464
2731988


1789




CAV18533.1
6525
13096
362
1475653
1479223


1790




CEO93971.1
6528
13099
261
126
3047


1791




CDT36087.1
6531
13102
383
162067
165622


1792




CDT66912.1
6534
13105
383
1519
5074


1793




EIY57318.1
6537
13108
296
805872
809052


1794




EPR32277.1
6540
13111
293
3145
6033


1795




ENO91779.1
6543
13114
362
17111
20509


1796




EAQ53527.1
6546
13117
282
673628
676748


1797




GAA81803.1
6549
13120
378
17567
21167


1798




EEF80509.1
6552
13123
137
187507
190453


1799




KVA10029.1
6555
13126
281
247235
250084


1800




GAD76291.1
6558
13129
378
52164
55758


1801




EFM21228.1
6561
13132
363
211867
215330


1802




KJF90750.1
6564
13135
361
53142
56685


1803




KKB47517.1
6567
13138
262
187119
190140


1804




EIM72583.1
6570
13141
262
115
2515


1805




EEX64651.1
6573
13144
372
390460
393529


1806




EEY99585.1
6576
13147
372
77969
81548


1807




EGW44489.1
6579
13150
293
176059
178904


1808




KHD25431.1
6582
13153
378
154792
158682


1809




GAL03974.1
6585
13156
273
103050
106823


1810




ELA08938.1
6588
13159
281
216422
219641


1811




AEH01977.1
6591
13162
264
2395689
2398415


1812




EKM24780.1
6594
13165
378
414659
418285


1813




EOD77075.1
6597
13168
361
2838
6384


1814




KEQ18610.1
6600
13171
380
51532
55402


1815




EJF07132.1
6603
13174
324
10761
15775


1816




KWU01631.1
6606
13177
361
1104
4932


1817




KHL11031.1
6609
13180
282
2470
5322


1818




AIL32427.1
6612
13183
268
682060
685211


1819




KIM02581.1
6615
13186
218
37
2584


1820




KIM12266.1
6618
13189
132
265881
268795


1821




EJU08779.1
6621
13192
273
341208
344700


1822




AJA69894.1
6624
13195
265
3038320
3041220


1823




KRG22678.1
6627
13198
288
262834
265878


1824




KLN64109.1
6630
13201
376
105944
109441


1825




KDM93484.1
6633
13204
375
115926
119449


1826




KLE39936.1
6636
13207
363
242443
245906


1827




KPZ54444.1
6639
13210
378
57960
61560


1828




KQN43370.1
6642
13213
361
53441
56884


1829




CVJ63634.1
6645
13216
281
59414
62268


1830




CVE16997.1
6648
13219
363
215644
219107









The ZORYA system was not found in archaea. The system is present mainly in Proteobacteria and is markedly under-represented in Gram positive bacteria (Firmicutes and Actinobacteria), suggesting that its functionality depends on the double membrane organization of Gram negative bacteria (Table 8).


The gene composition of the Zorya system may point to several hypotheses as to its mechanism of action: It is possible that the system has adopted the MotAB proton channel to achieve depolarization of membrane potential upon phage infection. Possibly, ZorC, ZorD and ZorE may be involved in the sensing and inactivation of phage DNA, and if phage inactivation fails, the ZorAB proton channel opens up, leading to membrane depolarization and cell death. Under this hypothesis Zorya may be a conditional abortive infection system.


Interestingly, although Zorya-containing cells that were infected by phage T7 did not yield phage progeny in greater than 80% of infection events, infection of Zorya-containing cells in liquid cultures led to an eventual culture collapse, suggesting that Zorya-mediated defense involves death or metabolic arrest of the infected cell (FIGS. 4G-4I).


A second, more far-fetched hypothesis as to the function of Zorya may be that ZorAB localizes to the flagellar motor and alters the activity of the flagella in response to phage infection, presumably to evade infection or to avoid infection spreading.


Example 4
Analysis of the Type I ZORYA System Components

Objective:


To analyze the functionality of the Type I ZORYA system.


Methods:


In order to study the four gene components of the ZORYA type I system, functionality was analyzed with mutated forms of each of the genes of the Type I ZORYA. Deletion mutants were made and the cloned vectors comprising specific gene deletions were transformed into E. coli MG1655 cells. Similarly, point mutations were generated and vectors comprising the point mutation constructs were transformed into E. coli MG1655 cells.


Results:


All four genes in the system appear to be essential for its functionality, as deletion of each of the genes resulted in loss of protection from phage infection (FIG. 4J). Moreover, the activity of the ZorAB proton channel appears to be necessary for the system's functionality, as point mutations in residues predicted to be critical for proton translocation through the channel (either ZorA: T147A/S184A or ZorB:D26N) yielded a non-functional system (FIG. 4J). Similarly, point mutations inactivating the Walker B motif of the helicase domain of ZorD, predicted to prevent ATP hydrolysis, resulted in loss of protection from phage infection.


Example 5
Genomic Identification and Analysis of the Thoeris System

Objective:


Identify the candidate defense system based on the enrichment of the anchor pfam08937 (TIR domain).


Methods:


The Thoeris system was one of the systems identified in the first round of prediction. The Thoeris (Egyptian protective deity of childbirth and fertility) defense system is a two-gene system that was detected based on the enrichment of pfam08937 (TIR domain) next to defense genes (FIG. 3B and FIG. 5A). The Thoeris system in some embodiments, is termed the SIR2-TIR system. The TIR domain was previously reported as associated with prokaryotic argonaute genes.


Genomic Identification and Analysis of Thoeris (SIR2-TIR) Systems—


The anchor genes family for SIR2-TIR was pfam08937, a TIR-like domain (also annotated as DUF1863). It had a defense score of 0.68 and a diversity score of 0.33. It produced several subsystems, one of which was the SIR2-TIR subsystem with a defense score of 0.58 and diversity score of 0.91. It is composed of a SIR2-domain gene, with one or more TIR-domain genes in the immediate vicinity of +/−5 genes from the SIR2 gene. Initially 78 appearances were found in the dataset that was used in the automatic prediction. Later, by manual expansion using the most up-to-date IMG dataset, and via homologs of the SIR2 gene, additional 1162 appearances were found, totaling in 1240 appearances in microbial genomes. The genes domains, properties and environment were explored using known bioinformatics tools.


Cloning of SIR2-TIR into B. subtilis BES7003—


A cloning vector for large fragments was constructed by assembling the p15a origin of replication (ori) from pACYCDuet-1 and the amyE integration cassette from plasmid pDR110 (see https://www(dot)ncbi(dot)nlm(dot)nih(dot)gov/pmc/articles/PMC3814332/#pgen.1003892.s005). The p15a ori was amplified using primers OGO174+OGO175 (a list of all primers is provided in Table 5). The amyE integration cassette was amplified using primers OGO176+OGO185. The two fragments were assembled and transformed into E. coli cells using Gibson assembly cloning kit (NEB E5510S), and assembled plasmids were verified by restriction pattern and full sequencing.


The backbone of the above described vector was amplified using primers OGO309+OGO310, adding to it a BamHI restriction site and a terminator site. The multiple cloning site of plasmid pBS1C (received from the BGSC) was amplified using primers OGO311+OGO312. Both fragments were digested using AscI and BamHI, ligated using T4 ligase and transformed into E. coli, resulting in plasmid pSG1-rfp. The plasmid was digestion verified and fully sequenced.


The SIR2-TIR locus of Bacillus cereus MSX-D12 (RefSeq accession AHEQ01000050, coordinates 16453-19685 of the forward strand, SEQ ID NO: XXXXX) was commercially synthesized (GenScript) directly into pSG1-rfp between the AscI and NotI sites of the multiple cloning site. The cloned vector was transformed into B. subtilis BEST7003 [SD1] cells, and the resulting transformants were verified by PCR and whole genome sequencing.


Phage Cultivation and Plaque Assay—


In the initial studies, phi3T, SPO1, phi29 and phi105 phages were obtained from the Bacillus Genetic Stock Center (BGSC). Phages were propagated on B. subtilis BEST7003 using the plate lysate method as described by Fortier & Moineau (Fortier and Moineau (2009) Phage Production and Maintenance of Stocks, Including Expected Stock Lifetimes. In: Clokie M. R., Kropinski A. M. (eds) Bacteriophages. Methods in Molecular Biology™, vol 501. Humana Press)


Lysate titer was determined using the small drop plaque assay method as described by Mazzocco et al. (Mazzocco et al., 2009 ibid). Efficiency of plating (EOP) was measured by performing small drop plaque assay with the same phage lysate concentrations on control bacteria and bacteria containing the SIR2-TIR system and comparing the ratio of plaque formation. Follow-up experiments included plaque assays testing the EOP against JER, Chloro, SpBeta, SPR, phi105, rho14, and SPP1.


Results:


Thoeris (Egyptian protective deity of childbirth and fertility) is a system that was detected based on the enrichment of pfam08937 (TIR domain) next to known defense genes (FIG. 5A). This domain was previously reported as associated with prokaryotic argonaute genes. The pfam08937 (DUF1863) domain was found to be significantly associated with known defense systems (defense score of 0.68). pfam08937 is a protein domain of unknown function, which was found to have structural homology with the TIR-domain (TIR=Toll-Interleukin receptor). TIR domains are known to be involved in bacterial immune system evasion in animals and plants.


As defense systems are frequently encoded by multiple genes working in concert that are co-localized in the genome (i.e. defense islands), the genetic context of the pfam08937-containing genes was analyzed. It was found that there is a subsystem in which upstream of the genes with a pfam08937 domain there is a gene with a SIR2 domain (pfam13289). Also, in many cases there was more than one TIR-domain gene in proximity (FIG. 5A). The defense score of this subsystem was 0.58, raising the hypothesis that these two (or more) genes together form an anti-phage defense system, denoted herein as SIR2-TIR. The SIR2 gene (pfam13289) encodes a protein with a median size of 483 amino acids. The TIR genes can have one of two pfams, pfam08937 or pfam13676 or pfam 08357. They encode proteins with a median size of 202 amino acids.


The first gene in the Thoeris system, denoted thsA, has NAD-binding domain that is sometimes annotated as a sirtuin (SIR2)-like domain or Macro domain. The second gene was denoted thsB, and contains the TIR domain, and can appear in one or more copies (FIG. 5A). In some versions of the Thoeris system, ThsA polypeptide has a multi-transmembrane N-terminal domain.


Two instances of this system, one from Bacillus cereus MSX-D12 (SEQ ID NO: 10; where ThsA is predicted to be cytoplasmic) and the other from Bacillus amyloliquefaciens Y2 (SEQ ID NO: 11; where ThsA is predicted to be membrane-associated) (FIG. 5B), were engineered into B. subtilis BEST7003, which does not contain an endogenous Thoeris defense system. The correct insertion of the system into the B. subtilis BEST7003 genome was verified by whole genome sequencing. The Thoeris system containing B. subtilis BEST7003 strains were challenged with multiple phages spanning the three families of the dsDNA tailed phages Caudavirales, as detailed above in the methods. The mycophages and podophages are obligatory lytic phages, while the siphophages are temperate.


The cloned systems were found to confer defense against myophages (FIGS. 3B and 3E, and FIGS. 5C and 5D). As the 3 tested myophages are very different from each other and share little gene homologies, it is possible that the Thoeris system is sensing or targeting a general feature in the biology of myophages rather than a specific sequence or genome modification. Both Thoeris genes, thsA and thsB, are essential in the system as deletion of either of them rendered the system inactive (FIG. 5C).


Interestingly, the TIR domain (acronym for Toll-Interleukin Receptor) is an important component of the innate immune systems of mammals, plants and invertebrates, where it mainly serves as a connector domain that transfers the immune signal once a molecular pattern of an offensive pathogen is sensed. In animals this domain frequently forms the intracellular portion of membrane-bound Toll-like receptors, whereas in plants it is often connected to intracellular R genes and can also be involved in direct recognition of pathogens. The findings presented here mark a common role for TIR domains in innate immunity across the three domains of life, and implies that the ancestry of this important component of eukaryotic innate immune systems may have stemmed from prokaryotic defense against phages.


The Thoeris system is broadly distributed in bacteria and archaea, and can be detected in at least 4% of the sequenced genomes we analyzed (2070 genomes; Table 9; FIG. 3H).









TABLE 9





The Thoeris Defense System and Components Thereof


This table is presented in landscape orientation. Due to the number of columns, the table


has been split into parts. Part A includes the first set of columns and therefore should


be place to the left of subsequent parts (Part B and where relevant Part C). To avoid any


doubt, the rows of the table in each part line up once the tables are placed together.







(Part A)


























I








E

G
H
ThsA
J



A
B
C
D
infra-
F
genomic_acces-
#genes
protein_acces-
PRT SEQ


1
assembly_accession
taxid
species_taxid
organism_name
specific_name
phylum
sion
identified
sion
ID NO:





2
GCA_000166815.1
333849
1352

Enterococcus faecium DO
DO
Firmicutes
AAAK03000018.1
3
EAN09999.1
13220


3
GCA_000169315.1
388400
388400

Bacillus sp. B14905
B14905
Firmicutes
AAXV01000012.1
2
EAZ85483.1
13223


4
GCA_000172675.1
535206
1352

Enterococcus faecium E1162
E1162
Firmicutes
ABQJ01000097.1
3
EFF33950.1
13225


5
GCA_000172915.1
547468
1352

Enterococcus faecium U0317
U0317
Firmicutes
ABSW01000016.1
3
EFF30624.1
13228


6
GCA_000176955.1
596330
33031

Peptoniphilus lacrimalis 315-B
315-B
Firmicutes
ADDO01000017.1
2
EFA90661.1
13231


7
GCA_000147675.2
596315
341694

Peptostreptococcus stomatis DSM 17678
DSM 17678
Firmicutes
ADGQ01000022.1
2
EFM65150.1
13233


8
GCA_000178275.1
702443
28116

Bacteroides ovatus SD CMC 3f
SD CMC 3f
Bacteroidetes
ADMO01000088.1
3
EFF51768.1
13235


9
GCA_000007825.1
226900
1396

Bacillus cereus ATCC 14579
ATCC 14579
Firmicutes
AE016877.1
2
AAP11368.1
13238


10
GCA_000179615.1
717606
59840

Paenibacillus curdlanolyticus YK9
YK9
Firmicutes
AEDD01000013.1
3
EFM08817.1
13240


11
GCA_000226815.3
907491
714

Aggregatibacter actinomycetemcomitans

SCC1398
Proteobacteria
AEJP02000033.1
3
KND82314.1
13243






serotype b str. SCC1398


12
GCA_000226835.3
907492
714

Aggregatibacter actinomycetemcomitans

I23C
Proteobacteria
AEJQ02000012.1
3
KOE55210.1
13246






serotype b str. I23C


13
GCA_000239115.2
933356
1352

Enterococcus faecium E4452
E4452
Firmicutes
AEOU01000033.1
3
EHM35989.1
13249


14
GCA_000298315.2
990285
1120045

Rhizobium grahamii CCGE 502
CCGE 502
Proteobacteria
AEYE02000011.1
2
EPE98431.1
13252


15
GCA_000223275.2
1035188
249188

Haemophilus pittmaniae HK 85
HK 85
Proteobacteria
AFUV01000004.1
3
EGV07449.1
13254


16
GCA_000231965.2
760839
1313

Streptococcus pneumoniae GA47502
GA47502
Firmicutes
AGNV01000008.1
3
EHD29827.1
13257


17
GCA_000239555.2
904766
1280

Staphylococcus aureus subsp.
21331
Firmicutes
AGTV01000033.1
3
EHM75393.1
13260







aureus 21331


18
GCA_000259915.1
1089447
714

Aggregatibacter actinomycetemcomitans

RhAA1
Proteobacteria
AHGR01000001.1
3
EHK91559.1
13263






RhAA1


19
GCA_000401595.1
1137132
1280

Staphylococcus aureus subsp.
112808A
Firmicutes
AHZK01000035.1
3
EOR48149.1
13266







aureus 112808A


20
GCA_000257805.1
1095735
28037

Streptococcus mitis SK616
SK616
Firmicutes
AICR01000116.1
3
EID19247.1
13269


21
GCA_000252405.2
1155079
1280

Staphylococcus aureus subsp.
DR10
Firmicutes
AIDT01000006.1
3
EIA14317.1
13272







aureus DR10


22
GCA_000257705.1
1095750
467210

Lachnoanaerobaculum saburreum F0468
F0468
Firmicutes
AJGH01000082.1
2
EIC95439.1
13275


23
GCA_000256585.3
406819
406819

Burkholderia sp. SJ98
SJ98
Proteobacteria
AJHK02000012.1
2
EKS70339.1
13277


24
GCA_000332935.2
1167009
714

Aggregatibacter actinomycetemcomitans

SCC4092
Proteobacteria
AJMF02000026.1
3
KOE52661.1
13279






serotype b str. SCC4092


25
GCA_000332955.2
1167008
714

Aggregatibacter actinomycetemcomitans

S23A
Proteobacteria
AJMH02000015.1
3
KOE56127.1
13282






serotype b str. S23A


26
GCA_000262265.1
1095744
735

Haemophilus parahaemolyticus HK385
HK385
Proteobacteria
AJSW01000041.1
3
EIJ69644.1
13285


27
GCA_000264155.1
752788
562

Escherichia coli 75
75
Proteobacteria
AJWT01000218.1
2
EIL59628.1
13288


28
GCA_000279285.1
991946
666

Vibrio cholerae HE-45
HE-45
Proteobacteria
ALED01000025.1
2
EJH65283.1
13290


29
GCA_000290475.1
1154930
1311

Streptococcus agalactiae GB00679
GB00679
Firmicutes
ALTY01000018.1
2
EPV35489.1
13292


30
GCA_000067165.1
448385
56

Sorangium cellulosum So ce56
So ce 56
Proteobacteria
AM746676.1
2
CAN93966.1
13294


31
GCA_000009585.1
523796
1280

Staphylococcus aureus subsp.
type strain:
Firmicutes
AM990992.1
3
CAQ50582.1
13296







aureus ST398
ST398


32
GCA_000300515.1
1231190
721133

Nitratireductor indicus C115
C115
Proteobacteria
AMSI01000038.1
3
EKF39860.1
13299


33
GCA_000468975.2
1232203
1428

Bacillus thuringiensis serovar
Leapi01
Firmicutes
AMXS02000100.1
2
ETE93554.1
13302






aizawai str. Leapi01


34
GCA_000468995.3
1238885
1428

Bacillus thuringiensis serovar
Hu4-2
Firmicutes
AMXT02000117.1
2
ETE97368.1
13304






aizawai str. Hu4-2


35
GCA_000410435.1
1256211
1597

Lactobacillus paracasei subsp.
CNCM
Firmicutes
ANKH01000630.1
2
EPC81228.1
13306







paracasei CNCM I-4649
I-4649


36
GCA_000326585.1
1169377
562

Escherichia coli KTE113
KTE113
Proteobacteria
ANXQ01000026.1
2
ELI26319.1
13308


37
GCA_000326445.1
1169399
562

Escherichia coli KTE168
KTE168
Proteobacteria
ANYM01000035.1
2
ELJ29820.1
13310


38
GCA_000341815.1
1278077
334542

Rhodococcus qingshengii BKS 20-40
BKS 20-40
Actinobacteria
AODN01000101.1
3
EME14866.1
13312


39
GCA_000342205.1
1263833
615

Serratia marcescens VGH107
VGH107
Proteobacteria
AORJ01000083.1
2
EMF02811.1
13315


40
GCA_000828775.1
1334564
615

Serratia marcescens SM39
SM39
Proteobacteria
AP013063.1
2
BAO35114.1
13317


41
GCA_000828875.1
758796
758796

Burkholderia sp. RPE67
RPE67
Proteobacteria
AP014579.1
2
BAO91362.1
13319


42
GCA_001547895.1
1500686
1500686

Pseudomonas sp. Os17
Os17
Proteobacteria
AP014627.1
5
BAQ74702.1
13321


43
GCA_000372645.1
1292034
155892

Caulobacter crescentus OR37
OR37
Proteobacteria
APMP01000003.1
3
ENZ83250.1
13326


44
GCA_000445085.1
428994
428994

Sphingobium sp. HDIP04
HDIP04
Proteobacteria
ATDO01000049.1
2
EQB07550.1
13329


45
GCA_000416235.1
911242
911242

Pseudomonas sp. CFII64
CFII64
Proteobacteria
ATLO01000035.1
2
EPJ82189.1
13331


46
GCA_000421925.1
1346790
420233

Sphingobium chinhatense IP26
IP26
Proteobacteria
AUDA01000159.1
2
EPR14527.1
13333


47
GCA_000455725.2
1344577
1280

Staphylococcus aureus S1
S1
Firmicutes
AUPS01000015.1
3
EQM91604.1
13335


48
GCA_000443245.1
1344578
1280

Staphylococcus aureus S130
S130
Firmicutes
AUPT01000016.1
3
EPZ04960.1
13338


49
GCA_000443265.1
1344579
1280

Staphylococcus aureus S123
S123
Firmicutes
AUPU01000015.1
3
EPZ06671.1
13341


50
GCA_000443125.1
1344580
1280

Staphylococcus aureus S100
S100
Firmicutes
AUPV01000016.1
3
EPZ03686.1
13344


51
GCA_000443285.1
1344581
1280

Staphylococcus aureus S94
S94
Firmicutes
AUPW01000016.1
3
EPZ11495.1
13347


52
GCA_000477515.1
1366052
1613

Lactobacillus fermentum MTCC 8711
MTCC 8711
Firmicutes
AVAB01000001.1
2
EQC60101.1
13350


53
GCA_000449945.2
1151319
1496

Peptoclostridium difficile DA00065
DA00065
Firmicutes
AVIU01000072.1
2
EQG20075.1
13352


54
GCA_000452125.2
1151436
1496

Peptoclostridium difficile P71
P71
Firmicutes
AVMW01000033.1
2
EQK22995.1
13354


55
GCA_000516615.2
1343073
470

Acinetobacter baumannii CI78
CI78
Proteobacteria
AVOE01000023.1
6
ETR94925.1
13356


56
GCA_000454165.1
1238193
670

Vibrio parahaemolyticus VP2007-095
VP2007-095
Proteobacteria
AVOI01000015.1
3
EQL89245.1
13362


57
GCA_000465615.2
1357297
615

Serratia marcescens EGD-HP20
EGD-HP20
Proteobacteria
AVSR01000008.1
2
ERH73216.1
13365


58
GCA_000478965.1
1111454
1111454

Megasphaera sp. BV3C16-1
BV3C16-1
Firmicutes
AWXA01000003.1
2
ERT62562.1
13367


59
GCA_000478985.1
1111134
1111134

Peptoniphilus sp. BV3C26
BV3C26
Firmicutes
AWXB01000008.1
3
ERT61554.1
13369


60
GCA_000478985.1
1111134
1111134

Peptoniphilus sp. BV3C26
BV3C26
Firmicutes
AWXB01000046.1
2
ERT58436.1
13372


61
GCA_000478865.2
1388760
303

Pseudomonas putida SJ3
SJ3
Proteobacteria
AXDX02000039.1
5
ERT19168.2
13374


62
GCA_000496325.1
1408193
287

Pseudomonas aeruginosa VRFPA05
VRFPA05
Proteobacteria
AXZJ01000100.1
3
ESR69982.1
13379


63
GCA_000648195.1
1400808
1351

Enterococcus faecalis NY9
NY9
Firmicutes
AYOL01000045.1
3
KAJ84751.1
13382


64
GCA_000648195.1
1400808
1351

Enterococcus faecalis NY9
NY9
Firmicutes
AYOL01000110.l
2
KAJ82225.1
13385


65
GCA_000506425.2
1415162
1061

Rhodobacter capsulatus B6
B6
Proteobacteria
AYQA01000057.1
2
ETD82032.1
13387


66
GCA_000503195.1
1419876
1419876

Blastomonas sp. CACIA14H2

Proteobacteria
AYSC01000003.1
3
ESZ88708.1
13389


67
GCA_000510425.1
1161902
35518

Eubacterium nodatum ATCC 33099
ATCC 33099
Firmicutes
AZKM01000022.1
2
ETJ99320.1
13392


68
GCA_001596225.1
1434263
714

Aggregatibacter actinomycetemcomitans

SA2149
Proteobacteria
AZTT01000065.1
3
KYK73940.1
13394






serotype e str. SA2149


69
GCA_000512995.1
936596
936596

Lachnoanaerobaculum sp. MSX33
MSX33
Firmicutes
AZXX01000025.1
2
ETO98932.1
13397


70
GCA_000513095.1
1236970
127891

Bacillus wakoensis JCM 9140
JCM 9140
Firmicutes
BAUT01000052.1
2
GAE27470.1
13399


71
GCA_000787715.1
1219049
28213

Sphingomonas parapaucimobilis NBRC 15100
NBRC 15100
Proteobacteria
BBPI01000099.1
3
GAM02795.1
13401


72
GCA_000195675.1
257310
518

Bordetella bronchiseptica RB50
RB50
Proteobacteria
BX470250.1
3
CAE30982.1
13404


73
GCA_000355725.1
1118157
40324

Stenotrophomonas maltophilia RA8
RA8
Proteobacteria
CALM01001187.1
3
CCP18523.1
13407


74
GCA_000985975.1
323656
399

Neorhizobium galegae bv. officinalis

Proteobacteria
CCRK01000014.1
2
CDZ53063.1
13410


75
GCA_000820425.1
1363
1363

Lactococcus garvieae

M14
Firmicutes
CCXC01000004.1
2
CEF52297.1
13412


76
GCA_001113365.1
1313
1313

Streptococcus pneumoniae

SMRU2014
Firmicutes
CKYA01000015.1
2
CJD59524.1
13414


77
GCA_000161115.1
526978
1396

Bacillus cereus BDRD-Cer4
BDRD-Cer4
Firmicutes
CM000726.1
2
EEL09527.1
13416


78
GCA_000161395.1
526993
1396

Bacillus cereus AH1272
AH1272
Firmicutes
CM000740.1
3
EEL84782.1
13418


79
GCA_000003955.1
526994
1396

Bacillus cereus AH1273
AH1273
Firmicutes
CM000741.1
3
EEL90114.1
13421


80
GCA_000159695.1
525282
1260

Finegoldia magna ATCC 53516
ATCC 53516
Firmicutes
CM000955.1
2
EFH92719.1
13424


81
GCA_000183885.1
702456
1642

Listeria innocua FSLS4-378
FSLS4-378
Firmicutes
CM001048.1
2
EFR92171.1
13426


82
GCA_000263675.2
1038924
294

Pseudomonas fluorescens SS101
SS101
Proteobacteria
CM001513.1
3
EIK62927.1
13428


83
GCA_000012605.1
317025
39765

Thiomicrospira crunogena XCL-2
XCL-2
Proteobacteria
CP000109.2
4
ABB40969.1
13431


84
GCA_000013605.1
338969
192843

Rhodoferax ferrireducens T118
DSM 15236
Proteobacteria
CP000267.1
2
ABD68809.1
13435


85
GCA_000013625.1
375286
375286

Janthinobacterium sp. Marseille
Marseille
Proteobacteria
CP000269.1
3
ABR91460.1
13437


86
GCA_000014665.1
60481
60481

Shewanella sp. MR-7
MR-7
Proteobacteria
CP000444.1
3
ABI42036.1
13440


87
GCA_000015885.1
416269
715

Actinobacillus pleuropneumoniae

L20
Proteobacteria
CP000569.1
3
ABN74271.1
13443






serovar 5b str. L20


88
GCA_000016125.1
402880
39152

Methanococcus maripaludis C5
C5
Euryarchaeota
CP000609.1
2
ABO35466.1
13446


89
GCA_000016405.1
349102
1063

Rhodobacter sphaeroides ATCC 17025
ATCC 17025
Proteobacteria
CP000665.1
3
ABP73209.1
13448


90
GCA_000016965.1
290402
1520

Clostridium beijerinckii NCIMB8052
NCIMB 8052
Firmicutes
CP000721.1
5
ABR34958.1
13451


91
GCA_000017145.1
366394
110321

Sinorhizobium medicae WSM419
WSM419
Proteobacteria
CP000741.1
2
ABR65059.1
13456


92
GCA_000019445.1
390235
303

Pseudomonas putida W619
W619
Proteobacteria
CP000949.1
5
ACA73845.1
13458


93
GCA_000019925.1
398577
152480

Burkholderia ambifaria MC40-6
MC40-6
Proteobacteria
CP001026.1
3
ACB66894.1
13463


94
GCA_000146265.2
668336
714

Aggregatibacter actinomycetemcomitans

D11S-1
Proteobacteria
CP001733.1
3
ACX81594.1
13466






D11S-1


95
GCA_000024405.1
526218
826

Sebaldella termitidis ATCC 33386
ATCC 33386
Fusobacteria
CP001740.1
2
ACZ11005.1
13469


96
GCA_000025345.1
526225
1861

Geodermatophilus obscurus DSM 43160
DSM 43160
Actinobacteria
CP001867.1
3
ADB76077.1
13471


97
GCA_000192635.1
861208
861208

Agrobacterium sp. H13-3
H13-3
Proteobacteria
CP002250.1
4
ADY67727.1
13474


98
GCA_000166135.1
298654
298654

Frankia sp. Eul1c
Eul1c
Actinobacteria
CP002299.1
2
ADP84996.1
13478


99
GCA_000195575.1
208596
208596

Carnobacterium sp. 17-4
17-4
Firmicutes
CP002563.1
3
AEB29797.1
13480


100
GCA_000194745.1
999541
28095

Burkholderia gladioli BSR3
BSR3
Proteobacteria
CP002599.1
6
AEA61152.1
13483


101
GCA_000258685.1
1155084
1280

Staphylococcus aureus subsp.
71193
Firmicutes
CP003045.1
3
AFH70387.1
13489







aureus 71193


102
GCA_000241025.2
754507
714

Aggregatibacter actinomycetemcomitans

ANH9381
Proteobacteria
CP003099.1
3
AEW76524.1
13492






ANH9381


103
GCA_000239195.1
347495
1396

Bacillus cereus F837/76
F837/76
Firmicutes
CP003187.1
2
AEW57570.1
13495


104
GCA_000264455.2
1110502
171437

Tistrella mobilis KA081020-065
KA081020-065
Proteobacteria
CP003236.1
4
AFK54067.1
13497


105
GCA_000747565.1
488142
488142

Serratia sp. SCBI
SCBI
Proteobacteria
CP003424.1
2
AIM23120.1
13501


106
GCA_000230695.3
666685
666685

Rhodanobacter denitrificans

2APBS1
Proteobacteria
CP003470.1
2
AGG89637.1
13503


107
GCA_000174395.2
333849
1352

Enterococcus faecium DO
DO
Firmicutes
CP003583.1
3
AFK58216.1
13505


108
GCA_000281215.1
1196325
303

Pseudomonas putida DOT-T1E
DOT-TIE
Proteobacteria
CP003734.1
4
AF049035.1
13508


109
GCA_000296595.1
1229492
1280

Staphylococcus aureus 08BA02176
08BA02176
Firmicutes
CP003808.1
3
AFR74120.1
13512


110
GCA_000599545.1
543736
37919

Rhodococcus opacus PD630
PD630
Actinobacteria
CP003949.1
2
AHK33011.1
13515


111
GCA_000336425.1
435998
615

Serratia marcescens WW4
WW4
Proteobacteria
CP003959.1
2
AGE19433.1
13517


112
GCA_000257545.3
1147786
75612

Pseudomonas mandelii JR-1
JR-1
Proteobacteria
CP005960.1
4
AHZ68662.1
13519


113
GCA_000401555.1
1288394
644

Aeromonas hydrophila ML09-119
ML09-119
Proteobacteria
CP005966.1
2
AGM44765.1
13523


114
GCA_000338115.2
1284663
1590

Lactobacillus plantarum ZJ316
ZJ316
Firmicutes
CP006247.1
2
AGS26695.1
13525


115
GCA_000176835.2
682634
82996

Serratia plymuthica 4Rx13
4Rx13
Proteobacteria
CP006250.1
2
AGO56414.1
13527


116
GCA_000418305.1
571800
571800

Psychrobacter sp. G
G
Proteobacteria
CP006265.1
3
AGP48697.1
13529


117
GCA_000767745.1
864803
1520

Clostridium beijerinckii ATCC 35702
SA-1
Firmicutes
CP006777.1
5
AIU01497.1
13532


118
GCA_000504585.1
1380774
1380774

Pandoraea sp. RB-44
RB-44
Proteobacteria
CP006938.1
3
AHB77236.1
13537


119
GCA_000835085.1
1124992
2095

Mycoplasma capricolum subsp.
87001
Tenericutes
CP006959.1
2
AJK51071.1
13540







capripneumoniae 87001


120
GCA_000510285.1
1435044
76759

Pseudomonas monteilii SB3078
SB3078
Proteobacteria
CP006978.1
3
AHC80715.1
13542


121
GCA_000510325.1
1435058
76759

Pseudomonas monteilii SB3101
SB3101
Proteobacteria
CP006979.1
3
AHC86147.1
13545


122
GCA_000604045.1
272556
714

Aggregatibacter actinomycetemcomitans

HK1651
Proteobacteria
CP007502.1
3
AHN71072.1
13548






HK1651


123
GCA_001191585.1
272556
714

Aggregatibacter actinomycetemcomitans

HK1651
Proteobacteria
CP008984.1
3
AKU28345.1
13551






HK1651


124
GCA_000834215.1
1454377
29484

Yersinia frederiksenii Y225
Y225
Proteobacteria
CP009364.1
3
AJI87975.1
13554


125
GCA_000758725.1
189426
189426

Paenibacillus odorifer

DSM 15391
Firmicutes
CP009428.1
3
AIQ75144.1
13557


126
GCA_000477035.2
1348585
76594

Cellulophaga baltica NN016038
NN016038
Bacteroidetes
CP009887.1
2
AIY12608.1
13560


127
GCA_000834865.1
28152
28152

Yersinia kristensenii

Y231
Proteobacteria
CP009997.1
3
AJJ37542.1
13562


128
GCA_000831585.1
70775
70775

Pseudomonas plecoglossicida

NyZ12
Proteobacteria
CP010359.1
3
AJG12527.1
13565


129
GCA_000961035.1
35554
35554

Geobacter sulfurreducens

AM-1
Proteobacteria
CP010430.1
3
AJY68818.1
13568


130
GCA_000934565.1
294
294

Pseudomonas fluorescens

PCL1751
Proteobacteria
CP010896.1
2
AJP52231.1
13571


131
GCA_000934525.1
589873
589873

Alteromonas australica

DE170
Proteobacteria
CP010912.1
2
AJP42564.1
13573


132
GCA_001023535.1
587753
587753

Pseudomonas chlororaphis

UFB2
Proteobacteria
CP011020.1
3
AKK01414.1
13575


133
GCA_000973085.1
187101
187101

Sneathia amnii

SN35
Fusobacteria
CP011280.1
4
AKC95051.1
13578


134
GCA_001043175.1
330734
330734

Marinobacter psychrophilus

20041
Proteobacteria
CP011494.1
2
AKO52328.1
13582


135
GCA_001266795.1
1671721
1671721

Marinobacter sp. CP1
CP1
Proteobacteria
CP011929.1
2
AKV98647.1
13584


136
GCA_001294565.1
615
615

Serratia marcescens

SmUNAM836
Proteobacteria
CP012685.1
2
ALE97361.1
13586


137
GCA_001310255.1
1532555
1532555

Brevundimonas sp. DS20
DS20
Proteobacteria
CP012897.1
4
ALJ08795.1
13588


138
GCA_001594245.1
714
714

Aggregatibacter actinomycetemcomitans

VT1169
Proteobacteria
CP012958.1
3
AMQ92899.1
13592


139
GCA_001414055.1
69395
69395

Caulobacter henricii

CB4
Proteobacteria
CP013002.1
3
ALL13164.1
13595


140
GCA_001455365.1
644
644

Aeromonas hydrophila

JBN2301
Proteobacteria
CP013178.1
3
ALQ62810.1
13598


141
GCA_001465635.1
1280
1280

Staphylococcus aureus

RIVM1295
Firmicutes
CP013616.1
3
ALS70450.1
13601


142
GCA_001465675.1
1280
1280

Staphylococcus aureus

RIVM1607
Firmicutes
CP013619.1
3
ALS73061.1
13604


143
GCA_001465755.1
1280
1280

Staphylococcus aureus

RIVM3897
Firmicutes
CP013621.1
3
ALS86458.1
13607


144
GCA_001518915.1
1763998
1763998

Rheinheimera sp. F8
F8
Proteobacteria
CP013656.1
2
ALZ77344.1
13610


145
GCA_001518775.1
644
644

Aeromonas hydrophila

D4
Proteobacteria
CP013965.1
3
ALZ79510.1
13612


146
GCA_001518735.1
1352
1352

Enterococcus faecium

6E6
Firmicutes
CP013994.1
3
ALZ52747.1
13615


147
GCA_001561955.1
991789
28446
[Clostridium] propionicum DSM 1682
X2
Firmicutes
CP014223.1
4
AMJ40926.1
13618


148
GCA_001560895.1
28037
28037

Streptococcus mitis

SVGS_061
Firmicutes
CP014326.1
3
AMH88749.1
13622


149
GCA_001515585.2
303
303

Pseudomonas putida

1A00316
Proteobacteria
CP014343.1
2
AMK33280.1
13625


150
GCA_001112925.1
685706
685706

Yersinia nurmii

type strain:
Proteobacteria
CPYD01000022.1
2
CNF27344.1
13627







CIP110231


151
GCA_001140625.1
633
633

Yersinia pseudotuberculosis

R819
Proteobacteria
CPZI01000008.1
3
CNF62528.1
13629


152
GCA_001121225.1
29484
29484

Yersinia frederiksenii

IP25924
Proteobacteria
CQBF01000033.1
3
CNI82010.1
13632


153
GCA_001114105.1
367190
367190

Yersinia similis

Y233
Proteobacteria
CQBK01000054.1
3
CNI72044.1
13635


154
GCA_001368815.1
1462524
1462524

Paraliobacillus sp. PM-2
PM-2
Firmicutes
CTEI01000001.1
2
CQR45868.1
13638


155
GCA_001222805.1
630
630

Yersinia enterocolitica

YE09/03
Proteobacteria
CTKQ01000009.1
5
CQJ38356.1
13640


156
GCA_001499695.1
40324
40324

Stenotrophomonas maltophilia


Proteobacteria
CVIU01000014.1
4
CRD50721.1
13645


157
GCA_001406815.1
301302
301302

Roseburia faecis

M72
Firmicutes
CVRR01000033.1
2
CRL40092.1
13649


158
GCA_001177845.1
148942
1336

Streptococcus equi subsp. equi
EQUI0003
Firmicutes
CVWY01000044.1
2
CRR05859.1
13651


159
GCA_001179425.1
148942
1336

Streptococcus equi subsp. equi
EQUI0005
Firmicutes
CVXE01000065.1
2
CRR37079.1
13653


160
GCA_001179085.1
148942
1336

Streptococcus equi subsp. equi
EQUI0004
Firmicutes
CVXF01000062.1
2
CRR43612.1
13655


161
GCA_001178765.1
148942
1336

Streptococcus equi subsp. equi
EQUI0007
Firmicutes
CVXG01000062.1
2
CRR34883.1
13657


162
GCA_001178485.1
148942
1336

Streptococcus equi subsp. equi
EQUI0006
Firmicutes
CVXI01000065.1
2
CRR50108.1
13659


163
GCA_001175105.1
148942
1336

Streptococcus equi subsp. equi
EQUI0008
Firmicutes
CVXJ01000058.1
2
CRR37365.1
13661


164
GCA_001175965.1
148942
1336

Streptococcus equi subsp. equi
EQUI0009
Firmicutes
CVXK01000003.1
2
CRR01737.1
13663


165
GCA_001175845.1
148942
1336

Streptococcus equi subsp. equi
EQUI0010
Firmicutes
CVXM01000058.1
2
CRR52905.1
13665


166
GCA_001176705.1
148942
1336

Streptococcus equi subsp. equi
EQUI0011
Firmicutes
CVX001000058.1
2
CRR41690.1
13667


167
GCA_001178165.1
148942
1336

Streptococcus equi subsp. equi
EQUI0033
Firmicutes
CVXQ01000063.1
2
CRS57164.1
13669


168
GCA_001178685.1
148942
1336

Streptococcus equi subsp. equi
EQUI0035
Firmicutes
CVXR01000068.1
2
CRS58226.1
13671


169
GCA_001178905.1
148942
1336

Streptococcus equi subsp. equi
EQUI0036
Firmicutes
CVXS01000068.1
2
CRS57780.1
13673


170
GCA_001178025.1
148942
1336

Streptococcus equi subsp. equi
EQUI0034
Firmicutes
CVXT01000066.1
2
CRS58151.1
13675


171
GCA_001178585.1
148942
1336

Streptococcus equi subsp. equi
EQUI0037
Firmicutes
CVXU01000042.1
2
CRS55109.1
13677


172
GCA_001175585.1
148942
1336

Streptococcus equi subsp. equi
EQUI0039
Firmicutes
CVXV01000043.1
2
CRS48588.1
13679


173
GCA_001175365.1
148942
1336

Streptococcus equi subsp. equi
EQUI0040
Firmicutes
CVXW01000043.1
2
CRS51337.1
13681


174
GCA_001175305.1
148942
1336

Streptococcus equi subsp. equi
EQUI0038
Firmicutes
CVXX01000041.1
2
CRS48392.1
13683


175
GCA_001175645.1
148942
1336

Streptococcus equi subsp. equi
EQUI0041
Firmicutes
CVXY01000044.1
2
CRS50262.1
13685


176
GCA_001176045.1
148942
1336

Streptococcus equi subsp. equi
EQUI0042
Firmicutes
CVXZ01000043.1
2
CRS50718.1
13687


177
GCA_001176505.1
148942
1336

Streptococcus equi subsp. equi
EQUI0043
Firmicutes
CVYA01000044.1
2
CRS54427.1
13689


178
GCA_001176825.1
148942
1336

Streptococcus equi subsp. equi
EQUI0044
Firmicutes
CVYB01000042.1
2
CRS57080.1
13691


179
GCA_001176965.1
148942
1336

Streptococcus equi subsp. equi
EQUI0045
Firmicutes
CVYC01000044.1
2
CRS58973.1
13693


180
GCA_001177245.1
148942
1336

Streptococcus equi subsp. equi
EQUI0046
Firmicutes
CVYD01000043.1
2
CRS51127.1
13695


181
GCA_001177205.1
148942
1336

Streptococcus equi subsp. equi
EQUI0047
Firmicutes
CVYE01000045.1
2
CRS51981.1
13697


182
GCA_001177785.1
148942
1336

Streptococcus equi subsp. equi
EQUI0220
Firmicutes
CVYF01000064.1
2
CRS77740.1
13699


183
GCA_001179185.1
148942
1336

Streptococcus equi subsp. equi
EQUI0222
Firmicutes
CVYG01000060.1
2
CRS83912.1
13701


184
GCA_001178625.1
148942
1336

Streptococcus equi subsp. equi
EQUI0048
Firmicutes
CVYH01000042.1
2
CRS76791.1
13703


185
GCA_001178345.1
148942
1336

Streptococcus equi subsp. equi
EQUI0218
Firmicutes
CVYI01000043.1
2
CRS78515.1
13705


186
GCA_001177385.1
148942
1336

Streptococcus equi subsp. equi
EQUI0219
Firmicutes
CVYJ01000068.1
2
CRS90898.1
13707


187
GCA_001179045.1
148942
1336

Streptococcus equi subsp. equi
EQUI0221
Firmicutes
CVYK01000065.1
2
CRS79977.1
13709


188
GCA_001178545.1
148942
1336

Streptococcus equi subsp. equi
EQUI0224
Firmicutes
CVYL01000063.1
2
CRS84436.1
13711


189
GCA_001179445.1
148942
1336

Streptococcus equi subsp. equi
EQUI0223
Firmicutes
CVYM01000062.1
2
CRS81776.1
13713


190
GCA_001178925.1
148942
1336

Streptococcus equi subsp. equi
EQUI0049
Firmicutes
CVYN01000043.1
2
CRS82433.1
13715


191
GCA_001177665.1
148942
1336

Streptococcus equi subsp. equi
EQUI0234
Firmicutes
CVYO01000041.1
2
CRS93257.1
13717


192
GCA_001175485.1
148942
1336

Streptococcus equi subsp. equi
EQUI0226
Firmicutes
CVYP01000057.1
2
CRT34694.1
13719


193
GCA_001178205.1
148942
1336

Streptococcus equi subsp. equi
EQUI0237
Firmicutes
CVYQ01000063.1
2
CRT26926.1
13721


194
GCA_001178065.1
148942
1336

Streptococcus equi subsp. equi
EQUI0236
Firmicutes
CVYR01000064.1
2
CRT43878.1
13723


195
GCA_001177345.1
148942
1336

Streptococcus equi subsp. equi
EQUI0232
Firmicutes
CVYS01000043.1
2
CRT34280.1
13725


196
GCA_001177405.1
148942
1336

Streptococcus equi subsp. equi
EQUI0233
Firmicutes
CVYT01000065.1
2
CRT48070.1
13727


197
GCA_001176725.1
148942
1336

Streptococcus equi subsp. equi
EQUI0230
Firmicutes
CVYU01000041.1
2
CRT42031.1
13729


198
GCA_001175145.1
148942
1336

Streptococcus equi subsp. equi
EQUI0239
Firmicutes
CVYV01000040.1
2
CRT45621.1
13731


199
GCA_001176105.1
148942
1336

Streptococcus equi subsp. equi
EQUI0060
Firmicutes
CVYW01000044.1
2
CRT37702.1
13733


200
GCA_001177885.1
148942
1336

Streptococcus equi subsp. equi
EQUI0235
Firmicutes
CVYX01000041.1
2
CRT44937.1
13735


201
GCA_001176125.1
148942
1336

Streptococcus equi subsp. equi
EQUI0228
Firmicutes
CVYY01000066.1
2
CRT51318.1
13737


202
GCA_001175185.1
148942
1336

Streptococcus equi subsp. equi
EQUI0059
Firmicutes
CVYZ01000043.1
2
CRT46051.1
13739


203
GCA_001178845.1
148942
1336

Streptococcus equi subsp. equi
EQUI0225
Firmicutes
CVZA01000065.1
2
CRT46015.1
13741


204
GCA_001176025.1
148942
1336

Streptococcus equi subsp. equi
EQUI0238
Firmicutes
CVZB01000068.1
2
CRT64519.1
13743


205
GCA_001175885.1
148942
1336

Streptococcus equi subsp. equi
EQUI0062
Firmicutes
CVZC01000026.1
2
CRT20938.1
13745


206
GCA_001175665.1
148942
1336

Streptococcus equi subsp. equi
EQUI0061
Firmicutes
CVZD01000042.1
2
CRT55748.1
13747


207
GCA_001178425.1
148942
1336

Streptococcus equi subsp. equi
EQUI0063
Firmicutes
CVZE01000061.1
2
CRT61683.1
13749


208
GCA_001179245.1
148942
1336

Streptococcus equi subsp. equi
HO51380626
Firmicutes
CVZF01000040.1
2
CRT39243.1
13751


209
GCA_001175405.1
148942
1336

Streptococcus equi subsp. equi
EQUI0240
Firmicutes
CVZG01000039.1
2
CRT66749.1
13753


210
GCA_001176385.1
148942
1336

Streptococcus equi subsp. equi
EQUI0229
Firmicutes
CVZH01000065.1
2
CRT72248.1
13755


211
GCA_001178805.1
148942
1336

Streptococcus equi subsp. equi
EQUI0064
Firmicutes
CVZI01000059.1
2
CRT58939.1
13757


212
GCA_001179125.1
148942
1336

Streptococcus equi subsp. equi
EQUI0065
Firmicutes
CVZJ01000061.1
2
CRT49564.1
13759


213
GCA_001175225.1
148942
1336

Streptococcus equi subsp. equi
EQUI0227
Firmicutes
CVZK01000068.1
2
CRT72921.1
13761


214
GCA_001176925.1
148942
1336

Streptococcus equi subsp. equi
EQUI0231
Firmicutes
CVZL01000044.1
2
CRT74944.1
13763


215
GCA_001179345.1
148942
1336

Streptococcus equi subsp. equi
EQUI0067
Firmicutes
CVZM01000061.1
2
CRT61440.1
13765


216
GCA_001176525.1
148942
1336

Streptococcus equi subsp. equi
EQUI0068
Firmicutes
CVZN01000058.1
2
CRT76644.1
13767


217
GCA_001178305.1
148942
1336

Streptococcus equi subsp. equi
EQUI0071
Firmicutes
CVZO01000056.1
2
CRT71332.1
13769


218
GCA_001176765.1
148942
1336

Streptococcus equi subsp. equi
EQUI0069
Firmicutes
CVZP01000060.1
2
CRT68258.1
13771


219
GCA_001178085.1
148942
1336

Streptococcus equi subsp. equi
EQUI0070
Firmicutes
CVZQ01000059.1
2
CRT74820.1
13773


220
GCA_001177605.1
148942
1336

Streptococcus equi subsp. equi
EQUI0072
Firmicutes
CVZR01000059.1
2
CRT73973.1
13775


221
GCA_001179065.1
148942
1336

Streptococcus equi subsp. equi
EQUI0075
Firmicutes
CVZS01000059.1
2
CRT75021.1
13777


222
GCA_001179405.1
148942
1336

Streptococcus equi subsp. equi
EQUI0076
Firmicutes
CVZT01000062.1
2
CRT66743.1
13779


223
GCA_001177545.1
148942
1336

Streptococcus equi subsp. equi
EQUI0053
Firmicutes
CVZU01000044.1
2
CRT70587.1
13781


224
GCA_001177965.1
148942
1336

Streptococcus equi subsp. equi
EQUI0052
Firmicutes
CVZV01000039.1
2
CRT64134.1
13783


225
GCA_001177065.1
148942
1336

Streptococcus equi subsp. equi
EQUI0058
Firmicutes
CVZW01000041.1
2
CRT58016.1
13785


226
GCA_001178565.1
148942
1336

Streptococcus equi subsp. equi
EQUI0077
Firmicutes
CVZX01000060.1
2
CRT66308.1
13787


227
GCA_001177485.1
148942
1336

Streptococcus equi subsp. equi
EQUI0074
Firmicutes
CVZY01000060.1
2
CRT75771.1
13789


228
GCA_001177865.1
148942
1336

Streptococcus equi subsp. equi
EQUI0054
Firmicutes
CWAA01000064.1
2
CRT69364.1
13791


229
GCA_001176905.1
148942
1336

Streptococcus equi subsp. equi
EQUI0055
Firmicutes
CWAB01000063.1
2
CRT79535.1
13793


230
GCA_001178105.1
148942
1336

Streptococcus equi subsp. equi
EQUI0050
Firmicutes
CWAC01000043.1
2
CRT65384.1
13795


231
GCA_001175245.1
148942
1336

Streptococcus equi subsp. equi
EQUI0078
Firmicutes
CWAD01000060.1
2
CRT80463.1
13797


232
GCA_001175925.1
148942
1336

Streptococcus equi subsp. equi
EQUI0080
Firmicutes
CWAE01000060.1
2
CRT86531.1
13799


233
GCA_001176325.1
148942
1336

Streptococcus equi subsp. equi
EQUI0082
Firmicutes
CWAF01000061.1
2
CRT83007.1
13801


234
GCA_001175985.1
148942
1336

Streptococcus equi subsp. equi
EQUI0081
Firmicutes
CWAG01000061.1
2
CRT86803.1
13803


235
GCA_001176605.1
148942
1336

Streptococcus equi subsp. equi
EQUI0083
Firmicutes
CWAH01000060.1
2
CRT85044.1
13805


236
GCA_001177025.1
148942
1336

Streptococcus equi subsp. equi
EQUI0085
Firmicutes
CWAI01000060.1
2
CRT84205.1
13807


237
GCA_001177285.1
148942
1336

Streptococcus equi subsp. equi
EQUI0086
Firmicutes
CWAJ01000043.1
2
CRT81920.1
13809


238
GCA_001176785.1
148942
1336

Streptococcus equi subsp. equi
EQUI0084
Firmicutes
CWAK01000064.1
2
CRT86927.1
13811


239
GCA_001177625.1
148942
1336

Streptococcus equi subsp. equi
EQUI0087
Firmicutes
CWAL01000044.1
2
CRT82847.1
13813


240
GCA_001175285.1
148942
1336

Streptococcus equi subsp. equi
EQUI0088
Firmicutes
CWAM01000044.1
2
CRT86345.1
13815


241
GCA_001175545.1
148942
1336

Streptococcus equi subsp. equi
EQUI0079
Firmicutes
CWAN01000059.1
2
CRT89319.1
13817


242
GCA_001175525.1
148942
1336

Streptococcus equi subsp. equi
EQUI0089
Firmicutes
CWAO01000054.1
2
CRT87540.1
13819


243
GCA_001175805.1
148942
1336

Streptococcus equi subsp. equi
EQUI0090
Firmicutes
CWAP01000063.1
2
CRT90533.1
13821


244
GCA_001176065.1
148942
1336

Streptococcus equi subsp. equi
EQUI0092
Firmicutes
CWAQ01000063.1
2
CRT91761.1
13823


245
GCA_001175625.1
148942
1336

Streptococcus equi subsp. equi
EQUI0091
Firmicutes
CWAR01000063.1
2
CRU00009.1
13825


246
GCA_001176265.1
148942
1336

Streptococcus equi subsp. equi
EQUI0094
Firmicutes
CWAS01000062.1
2
CRT98477.1
13827


247
GCA_001176945.1
148942
1336

Streptococcus equi subsp. equi
EQUI0095
Firmicutes
CWAT01000059.1
2
CRT99301.1
13829


248
GCA_001177265.1
148942
1336

Streptococcus equi subsp. equi
EQUI0096
Firmicutes
CWAU01000061.1
2
CRT99600.1
13831


249
GCA_001177225.1
148942
1336

Streptococcus equi subsp. equi
EQUI0097
Firmicutes
CWAV01000039.1
2
CRU04445.1
13833


250
GCA_001178005.1
148942
1336

Streptococcus equi subsp. equi
EQUI0099
Firmicutes
CWAW01000041.1
2
CRU03267.1
13835


251
GCA_001178145.1
148942
1336

Streptococcus equi subsp. equi
EQUI0098
Firmicutes
CWAX01000042.1
2
CRU09874.1
13837


252
GCA_001178785.1
148942
1336

Streptococcus equi subsp. equi
EQUI0100
Firmicutes
CWAY01000043.1
2
CRU07135.1
13839


253
GCA_001179105.1
148942
1336

Streptococcus equi subsp. equi
EQUI0105
Firmicutes
CWAZ01000043.1
2
CRU20234.1
13841


254
GCA_001178385.1
148942
1336

Streptococcus equi subsp. equi
EQUI0106
Firmicutes
CWBA01000062.1
2
CRU18218.1
13843


255
GCA_001178365.1
148942
1336

Streptococcus equi subsp. equi
EQUI0103
Firmicutes
CWBB01000068.1
2
CRU22358.1
13845


256
GCA_001179205.1
148942
1336

Streptococcus equi subsp. equi
EQUI0107
Firmicutes
CWBC01000062.1
2
CRU18024.1
13847


257
GCA_001177725.1
148942
1336

Streptococcus equi subsp. equi
EQUI0108
Firmicutes
CWBD01000063.1
2
CRU21807.1
13849


258
GCA_001177805.1
148942
1336

Streptococcus equi subsp. equi
EQUI0109
Firmicutes
CWBE01000063.1
2
CRU20295.1
13851


259
GCA_001177985.1
148942
1336

Streptococcus equi subsp. equi
EQUI0110
Firmicutes
CWBF01000047.1
2
CRU20891.1
13853


260
GCA_001176645.1
148942
1336

Streptococcus equi subsp. equi
EQUI0114
Firmicutes
CWBG01000041.1
2
CRU31596.1
13855


261
GCA_001176425.1
148942
1336

Streptococcus equi subsp. equi
EQUI0112
Firmicutes
CWBH01000044.1
2
CRU58975.1
13857


262
GCA_001176365.1
148942
1336

Streptococcus equi subsp. equi
EQUI0113
Firmicutes
CWBI01000040.1
2
CRU85987.1
13859


263
GCA_001178185.1
148942
1336

Streptococcus equi subsp. equi
EQUI0111
Firmicutes
CWBJ01000064.1
2
CRU70022.1
13861


264
GCA_900004825.1
148942
1336

Streptococcus equi subsp. equi
EQUI0117
Firmicutes
CWBK01000065.1
2
CRU80198.1
13863


265
GCA_001175085.1
148942
1336

Streptococcus equi subsp. equi
EQUI0119
Firmicutes
CWBL01000061.1
2
CRU71456.1
13865


266
GCA_001176845.1
148942
1336

Streptococcus equi subsp. equi
EQUI0115
Firmicutes
CWBM01000065.1
2
CRU70674.1
13867


267
GCA_001175425.1
148942
1336

Streptococcus equi subsp. equi
EQUI0118
Firmicutes
CWBN01000062.1
2
CRU61491.1
13869


268
GCA_001175505.1
148942
1336

Streptococcus equi subsp. equi
EQUI0128
Firmicutes
CWBO01000044.1
2
CRU48069.1
13871


269
GCA_001178225.1
148942
1336

Streptococcus equi subsp. equi
EQUI0126
Firmicutes
CWBP01000061.1
2
CRU68120.1
13873


270
GCA_001175325.1
148942
1336

Streptococcus equi subsp. equi
EQUI0129
Firmicutes
CWBQ01000061.1
2
CRU71296.1
13875


271
GCA_001179025.1
148942
1336

Streptococcus equi subsp. equi
EQUI0120
Firmicutes
CWBR01000065.1
2
CRU93798.1
13877


272
GCA_001176145.1
148942
1336

Streptococcus equi subsp. equi
EQUI0130
Firmicutes
CWBS01000043.1
2
CRU91202.1
13879


273
GCA_001177505.1
148942
1336

Streptococcus equi subsp. equi
EQUI0127
Firmicutes
CWBT01000042.1
2
CRU91151.1
13881


274
GCA_001178045.1
148942
1336

Streptococcus equi subsp. equi
EQUI0125
Firmicutes
CWBU01000045.1
2
CRU94321.1
13883


275
GCA_001178825.1
148942
1336

Streptococcus equi subsp. equi
EQUI0123
Firmicutes
CWBV01000042.1
2
CRU82344.1
13885


276
GCA_001178465.1
148942
1336

Streptococcus equi subsp. equi
EQUI0122
Firmicutes
CWBW01000043.1
2
CRU80816.1
13887


277
GCA_001175725.1
148942
1336

Streptococcus equi subsp. equi
EQUI0131
Firmicutes
CWBX01000064.1
2
CRU91403.1
13889


278
GCA_001179225.1
148942
1336

Streptococcus equi subsp. equi
EQUI0121
Firmicutes
CWBY01000040.1
2
CRU86635.1
13891


279
GCA_001177145.1
148942
1336

Streptococcus equi subsp. equi
EQUI0134
Firmicutes
CWBZ01000059.1
2
CRU82566.1
13893


280
GCA_001177045.1
148942
1336

Streptococcus equi subsp. equi
EQUI0136
Firmicutes
CWCA01000061.1
2
CRU96729.1
13895


281
GCA_001177465.1
148942
1336

Streptococcus equi subsp. equi
EQUI0139
Firmicutes
CWCB01000061.1
2
CRU83052.1
13897


282
GCA_001179305.1
148942
1336

Streptococcus equi subsp. equi
EQUI0140
Firmicutes
CWCC01000060.1
2
CRU80987.1
13899


283
GCA_001178965.1
148942
1336

Streptococcus equi subsp. equi
EQUI0141
Firmicutes
CWCD01000060.1
2
CRU78242.1
13901


284
GCA_001176665.1
148942
1336

Streptococcus equi subsp. equi
EQUI0132
Firmicutes
CWCE01000060.1
2
CRV00464.1
13903


285
GCA_001178865.1
148942
1336

Streptococcus equi subsp. equi
EQUI0124
Firmicutes
CWCF01000043.1
2
CRV01108.1
13905


286
GCA_001177425.1
148942
1336

Streptococcus equi subsp. equi
EQUI0137
Firmicutes
CWCG01000042.1
2
CRU80203.1
13907


287
GCA_001178945.1
148942
1336

Streptococcus equi subsp. equi
EQUI0142
Firmicutes
CWCH01000042.1
2
CRU93107.1
13909


288
GCA_001177305.1
148942
1336

Streptococcus equi subsp. equi
EQUI0135
Firmicutes
CWCI01000040.1
2
CRU95695.1
13911


289
GCA_001178605.1
148942
1336

Streptococcus equi subsp. equi
EQUI0143
Firmicutes
CWCJ01000060.1
2
CRU99763.1
13913


290
GCA_001177685.1
148942
1336

Streptococcus equi subsp. equi
EQUI0138
Firmicutes
CWCK01000040.1
2
CRV05021.1
13915


291
GCA_001177125.1
148942
1336

Streptococcus equi subsp. equi
EQUI0155
Firmicutes
CWCL01000043.1
2
CRU97029.1
13917


292
GCA_001175205.1
148942
1336

Streptococcus equi subsp. equi
EQUI0156
Firmicutes
CWCM01000063.1
2
CRV01704.1
13919


293
GCA_001175265.1
148942
1336

Streptococcus equi subsp. equi
EQUI0157
Firmicutes
CWCN01000060.1
2
CRV11871.1
13921


294
GCA_001175605.1
148942
1336

Streptococcus equi subsp. equi
EQUI0158
Firmicutes
CWCO01000063.1
2
CRV20248.1
13923


295
GCA_001178525.1
148942
1336

Streptococcus equi subsp. equi
EQUI0160
Firmicutes
CWCP01000061.1
2
CRV16484.1
13925


296
GCA_001176005.1
148942
1336

Streptococcus equi subsp. equi
EQUI0145
Firmicutes
CWCQ01000042.1
2
CRV16534.1
13927


297
GCA_001178885.1
148942
1336

Streptococcus equi subsp. equi
EQUI0159
Firmicutes
CWCR01000064.1
2
CRV08843.1
13925


298
GCA_001176345.1
148942
1336

Streptococcus equi subsp. equi
EQUI0133
Firmicutes
CWCS01000043.1
2
CRV21833.1
13931


299
GCA_001178505.1
148942
1336

Streptococcus equi subsp. equi
EQUI0161
Firmicutes
CWCT01000071.1
2
CRV22383.1
13933


300
GCA_001177905.1
148942
1336

Streptococcus equi subsp. equi
EQUI0164
Firmicutes
CWCU01000062.1
2
CRV15611.1
13935


301
GCA_001179005.1
148942
1336

Streptococcus equi subsp. equi
EQUI0163
Firmicutes
CWCV01000063.1
2
CRV21784.1
13937


302
GCA_001179285.1
148942
1336

Streptococcus equi subsp. equi
EQUI0162
Firmicutes
CWCW01000068.1
2
CRV18917.1
13935


303
GCA_001175785.1
148942
1336

Streptococcus equi subsp. equi
EQUI0146
Firmicutes
CWCX01000062.1
2
CRV22810.1
13941


304
GCA_001178325.1
148942
1336

Streptococcus equi subsp. equi
EQUI0166
Firmicutes
CWCY01000063.1
2
CRV26120.1
13943


305
GCA_001177565.1
148942
1336

Streptococcus equi subsp. equi
EQUI0165
Firmicutes
CWCZ01000062.1
2
CRV22947.1
13945


306
GCA_001178125.1
148942
1336

Streptococcus equi subsp. equi
EQUI0167
Firmicutes
CWDA01000061.1
2
CRV22945.1
13947


307
GCA_001177005.1
148942
1336

Streptococcus equi subsp. equi
EQUI0168
Firmicutes
CWDB01000062.1
2
CRV23365.1
13945


308
GCA_001176625.1
148942
1336

Streptococcus equi subsp. equi
EQUI0169
Firmicutes
CWDC01000065.1
2
CRV25535.1
13951


309
GCA_001175565.1
148942
1336

Streptococcus equi subsp. equi
EQUI0147
Firmicutes
CWDD01000044.1
2
CRV23988.1
13953


310
GCA_001177185.1
148942
1336

Streptococcus equi subsp. equi
EQUI0148
Firmicutes
CWDE01000094.1
2
CRV35426.1
13955


311
GCA_001176305.1
148942
1336

Streptococcus equi subsp. equi
EQUI0149
Firmicutes
CWDF01000064.1
2
CRV28496.1
13957


312
GCA_001176545.1
148942
1336

Streptococcus equi subsp. equi
EQUI0150
Firmicutes
CWDG01000061.1
2
CRV30744.1
13955


313
GCA_001176445.1
148942
1336

Streptococcus equi subsp. equi
EQUI0152
Firmicutes
CWDH01000059.1
2
CRV37963.1
13961


314
GCA_001176805.1
148942
1336

Streptococcus equi subsp. equi
EQUI0151
Firmicutes
CWDI01000059.1
2
CRV37002.1
13963


315
GCA_001176865.1
148942
1336

Streptococcus equi subsp. equi
EQUI0154
Firmicutes
CWDJ01000042.1
2
CRV38823.1
13965


316
GCA_001176685.1
148942
1336

Streptococcus equi subsp. equi
EQUI0153
Firmicutes
CWDK01000064.1
2
CRV39782.1
13967


317
GCA_001176245.1
148942
1336

Streptococcus equi subsp. equi
EQUI0170
Firmicutes
CWDL01000040.1
2
CRV45924.1
13965


318
GCA_001175945.1
148942
1336

Streptococcus equi subsp. equi
EQUI0171
Firmicutes
CWDM01000043.1
2
CRV48900.1
13971


319
GCA_001176225.1
148942
1336

Streptococcus equi subsp. equi
EQUI0172
Firmicutes
CWDN01000043.1
2
CRV53138.1
13973


320
GCA_001175465.1
148942
1336

Streptococcus equi subsp. equi
EQUI0174
Firmicutes
CWDO01000043.1
2
CRV61840.1
13975


321
GCA_001175825.1
148942
1336

Streptococcus equi subsp. equi
EQUI0173
Firmicutes
CWDP01000041.1
2
CRV60058.1
13977


322
GCA_001175125.1
148942
1336

Streptococcus equi subsp. equi
EQUI0175
Firmicutes
CWDQ01000043.1
2
CRV55434.1
13975


323
GCA_001178265.1
148942
1336

Streptococcus equi subsp. equi
EQUI0178
Firmicutes
CWDR01000044.1
2
CRV60803.1
13981


324
GCA_001178665.1
148942
1336

Streptococcus equi subsp. equi
EQUI0179
Firmicutes
CWDS01000044.1
2
CRW03962.1
13983


325
GCA_001179365.1
148942
1336

Streptococcus equi subsp. equi
EQUI0176
Firmicutes
CWDT01000009.1
2
CRV54211.1
13985


326
GCA_001179165.1
148942
1336

Streptococcus equi subsp. equi
EQUI0177
Firmicutes
CWDU01000042.1
2
CRV83270.1
13987


327
GCA_001179385.1
148942
1336

Streptococcus equi subsp. equi
EQUI0183
Firmicutes
CWDV01000041.1
2
CRV91455.1
13985


328
GCA_001175445.1
148942
1336

Streptococcus equi subsp. equi
EQUI0184
Firmicutes
CWDW01000042.1
2
CRV92191.1
13991


329
GCA_001177165.1
148942
1336

Streptococcus equi subsp. equi
EQUI0195
Firmicutes
CWDX01000062.1
2
CRV87136.1
13993


330
GCA_001177325.1
148942
1336

Streptococcus equi subsp. equi
EQUI0196
Firmicutes
CWDY01000065.1
2
CRV84626.1
13995


331
GCA_001178985.1
148942
1336

Streptococcus equi subsp. equi
EQUI0181
Firmicutes
CWDZ01000042.1
2
CRW02988.1
13997


332
GCA_001178725.1
148942
1336

Streptococcus equi subsp. equi
EQUI0180
Firmicutes
CWEA01000042.1
2
CRV97209.1
13995


333
GCA_001177765.1
148942
1336

Streptococcus equi subsp. equi
EQUI0192
Firmicutes
CWEB01000061.1
2
CRW00524.1
14001


334
GCA_001179265.1
148942
1336

Streptococcus equi subsp. equi
EQUI0182
Firmicutes
CWEC01000045.1
2
CRW01316.1
14003


335
GCA_001178285.1
148942
1336

Streptococcus equi subsp. equi
EQUI0191
Firmicutes
CWED01000041.1
2
CRV92086.1
14005


336
GCA_001177705.1
148942
1336

Streptococcus equi subsp. equi
EQUI0194
Firmicutes
CWEE01000065.1
2
CRV95671.1
14007


337
GCA_001176085.1
148942
1336

Streptococcus equi subsp. equi
EQUI0199
Firmicutes
CWEF01000062.1
2
CRV97947.1
14005


338
GCA_001175045.1
148942
1336

Streptococcus equi subsp. equi
EQUI0185
Firmicutes
CWEG01000008.1
2
CRV78527.1
14011


339
GCA_001178645.1
148942
1336

Streptococcus equi subsp. equi
EQUI0188
Firmicutes
CWEH01000043.1
2
CRW03687.1
14013


340
GCA_001175025.1
148942
1336

Streptococcus equi subsp. equi
EQUI0198
Firmicutes
CWEI01000062.1
2
CRV92165.1
14015


341
GCA_001176465.1
148942
1336

Streptococcus equi subsp. equi
EQUI0197
Firmicutes
CWEJ01000060.1
2
CRV95850.1
14017


342
GCA_001175685.1
148942
1336

Streptococcus equi subsp. equi
EQUI0200
Firmicutes
CWEK01000061.1
2
CRV90197.1
14015


343
GCA_001176205.1
148942
1336

Streptococcus equi subsp. equi
EQUI0186
Firmicutes
CWEL01000046.1
2
CRW02430.1
14021


344
GCA_001175905.1
148942
1336

Streptococcus equi subsp. equi
EQUI0187
Firmicutes
CWEM01000042.1
2
CRW06361.1
14023


345
GCA_001175745.1
148942
1336

Streptococcus equi subsp. equi
EQUI0201
Firmicutes
CWEN01000063.1
2
CRW10290.1
14025


346
GCA_001176565.1
148942
1336

Streptococcus equi subsp. equi
EQUI0012
Firmicutes
CWEP01000057.1
2
CRV93329.1
14027


347
GCA_001178445.1
148942
1336

Streptococcus equi subsp. equi
EQUI0203
Firmicutes
CWEQ01000063.1
2
CRW10487.1
14029


348
GCA_001178705.1
148942
1336

Streptococcus equi subsp. equi
EQUI0202
Firmicutes
CWES01000061.1
2
CRW11899.1
14031


349
GCA_001179465.1
148942
1336

Streptococcus equi subsp. equi
EQUI0205
Firmicutes
CWEV01000037.1
2
CRW12157.1
14033


350
GCA_001178245.1
148942
1336

Streptococcus equi subsp. equi
EQUI0208
Firmicutes
CWEW01000061.1
2
CRW18036.1
14035


351
GCA_001177925.1
148942
1336

Streptococcus equi subsp. equi
EQUI0206
Firmicutes
CWEX01000064.1
2
CRW22900.1
14037


352
GCA_001177745.1
148942
1336

Streptococcus equi subsp. equi
EQUI0207
Firmicutes
CWEY01000063.1
2
CRW16828.1
14039


353
GCA_001176185.1
148942
1336

Streptococcus equi subsp. equi
EQUI0209
Firmicutes
CWEZ01000060.1
2
CRW17377.1
14041


354
GCA_001175865.1
148942
1336

Streptococcus equi subsp. equi
EQUI0211
Firmicutes
CWFA01000062.1
2
CRW41572.1
14043


355
GCA_001175385.1
148942
1336

Streptococcus equi subsp. equi
EQUI0212
Firmicutes
CWFB01000064.1
2
CRW33338.1
14045


356
GCA_001175165.1
148942
1336

Streptococcus equi subsp. equi
EQUI0213
Firmicutes
CWFC01000062.1
2
CRW28598.1
14047


357
GCA_001176745.1
148942
1336

Streptococcus equi subsp. equi
EQUI0216
Firmicutes
CWFD01000040.1
2
CRW38404.1
14049


358
GCA_001176405.1
148942
1336

Streptococcus equi subsp. equi
EQUI0217
Firmicutes
CWFE01000062.1
2
CRW56664.1
14051


359
GCA_001177085.1
148942
1336

Streptococcus equi subsp. equi
EQUI0214
Firmicutes
CWFF01000066.1
2
CRW57488.1
14053


360
GCA_001177525.1
148942
1336

Streptococcus equi subsp. equi
EQUI0002
Firmicutes
CWFG01000057.1
2
CRW51150.1
14055


361
GCA_001176985.1
148942
1336

Streptococcus equi subsp. equi
EQUI0215
Firmicutes
CWFI01000066.1
2
CRW56037.1
14057


362
GCA_001177365.1
148942
1336

Streptococcus equi subsp. equi
EQUI0013
Firmicutes
CWFJ01000060.1
2
CRW51019.1
14059


363
GCA_001177105.1
148942
1336

Streptococcus equi subsp. equi
EQUI0014
Firmicutes
CWFK01000062.1
2
CRW62422.1
14061


364
GCA_001176885.1
148942
1336

Streptococcus equi subsp. equi
EQUI0015
Firmicutes
CWFL01000059.1
2
CRW52635.1
14063


365
GCA_001177585.1
148942
1336

Streptococcus equi subsp. equi
EQUI0016
Firmicutes
CWFM01000059.1
2
CRW57925.1
14065


366
GCA_001177825.1
148942
1336

Streptococcus equi subsp. equi
EQUI0017
Firmicutes
CWFN01000059.1
2
CRW58490.1
14067


367
GCA_001177645.1
148942
1336

Streptococcus equi subsp. equi
EQUI0018
Firmicutes
CWFO01000060.1
2
CRW59062.1
14069


368
GCA_001179325.1
148942
1336

Streptococcus equi subsp. equi
EQUI0019
Firmicutes
CWFS01000065.1
2
CRW78794.1
14071


369
GCA_001179145.1
148942
1336

Streptococcus equi subsp. equi
EQUI0020
Firmicutes
CWFT01000065.1
2
CRW72044.1
14073


370
GCA_001178745.1
148942
1336

Streptococcus equi subsp. equi
EQUI0021
Firmicutes
CWFU01000062.1
2
CRW79959.1
14075


371
GCA_001178405.1
148942
1336

Streptococcus equi subsp. equi
EQUI0022
Firmicutes
CWFV01000063.1
2
CRW76315.1
14077


372
GCA_001176165.1
148942
1336

Streptococcus equi subsp. equi
EQUI0023
Firmicutes
CWFW01000065.1
2
CRW80108.1
14079


373
GCA_001175765.1
148942
1336

Streptococcus equi subsp. equi
EQUI0024
Firmicutes
CWFX01000059.1
2
CRW66993.1
14081


374
GCA_001175705.1
148942
1336

Streptococcus equi subsp. equi
EQUI0025
Firmicutes
CWFY01000062.1
2
CRW70529.1
14083


375
GCA_001175345.1
148942
1336

Streptococcus equi subsp. equi
EQUI0026
Firmicutes
CWFZ01000062.1
2
CRW76738.1
14085


376
GCA_001175065.1
148942
1336

Streptococcus equi subsp. equi
EQUI0027
Firmicutes
CWGA01000061.1
2
CRW76864.1
14087


377
GCA_001176485.1
148942
1336

Streptococcus equi subsp. equi
EQUI0028
Firmicutes
CWGB01000067.1
2
CRW80973.1
14089


378
GCA_001176285.1
148942
1336

Streptococcus equi subsp. equi
EQUI0029
Firmicutes
CWGC01000064.1
2
CRW81695.1
14091


379
GCA_001176585.1
148942
1336

Streptococcus equi subsp. equi
EQUI0030
Firmicutes
CWGD01000063.1
2
CRW77653.1
14093


380
GCA_001177945.1
148942
1336

Streptococcus equi subsp. equi
EQUI0031
Firmicutes
CWGE01000064.1
2
CRW79780.1
14095


381
GCA_001177445.1
148942
1336

Streptococcus equi subsp. equi
EQUI0032
Firmicutes
CWGF01000063.1
2
CRW80948.1
14097


382
GCA_001285185.1
562
562

Escherichia coli

102485_aEPEC
Proteobacteria
CYBC01000016.1
2
CTT29869.1
14099


383
GCA_001286125.1
562
562

Escherichia coli

302710
Proteobacteria
CYFG01000018.1
2
CTZ05351.1
14101


384
GCA_001286985.1
1408
1408

Bacillus pumilus


Firmicutes
CYHK01000004.1
2
CUB16899.1
14103


385
GCA_001299055.1
1806504
1806504

Achromobacter sp. 2789STDY5608606
2789STDY5608606
Proteobacteria
CYTI01000001.1
5
CUI41065.1
14105


386
GCA_001298995.1
1806492
1806492

Achromobacter sp. 2789STDY5608615
2789STDY5608615
Proteobacteria
CYTY01000055.1
3
CUK22707.1
14110


387
GCA_001564615.1
1639
1639

Listeria monocytogenes

LM06-00444
Firmicutes
CYUX01000002.1
2
CUK50734.1
14113


388
GCA_001564675.1
1639
1639

Listeria monocytogenes

LM06-00918
Firmicutes
CYVA01000003.1
2
CUK61280.1
14115


389
GCA_001564895.1
1639
1639

Listeria monocytogenes

LM07-01042
Firmicutes
CYVK01000002.1
2
CUK91820.1
14117


390
GCA_000153885.1
411463
39496

Eubacterium ventriosum ATCC 27560
ATCC 27560
Firmicutes
DS264285.1
4
EDM51055.1
14119


391
GCA_001537545.1
615
615

Serratia marcescens

2880STDY5682911
Proteobacteria
FCFC01000005.1
2
CUY08442.1
14123


392
GCA_001538985.1
615
615

Serratia marcescens

2880STDY5683036
Proteobacteria
FCFE01000005.1
2
CUZ68635.1
14125


393
GCA_001538605.1
615
615

Serratia marcescens

2880STDY5682822
Proteobacteria
FCFF01000005.1
2
CUZ82287.1
14127


394
GCA_001537885.1
615
615

Serratia marcescens

2880STDY5682825
Proteobacteria
FCFG01000007.1
2
CUZ53146.1
14129


395
GCA_001539305.1
615
615

Serratia marcescens

2880STDY5683007
Proteobacteria
FCFH01000009.1
2
CVA27382.1
14131


396
GCA_001537405.1
615
615

Serratia marcescens

2880STDY5683035
Proteobacteria
FCFI01000002.1
2
CUZ41368.1
14133


397
GCA_001540125.1
615
615

Serratia marcescens

2880STDY5683037
Proteobacteria
FCFJ01000004.1
2
CVA08047.1
14135


398
GCA_001538905.1
615
615

Serratia marcescens

2880STDY5682814
Proteobacteria
FCFK01000006.1
2
CUZ42305.1
14137


399
GCA_001537445.1
615
615

Serratia marcescens

2880STDY5683014
Proteobacteria
FCFL01000006.1
2
CVA28869.1
14139


400
GCA_001539185.1
615
615

Serratia marcescens

2880STDY5683009
Proteobacteria
FCFM01000003.1
2
CUZ16125.1
14141


401
GCA_001540805.1
615
615

Serratia marcescens

2880STDY5682837
Proteobacteria
FCFN01000007.1
2
CUZ60995.1
14143


402
GCA_001538525.1
615
615

Serratia marcescens

2880STDY5682824
Proteobacteria
FCFO01000009.1
2
CUZ90935.1
14145


403
GCA_001539805.1
615
615

Serratia marcescens

2880STDY5682834
Proteobacteria
FCFP01000006.1
2
CUZ73394.1
14147


404
GCA_001538705.1
615
615

Serratia marcescens

2880STDY5683032
Proteobacteria
FCFQ01000004.1
2
CVA13553.1
14149


405
GCA_001539125.1
615
615

Serratia marcescens

2880STDY5683011
Proteobacteria
FCFR01000005.1
2
CVA22943.1
14151


406
GCA_001538465.1
615
615

Serratia marcescens

2880STDY5683010
Proteobacteria
FCFS01000001.1
2
CUY16546.1
14153


407
GCA_001539505.1
615
615

Serratia marcescens

2880STDY5682831
Proteobacteria
FCFT01000005.1
2
CUZ58663.1
14155


408
GCA_001538485.1
615
615

Serratia marcescens

2880STDY5683021
Proteobacteria
FCFU01000011.1
2
CUZ73629.1
14157


409
GCA_001539785.1
615
615

Serratia marcescens

2880STDY5682827
Proteobacteria
FCFV01000002.1
2
CUZ84855.1
14159


410
GCA_001537205.1
615
615

Serratia marcescens

2880STDY5682828
Proteobacteria
FCFW01000002.1
2
CUZ51222.1
14161


411
GCA_001536485.1
615
615

Serratia marcescens

2880STDY5682815
Proteobacteria
FCFX01000005.1
2
CVA06032.1
14163


412
GCA_001537765.1
615
615

Serratia marcescens

2880STDY5682820
Proteobacteria
FCFY01000007.1
2
CUZ66191.1
14165


413
GCA_001537525.1
615
615

Serratia marcescens

2880STDY5682816
Proteobacteria
FCFZ01000005.1
2
CUZ96331.1
14167


414
GCA_001540665.1
615
615

Serratia marcescens

2880STDY5683018
Proteobacteria
FCGA01000006.1
2
CUZ56035.1
14169


415
GCA_001538625.1
615
615

Serratia marcescens

2880STDY5682836
Proteobacteria
FCGB01000003.1
2
CUZ47627.1
14171


416
GCA_001537105.1
615
615

Serratia marcescens

2880STDY5683024
Proteobacteria
FCGC01000005.1
2
CUZ65513.1
14173


417
GCA_001537145.1
615
615

Serratia marcescens

2880STDY5682819
Proteobacteria
FCGD01000005.1
2
CUZ64473.1
14175


418
GCA_001539985.1
615
615

Serratia marcescens

2880STDY5683033
Proteobacteria
FCGF01000007.1
2
CUZ76085.1
14177


419
GCA_001536605.1
615
615

Serratia marcescens

2880STDY5683026
Proteobacteria
FCGG01000006.1
2
CVA13444.1
14179


420
GCA_001537845.1
615
615

Serratia marcescens

2880STDY5682823
Proteobacteria
FCGH01000006.1
2
CVA27078.1
14181


421
GCA_001539225.1
615
615

Serratia marcescens

2880STDY5683013
Proteobacteria
FCGI01000005.1
2
CVA15880.1
14183


422
GCA_001540225.1
615
615

Serratia marcescens

2880STDY5683031
Proteobacteria
FCGJ01000005.1
2
CUZ46954.1
14185


423
GCA_001537565.1
615
615

Serratia marcescens

2880STDY5683034
Proteobacteria
FCGK01000008.1
2
CUZ31026.1
14187


424
GCA_001539965.1
615
615

Serratia marcescens

2880STDY5682829
Proteobacteria
FCGL01000002.1
2
CUZ02629.1
14189


425
GCA_001537645.1
615
615

Serratia marcescens

2880STDY5682830
Proteobacteria
FCGM01000004.1
2
CUZ51326.1
14191


426
GCA_001539485.1
615
615

Serratia marcescens

2880STDY5683008
Proteobacteria
FCGN01000006.1
2
CUZ55076.1
14193


427
GCA_001537285.1
615
615

Serratia marcescens

2880STDY5683022
Proteobacteria
FCGO01000004.1
2
CVA20194.1
14195


428
GCA_001539645.1
615
615

Serratia marcescens

2880STDY5682838
Proteobacteria
FCGP01000007.1
2
CUZ69684.1
14197


429
GCA_001538765.1
615
615

Serratia marcescens

2880STDY5682826
Proteobacteria
FCGQ01000005.1
2
CUZ82709.1
14199


430
GCA_001537825.1
615
615

Serratia marcescens

2880STDY5683030
Proteobacteria
FCGR01000003.1
2
CUZ92205.1
14201


431
GCA_001538195.1
615
615

Serratia marcescens

2880STDY5683020
Proteobacteria
FCGS01000007.1
2
CUZ80077.1
14203


432
GCA_001540185.1
615
615

Serratia marcescens

2880STDY5682832
Proteobacteria
FCGT01000002.1
2
CUZ43216.1
14205


433
GCA_001539025.1
615
615

Serratia marcescens

2880STDY5682818
Proteobacteria
FCGU01000004.1
2
CVA39165.1
14207


434
GCA_001540205.1
615
615

Serratia marcescens

2880STDY5682842
Proteobacteria
FCGV01000008.1
2
CVA66719.1
14209


435
GCA_001539725.1
615
615

Serratia marcescens

2880STDY5682839
Proteobacteria
FCGW01000003.1
2
CUZ78091.1
14211


436
GCA_001537425.1
615
615

Serratia marcescens

2880STDY5682840
Proteobacteria
FCGX01000008.1
2
CUZ53769.1
14213


437
GCA_001540725.1
615
615

Serratia marcescens

2880STDY5682844
Proteobacteria
FCGY01000002.1
2
CVA07127.1
14215


438
GCA_001539705.1
615
615

Serratia marcescens

2880STDY5682843
Proteobacteria
FCGZ01000005.1
2
CUZ96183.1
14217


439
GCA_001537325.1
615
615

Serratia marcescens

2880STDY5682845
Proteobacteria
FCHA01000004.1
2
CVA63405.1
14219


440
GCA_001538805.1
615
615

Serratia marcescens

2880STDY5682847
Proteobacteria
FCHB01000006.1
2
CVB19728.1
14221


441
GCA_001537025.1
615
615

Serratia marcescens

2880STDY5682846
Proteobacteria
FCHC01000005.1
2
CVB15259.1
14223


442
GCA_001538445.1
615
615

Serratia marcescens

2880STDY5682848
Proteobacteria
FCHD01000004.1
2
CVB18641.1
14225


443
GCA_001540265.1
615
615

Serratia marcescens

2880STDY5682849
Proteobacteria
FCHE01000016.1
2
CVC33418.1
14227


444
GCA_001539365.1
615
615

Serratia marcescens

2880STDY5682850
Proteobacteria
FCHF01000016.1
2
CVC43508.1
14229


445
GCA_001537605.1
615
615

Serratia marcescens

2880STDY5682851
Proteobacteria
FCHG01000004.1
2
CVB44191.1
14231


446
GCA_001538725.1
615
615

Serratia marcescens

2880STDY5682852
Proteobacteria
FCHH01000006.1
2
CVC13530.1
14233


447
GCA_001536765.1
615
615

Serratia marcescens

2880STDY5682859
Proteobacteria
FCHI01000001.1
2
CVB24153.1
14235


448
GCA_001540425.1
615
615

Serratia marcescens

2880STDY5682855
Proteobacteria
FCHJ01000002.1
2
CVB63296.1
14237


449
GCA_001539265.1
615
615

Serratia marcescens

2880STDY5682854
Proteobacteria
FCHK01000007.1
2
CVB59022.1
14239


450
GCA_001536505.1
615
615

Serratia marcescens

2880STDY5682857
Proteobacteria
FCHL01000009.1
2
CVB73355.1
14241


451
GCA_001539765.1
615
615

Serratia marcescens

2880STDY5682858
Proteobacteria
FCHM01000001.1
2
CVA22576.1
14243


452
GCA_001536445.1
615
615

Serratia marcescens

2880STDY5682856
Proteobacteria
FCHN01000007.1
2
CVC54922.1
14245


453
GCA_001536345.1
615
615

Serratia marcescens

2880STDY5682861
Proteobacteria
FCHO01000009.1
2
CVC47630.1
14247


454
GCA_001539585.1
615
615

Serratia marcescens

2880STDY5682863
Proteobacteria
FCHP01000005.1
2
CVC16906.1
14249


455
GCA_001540365.1
615
615

Serratia marcescens

2880STDY5682862
Proteobacteria
FCHQ01000002.1
2
CVA94601.1
14251


456
GCA_001536465.1
615
615

Serratia marcescens

2880STDY5682864
Proteobacteria
FCHR01000005.1
2
CVB98029.1
14253


457
GCA_001537225.1
615
615

Serratia marcescens

2880STDY5682866
Proteobacteria
FCHS01000005.1
2
CVB27596.1
14255


458
GCA_001539885.1
615
615

Serratia marcescens

2880STDY5682865
Proteobacteria
FCHT01000005.1
2
CVC12754.1
14257


459
GCA_001539845.1
615
615

Serratia marcescens

2880STDY5682867
Proteobacteria
FCHU01000005.1
2
CVB94192.1
14259


460
GCA_001538425.1
615
615

Serratia marcescens

2880STDY5682868
Proteobacteria
FCHV01000005.1
2
CVC34459.1
14261


461
GCA_001537485.1
615
615

Serratia marcescens

2880STDY5682869
Proteobacteria
FCHW01000006.1
2
CVC37208.1
14263


462
GCA_001540525.1
615
615

Serratia marcescens

2880STDY5682870
Proteobacteria
FCHX01000005.1
2
CVC09911.1
14265


463
GCA_001537245.1
615
615

Serratia marcescens

2880STDY5682871
Proteobacteria
FCHY01000004.1
2
CVB52010.1
14267


464
GCA_001537345.1
615
615

Serratia marcescens

2880STDY5682872
Proteobacteria
FCHZ01000007.1
2
CVB83712.1
14269


465
GCA_001536985.1
615
615

Serratia marcescens

2880STDY5682874
Proteobacteria
FCIA01000006.1
2
CVB86127.1
14271


466
GCA_001539925.1
615
615

Serratia marcescens

2880STDY5682875
Proteobacteria
FCIB01000006.1
2
CVC63966.1
14273


467
GCA_001539425.1
615
615

Serratia marcescens

2880STDY5682877
Proteobacteria
FCIC01000002.1
2
CVB86015.1
14275


468
GCA_001537465.1
615
615

Serratia marcescens

2880STDY5682878
Proteobacteria
FCID01000006.1
2
CVC85484.1
14277


469
GCA_001540385.1
615
615

Serratia marcescens

2880STDY5682880
Proteobacteria
FCIE01000007.1
2
CVC33567.1
14279


470
GCA_001540605.1
615
615

Serratia marcescens

2880STDY5682879
Proteobacteria
FCIF01000008.1
2
CVC90980.1
14281


471
GCA_001537665.1
615
615

Serratia marcescens

2880STDY5682881
Proteobacteria
FCIG01000006.1
2
CVC23364.1
14283


472
GCA_001539345.1
615
615

Serratia marcescens

2880STDY5682884
Proteobacteria
FCIH01000009.1
2
CVC01499.1
14285


473
GCA_001540625.1
615
615

Serratia marcescens

2880STDY5682885
Proteobacteria
FCII01000005.1
2
CVC17928.1
14287


474
GCA_001536685.1
615
615

Serratia marcescens

2880STDY5682882
Proteobacteria
FCIJ01000008.1
2
CVC49211.1
14289


475
GCA_001538825.1
615
615

Serratia marcescens

2880STDY5682883
Proteobacteria
FCIK01000010.1
2
CVD13430.1
14291


476
GCA_001538365.1
615
615

Serratia marcescens

2880STDY5682887
Proteobacteria
FCIL01000005.1
2
CVC16315.1
14293


477
GCA_001539745.1
615
615

Serratia marcescens

2880STDY5682889
Proteobacteria
FCIM01000006.1
2
CVC38417.1
14295


478
GCA_001538345.1
615
615

Serratia marcescens

2880STDY5682888
Proteobacteria
FCIN01000006.1
2
CVC81451.1
14297


479
GCA_001540765.1
615
615

Serratia marcescens

2880STDY5682892
Proteobacteria
FCIO01000006.1
2
CVC81532.1
14299


480
GCA_001540325.1
615
615

Serratia marcescens

2880STDY5682891
Proteobacteria
FCIP01000007.1
2
CVC86644.1
14301


481
GCA_001540305.1
615
615

Serratia marcescens

2880STDY5682890
Proteobacteria
FCIQ01000005.1
2
CVC98809.1
14303


482
GCA_001539565.1
615
615

Serratia marcescens

2880STDY5682893
Proteobacteria
FCIR01000006.1
2
CVC91105.1
14305


483
GCA_001540105.1
615
615

Serratia marcescens

2880STDY5682902
Proteobacteria
FCIS01000005.1
2
CVC94637.1
14307


484
GCA_001539865.1
615
615

Serratia marcescens

2880STDY5682903
Proteobacteria
FCIT01000007.1
2
CVC52261.1
14309


485
GCA_001539085.1
615
615

Serratia marcescens

2880STDY5682904
Proteobacteria
FCIU01000005.1
2
CVC98188.1
14311


486
GCA_001537065.1
615
615

Serratia marcescens

2880STDY5682905
Proteobacteria
FCIV01000001.1
2
CVB21709.1
14313


487
GCA_001536725.1
615
615

Serratia marcescens

2880STDY5682906
Proteobacteria
FCIW01000004.1
2
CVC48171.1
14315


488
GCA_001538645.1
615
615

Serratia marcescens

2880STDY5682907
Proteobacteria
FCIX01000005.1
2
CVC71605.1
14317


489
GCA_001539145.1
615
615

Serratia marcescens

2880STDY5682908
Proteobacteria
FCIY01000004.1
2
CVC84156.1
14319


490
GCA_001539385.1
615
615

Serratia marcescens

2880STDY5682913
Proteobacteria
FCIZ01000002.1
2
CVC59811.1
14321


491
GCA_001537385.1
1805636
1805636

Serratia sp. 2880STDY5682894
2880STDY5682894
Proteobacteria
FCJA01000011.1
2
CVE09029.1
14323


492
GCA_001537125.1
615
615

Serratia marcescens

2880STDY5682916
Proteobacteria
FCJB01000006.1
2
CVD69842.1
14325


493
GCA_001540245.1
615
615

Serratia marcescens

2880STDY5682918
Proteobacteria
FCJC01000003.1
2
CVD51978.1
14327


494
GCA_001540285.1
615
615

Serratia marcescens

2880STDY5682917
Proteobacteria
FCJD01000005.1
2
CVD94616.1
14329


495
GCA_001540485.1
615
615

Serratia marcescens

2880STDY5682919
Proteobacteria
FCJE01000006.1
2
CVD41075.1
14331


496
GCA_001539245.1
615
615

Serratia marcescens

2880STDY5682921
Proteobacteria
FCJF01000005.1
2
CVD28911.1
14333


497
GCA_001537185.1
615
615

Serratia marcescens

2880STDY5682924
Proteobacteria
FCJG01000001.1
2
CVC37101.1
14335


498
GCA_001537625.1
615
615

Serratia marcescens

2880STDY5682926
Proteobacteria
FCJH01000006.1
2
CVE33560.1
14337


499
GCA_001536385.1
615
615

Serratia marcescens

2880STDY5682927
Proteobacteria
FCJI01000001.1
2
CVC40389.1
14339


500
GCA_001536405.1
615
615

Serratia marcescens

2880STDY5682928
Proteobacteria
FCJJ01000009.1
2
CVE27784.1
14341


501
GCA_001536845.1
615
615

Serratia marcescens

2880STDY5682929
Proteobacteria
FCJK01000007.1
2
CVE60658.1
14343


502
GCA_001537265.1
1805637
1805637

Serratia sp. 2880STDY5682895
2880STDY5682895
Proteobacteria
FCJL01000004.1
2
CVE69225.1
14345


503
GCA_001540145.1
615
615

Serratia marcescens

2880STDY5682932
Proteobacteria
FCJM01000004.1
2
CVE06185.1
14347


504
GCA_001538885.1
615
615

Serratia marcescens

2880STDY5682931
Proteobacteria
FCJN01000006.1
2
CVE70644.1
14349


505
GCA_001538945.1
615
615

Serratia marcescens

2880STDY5682933
Proteobacteria
FCJO01000002.1
2
CVD68108.1
14351


506
GCA_001539285.1
615
615

Serratia marcescens

2880STDY5682936
Proteobacteria
FCJP01000008.1
2
CVE19652.1
14353


507
GCA_001538965.1
615
615

Serratia marcescens

2880STDY5682938
Proteobacteria
FCJQ01000005.1
2
CVE94858.1
14355


508
GCA_001538745.1
615
615

Serratia marcescens

2880STDY5682934
Proteobacteria
FCJR01000005.1
2
CVE73969.1
14357


509
GCA_001539405.1
615
615

Serratia marcescens

2880STDY5682937
Proteobacteria
FCJS01000004.1
2
CVE69307.1
14359


510
GCA_001540745.1
615
615

Serratia marcescens

2880STDY5682896
Proteobacteria
FCJU01000008.1
2
CVD84033.1
14361


511
GCA_001540025.1
615
615

Serratia marcescens

2880STDY5682940
Proteobacteria
FCJV01000010.1
2
CVE29057.1
14363


512
GCA_001539625.1
615
615

Serratia marcescens

2880STDY5682943
Proteobacteria
FCJW01000006.1
2
CVD89429.1
14365


513
GCA_001536965.1
615
615

Serratia marcescens

2880STDY5682942
Proteobacteria
FCJX01000004.1
2
CVE62947.1
14367


514
GCA_001538505.1
615
615

Serratia marcescens

2880STDY5682945
Proteobacteria
FCJY01000006.1
2
CVE95724.1
14369


515
GCA_001538005.1
615
615

Serratia marcescens

2880STDY5682947
Proteobacteria
FCJZ01000006.1
2
CVF11414.1
14371


516
GCA_001537005.1
615
615

Serratia marcescens

2880STDY5682951
Proteobacteria
FCKA01000009.1
2
CVF28618.1
14373


517
GCA_001536895.1
615
615

Serratia marcescens

2880STDY5682950
Proteobacteria
FCKB01000001.1
2
CVC97408.1
14375


518
GCA_001537365.1
615
615

Serratia marcescens

2880STDY5682897
Proteobacteria
FCKC01000002.1
2
CVD52669.1
14377


519
GCA_001536525.1
615
615

Serratia marcescens

2880STDY5682952
Proteobacteria
FCKD01000005.1
2
CVE22718.1
14379


520
GCA_001539545.1
615
615

Serratia marcescens

2880STDY5682953
Proteobacteria
FCKE01000005.1
2
CVE97488.1
14381


521
GCA_001539665.1
615
615

Serratia marcescens

2880STDY5682954
Proteobacteria
FCKF01000005.1
2
CVF28196.1
14383


522
GCA_001536325.1
615
615

Serratia marcescens

2880STDY5682955
Proteobacteria
FCKG01000004.1
2
CVE60557.1
14385


523
GCA_001539325.1
615
615

Serratia marcescens

2880STDY5682956
Proteobacteria
FCKH01000006.1
2
CVE66029.1
14387


524
GCA_001540825.1
615
615

Serratia marcescens

2880STDY5682957
Proteobacteria
FCKI01000006.1
2
CVF01432.1
14389


525
GCA_001540005.1
615
615

Serratia marcescens

2880STDY5682958
Proteobacteria
FCKJ01000007.1
2
CVE93279.1
14391


526
GCA_001536625.1
615
615

Serratia marcescens

2880STDY5682959
Proteobacteria
FCKK01000007.1
2
CVF50179.1
14393


527
GCA_001539905.1
615
615

Serratia marcescens

2880STDY5682961
Proteobacteria
FCKL01000003.1
2
CVF09863.1
14395


528
GCA_001536665.1
615
615

Serratia marcescens

2880STDY5682960
Proteobacteria
FCKM01000009.1
2
CVE63433.1
14397


529
GCA_001539205.1
615
615

Serratia marcescens

2880STDY5682962
Proteobacteria
FCKN01000002.1
2
CVE05426.1
14399


530
GCA_001540685.1
615
615

Serratia marcescens

2880STDY5682899
Proteobacteria
FCKO01000003.1
2
CVE67637.1
14401


531
GCA_001539945.1
615
615

Serratia marcescens

2880STDY5682963
Proteobacteria
FCKP01000005.1
2
CVE73588.1
14403


532
GCA_001536705.1
615
615

Serratia marcescens

2880STDY5682964
Proteobacteria
FCKQ01000006.1
2
CVF13093.1
14405


533
GCA_001539445.1
615
615

Serratia marcescens

2880STDY5682965
Proteobacteria
FCKR01000003.1
2
CVE92971.1
14407


534
GCA_001538685.1
615
615

Serratia marcescens

2880STDY5682967
Proteobacteria
FCKS01000007.1
2
CVF15693.1
14409


535
GCA_001536945.1
615
615

Serratia marcescens

2880STDY5682966
Proteobacteria
FCKT01000001.1
2
CVE70328.1
14411


536
GCA_001538405.1
615
615

Serratia marcescens

2880STDY5682968
Proteobacteria
FCKU01000005.1
2
CVF77852.1
14413


537
GCA_001538115.1
615
615

Serratia marcescens

2880STDY5682971
Proteobacteria
FCKV01000009.1
2
CVF08013.1
14415


538
GCA_001540545.1
615
615

Serratia marcescens

2880STDY5682969
Proteobacteria
FCKW01000004.1
2
CVF84175.1
14417


539
GCA_001540345.1
615
615

Serratia marcescens

2880STDY5682970
Proteobacteria
FCKX01000005.1
2
CVF82181.1
14419


540
GCA_001540705.1
615
615

Serratia marcescens

2880STDY5682973
Proteobacteria
FCKZ01000006.1
2
CVG26740.1
14421


541
GCA_001537585.1
615
615

Serratia marcescens

2880STDY5682974
Proteobacteria
FCLA01000006.1
2
CVG63931.1
14423


542
GCA_001540445.1
615
615

Serratia marcescens

2880STDY5682976
Proteobacteria
FCLB01000006.1
2
CVG49466.1
14425


543
GCA_001536645.1
615
615

Serratia marcescens

2880STDY5682977
Proteobacteria
FCLC01000007.1
2
CVF96122.1
14427


544
GCA_001538585.1
615
615

Serratia marcescens

2880STDY5682979
Proteobacteria
FCLD01000006.1
2
CVG60878.1
14429


545
GCA_001539825.1
615
615

Serratia marcescens

2880STDY5682978
Proteobacteria
FCLE01000011.1
2
CVG18609.1
14431


546
GCA_001536365.1
615
615

Serratia marcescens

2880STDY5682980
Proteobacteria
FCLF01000004.1
2
CVG60220.1
14433


547
GCA_001540505.1
615
615

Serratia marcescens

2880STDY5682982
Proteobacteria
FCLG01000005.1
2
CVG00307.1
14435


548
GCA_001540045.1
615
615

Serratia marcescens

2880STDY5682981
Proteobacteria
FCLH01000005.1
2
CVG18150.1
14437


549
GCA_001539685.1
615
615

Serratia marcescens

2880STDY5682983
Proteobacteria
FCLI01000006.1
2
CVG66356.1
14439


550
GCA_001539605.1
615
615

Serratia marcescens

2880STDY5682984
Proteobacteria
FCLJ01000002.1
2
CVF82688.1
14441


551
GCA_001564475.1
615
615

Serratia marcescens

2880STDY5682985
Proteobacteria
FCLK01000006.1
2
CVG27221.1
14443


552
GCA_001537705.1
615
615

Serratia marcescens

2880STDY5682986
Proteobacteria
FCLL01000011.1
2
CVH08342.1
14445


553
GCA_001540785.1
615
615

Serratia marcescens

2880STDY5682987
Proteobacteria
FCLM01000006.1
2
CVG82373.1
14447


554
GCA_001540065.1
615
615

Serratia marcescens

2880STDY5682990
Proteobacteria
FCLN01000007.1
2
CVG89997.1
14449


555
GCA_001540585.1
615
615

Serratia marcescens

2880STDY5682991
Proteobacteria
FCLO01000004.1
2
CVG75154.1
14451


556
GCA_001536745.1
615
615

Serratia marcescens

2880STDY5682992
Proteobacteria
FCLP01000006.1
2
CVG91933.1
14453


557
GCA_001538865.1
615
615

Serratia marcescens

2880STDY5682993
Proteobacteria
FCLQ01000006.1
2
CVG61761.1
14455


558
GCA_001536545.1
615
615

Serratia marcescens

2880STDY5682994
Proteobacteria
FCLR01000006.1
2
CVG55708.1
14457


559
GCA_001537925.1
615
615

Serratia marcescens

2880STDY5682995
Proteobacteria
FCLS01000005.1
2
CVG99558.1
14459


560
GCA_001538925.1
615
615

Serratia marcescens

2880STDY5682901
Proteobacteria
FCLT01000009.1
2
CVG85830.1
14461


561
GCA_001538845.1
615
615

Serratia marcescens

2880STDY5682996
Proteobacteria
FCLU01000006.1
2
CVH13287.1
14463


562
GCA_001536425.1
615
615

Serratia marcescens

2880STDY5682998
Proteobacteria
FCLV01000007.1
2
CVH22095.1
14465


563
GCA_001540165.1
615
615

Serratia marcescens

2880STDY5682997
Proteobacteria
FCLW01000007.1
2
CVG79620.1
14467


564
GCA_001540565.1
615
615

Serratia marcescens

2880STDY5683002
Proteobacteria
FCLX01000006.1
2
CVH31735.1
14469


565
GCA_001537085.1
615
615

Serratia marcescens

2880STDY5683001
Proteobacteria
FCLY01000002.1
2
CVG61510.1
14471


566
GCA_001539005.1
615
615

Serratia marcescens

2880STDY5682873
Proteobacteria
FCLZ01000001.1
2
CVF47731.1
14473


567
GCA_001538565.1
615
615

Serratia marcescens

2880STDY5683004
Proteobacteria
FCMA01000007.1
2
CVH23270.1
14475


568
GCA_001537745.1
615
615

Serratia marcescens

2880STDY5683003
Proteobacteria
FCMB01000010.1
2
CVG86995.1
14477


569
GCA_001538385.1
615
615

Serratia marcescens

2880STDY5682835
Proteobacteria
FCMC01000007.1
2
CVG92563.1
14479


570
GCA_001537685.1
615
615

Serratia marcescens

2880STDY5682853
Proteobacteria
FCMD01000007.1
2
CVH34087.1
14481


571
GCA_001537905.1
615
615

Serratia marcescens

2880STDY5682876
Proteobacteria
FCME01000005.1
2
CVG73776.1
14483


572
GCA_001537505.1
615
615

Serratia marcescens

2880STDY5682898
Proteobacteria
FCMF01000005.1
2
CVH31066.1
14485


573
GCA_001538275.1
615
615

Serratia marcescens

2880STDY5682912
Proteobacteria
FCMG01000007.1
2
CVH30715.1
14487


574
GCA_001537045.1
615
615

Serratia marcescens

2880STDY5682914
Proteobacteria
FCMH01000006.1
2
CVG97897.1
14489


575
GCA_001540465.1
615
615

Serratia marcescens

2880STDY5682915
Proteobacteria
FCMI01000011.1
2
CVH42932.1
14491


576
GCA_001540085.1
615
615

Serratia marcescens

2880STDY5682925
Proteobacteria
FCMJ01000003.1
2
CVH11685.1
14493


577
GCA_001536585.1
615
615

Serratia marcescens

2880STDY5682922
Proteobacteria
FCMK01000007.1
2
CVH39732.1
14495


578
GCA_001537305.1
615
615

Serratia marcescens

2880STDY5682930
Proteobacteria
FCML01000005.1
2
CVH33868.1
14497


579
GCA_001538325.1
615
615

Serratia marcescens

2880STDY5682939
Proteobacteria
FCMM01000005.1
2
CVG91272.1
14499


580
GCA_001537165.1
615
615

Serratia marcescens

2880STDY5682944
Proteobacteria
FCMN01000005.1
2
CVH37766.1
14501


581
GCA_001540405.1
615
615

Serratia marcescens

2880STDY5682948
Proteobacteria
FCMO01000007.1
2
CVH21028.1
14503


582
GCA_001537865.1
615
615

Serratia marcescens

2880STDY5682949
Proteobacteria
FCMP01000001.1
2
CVG01710.1
14505


583
GCA_001538665.1
615
615

Serratia marcescens

2880STDY5682975
Proteobacteria
FCMQ01000009.1
2
CVH35272.1
14507


584
GCA_001536565.1
615
615

Serratia marcescens

2880STDY5682999
Proteobacteria
FCMS01000001.1
2
CVH07248.1
14509


585
GCA_001539465.1
615
615

Serratia marcescens

2880STDY5683000
Proteobacteria
FCMT01000008.1
2
CVH30929.1
14511


586
GCA_001537805.1
615
615

Serratia marcescens

2880STDY5683016
Proteobacteria
FCMU01000006.1
2
CVH50698.1
14513


587
GCA_001539525.1
615
615

Serratia marcescens

2880STDY5683027
Proteobacteria
FCMV01000005.1
2
CVH40520.1
14515


588
GCA_001539105.1
615
615

Serratia marcescens

2880STDY5683015
Proteobacteria
FCMW01000009.1
2
CVH64627.1
14517


589
GCA_001537785.1
615
615

Serratia marcescens

2880STDY5683006
Proteobacteria
FCMX01000005.1
2
CVH70545.1
14519


590
GCA_001540645.1
615
615

Serratia marcescens

2880STDY5683019
Proteobacteria
FCMY01000005.1
2
CVH72214.1
14521


591
GCA_001538545.1
615
615

Serratia marcescens

2880STDY5683017
Proteobacteria
FCMZ01000004.1
2
CVH65591.1
14523


592
GCA_001544575.1
1353886
1353886

Burkholderia cordobensis


Proteobacteria
FCNY01000004.1
2
CVJ13885.1
14525


593
GCA_001544455.1
196367
196367

Paraburkholderia sordidicola


Proteobacteria
FCOC01000002.1
3
CVJ11200.1
14527


594
GCA_001544535.1
326476
326476

Paraburkholderia choica


Proteobacteria
FCON01000032.1
2
CVJ34937.1
14530


595
GCA_900022065.1
1639
1639

Listeria monocytogenes

2842STDY5753889
Firmicutes
FFEW01000009.1
2
CWV39688.1
14532


596
GCA_900034805.1
1639
1639

Listeria monocytogenes

2842STDY5753890
Firmicutes
FFGS01000008.1
2
CWW37500.1
14534


597
GCA_900051225.1
1313
1313

Streptococcus pneumoniae

2245STDY5982743
Firmicutes
FHVI01000002.1
3
CYO51328.1
14536


598
GCA_900059415.1
1307
1307

Streptococcus suis

LSS12
Firmicutes
FIFP01000001.1
2
CYT98259.1
14539


599
GCA_900049685.1
1307
1307

Streptococcus suis

FX275
Firmicutes
FISX01000005.1
3
CZB10988.1
14541


600
GCA_900058075.1
1307
1307

Streptococcus suis

FX483_3
Firmicutes
FITF01000040.1
3
CZB35771.1
14544


601
GCA_900050515.1
1313
1313

Streptococcus pneumoniae

72D37909
Firmicutes
FIWN01000018.1
2
CZD24115.1
14547


602
GCA_900052575.1
1313
1313

Streptococcus pneumoniae

D30716
Firmicutes
FIXA01000003.1
2
CZC77630.1
14549


603
GCA_900049745.1
1313
1313

Streptococcus pneumoniae

A32279
Firmicutes
FIXS01000003.1
2
CZD72536.1
14551


604
GCA_900051625.1
1313
1313

Streptococcus pneumoniae

C14560X
Firmicutes
FIXT01000039.1
2
CZE23674.1
14553


605
GCA_000026585.1
553482
1336

Streptococcus equi subsp. equi
4047
Firmicutes
FM204883.1
2
CAW93164.1
14555






4047


606
GCA_000209955.1
657317
39491
[Eubacterium] rectale M104/1
M104/1
Firmicutes
FP929043.1
2
CBK94114.1
14557


607
GCA_000236925.1
985002
985002

Staphylococcus argenteus

MSHR1132
Firmicutes
FR821777.2
3
CCE59808.1
14559


608
GCA_000435855.1
1262967
1262967

Ruminococcus sp. CAG:9

Firmicutes
FR896087.1
3
CDD80086.1
14562


609
GCA_000156515.1
553973
89153
[Clostridium] hylemonae DSM 15053
DSM 15053
Firmicutes
GG657761.1
2
EEG72544.1
14565


610
GCA_000160115.1
626523
177972

Shuttleworthia satelles DSM 14600
DSM 14600
Firmicutes
GG665867.1
4
EEP27313.1
14567


611
GCA_000159095.1
525255
33036

Anaerococcus tetradius ATCC 35098
ATCC 35098
Firmicutes
GG666297.1
2
EEI83075.1
14571


612
GCA_000157535.1
565657
1352

Enterococcus faecium 1,231,502
1,231,502
Firmicutes
GG688488.1
3
EEV44995.1
14573


613
GCA_000159955.1
621372
652715

Paenibacillus sp. oral taxon 786 str. D14
D14
Firmicutes
GG695991.1
2
EES71591.1
14576


614
GCA_000162075.1
575587
40215

Acinetobacter junii SH205
SH205
Proteobacteria
GG705011.1
3
EEY94494.1
14578


615
GCA_000148025.1
749520
1352

Enterococcus faecium TX0082
TX0082
Firmicutes
GL455872.1
3
EFS10290.1
14581


616
GCA_000195045.1
888818
1305

Streptococcus sanguinis SK408
SK408
Firmicutes
GL878559.1
3
EGF19709.1
14584


617
GCA_000213555.1
742766
156974

Dysgonomonas gadei ATCC BAA-286
ATCC BAA-286
Bacteroidetes
GL891989.1
3
EGK00063.1
14587


618
GCA_000328705.1
1179773
103731

Saccharothrix espanaensis DSM 44229
type strain:
Actinobacteria
HE804045.1
2
CCH29383.1
14590







DSM 44229


619
GCA_000313065.1
1208659
518

Bordetella bronchiseptica Bbr77
Bbr77
Proteobacteria
HE983628.1
2
CCN04569.1
14592


620
GCA_000513215.1
273526
615

Serratia marcescens subsp. marcescens Db11
Db11
Proteobacteria
HG326223.1
2
CDG13494.1
14594


621
GCA_000736695.1
1398204
40576

Xenorhabdus bovienii str. kraussei Becker

kraussei Becker
Proteobacteria
HG428180.1
2
CDH26046.1
14596






Underwood
Underwood


622
GCA_000632355.1
1442605
1352

Enterococcus faecium VSE1036
VSE1036
Firmicutes
JAAJ01000002.1
3
EZP94706.1
14598


623
GCA_000632295.1
1442604
1352

Enterococcus faecium VRE0576
VRE0576
Firmicutes
JAAK01000036.1
3
EZP99085.1
14601


624
GCA_000632315.1
1442606
1352

Enterococcus faecium VRE1044
VRE1044
Firmicutes
JAAL01000002.1
3
EZP92278.1
14604


625
GCA_000523375.1
1449358
670

Vibrio parahaemolyticus M0605
M0605
Proteobacteria
JALL01000080.1
2
ETZ11576.1
14607


626
GCA_000633575.2
1450518
440518

Sphingobium lucknowense F2
F2
Proteobacteria
JANF02000091.1
2
KER34865.1
14609


627
GCA_000564995.1
1190620
1190620

Atopobium sp. ICM42b
ICM42b
Actinobacteria
JDFH01000020.1
2
EWC94460.1
14611


628
GCA_001589275.1
56
56

Sorangium cellulosum

So0003-19-2
Proteobacteria
JELZ01001521.1
2
KYF75625.1
14613


629
GCA_001589185.1
56
56

Sorangium cellulosum

So0011-07
Proteobacteria
JEMB01003116.1
2
KYF75483.1
14615


630
GCA_000581895.1
1310692
470

Acinetobacter baumannii 532279
532279
Proteobacteria
JEYH01000003.1
6
EXE88617.1
14617


631
GCA_000695685.1
212667
212667

Vibrio fortis

Dalian14
Proteobacteria
JFFR01000027.1
2
KDN26971.1
14623


632
GCA_000705595.1
1408224
194963

Sinorhizobium americanum CCGM7
CCGM7
Proteobacteria
JFG001000039.1
3
KEC78309.1
14625


633
GCA_000689815.1
1331227
518

Bordetella bronchiseptica MBORD675
MBORD675
Proteobacteria
JGX001000020.1
2
KDC94426.1
14628


634
GCA_000227315.1
997350
33030

Peptoniphilus indolicus ATCC 29427
ATCC 29427
Firmicutes
JH165061.1
2
EGY80387.1
14630


635
GCA_000234335.1
543736
37919

Rhodococcus opacus PD630
PD630
Actinobacteria
JH377359.1
2
EHI41035.1
14632


636
GCA_000235505.1
742737
154046

Hungatella hathewayi WAL-18680
WAL-18680
Firmicutes
JH379027.1
2
EHI61291.1
14634


637
GCA_000243215.1
742817
626933

Odoribacter laneus YIT 12061
YIT 12061
Bacteroidetes
JH594596.1
3
EHP50820.1
14636


638
GCA_000245755.1
883114
40091

Helcococcus kunzii ATCC 51366
ATCC 51366
Firmicutes
JH601089.1
2
EHR31702.1
14639


639
GCA_000273035.1
997875
357276

Bacteroides dorei CL02T00C15
CL02T00C15
Bacteroidetes
JH724115.1
4
EIY18768.1
14641


640
GCA_000273055.1
997876
357276

Bacteroides dorei CL02T12C06
CL02T12C06
Bacteroidetes
JH724132.1
4
EIY40460.1
14645


641
GCA_000273765.1
997880
817

Bacteroides fragilis CL05T00C42
CL05T00C42
Bacteroidetes
JH724188.1
2
EIY98048.1
14649


642
GCA_000273765.1
997880
817

Bacteroides fragilis CL05T00C42
CL05T00C42
Bacteroidetes
JH724189.1
2
EIY91470.1
14651


643
GCA_000273765.1
997880
817

Bacteroides fragilis CL05T00C42
CL05T00C42
Bacteroidetes
JH724190.1
2
EIY90206.1
14653


644
GCA_000273135.1
997881
817

Bacteroides fragilis CL05T12C13
CL05T12C13
Bacteroidetes
JH724193.1
2
EIY98754.1
14655


645
GCA_000273135.1
997881
817

Bacteroides fragilis CL05T12C13
CL05T12C13
Bacteroidetes
JH724195.1
2
EIY95127.1
14657


646
GCA_000273135.1
997881
817

Bacteroides fragilis CL05T12C13
CL05T12C13
Bacteroidetes
JH724196.1
2
EIY94597.1
14659


647
GCA_000273135.1
997881
817

Bacteroides fragilis CL05T12C13
CL05T12C13
Bacteroidetes
JH724198.1
2
EIY90857.1
14661


648
GCA_000290655.1
1053250
1396

Bacillus cereus VDM062
VDM062
Firmicutes
JH791805.1
2
EJS10770.1
14663


649
GCA_000290695.1
1053247
1396

Bacillus cereus VDM022
VDM022
Firmicutes
JH791837.1
2
EJS00271.1
14665


650
GCA_000291275.1
1053222
1396

Bacillus cereus MSX-D12
MSX-D12
Firmicutes
JH792019.1
3
EJR09240.1
14667


651
GCA_000293705.1
1053201
1396

Bacillus cereus HuA2-1
HuA2-1
Firmicutes
JH804676.1
2
EJV74397.1
14670


652
GCA_000293985.2
1134784
1351

Enterococcus faecalis 599
599
Firmicutes
JH805574.1
3
EJU93680.1
14672


653
GCA_000294835.2
1134840
1352

Enterococcus faecium S447
S447
Firmicutes
JH806853.1
3
EJX46905.1
14675


654
GCA_000294955.2
1134834
1352

Enterococcus faecium R446
R446
Firmicutes
JH808093.1
3
EJX62525.1
14678


655
GCA_000294975.2
1134833
1352

Enterococcus faecium P1986
P1986
Firmicutes
JH808384.1
3
EJX62294.1
14681


656
GCA_000294915.2
1134836
1352

Enterococcus faecium R496
R496
Firmicutes
JH808647.1
3
EJX50428.1
14684


657
GCA_000295015.1
1134831
1352

Enterococcus faecium P1140
P1140
Firmicutes
JH809135.1
3
EJX67854.1
14687


658
GCA_000295075.2
1134823
1352

Enterococcus faecium ERV168
ERV168
Firmicutes
JH809674.1
3
EJX96647.1
14690


659
GCA_000295235.2
1134822
1352

Enterococcus faecium ERV165
ERV165
Firmicutes
JH811082.1
3
EJX94481.1
14693


660
GCA_000295255.2
1134821
1352

Enterococcus faecium ERV161
ERV161
Firmicutes
JH811267.1
3
EJX98618.1
14696


661
GCA_000295355.2
1134820
1352

Enterococcus faecium ERV102
ERV102
Firmicutes
JH811829.1
3
EJY06338.1
14699


662
GCA_000295395.2
1134816
1352

Enterococcus faecium C621
C621
Firmicutes
JH813401.1
3
EJY12738.1
14702


663
GCA_000295455.2
1134818
1352

Enterococcus faecium E422
E422
Firmicutes
JH814230.1
3
EJY15300.1
14705


664
GCA_000298035.1
1073385
654

Aeromonas veronii AMC35
AMC35
Proteobacteria
JH815589.1
3
EKB22093.1
14708


665
GCA_000302795.1
1154761
317

Pseudomonas syringae pv. avellanae str.
ISPaVe013
Proteobacteria
JH951825.1
2
EKG43671.1
14711






ISPaVe013


666
GCA_000601255.1
1444050
562

Escherichia coli 1-176-05_S1_C1
1-176-05_S1_C1
Proteobacteria
JHDH01000118.1
2
EYD87721.1
14713


667
GCA_000682795.1
1413578
1280

Staphylococcus aureus ZTA11/03130-3ST
ZTA11/03130-3ST
Firmicutes
JIFC01000010.1
3
EZR33643.1
14715


668
GCA_000682815.1
1413583
1280

Staphylococcus aureus ZTA09/03739-9HSA
ZTA09/03739-9HSA
Firmicutes
JIFJ01000017.1
3
EZR32908.1
14718


669
GCA_000682835.1
1413575
1280

Staphylococcus aureus ZTA09/03576-9HST
ZTA09/03576-9HST
Firmicutes
JIFL01000015.1
3
EZR32079.1
14721


670
GCA_000682855.1
1422806
1280

Staphylococcus aureus VET1918S
VET1918S
Firmicutes
JIFS01000014.1
3
EZR40124.1
14724


671
GCA_000682875.1
1422751
1280

Staphylococcus aureus VET1915R
VET1915R
Firmicutes
JIFU01000012.1
3
EZR39627.1
14727


672
GCA_000682895.1
1422746
1280

Staphylococcus aureus VET1910R
VET1910R
Firmicutes
JIFZ01000014.1
3
EZR44611.1
14730


673
GCA_000682915.1
1422743
1280

Staphylococcus aureus VET1907R
VET1907R
Firmicutes
JIGC01000014.1
3
EZR45907.1
14733


674
GCA_000682935.1
1422737
1280

Staphylococcus aureus VET1898R
VET1898R
Firmicutes
JIGI01000039.1
3
EZR45668.1
14736


675
GCA_000682955.1
1422735
1280

Staphylococcus aureus VET1896R
VET1896R
Firmicutes
JIGK01000023.1
3
EZR50025.1
14739


676
GCA_000682975.1
1422726
1280

Staphylococcus aureus VET1876R
VET1876R
Firmicutes
JIGT01000015.1
3
EZR55035.1
14742


677
GCA_000682995.1
1422721
1280

Staphylococcus aureus VET1869R
VET1869R
Firmicutes
JIGY01000015.1
3
EZR57945.1
14745


678
GCA_000683015.1
1422713
1280

Staphylococcus aureus VET1858R
VET1858R
Firmicutes
JIHG01000011.1
3
EZR61549.1
14748


679
GCA_000683035.1
1422699
1280

Staphylococcus aureus VET1842R
VET1842R
Firmicutes
JIHU01000011.1
3
EZR61336.1
14751


680
GCA_000683055.1
1422694
1280

Staphylococcus aureus VET1833R
VET1833R
Firmicutes
JIHZ01000024.1
3
EZR64331.1
14754


681
GCA_000683075.1
1422793
1280

Staphylococcus aureus VET1515S
VET1515S
Firmicutes
JIIN01000014.1
3
EZR68241.1
14757


682
GCA_000683095.1
1422788
1280

Staphylococcus aureus VET1422S
VET1422S
Firmicutes
JIIS01000014.1
3
EZR69014.1
14760


683
GCA_000683115.1
1422787
1280

Staphylococcus aureus VET1419S
VET1419S
Firmicutes
JIIT01000011.1
3
EZR71841.1
14763


684
GCA_000683175.1
1422779
1280

Staphylococcus aureus VET1103S
VET1103S
Firmicutes
JIJB01000012.1
3
EZR76991.1
14766


685
GCA_000683195.1
1422762
1280

Staphylococcus aureus VET0798S
VET0798S
Firmicutes
JIJR01000008.1
3
EZR83388.1
14769


686
GCA_000683215.1
1422759
1280

Staphylococcus aureus VET0765S
VET0765S
Firmicutes
JIJU01000014.1
3
EZR85552.1
14772


687
GCA_000683235.1
1422753
1280

Staphylococcus aureus VET0612S
VET0612S
Firmicutes
JIKA01000011.1
3
EZR86482.1
14775


688
GCA_000683255.1
1422690
1280

Staphylococcus aureus VET0489R
VET0489R
Firmicutes
JIKD01000012.1
3
EZR91407.1
14778


689
GCA_000683275.1
1422684
1280

Staphylococcus aureus VET0473R
VET0473R
Firmicutes
JIKJ01000007.1
3
EZR97101.1
14781


690
GCA_000683295.1
1422683
1280

Staphylococcus aureus VET0472R
VET0472R
Firmicutes
JIKK01000013.1
3
EZR91808.1
14784


691
GCA_000683315.1
1422682
1280

Staphylococcus aureus VET0471R
VET0471R
Firmicutes
JIKL01000010.1
3
EZS01238.1
14787


692
GCA_000683335.1
1422680
1280

Staphylococcus aureus VET0469R
VET0469R
Firmicutes
JIKN01000014.1
3
EZR98553.1
14790


693
GCA_000683355.1
1422678
1280

Staphylococcus aureus VET0467R
VET0467R
Firmicutes
JIKP01000012.1
3
EZS03613.1
14793


694
GCA_000683375.1
1422659
1280

Staphylococcus aureus VET0437R
VET0437R
Firmicutes
JILI01000022.1
3
EZS03317.1
14796


695
GCA_000683395.1
1422658
1280

Staphylococcus aureus VET0436R
VET0436R
Firmicutes
JILJ01000008.1
3
EZS19480.1
14799


696
GCA_000683415.1
1422650
1280

Staphylococcus aureus VET0426R
VET0426R
Firmicutes
JILR01000018.1
3
EZS08904.1
14802


697
GCA_000683435.1
1422648
1280

Staphylococcus aureus VET0424R
VET0424R
Firmicutes
JILT01000015.1
3
EZS11744.1
14805


698
GCA_000683455.1
1422646
1280

Staphylococcus aureus VET0422R
VET0422R
Firmicutes
JILV01000006.1
3
EZS15735.1
14808


699
GCA_000683475.1
1422641
1280

Staphylococcus aureus VET0414R
VET0414R
Firmicutes
JIMA01000009.1
3
EZS17716.1
14811


700
GCA_000683495.1
1422631
1280

Staphylococcus aureus VET0400R
VET0400R
Firmicutes
JIMK01000012.1
3
EZS22505.1
14814


701
GCA_000683515.1
1422615
1280

Staphylococcus aureus VET0368R
VET0368R
Firmicutes
JINA01000007.1
3
EZS28196.1
14817


702
GCA_000683535.1
1422610
1280

Staphylococcus aureus VET0361R
VET0361R
Firmicutes
JINE01000013.1
3
EZS23872.1
14820


703
GCA_000683555.1
1422607
1280

Staphylococcus aureus VET0358R
VET0358R
Firmicutes
JINH01000013.1
3
EZS29422.1
14823


704
GCA_000683575.1
1422604
1280

Staphylococcus aureus VET0353R
VET0353R
Firmicutes
JINK01000012.1
3
EZS31414.1
14826


705
GCA_000683595.1
1422602
1280

Staphylococcus aureus VET0343R
VET0343R
Firmicutes
JINM01000020.1
3
EZS33213.1
14829


706
GCA_000683615.1
1422601
1280

Staphylococcus aureus VET0342R
VET0342R
Firmicutes
JINN01000024.1
3
EZS35185.1
14832


707
GCA_000683635.1
1422592
1280

Staphylococcus aureus VET0332R
VET0332R
Firmicutes
JINW01000011.1
3
EZS39162.1
14835


708
GCA_000683655.1
1422584
1280

Staphylococcus aureus VET0319R
VET0319R
Firmicutes
JIOE01000008.1
3
EZS43277.1
14838


709
GCA_000683675.1
1422573
1280

Staphylococcus aureus VET0306R
VET0306R
Firmicutes
JIOP01000015.1
3
EZS45538.1
14841


710
GCA_000683695.1
1422568
1280

Staphylococcus aureus VET0301R
VET0301R
Firmicutes
JIOU01000001.1
3
EZS50847.1
14844


711
GCA_000683715.1
1422565
1280

Staphylococcus aureus VET0298R
VET0298R
Firmicutes
JIOX01000011.1
3
EZS49647.1
14847


712
GCA_000683735.1
1422560
1280

Staphylococcus aureus VET0293R
VET0293R
Firmicutes
JIPC01000010.1
3
EZS53448.1
14850


713
GCA_000683755.1
1422532
1280

Staphylococcus aureus VET0251R
VET0251R
Firmicutes
JIQE01000003.1
3
EZS57832.1
14853


714
GCA_000683775.1
1422529
1280

Staphylococcus aureus VET0244R
VET0244R
Firmicutes
JIQH01000007.1
3
EZS59105.1
14856


715
GCA_000683795.1
1422524
1280

Staphylococcus aureus VET0235R
VET0235R
Firmicutes
JIQM01000010.1
3
EZS59928.1
14859


716
GCA_000683815.1
1422523
1280

Staphylococcus aureus VET0232R
VET0232R
Firmicutes
JIQN01000013.1
3
EZS62658.1
14862


717
GCA_000683835.1
1422521
1280

Staphylococcus aureus VET0229R
VET0229R
Firmicutes
JIQP01000009.1
3
EZS64792.1
14865


718
GCA_000683855.1
1422515
1280

Staphylococcus aureus VET0219R
VET0219R
Firmicutes
JIQV01000013.1
3
EZS69843.1
14868


719
GCA_000683875.1
1422503
1280

Staphylococcus aureus VET0203R
VET0203R
Firmicutes
JIRD01000012.1
3
EZS69138.1
14871


720
GCA_000683895.1
1422497
1280

Staphylococcus aureus VET0197R
VET0197R
Firmicutes
JIRG01000010.1
3
EZS72362.1
14874


721
GCA_000683915.1
1422491
1280

Staphylococcus aureus VET0191R
VET0191R
Firmicutes
JIRL01000031.1
3
EZS75507.1
14877


722
GCA_000683935.1
1422485
1280

Staphylococcus aureus VET0184R
VET0184R
Firmicutes
JIRP01000014.1
3
EZS76928.1
14880


723
GCA_000683955.1
1422484
1280

Staphylococcus aureus VET0183R
VET0183R
Firmicutes
JIRQ01000012.1
3
EZS80907.1
14883


724
GCA_000683975.1
1422471
1280

Staphylococcus aureus VET0159R
VET0159R
Firmicutes
JISD01000013.1
3
EZS87845.1
14886


725
GCA_000683995.1
1422470
1280

Staphylococcus aureus VET0158R
VET0158R
Firmicutes
JISE01000012.1
3
EZS84438.1
14889


726
GCA_000684015.1
1422469
1280

Staphylococcus aureus VET0157R
VET0157R
Firmicutes
JISF01000014.1
3
EZS87769.1
14892


727
GCA_000684035.1
1422466
1280

Staphylococcus aureus VET0154R
VET0154R
Firmicutes
JISI01000011.1
3
EZS90163.1
14895


728
GCA_000684055.1
1422463
1280

Staphylococcus aureus VET0150R
VET0150R
Firmicutes
JISL01000013.1
3
EZS94702.1
14898


729
GCA_000684075.1
1422461
1280

Staphylococcus aureus VET0141R
VET0141R
Firmicutes
JISN01000008.1
3
EZS98281.1
14901


730
GCA_000684095.1
1422459
1280

Staphylococcus aureus VET0136R
VET0136R
Firmicutes
JISP01000015.1
3
EZT00071.1
14904


731
GCA_000684115.1
1422450
1280

Staphylococcus aureus VET0125R
VET0125R
Firmicutes
JISY01000005.1
3
EZT04301.1
14907


732
GCA_000684135.1
1422447
1280

Staphylococcus aureus VET0120R
VET0120R
Firmicutes
JITB01000012.1
3
EZT04247.1
14910


733
GCA_000684155.1
1422441
1280

Staphylococcus aureus VET0113R
VET0113R
Firmicutes
JITH01000016.1
3
EZT06690.1
14913


734
GCA_000684175.1
1422439
1280

Staphylococcus aureus VET0111R
VET0111R
Firmicutes
JITJ01000011.1
3
EZT09552.1
14916


735
GCA_000684195.1
1422433
1280

Staphylococcus aureus VET0102R
VET0102R
Firmicutes
JITP01000023.1
3
EZT09961.1
14919


736
GCA_000684215.1
1422415
1280

Staphylococcus aureus VET0081R
VET0081R
Firmicutes
JIUH01000008.1
3
EZT16280.1
14922


737
GCA_000684235.1
1422413
1280

Staphylococcus aureus VET0078R
VET0078R
Firmicutes
JIUJ01000012.1
3
EZT18988.1
14925


738
GCA_000684255.1
1422397
1280

Staphylococcus aureus VET0058R
VET0058R
Firmicutes
JIUZ01000012.1
3
EZT18347.1
14928


739
GCA_000684275.1
1422390
1280

Staphylococcus aureus VET0050R
VET0050R
Firmicutes
JIVG01000012.1
3
EZT23523.1
14931


740
GCA_000684295.1
1413450
1280

Staphylococcus aureus VE08/02242ST1
VE08/02242ST1
Firmicutes
JIVI01000014.1
3
EZT25332.1
14934


741
GCA_000684315.1
1413603
1280

Staphylococcus aureus USA_6
USA_6
Firmicutes
JIV001000013.1
3
EZT27375.1
14937


742
GCA_000684335.1
1413566
1280

Staphylococcus aureus Tur-5
Tur-5
Firmicutes
JIVW01000016.1
3
EZT32068.1
14940


743
GCA_000684355.1
1413553
1280

Staphylococcus aureus Tur-4
Tur-4
Firmicutes
JIVX01000016.1
3
EZT32807.1
14943


744
GCA_000684375.1
1413487
1280

Staphylococcus aureus S64_POEL
S64_POEL
Firmicutes
JIWP01000013.1
3
EZT35387.1
14946


745
GCA_000684395.1
1413486
1280

Staphylococcus aureus S63_POEL
S63_POEL
Firmicutes
JIWQ01000014.1
3
EZT42046.1
14949


746
GCA_000684415.1
1413565
1280

Staphylococcus aureus Rd.290
Rd.290
Firmicutes
JIXA01000010.1
3
EZT39172.1
14952


747
GCA_000684435.1
1413494
1280

Staphylococcus aureus MSSA-47
MSSA-47
Firmicutes
JIX001000015.1
3
EZT44508.1
14955


748
GCA_000684455.1
1413493
1280

Staphylococcus aureus MSSA-37
MSSA-37
Firmicutes
JIXP01000012.1
3
EZT47451.1
14958


749
GCA_000684475.1
1413496
1280

Staphylococcus aureus MSSA-123
MSSA-123
Firmicutes
JIXQ01000009.1
3
EZT50536.1
14961


750
GCA_000684495.1
1413536
1280

Staphylococcus aureus GD2010-169
GD2010-169
Firmicutes
JIXZ01000015.1
3
EZT52625.1
14964


751
GCA_000684515.1
1413535
1280

Staphylococcus aureus GD2010-159
GD2010-159
Firmicutes
JIYB01000010.1
3
EZT54280.1
14967


752
GCA_000684535.1
1413473
1280

Staphylococcus aureus C3452
C3452
Firmicutes
JIZF01000012.1
3
EZT57811.1
14970


753
GCA_000684555.1
1413511
1280

Staphylococcus aureus C0676
C0676
Firmicutes
JIZR01000010.1
3
EZT60957.1
14973


754
GCA_000684575.1
1413507
1280

Staphylococcus aureus C0626
C0626
Firmicutes
JIZV01000007.1
3
EZT61426.1
14976


755
GCA_000684595.1
1413325
1280

Staphylococcus aureus 81629
81629
Firmicutes
JJAH01000015.1
3
EZT65757.1
14979


756
GCA_000684615.1
1413343
1280

Staphylococcus aureus 63-D10
63-D10
Firmicutes
JJAN01000014.1
3
EZT68345.1
14982


757
GCA_000684635.1
1413388
1280

Staphylococcus aureus 53180-1
53180-1
Firmicutes
JJAW01000011.1
3
EZT68418.1
14985


758
GCA_000684655.1
1413547
1280

Staphylococcus aureus 45(2607)
45(2607)
Firmicutes
JJAZ01000013.1
3
EZT73755.1
14988


759
GCA_000684675.1
1413544
1280

Staphylococcus aureus 28(3K2-5)
28(3K2-5)
Firmicutes
JJBI01000015.1
3
EZT75322.1
14991


760
GCA_000684695.1
1413543
1280

Staphylococcus aureus 22(2K81-5)
22(2K81-5)
Firmicutes
JJBX01000016.1
3
EZT77630.1
14994


761
GCA_000684715.1
1413522
1280

Staphylococcus aureus 2011-60-2275-7
2011-60-2275-7
Firmicutes
JJBY01000031.1
3
EZT80087.1
14997


762
GCA_000684735.1
1413394
1280

Staphylococcus aureus 1484-9
1484-9
Firmicutes
JJCS01000014.1
3
EZT82073.1
15000


763
GCA_000684795.1
1413430
1280

Staphylococcus aureus 1111001578
1111001578
Firmicutes
JJDU01000014.1
3
EZT89290.1
15003


764
GCA_000684815.1
1413357
1280

Staphylococcus aureus 10S00488
10S00488
Firmicutes
JJEI01000012.1
3
EZT93146.1
15006


765
GCA_000684835.1
1413560
1280

Staphylococcus aureus 1(04GN_04-02-52-07)
1(04GN_04-02-52-07)
Firmicutes
JJEJ01000010.1
3
EZT96081.1
15009


766
GCA_000684855.1
1413356
1280

Staphylococcus aureus 09S01694
09S01694
Firmicutes
JJEK01000015.1
3
EZT99582.1
15012


767
GCA_000684875.1
1413349
1280

Staphylococcus aureus 09-00736
09-00736
Firmicutes
JJEM01000015.1
3
EZU00841.1
15015


768
GCA_000684895.1
1413346
1280

Staphylococcus aureus 08-01229
08-01229
Firmicutes
JJET01000013.1
3
EZU03294.1
15018


769
GCA_000684915.1
1413345
1280

Staphylococcus aureus 08-01062
08-01062
Firmicutes
JJEW01000012.1
3
EZU07140.1
15021


770
GCA_000684955.1
1413344
1280

Staphylococcus aureus 08-01059
08-01059
Firmicutes
JJEX01000015.1
3
EZU08872.1
15024


771
GCA_000627945.1
1444105
562

Escherichia coli 1-176-05_S1_C3
1-176-05_S1_C3
Proteobacteria
JJLY01000082.1
2
EZK05852.1
15027


772
GCA_000627905.1
1444078
562

Escherichia coli 1-176-05_S1_C2
1-176-05_S1_C2
Proteobacteria
JJMA01000042.1
2
EZK20524.1
15029


773
GCA_000705535.1
95486
95486

Burkholderia cenocepacia

869T2
Proteobacteria
JJOA01000083.1
3
KEA54804.1
15031


774
GCA_000764325.1
29495
29495

Vibrio navarrensis

ATCC 51183
Proteobacteria
JMCG01000001.1
2
KGK10824.1
15034


775
GCA_000695795.1
1492738
1492738

Flavobacterium seoulense

EM1321
Bacteroidetes
JNCA01000003.1
3
KDN56466.1
15036


776
GCA_000699865.1
1339352
821

Bacteroides vulgatus str. 3975 RP4
3975 RP4
Bacteroidetes
JNHM01000174.1
3
KDS43697.1
15039


777
GCA_000700705.1
1444060
562

Escherichia coli 4-203-08_S1_C1
4-203-08_S1_C1
Proteobacteria
JNMY01000013.1
2
KDU61955.1
15042


778
GCA_000704125.1
1444070
562

Escherichia coli 2-222-05_S1_C2
2-222-05_S1_C2
Proteobacteria
JNQL01000002.1
2
KDX77544.1
15044


779
GCA_000704285.1
1444098
562

Escherichia coli 2-222-05_S1_C3
2-222-05_S1_C3
Proteobacteria
JNQM01000001.1
2
KDX82612.1
15046


780
GCA_000704405.1
1444183
562

Escherichia coli 2-427-07_S3_C3
2-427-07_S3_C3
Proteobacteria
JNQY01000031.1
2
KDY27416.1
15048


781
GCA_000707425.1
670
670

Vibrio parahaemolyticus

CFSAN007430
Proteobacteria
JNSN01000106.1
2
KED12527.1
15050


782
GCA_000707385.1
670
670

Vibrio parahaemolyticus

CFSAN007431
Proteobacteria
JNSO01000031.1
2
KED15841.1
15052


783
GCA_000707465.1
670
670

Vibrio parahaemolyticus

CFSAN007433
Proteobacteria
JNSQ01000049.1
3
KED29323.1
15054


784
GCA_000707485.1
670
670

Vibrio parahaemolyticus

CFSAN007434
Proteobacteria
JNSR01000049.1
3
KED25553.1
15057


785
GCA_000707505.1
670
670

Vibrio parahaemolyticus

CFSAN007435
Proteobacteria
JNSS01000023.1
3
KED36896.1
15060


786
GCA_000706885.1
670
670

Vibrio parahaemolyticus

CFSAN007436
Proteobacteria
JNST01000065.1
2
KED34398.1
15063


787
GCA_000707685.1
670
670

Vibrio parahaemolyticus

CFSAN007446
Proteobacteria
JNTD01000023.1
2
KED69849.1
15065


788
GCA_000764405.1
70775
70775

Pseudomonas plecoglossicida

TND35
Proteobacteria
JOJY01000001.1
3
KGK23635.1
15067


789
GCA_000713945.1
1444088
562

Escherichia coli 4-203-08_S1_C2
4-203-08_S1_C2
Proteobacteria
JOQF01000029.1
2
KEK91460.1
15070


790
GCA_000713975.1
1444113
562

Escherichia coli 4-203-08_S1_C3
4-203-08_S1_C3
Proteobacteria
JOQG01000030.1
2
KEK94906.1
15072


791
GCA_000713975.1
1444113
562

Escherichia coli 4-203-08_S1_C3
4-203-08_S1_C3
Proteobacteria
JOQG01000030.1
2
KEK94966.1
15074


792
GCA_000713975.1
1444113
562

Escherichia coli 4-203-08_S1_C3
4-203-08_S1_C3
Proteobacteria
JOQG01000115.1
2
KEK89446.1
15076


793
GCA_000722685.1
28037
28037

Streptococcus mitis

SK667
Firmicutes
JPFV01000011.1
3
KEQ37439.1
15078


794
GCA_000722755.1
28037
28037

Streptococcus mitis

SK578
Firmicutes
JPFY01000013.1
3
KEQ45048.1
15081


795
GCA_000734475.1
615
615

Serratia marcescens

YDC563
Proteobacteria
JPOB01000015.1
2
KFB55438.1
15084


796
GCA_000738535.1
615
615

Serratia marcescens

MCB
Proteobacteria
JPQY01000010.1
2
KFF79466.1
15086


797
GCA_000738105.1
180957
554

Pectobacterium carotovorum subsp. brasiliense
CFIA1009
Proteobacteria
JPSN01000039.1
5
KFF62084.1
15088


798
GCA_001466295.1
1639
1639

Listeria monocytogenes

G4599
Firmicutes
JPTX01000012.1
2
KTA63996.1
15093


799
GCA_001190115.1
1089447
714

Aggregatibacter actinomycetemcomitans

RHAA1
Proteobacteria
JPZI01000001.1
2
KNE78570.1
15095






RhAA1


800
GCA_000743165.1
672
672

Vibrio vulnificus

2322
Proteobacteria
JQDS01000004.1
3
KFK51887.1
15097


801
GCA_000754695.1
180957
554

Pectobacterium carotovorum subsp. brasiliense
LMG 21371
Proteobacteria
JQOE01000001.1
2
KGA25874.1
15100


802
GCA_000768895.1
1515614
1515614

Porphyromonas sp. COT-108 OH2963
COT-108 OH2963
Bacteroidetes
JRAP01000021.1
2
KGN93833.1
15102


803
GCA_000764975.1
1352
1352

Enterococcus faecium

UC7266
Firmicutes
JRJW01000071.1
3
KGK75437.1
15104


804
GCA_000759165.1
1401072
28125

Prevotella bivia DNF00650
DNF00650
Bacteroidetes
JRNM01000003.1
3
KGF38953.1
15107


805
GCA_000785785.1
1349
1349

Streptococcus uberis

CAIM 1894
Firmicutes
JRQN01000035.1
2
KHD43839.1
15110


806
GCA_000772505.1
1352
1352

Enterococcus faecium

VRE3
Firmicutes
JSET01000005.1
3
KGQ80278.1
15112


807
GCA_000817445.1
715
715

Actinobacillus pleuropneumoniae

1022
Proteobacteria
JSVF01000019.1
3
KIE90685.1
15115


808
GCA_000817465.1
715
715

Actinobacillus pleuropneumoniae

460
Proteobacteria
JSVG01000021.1
3
KIE90602.1
15118


809
GCA_000817515.1
715
715

Actinobacillus pleuropneumoniae

780
Proteobacteria
JSVV01000021.1
3
KIE97285.1
15121


810
GCA_000817535.1
715
715

Actinobacillus pleuropneumoniae

597
Proteobacteria
JSVX01000022.1
3
KIE97672.1
15124


811
GCA_000817525.1
715
715

Actinobacillus pleuropneumoniae

5651
Proteobacteria
JSVY01000018.1
3
KIE96199.1
15127


812
GCA_000817485.1
715
715

Actinobacillus pleuropneumoniae

518
Proteobacteria
JSVZ01000017.1
3
KIE90357.1
15130


813
GCA_000803215.1
554
554

Pectobacterium carotovorum

M022
Proteobacteria
JSXC01000002.1
5
KHN56276.1
15133


814
GCA_000827155.1
1280
1280

Staphylococcus aureus

K12PJN53
Firmicutes
JSYA01000018.1
3
KII20612.1
15138


815
GCA_000817375.1
562
562

Escherichia coli

SCB11
Proteobacteria
JSYT01000001.1
2
KIE70777.1
15141


816
GCA_000783635.1
644
644

Aeromonas hydrophila

FDAARGOS_78
Proteobacteria
JTBD01000005.1
2
KGY52609.1
15143


817
GCA_000783915.1
615
615

Serratia marcescens

FDAARGOS_65
Proteobacteria
JTBR01000001.1
2
KGZ13596.1
15145


818
GCA_000803085.1
1315273
137779

Pseudoalteromonas flavipulchra NCIMB
ATCC BAA-314
Proteobacteria
JTDZ01000035.1
2
KHM45375.1
15147






2033 = ATCC BAA-314


819
GCA_000814675.1
77608
77608

Pseudoalteromonas distincta

ATCC 700518
Proteobacteria
JWIG01000011.1
2
KID39107.1
15149


820
GCA_000805875.1
615
615

Serratia marcescens

RM66262
Proteobacteria
JWL001000004.1
2
KHO41399.1
15151


821
GCA_000830335.1
40479
2095

Mycoplasma capricolum subsp. capricolum
GM508D
Tenericutes
JXQB01000001.1
2
KIM13727.1
15153


822
GCA_001042915.1
47884
47884

Pseudomonas taetrolens
DSM 21104
Proteobacteria
JYLA01000003.1
2
KMM85341.1
15155


823
GCA_000321685.1
1138891
1352

Enterococcus faecium EnGen0011
E1185
Firmicutes
KB029511.1
3
ELA78317.1
15157


824
GCA_000322365.1
1138931
1352

Enterococcus faecium EnGen0051
E1644
Firmicutes
KB030041.1
3
ELB72564.1
15160


825
GCA_000322385.1
1138932
1352

Enterococcus faecium EnGen0050
E2369
Firmicutes
KB030078.1
3
ELB70911.1
15163


826
GCA_000322405.1
1138933
1352

Enterococcus faecium EnGen0046
E2560
Firmicutes
KB030094.1
3
ELB76087.1
15166


827
GCA_000322465.1
1138936
1352

Enterococcus faecium EnGen0049
E6045
Firmicutes
KB030126.1
3
ELB84571.1
15169


828
GCA_000322445.1
1138935
1352

Enterococcus faecium EnGen0045
E6012
Firmicutes
KB030159.1
3
ELB85483.1
15172


829
GCA_000314675.2
883078
56946

Afipia broomeae ATCC 49717
ATCC 49717
Proteobacteria
KB375284.1
2
EKS34044.1
15175


830
GCA_000350765.1
1169335
562

Escherichia coli KTE16
KTE16
Proteobacteria
KB732288.1
2
ELC28356.1
15177


831
GCA_000351265.1
1181770
562

Escherichia coli KTE224
KTE224
Proteobacteria
KB732567.1
2
ELD53295.1
15179


832
GCA_000352025.1
1182736
562

Escherichia coli KTE169
KTE169
Proteobacteria
KB732976.1
2
ELF38886.1
15181


833
GCA_000352185.1
1169359
562

Escherichia coli KTE42
KTE42
Proteobacteria
KB733011.1
2
ELF73880.1
15183


834
GCA_000352805.1
1181740
562

Escherichia coli KTE194
KTE194
Proteobacteria
KB733150.1
2
ELH15113.1
15185


835
GCA_000352225.1
1169360
562

Escherichia coli KTE43
KTE43
Proteobacteria
KB733426.1
2
ELF82585.1
15187


836
GCA_000368165.1
1217669
28090

Acinetobacter Iwoffii NIPH 715
NIPH 715
Proteobacteria
KB849267.1
3
ENU62565.1
15189


837
GCA_000369545.1
1217702
1217702

Acinetobacter sp. NIPH 1867
NIPH 1867
Proteobacteria
KB850085.1
3
ENX56755.1
15192


838
GCA_000369685.1
1144665
1144665

Acinetobacter sp. CIP 102136
CIP 102136
Proteobacteria
KB850142.1
2
ENX19931.1
15195


839
GCA_000369725.1
1144662
1144662

Acinetobacter sp. CIP 101966
CIP 101966
Proteobacteria
KB850160.1
3
ENX27881.1
15197


840
GCA_000371465.1
999411
179628

Clostridium colicanis 209318
209318
Firmicutes
KB850956.1
3
ENZ03437.1
15200


841
GCA_000371465.1
999411
179628

Clostridium colicanis 209318
209318
Firmicutes
KB850956.1
3
ENZ02555.1
15203


842
GCA_000393775.1
1158555
1352

Enterococcus faecium EnGen0265
UAA1484
Firmicutes
KB946149.1
3
EOH58476.1
15206


843
GCA_000394575.1
1158644
1352

Enterococcus faecium EnGen0320
UAA949
Firmicutes
KB946824.1
3
EOL74786.1
15209


844
GCA_000394595.1
1158645
1352

Enterococcus faecium EnGen0322
UAA950
Firmicutes
KB946830.1
3
EOI52382.1
15212


845
GCA_000395645.1
1157463
1352

Enterococcus faecium EnGen0168
UAA725
Firmicutes
KB947813.1
3
EOG00796.1
15215


846
GCA_000395665.1
1157464
1352

Enterococcus faecium EnGen0169
UAA825
Firmicutes
KB947831.1
3
EOG00999.1
15218


847
GCA_000395825.1
1157472
1352

Enterococcus faecium EnGen0177
VRE 108
Firmicutes
KB948035.1
3
EOG17544.1
15221


848
GCA_000395865.1
1157474
1352

Enterococcus faecium EnGen0179
VRE 13
Firmicutes
KB948120.1
3
EOG17727.1
15224


849
GCA_000395885.1
1157475
1352

Enterococcus faecium EnGen0180
VRE 84
Firmicutes
KB948121.1
3
EOG29141.1
15227


850
GCA_000396925.1
1158543
1352

Enterococcus faecium EnGen0255
UAA951
Firmicutes
KB949696.1
3
EOM31821.1
15230


851
GCA_000399545.1
1053235
1396

Bacillus cereus VD140
VD140
Firmicutes
KB976803.1
2
EOQ01914.1
15233


852
GCA_000406925.1
1121865
1355

Enterococcus columbae DSM 7374 =
ATCC 51263
Firmicutes
KE136347.1
2
EOT43559.1
15235






ATCC 51263


853
GCA_000407225.1
1121865
1355

Enterococcus columbae DSM 7374 =
ATCC 51263
Firmicutes
KE136492.1
2
EOW87387.1
15237






ATCC 51263


854
GCA_000411115.1
641143
45242

Capnocytophaga granulosa ATCC 51502
ATCC 51502
Bacteroidetes
KE150244.1
4
EPD26424.1
15239


855
GCA_000415365.1
1244150
1352

Enterococcus faecium LA4B-2
LA4B-2
Firmicutes
KE352415.1
2
EPI22405.1
15243


856
GCA_000456145.1
1280963
562

Escherichia coli HVH 9 (4-6942539)
HVH 9 (4-6942539)
Proteobacteria
KE698882.1
2
EQN31627.1
15245


857
GCA_000456585.1
1280988
562

Escherichia coli HVH 38 (4-2774682)
HVH 38 (4-2774682)
Proteobacteria
KE699187.1
2
EQO47878.1
15247


858
GCA_000456745.1
1280996
562

Escherichia coli HVH 46 (4-2758776)
HVH 46 (4-2758776)
Proteobacteria
KE699286.1
2
EQO88544.1
15249


859
GCA_000458275.1
1281086
562

Escherichia coli HVH 153 (3-9344314)
HVH 153 (3-9344314)
Proteobacteria
KE700288.1
2
EQS52095.1
15251


860
GCA_000460435.1
1281198
562

Escherichia coli UMEA 3160-1
UMEA 3160-1
Proteobacteria
KE701742.1
2
EQX21241.1
15253


861
GCA_000469405.1
888055
157687

Leptotrichia wadei F0279
F0279
Fusobacteria
KI271427.1
2
ERK54360.1
15255


862
GCA_000481425.1
1402514
287

Pseudomonas aeruginosa BWHPSA014
BWHPSA014
Proteobacteria
KI519076.1
3
ERW54756.1
15257


863
GCA_000481625.1
1402504
287

Pseudomonas aeruginosa BWHPSA004
BWHPSA004
Proteobacteria
KI519157.1
3
ERW94009.1
15260


864
GCA_000507745.1
1073373
1305

Streptococcus sanguinis CC94A
CC94A
Firmicutes
KI669394.1
3
ETD07628.1
15263


865
GCA_000519605.1
1391479
1351

Enterococcus faecalis EnGen0409
EnGen0409
Firmicutes
KI912997.1
3
ETU12932.1
15266


866
GCA_000521925.1
1400186
615

Serratia marcescens BIDMC 44
BIDMC 44
Proteobacteria
KI929263.1
2
ETX46915.1
15269


867
GCA_000599425.1
1348563
28901

Salmonella enterica subsp. enterica serovar
05-2929
Proteobacteria
KK082454.1
2
EXX84012.1
15271






Namur str. 05-2929


868
GCA_000633715.1
1445864
615

Serratia marcescens BIDMC 80
BIDMC 80
Proteobacteria
KK214322.1
2
EZQ69339.1
15273


869
GCA_000636175.1
1413352
1280

Staphylococcus aureus 08-01084
08-01084
Firmicutes
KK218077.1
3
EZU15808.1
15275


870
GCA_000636195.1
1413353
1280

Staphylococcus aureus 08-01085
08-01085
Firmicutes
KK218112.1
3
EZU14925.1
15278


871
GCA_000636215.1
1413347
1280

Staphylococcus aureus 08-01728
08-01728
Firmicutes
KK218139.1
3
EZU22369.1
15281


872
GCA_000636255.1
1413597
1280

Staphylococcus aureus 08134-6
08134-6
Firmicutes
KK218219.1
3
EZU24877.1
15284


873
GCA_000636275.1
1413598
1280

Staphylococcus aureus 08139-6
08139-6
Firmicutes
KK218244.1
3
EZU30074.1
15287


874
GCA_000636295.1
1413599
1280

Staphylococcus aureus 08142-8
08142-8
Firmicutes
KK218289.1
3
EZU33076.1
15290


875
GCA_000636315.1
1413600
1280

Staphylococcus aureus 08143-5
08143-5
Firmicutes
KK218349.1
3
EZU39423.1
15293


876
GCA_000636335.1
1413355
1280

Staphylococcus aureus 09S00475
09S00475
Firmicutes
KK218433.1
3
EZU35477.1
15296


877
GCA_000636355.1
1413358
1280

Staphylococcus aureus 10S01493
10S01493
Firmicutes
KK218470.1
3
EZU41791.1
15299


878
GCA_000636375.1
1413423
1280

Staphylococcus aureus 110802495
110802495
Firmicutes
KK218519.1
3
EZU42124.1
15302


879
GCA_000636395.1
1413418
1280

Staphylococcus aureus 1110601704
1110601704
Firmicutes
KK218547.1
3
EZU46569.1
15305


880
GCA_000636415.1
1413419
1280

Staphylococcus aureus 1110601896
1110601896
Firmicutes
KK218599.1
3
EZU46770.1
15308


881
GCA_000636435.1
1413420
1280

Staphylococcus aureus 1110700562
1110700562
Firmicutes
KK218635.1
3
EZU48615.1
15311


882
GCA_000636455.1
1413421
1280

Staphylococcus aureus 1110700610
1110700610
Firmicutes
KK218658.1
3
EZU52018.1
15314


883
GCA_000636475.1
1413422
1280

Staphylococcus aureus 1110701127
1110701127
Firmicutes
KK218690.1
3
EZU55227.1
15317


884
GCA_000636495.1
1413424
1280

Staphylococcus aureus 1110802883
1110802883
Firmicutes
KK218732.1
3
EZU56168.1
15320


885
GCA_000636535.1
1413426
1280

Staphylococcus aureus 1110807699
1110807699
Firmicutes
KK218822.1
3
EZU61337.1
15323


886
GCA_000636555.1
1413427
1280

Staphylococcus aureus 1110904178
1110904178
Firmicutes
KK218847.1
3
EZU65300.1
15326


887
GCA_000636635.1
1413432
1280

Staphylococcus aureus 1111101949
1111101949
Firmicutes
KK219058.1
3
EZU73662.1
15329


888
GCA_000636655.1
1413433
1280

Staphylococcus aureus 1111102620
1111102620
Firmicutes
KK219075.1
3
EZU80187.1
15332


889
GCA_000636675.1
1413434
1280

Staphylococcus aureus 1111200013
1111200013
Firmicutes
KK219116.1
3
EZU80949.1
15335


890
GCA_000636695.1
1413435
1280

Staphylococcus aureus 1111203374
1111203374
Firmicutes
KK219160.1
3
EZU82981.1
15338


891
GCA_000636715.1
1413436
1280

Staphylococcus aureus 1111205429
1111205429
Firmicutes
KK219204.1
3
EZU87062.1
15341


892
GCA_000636735.1
1413437
1280

Staphylococcus aureus 1111206270
1111206270
Firmicutes
KK219261.1
3
EZU88265.1
15344


893
GCA_000636755.1
1413587
1280

Staphylococcus aureus 11P4
11P4
Firmicutes
KK219305.1
3
EZU90294.1
15347


894
GCA_000636775.1
1413588
1280

Staphylococcus aureus 11P8
11P8
Firmicutes
KK219338.1
3
EZU94768.1
15350


895
GCA_000636815.1
1413360
1280

Staphylococcus aureus 11S00627
11S00627
Firmicutes
KK219434.1
3
EZU96101.1
15353


896
GCA_000636855.1
1413363
1280

Staphylococcus aureus 11S01586
11S01586
Firmicutes
KK219518.1
3
EZV02408.1
15356


897
GCA_000636895.1
1413491
1280

Staphylococcus aureus 122
122
Firmicutes
KK219580.1
3
EZV09969.1
15359


898
GCA_000636915.1
1413416
1280

Staphylococcus aureus 12464
12464
Firmicutes
KK219611.1
3
EZV11275.1
15362


899
GCA_000636955.1
1413365
1280

Staphylococcus aureus 12S00579
12S00579
Firmicutes
KK219698.1
3
EZV17198.1
15365


900
GCA_000636975.1
1413366
1280

Staphylococcus aureus 12S00881
12S00881
Firmicutes
KK219743.1
3
EZV18375.1
15368


901
GCA_000636995.1
1413368
1280

Staphylococcus aureus 12S01153
12S01153
Firmicutes
KK219769.1
3
EZV22691.1
15371


902
GCA_000637015.1
1413369
1280

Staphylococcus aureus 12S01399
12S01399
Firmicutes
KK219813.1
3
EZV23635.1
15374


903
GCA_000637055.1
1413371
1280

Staphylococcus aureus 12-ST01988
12-ST01988
Firmicutes
KK219900.1
3
EZV30021.1
15377


904
GCA_000637095.1
1413562
1280

Staphylococcus aureus 14(11MN_17-
14(11MN_17-
Firmicutes
KK219997.1
3
EZV34240.1
15380






08-66-05)
08-66-05)


905
GCA_000637115.1
1413401
1280

Staphylococcus aureus 150211/pool 1
150211/pool 1
Firmicutes
KK220038.1
3
EZV37879.1
15383


906
GCA_000637135.1
1413558
1280

Staphylococcus aureus 16(11S1S4-09)
16(115154-09)
Firmicutes
KK220079.1
3
EZV41499.1
15386


907
GCA_000637155.1
1413402
1280

Staphylococcus aureus 18439-17
18439-17
Firmicutes
KK220114.1
3
EZV40173.1
15389


908
GCA_000637175.1
1413405
1280

Staphylococcus aureus 18439-62
18439-62
Firmicutes
KK220145.1
3
EZV45691.1
15392


909
GCA_000637215.1
1413333
1280

Staphylococcus aureus 19571
19571
Firmicutes
KK220240.1
3
EZV49483.1
15395


910
GCA_000637235.1
1413561
1280

Staphylococcus aureus 2(04HN_17-
2(04HN_17-
Firmicutes
KK220279.1
3
EZV51743.1
15398






03-52-05)
03-52-05)


911
GCA_000637255.1
1413519
1280

Staphylococcus aureus 2009-60-561-1
2009-60-561-1
Firmicutes
KK220312.1
3
EZV56161.1
15401


912
GCA_000637275.1
1413514
1280

Staphylococcus aureus 2010-60-1240-1
2010-60-1240-1
Firmicutes
KK220355.1
3
EZV60061.1
15404


913
GCA_000637295.1
1413328
1280

Staphylococcus aureus 2010-60-6063-29
2010-60-6063-29
Firmicutes
KK220412.1
3
EZV56179.1
15407


914
GCA_000637315.1
1413516
1280

Staphylococcus aureus 2010-60-6063-39
2010-60-6063-39
Firmicutes
KK220436.1
3
EZV62995.1
15410


915
GCA_000637355.1
1413517
1280

Staphylococcus aureus 2010-60-6511-39
2010-60-6511-39
Firmicutes
KK220514.1
3
EZV68414.1
15413


916
GCA_000637395.1
1413329
1280

Staphylococcus aureus 2010-60-7626-19
2010-60-7626-19
Firmicutes
KK220613.1
3
EZV73439.1
15416


917
GCA_000637415.1
1413524
1280

Staphylococcus aureus 2011-60-1490-31
2011-60-1490-31
Firmicutes
KK220641.1
3
EZV79302.1
15419


918
GCA_000637435.1
1413523
1280

Staphylococcus aureus 2011-60-2078-5
2011-60-2078-5
Firmicutes
KK220717.1
3
EZV78174.1
15422


919
GCA_000637455.1
1413330
1280

Staphylococcus aureus 2011-60-2256-5
2011-60-2256-5
Firmicutes
KK220763.1
3
EZV80246.1
15425


920
GCA_000637475.1
1413521
1280

Staphylococcus aureus 2011-60-2275-1
2011-60-2275-1
Firmicutes
KK220803.1
3
EZV86033.1
15428


921
GCA_000637495.1
1413334
1280

Staphylococcus aureus 22825
22825
Firmicutes
KK220854.1
3
EZV85085.1
15431


922
GCA_000637515.1
1413336
1280

Staphylococcus aureus 22835
22835
Firmicutes
KK220886.1
3
EZV88945.1
15434


923
GCA_000637535.1
1413337
1280

Staphylococcus aureus 22837
22837
Firmicutes
KK220922.1
3
EZV92667.1
15437


924
GCA_000637555.1
1413338
1280

Staphylococcus aureus 22838
22838
Firmicutes
KK220954.1
3
EZV94448.1
15440


925
GCA_000637575.1
1413339
1280

Staphylococcus aureus 22841
22841
Firmicutes
KK220987.1
3
EZV97126.1
15443


926
GCA_000637595.1
1413340
1280

Staphylococcus aureus 22843
22843
Firmicutes
KK221024.1
3
EZV98957.1
15446


927
GCA_000637615.1
1413341
1280

Staphylococcus aureus 22846
22846
Firmicutes
KK221058.1
3
EZW01628.1
15449


928
GCA_000637635.1
1413438
1280

Staphylococcus aureus 22P79
22P79
Firmicutes
KK221090.1
3
EZW04546.1
15452


929
GCA_000637655.1
1413342
1280

Staphylococcus aureus 23237
23237
Firmicutes
KK221128.1
3
EZW06685.1
15455


930
GCA_000637675.1
1413414
1280

Staphylococcus aureus 2393-15
2393-15
Firmicutes
KK221165.1
3
EZW08828.1
15458


931
GCA_000637695.1
1413415
1280

Staphylococcus aureus 2393-19
2393-19
Firmicutes
KK221201.1
3
EZW10960.1
15461


932
GCA_000637715.1
1413545
1280

Staphylococcus aureus 25(2889)
25(2889)
Firmicutes
KK221232.1
3
EZW14699.1
15464


933
GCA_000637735.1
1413406
1280

Staphylococcus aureus 27999-3
27999-3
Firmicutes
KK221262.1
3
EZW17376.1
15467


934
GCA_000637775.1
1413589
1280

Staphylococcus aureus 36P1
36P1
Firmicutes
KK221358.1
3
EZW21157.1
15470


935
GCA_000637795.1
1413590
1280

Staphylococcus aureus 36P5
36P5
Firmicutes
KK221386.1
3
EZW24847.1
15473


936
GCA_000637815.1
1413559
1280

Staphylococcus aureus 37(18S2S5-05)
37(18S2S5-05)
Firmicutes
KK221416.1
3
EZW30609.1
15476


937
GCA_000637835.1
1413592
1280

Staphylococcus aureus 40P10
40P10
Firmicutes
KK221466.1
3
EZW29484.1
15479


938
GCA_000637855.1
1413591
1280

Staphylococcus aureus 40P5 1_1
40P5 1_1
Firmicutes
KK221506.1
3
EZW34093.1
15482


939
GCA_000637875.1
1413593
1280

Staphylococcus aureus 43P3
43P3
Firmicutes
KK221549.1
3
EZW34360.1
15485


940
GCA_000637895.1
1413594
1280

Staphylococcus aureus 43P8
43P8
Firmicutes
KK221571.1
3
EZW38692.1
15488


941
GCA_000637915.1
1413546
1280

Staphylococcus aureus 44(2608)
44(2608)
Firmicutes
KK221597.1
3
EZW42269.1
15491


942
GCA_000637935.1
1413595
1280

Staphylococcus aureus 47P5
47P5
Firmicutes
KK221644.1
3
EZW41573.1
15494


943
GCA_000637955.1
1413596
1280

Staphylococcus aureus 47P9
47P9
Firmicutes
KK221684.1
3
EZW45924.1
15497


944
GCA_000637975.1
1413384
1280

Staphylococcus aureus 5670-1
5670-1
Firmicutes
KK221721.1
3
EZW48566.1
15500


945
GCA_000637995.1
1413410
1280

Staphylococcus aureus 56824-10
56824-10
Firmicutes
KK221759.1
3
EZW51956.1
15503


946
GCA_000638015.1
1413411
1280

Staphylococcus aureus 56824-15
56824-15
Firmicutes
KK221811.1
3
EZW52897.1
15506


947
GCA_000638035.1
1413407
1280

Staphylococcus aureus 56824-2
56824-2
Firmicutes
KK221853.1
3
EZW54604.1
15509


948
GCA_000638055.1
1413412
1280

Staphylococcus aureus 56824-21
56824-21
Firmicutes
KK221878.1
3
EZW61228.1
15512


949
GCA_000638075.1
1413408
1280

Staphylococcus aureus 56824-5
56824-5
Firmicutes
KK221926.1
3
EZW59349.1
15515


950
GCA_000638095.1
1413409
1280

Staphylococcus aureus 56824-7
56824-7
Firmicutes
KK221958.1
3
EZW64575.1
15518


951
GCA_000638135.1
1413385
1280

Staphylococcus aureus 6665-5
6665-5
Firmicutes
KK222053.1
3
EZW67819.1
15521


952
GCA_000638155.1
1413395
1280

Staphylococcus aureus 75495-3
75495-3
Firmicutes
KK222088.1
3
EZW72066.1
15524


953
GCA_000638175.1
1413396
1280

Staphylococcus aureus 76669-6
76669-6
Firmicutes
KK222133.1
3
EZW73745.1
15527


954
GCA_000638215.1
1413324
1280

Staphylococcus aureus 81070
81070
Firmicutes
KK222240.1
3
EZW78367.1
15530


955
GCA_000638235.1
1413397
1280

Staphylococcus aureus 84069-2
84069-2
Firmicutes
KK222292.1
3
EZW78068.1
15533


956
GCA_000638255.1
1413398
1280

Staphylococcus aureus 86770-7
86770-7
Firmicutes
KK222314.1
3
EZW85425.1
15536


957
GCA_000638275.1
1413389
1280

Staphylococcus aureus 87807-1
87807-1
Firmicutes
KK222349.1
3
EZW86269.1
15539


958
GCA_000638295.1
1413390
1280

Staphylococcus aureus 87807-11
87807-11
Firmicutes
KK222381.1
3
EZW90701.1
15542


959
GCA_000638315.1
1413392
1280

Staphylococcus aureus 87807-12
87807-12
Firmicutes
KK222425.1
3
EZW93348.1
15545


960
GCA_000638335.1
1413393
1280

Staphylococcus aureus 87807-16
87807-16
Firmicutes
KK222467.1
3
EZW94212.1
15548


961
GCA_000638355.1
1413391
1280

Staphylococcus aureus 87807-9
87807-9
Firmicutes
KK222503.1
3
EZW97015.1
15551


962
GCA_000638375.1
1413399
1280

Staphylococcus aureus 88088-1
88088-1
Firmicutes
KK222532.1
3
EZX00539.1
15554


963
GCA_000638395.1
1413400
1280

Staphylococcus aureus 88088-2
88088-2
Firmicutes
KK222577.1
3
EZX02277.1
15557


964
GCA_000638415.1
1413586
1280

Staphylococcus aureus 9P9
9P9
Firmicutes
KK222619.1
3
EZX04400.1
15560


965
GCA_000638435.1
1413383
1280

Staphylococcus aureus BG407
BG407
Firmicutes
KK222651.1
3
EZX08872.1
15563


966
GCA_000638475.1
1413509
1280

Staphylococcus aureus C0637
C0637
Firmicutes
KK222726.1
3
EZX10608.1
15566


967
GCA_000638515.1
1413466
1280

Staphylococcus aureus C1655
C1655
Firmicutes
KK222789.1
3
EZX16970.1
15569


968
GCA_000638535.1
1413470
1280

Staphylococcus aureus C1673
C1673
Firmicutes
KK222826.1
3
EZX19510.1
15572


969
GCA_000638555.1
1413461
1280

Staphylococcus aureus C1842
C1842
Firmicutes
KK222863.1
3
EZX23730.1
15575


970
GCA_000638575.1
1413458
1280

Staphylococcus aureus C1891
C1891
Firmicutes
KK222914.1
3
EZX26911.1
15578


971
GCA_000638595.1
1413459
1280

Staphylococcus aureus C1894
C1894
Firmicutes
KK222954.1
3
EZX30320.1
15581


972
GCA_000638615.1
1413481
1280

Staphylococcus aureus C2549
C2549
Firmicutes
KK222984.1
3
EZX30781.1
15584


973
GCA_000638635.1
1413482
1280

Staphylococcus aureus C2679
C2679
Firmicutes
KK223018.1
3
EZX33812.1
15587


974
GCA_000638655.1
1413467
1280

Staphylococcus aureus C2706
C2706
Firmicutes
KK223042.1
3
EZX38408.1
15590


975
GCA_000638675.1
1413474
1280

Staphylococcus aureus C2928
C2928
Firmicutes
KK223082.1
3
EZX39864.1
15593


976
GCA_000638695.1
1413472
1280

Staphylococcus aureus C2930
C2930
Firmicutes
KK223136.1
3
EZX38524.1
15596


977
GCA_000638715.1
1413475
1280

Staphylococcus aureus C2942
C2942
Firmicutes
KK223163.1
3
EZX45515.1
15599


978
GCA_000638735.1
1413454
1280

Staphylococcus aureus C3489
C3489
Firmicutes
KK223216.1
3
EZX46731.1
15602


979
GCA_000638755.1
1413476
1280

Staphylococcus aureus C3672
C3672
Firmicutes
KK223267.1
3
EZX48305.1
15605


980
GCA_000638775.1
1413456
1280

Staphylococcus aureus C3865
C3865
Firmicutes
KK223311.1
3
EZX53235.1
15608


981
GCA_000638795.1
1413483
1280

Staphylococcus aureus C3965
C3965
Firmicutes
KK223341.1
3
EZX53550.1
15611


982
GCA_000638815.1
1413477
1280

Staphylococcus aureus C4151
C4151
Firmicutes
KK223372.1
3
EZX56516.1
15614


983
GCA_000638835.1
1413471
1280

Staphylococcus aureus C4155
C4155
Firmicutes
KK223399.1
3
EZX60548.1
15617


984
GCA_000638855.1
1413457
1280

Staphylococcus aureus C4668
C4668
Firmicutes
KK223430.1
3
EZX62512.1
15620


985
GCA_000638875.1
1413455
1280

Staphylococcus aureus C5086
C5086
Firmicutes
KK223462.1
3
EZX64345.1
15623


986
GCA_000638895.1
1413480
1280

Staphylococcus aureus C5453
C5453
Firmicutes
KK223489.1
3
EZX67972.1
15626


987
GCA_000638915.1
1413549
1280

Staphylococcus aureus Chi-10
Chi-10
Firmicutes
KK223517.1
3
EZX70983.1
15629


988
GCA_000638935.1
1413548
1280

Staphylococcus aureus Chi-4
Chi-4
Firmicutes
KK223557.1
3
EZX70899.1
15632


989
GCA_000638955.1
1413550
1280

Staphylococcus aureus Chi-8
Chi-8
Firmicutes
KK223582.1
3
EZX78545.1
15635


990
GCA_000638975.1
1413577
1280

Staphylococcus aureus DICM09/
DICM09/
Firmicutes
KK223626.1
3
EZX83217.1
15638






00997-9HST2
00997-9HST2


991
GCA_000638995.1
1413580
1280

Staphylococcus aureus DICM09/
DICM09/
Firmicutes
KK223686.1
3
EZX78168.1
15641






01587-13HST
01587-13HST


992
GCA_000639015.1
1413439
1280

Staphylococcus aureus FP_N239
FP_N239
Firmicutes
KK223720.1
3
EZX83512.1
15644


993
GCA_000639035.1
1413440
1280

Staphylococcus aureus FP_N5203 OX
FP_N5203 OX
Firmicutes
KK223754.1
3
EZX85564.1
15647


994
GCA_000639055.1
1413441
1280

Staphylococcus aureus FP_N5208 OX
FP_N5208 OX
Firmicutes
KK223787.1
3
EZX88439.1
15650


995
GCA_000639075.1
1413567
1280

Staphylococcus aureus GD2010-052
GD2010-052
Firmicutes
KK223829.1
3
EZX90794.1
15653


996
GCA_000639095.1
1413568
1280

Staphylococcus aureus GD2010-061
GD2010-061
Firmicutes
KK223867.1
3
EZX93307.1
15656


997
GCA_000639115.1
1413526
1280

Staphylococcus aureus GD2010-090
GD2010-090
Firmicutes
KK223898.1
3
EZX97302.1
15659


998
GCA_000639135.1
1413569
1280

Staphylococcus aureus GD2010-102
GD2010-102
Firmicutes
KK223946.1
3
EZX98401.1
15662


999
GCA_000639155.1
1413528
1280

Staphylococcus aureus GD2010-107
GD2010-107
Firmicutes
KK223977.1
3
EZY04106.1
15665


1000
GCA_000639175.1
1413527
1280

Staphylococcus aureus GD2010-110
GD2010-110
Firmicutes
KK224019.1
3
EZY04548.1
15668


1001
GCA_000639195.1
1413530
1280

Staphylococcus aureus GD2010-112
GD2010-112
Firmicutes
KK224053.1
3
EZY06602.1
15671


1002
GCA_000639215.1
1413529
1280

Staphylococcus aureus GD2010-115
GD2010-115
Firmicutes
KK224086.1
3
EZY11332.1
15674


1003
GCA_000639235.1
1413531
1280

Staphylococcus aureus GD2010-131
GD2010-131
Firmicutes
KK224135.1
3
EZY13792.1
15677


1004
GCA_000639255.1
1413532
1280

Staphylococcus aureus GD2010-147
GD2010-147
Firmicutes
KK224189.1
3
EZY14132.1
15680


1005
GCA_000639275.1
1413533
1280

Staphylococcus aureus GD2010-155
GD2010-155
Firmicutes
KK224222.1
3
EZY14216.1
15683


1006
GCA_000639295.1
1413534
1280

Staphylococcus aureus GD2010-158
GD2010-158
Firmicutes
KK224237.1
3
EZY21814.1
15686


1007
GCA_000639315.1
1413537
1280

Staphylococcus aureus GD2010-168
GD2010-168
Firmicutes
KK224279.1
3
EZY21674.1
15689


1008
GCA_000639335.1
1413525
1280

Staphylococcus aureus GD2010-177
GD2010-177
Firmicutes
KK224318.1
3
EZY24519.1
15692


1009
GCA_000639355.1
1413323
1280

Staphylococcus aureus M118-B
M118-B
Firmicutes
KK224362.1
3
EZY26573.1
15695


1010
GCA_000639375.1
1413442
1280

Staphylococcus aureus M267-1
M267-1
Firmicutes
KK224385.1
3
EZY29473.1
15698


1011
GCA_000639395.1
1413443
1280

Staphylococcus aureus M357
M357
Firmicutes
KK224412.1
3
EZY31974.1
15701


1012
GCA_000639415.1
1413444
1280

Staphylococcus aureus M457-1
M457-1
Firmicutes
KK224434.1
3
EZY36828.1
15704


1013
GCA_000639435.1
1413445
1280

Staphylococcus aureus M520-1
M520-1
Firmicutes
KK224471.1
3
EZY36641.1
15707


1014
GCA_000639455.1
1413495
1280

Staphylococcus aureus MRSA-118
MRSA-118
Firmicutes
KK224503.1
3
EZY38136.1
15710


1015
GCA_000639475.1
1413497
1280

Staphylococcus aureus MRSA-136
MRSA-136
Firmicutes
KK224533.1
3
EZY43514.1
15713


1016
GCA_000639495.1
1413492
1280

Staphylococcus aureus MSSA-93
MSSA-93
Firmicutes
KK224580.1
3
EZY44867.1
15716


1017
GCA_000639515.1
1413498
1280

Staphylococcus aureus N0426
N0426
Firmicutes
KK224621.1
3
EZY46959.1
15719


1018
GCA_000639535.1
1413499
1280

Staphylococcus aureus N1343
N1343
Firmicutes
KK224655.1
3
EZY51217.1
15722


1019
GCA_000639555.1
1413512
1280

Staphylococcus aureus P0218
P0218
Firmicutes
KK224694.1
3
EZY52189.1
15725


1020
GCA_000639575.1
1413489
1280

Staphylococcus aureus PA11
PA11
Firmicutes
KK224731.1
3
EZY54364.1
15728


1021
GCA_000639595.1
1413490
1280

Staphylococcus aureus PA57
PA57
Firmicutes
KK224756.1
3
EZY58964.1
15731


1022
GCA_000639635.1
1413501
1280

Staphylococcus aureus R0353
R0353
Firmicutes
KK224861.1
3
EZY61861.1
15734


1023
GCA_000639655.1
1413502
1280

Staphylococcus aureus R0357
R0357
Firmicutes
KK224908.1
3
EZY66174.1
15737


1024
GCA_000639675.1
1413503
1280

Staphylococcus aureus R0487
R0487
Firmicutes
KK224950.1
3
EZY70311.1
15740


1025
GCA_000639695.1
1413504
1280

Staphylococcus aureus R0545
R0545
Firmicutes
KK225002.1
3
EZY70617.1
15743


1026
GCA_000639715.1
1413505
1280

Staphylococcus aureus R0611
R0611
Firmicutes
KK225056.1
3
EZY75196.1
15746


1027
GCA_000639735.1
1413506
1280

Staphylococcus aureus R0615
R0615
Firmicutes
KK225109.1
3
EZY78995.1
15749


1028
GCA_000639755.1
1413538
1280

Staphylococcus aureus Rd.3
Rd.3
Firmicutes
KK225169.1
3
EZY77812.1
15752


1029
GCA_000639775.1
1413540
1280

Staphylococcus aureus Rd.40
Rd.40
Firmicutes
KK225209.1
3
EZY80413.1
15755


1030
GCA_000639795.1
1413541
1280

Staphylococcus aureus Rd.51
Rd.51
Firmicutes
KK225236.1
3
EZY85273.1
15758


1031
GCA_000639815.1
1413563
1280

Staphylococcus aureus Rd.545
Rd.545
Firmicutes
KK225257.1
3
EZY90749.1
15761


1032
GCA_000639835.1
1413542
1280

Staphylococcus aureus Rd.60
Rd.60
Firmicutes
KK225318.1
3
EZY86733.1
15764


1033
GCA_000639855.1
1413564
1280

Staphylococcus aureus Rd.614
Rd.614
Firmicutes
KK225337.1
3
EZY93710.1
15767


1034
GCA_000639875.1
1413539
1280

Staphylococcus aureus Rd.9
Rd.9
Firmicutes
KK225372.1
3
EZY96337.1
15770


1035
GCA_000639895.1
1413484
1280

Staphylococcus aureus S56_POEL
S56_POEL
Firmicutes
KK225426.1
3
EZY99137.1
15773


1036
GCA_000639915.1
1413485
1280

Staphylococcus aureus S62_POEL
S62_POEL
Firmicutes
KK225491.1
3
EZZ00577.1
15776


1037
GCA_000639935.1
1413488
1280

Staphylococcus aureus S69_POEL
S69_POEL
Firmicutes
KK225547.1
3
EZZ04415.1
15779


1038
GCA_000639955.1
1413446
1280

Staphylococcus aureus SARM C4155
SARM C4155
Firmicutes
KK225609.1
3
EZZ04097.1
15782


1039
GCA_000639975.1
1413447
1280

Staphylococcus aureus SARM C5621
SARM C5621
Firmicutes
KK225630.1
3
EZZ07028.1
15785


1040
GCA_000639995.1
1413382
1280

Staphylococcus aureus Sau 194
Sau 194
Firmicutes
KK225664.1
3
EZZ11502.1
15788


1041
GCA_000640015.1
1413374
1280

Staphylococcus aureus Sau 44
Sau 44
Firmicutes
KK225696.1
3
EZZ12223.1
15791


1042
GCA_000640035.1
1413375
1280

Staphylococcus aureus Sau 46
Sau 46
Firmicutes
KK225732.1
3
EZZ13376.1
15794


1043
GCA_000640055.1
1413376
1280

Staphylococcus aureus Sau 47
Sau 47
Firmicutes
KK225762.1
3
EZZ20017.1
15797


1044
GCA_000640075.1
1413377
1280

Staphylococcus aureus Sau 74
Sau 74
Firmicutes
KK225802.1
3
EZZ20493.1
15800


1045
GCA_000640095.1
1413378
1280

Staphylococcus aureus Sau 93
Sau 93
Firmicutes
KK225836.1
3
EZZ22879.1
15803


1046
GCA_000640115.1
1413379
1280

Staphylococcus aureus Sau 95
Sau 95
Firmicutes
KK225869.1
3
EZZ27504.1
15806


1047
GCA_000640135.1
1413380
1280

Staphylococcus aureus Sau 98
Sau 98
Firmicutes
KK225900.1
3
EZZ27419.1
15809


1048
GCA_000640175.1
1413555
1280

Staphylococcus aureus Tur-12
Tur-12
Firmicutes
KK225980.1
3
EZZ33553.1
15812


1049
GCA_000640195.1
1413556
1280

Staphylococcus aureus Tur-15
Tur-15
Firmicutes
KK226022.1
3
EZZ35199.1
15815


1050
GCA_000640215.1
1413373
1280

Staphylococcus aureus Tur-16
Tur-16
Firmicutes
KK226052.1
3
EZZ38883.1
15818


1051
GCA_000640235.1
1413551
1280

Staphylococcus aureus Tur-20
Tur-20
Firmicutes
KK226092.1
3
EZZ42314.1
15821


1052
GCA_000640255.1
1413552
1280

Staphylococcus aureus Tur-22
Tur-22
Firmicutes
KK226129.1
3
EZZ43690.1
15824


1053
GCA_000640275.1
1413554
1280

Staphylococcus aureus Tur-6
Tur-6
Firmicutes
KK226169.1
3
EZZ46493.1
15827


1054
GCA_000640295.1
1413331
1280

Staphylococcus aureus UB 08-116
UB 08-116
Firmicutes
KK226203.1
3
EZZ50763.1
15830


1055
GCA_000640315.1
1413332
1280

Staphylococcus aureus UB 08-172
UB 08-172
Firmicutes
KK226235.1
3
EZZ51037.1
15833


1056
GCA_000640335.1
1413602
1280

Staphylococcus aureus USA_1
USA_1
Firmicutes
KK226264.1
3
EZZ53438.1
15836


1057
GCA_000640355.1
1413607
1280

Staphylococcus aureus USA_11
USA_11
Firmicutes
KK226275.1
3
EZZ62216.1
15839


1058
GCA_000640375.1
1413608
1280

Staphylococcus aureus USA_12
USA_12
Firmicutes
KK226308.1
3
EZZ58809.1
15842


1059
GCA_000640395.1
1413609
1280

Staphylococcus aureus USA_15
USA_15
Firmicutes
KK226326.1
3
EZZ63777.1
15845


1060
GCA_000640415.1
1413605
1280

Staphylococcus aureus USA_8
USA_8
Firmicutes
KK226363.1
3
EZZ66976.1
15848


1061
GCA_000640435.1
1413606
1280

Staphylococcus aureus USA_9
USA_9
Firmicutes
KK226405.1
3
EZZ65105.1
15851


1062
GCA_000640455.1
1413604
1280

Staphylococcus aureus USA7
USA7
Firmicutes
KK226422.1
3
EZZ70714.1
15854


1063
GCA_000640475.1
1413448
1280

Staphylococcus aureus VE07/03048STA
VE07/03048STA
Firmicutes
KK226453.1
3
EZZ73603.1
15857


1064
GCA_000640495.1
1413449
1280

Staphylococcus aureus VE08/02126ST1
VE08/02126ST1
Firmicutes
KK226495.1
3
EZZ75114.1
15860


1065
GCA_000640515.1
1413451
1280

Staphylococcus aureus VE08/02244ST1
VE08/02244ST1
Firmicutes
KK226529.1
3
EZZ75511.1
15863


1066
GCA_000640535.1
1422391
1280

Staphylococcus aureus VET0051R
VET0051R
Firmicutes
KK226556.1
3
EZZ82800.1
15866


1067
GCA_000640555.1
1422392
1280

Staphylococcus aureus VET0052R
VET0052R
Firmicutes
KK226598.1
3
EZZ83623.1
15869


1068
GCA_000640575.1
1422393
1280

Staphylococcus aureus VET0053R
VET0053R
Firmicutes
KK226639.1
3
EZZ82655.1
15872


1069
GCA_000640595.1
1422394
1280

Staphylococcus aureus VET0054R
VET0054R
Firmicutes
KK226674.1
3
EZZ89015.1
15875


1070
GCA_000640615.1
1422395
1280

Staphylococcus aureus VET0055R
VET0055R
Firmicutes
KK226711.1
3
EZZ92962.1
15878


1071
GCA_000640635.1
1422396
1280

Staphylococcus aureus VET0057R
VET0057R
Firmicutes
KK226773.1
3
EZZ92684.1
15881


1072
GCA_000640655.1
1422398
1280

Staphylococcus aureus VET0059R
VET0059R
Firmicutes
KK226834.1
3
EZZ95684.1
15884


1073
GCA_000640675.1
1422399
1280

Staphylococcus aureus VET0060R
VET0060R
Firmicutes
KK226872.1
3
KAA05377.1
15887


1074
GCA_000640695.1
1422400
1280

Staphylococcus aureus VET0061R
VET0061R
Firmicutes
KK226919.1
3
KAA05544.1
15890


1075
GCA_000640715.1
1422401
1280

Staphylococcus aureus VET0062R
VET0062R
Firmicutes
KK226958.1
3
KAA05953.1
15893


1076
GCA_000640735.1
1422402
1280

Staphylococcus aureus VET0063R
VET0063R
Firmicutes
KK226999.1
3
KAA13000.1
15896


1077
GCA_000640755.1
1422403
1280

Staphylococcus aureus VET0065R
VET0065R
Firmicutes
KK227042.1
3
KAA12393.1
15899


1078
GCA_000640775.1
1422404
1280

Staphylococcus aureus VET0066R
VET0066R
Firmicutes
KK227076.1
3
KAA13619.1
15902


1079
GCA_000640795.1
1422405
1280

Staphylococcus aureus VET0067R
VET0067R
Firmicutes
KK227106.1
3
KAA22643.1
15905


1080
GCA_000640815.1
1422406
1280

Staphylococcus aureus VET0069R
VET0069R
Firmicutes
KK227159.1
3
KAA21033.1
15908


1081
GCA_000640835.1
1422407
1280

Staphylococcus aureus VET0070R
VET0070R
Firmicutes
KK227206.1
3
KAA21282.1
15911


1082
GCA_000640855.1
1422408
1280

Staphylococcus aureus VET0072R
VET0072R
Firmicutes
KK227240.1
3
KAA28470.1
15914


1083
GCA_000640875.1
1422409
1280

Staphylococcus aureus VET0073R
VET0073R
Firmicutes
KK227288.1
3
KAA29978.1
15917


1084
GCA_000640895.1
1422410
1280

Staphylococcus aureus VET0075R
VET0075R
Firmicutes
KK227338.1
3
KAA28571.1
15920


1085
GCA_000640915.1
1422411
1280

Staphylococcus aureus VET0076R
VET0076R
Firmicutes
KK227375.1
3
KAA35386.1
15923


1086
GCA_000640935.1
1422412
1280

Staphylococcus aureus VET0077R
VET0077R
Firmicutes
KK227403.1
3
KAA38915.1
15926


1087
GCA_000640955.1
1422414
1280

Staphylococcus aureus VET0080R
VET0080R
Firmicutes
KK227448.1
3
KAA39462.1
15929


1088
GCA_000640975.1
1422416
1280

Staphylococcus aureus VET0083R
VET0083R
Firmicutes
KK227491.1
3
KAA42954.1
15932


1089
GCA_000640995.1
1422417
1280

Staphylococcus aureus VET0084R
VET0084R
Firmicutes
KK227523.1
3
KAA45225.1
15935


1090
GCA_000641015.1
1422418
1280

Staphylococcus aureus VET0085R
VET0085R
Firmicutes
KK227565.1
3
KAA46801.1
15938


1091
GCA_000641035.1
1422419
1280

Staphylococcus aureus VET0086R
VET0086R
Firmicutes
KK227605.1
3
KAA49913.1
15941


1092
GCA_000641055.1
1422420
1280

Staphylococcus aureus VET0087R
VET0087R
Firmicutes
KK227638.1
3
KAA51796.1
15944


1093
GCA_000641075.1
1422421
1280

Staphylococcus aureus VET0088R
VET0088R
Firmicutes
KK227658.1
3
KAA59416.1
15947


1094
GCA_000641095.1
1422422
1280

Staphylococcus aureus VET0089R
VET0089R
Firmicutes
KK227710.1
3
KAA58407.1
15950


1095
GCA_000641115.1
1422423
1280

Staphylococcus aureus VET0090R
VET0090R
Firmicutes
KK227736.1
3
KAA61962.1
15953


1096
GCA_000641135.1
1422424
1280

Staphylococcus aureus VET0091R
VET0091R
Firmicutes
KK227783.1
3
KAA63552.1
15956


1097
GCA_000641155.1
1422425
1280

Staphylococcus aureus VET0092R
VET0092R
Firmicutes
KK227826.1
3
KAA66140.1
15959


1098
GCA_000641175.1
1422426
1280

Staphylococcus aureus VET0093R
VET0093R
Firmicutes
KK227870.1
3
KAA68224.1
15962


1099
GCA_000641195.1
1422427
1280

Staphylococcus aureus VET0094R
VET0094R
Firmicutes
KK227907.1
3
KAA73513.1
15965


1100
GCA_000641215.1
1422428
1280

Staphylococcus aureus VET0095R
VET0095R
Firmicutes
KK227954.1
3
KAA74080.1
15968


1101
GCA_000641235.1
1422429
1280

Staphylococcus aureus VET0097R
VET0097R
Firmicutes
KK227993.1
3
KAA76198.1
15971


1102
GCA_000641255.1
1422430
1280

Staphylococcus aureus VET0098R
VET0098R
Firmicutes
KK228029.1
3
KAA79422.1
15974


1103
GCA_000641275.1
1422431
1280

Staphylococcus aureus VET0099R
VET0099R
Firmicutes
KK228070.1
3
KAA82180.1
15977


1104
GCA_000641295.1
1422432
1280

Staphylococcus aureus VET0101R
VET0101R
Firmicutes
KK228126.1
3
KAA82201.1
15980


1105
GCA_000641315.1
1422434
1280

Staphylococcus aureus VET0103R
VET0103R
Firmicutes
KK228153.1
3
KAA86323.1
15983


1106
GCA_000641335.1
1422435
1280

Staphylococcus aureus VET0104R
VET0104R
Firmicutes
KK228187.1
3
KAA89640.1
15986


1107
GCA_000641355.1
1422436
1280

Staphylococcus aureus VET0105R
VET0105R
Firmicutes
KK228218.1
3
KAA93204.1
15989


1108
GCA_000641375.1
1422437
1280

Staphylococcus aureus VET0107R
VET0107R
Firmicutes
KK228279.1
3
KAA93403.1
15992


1109
GCA_000641395.1
1422438
1280

Staphylococcus aureus VET0110R
VET0110R
Firmicutes
KK228324.1
3
KAA96433.1
15995


1110
GCA_000641415.1
1422440
1280

Staphylococcus aureus VET0112R
VET0112R
Firmicutes
KK228363.1
3
KAB00569.1
15998


1111
GCA_000641435.1
1422442
1280

Staphylococcus aureus VET0114R
VET0114R
Firmicutes
KK228395.1
3
KAB03847.1
16001


1112
GCA_000641455.1
1422443
1280

Staphylococcus aureus VET0115R
VET0115R
Firmicutes
KK228451.1
3
KAB06658.1
16004


1113
GCA_000641475.1
1422444
1280

Staphylococcus aureus VET0116R
VET0116R
Firmicutes
KK228505.1
3
KAB08922.1
16007


1114
GCA_000641495.1
1422445
1280

Staphylococcus aureus VET0117R
VET0117R
Firmicutes
KK228551.1
3
KAB10432.1
16010


1115
GCA_000641515.1
1422446
1280

Staphylococcus aureus VET0119R
VET0119R
Firmicutes
KK228588.1
3
KAB11616.1
16013


1116
GCA_000641535.1
1422448
1280

Staphylococcus aureus VET0123R
VET0123R
Firmicutes
KK228618.1
3
KAB16350.1
16016


1117
GCA_000641555.1
1422449
1280

Staphylococcus aureus VET0124R
VET0124R
Firmicutes
KK228659.1
3
KAB18689.1
16019


1118
GCA_000641575.1
1422451
1280

Staphylococcus aureus VET0126R
VET0126R
Firmicutes
KK228701.1
3
KAB19935.1
16022


1119
GCA_000641595.1
1422452
1280

Staphylococcus aureus VET0127R
VET0127R
Firmicutes
KK228748.1
3
KAB24080.1
16025


1120
GCA_000641615.1
1422453
1280

Staphylococcus aureus VET0128R
VET0128R
Firmicutes
KK228781.1
3
KAB29327.1
16028


1121
GCA_000641635.1
1422454
1280

Staphylococcus aureus VET0129R
VET0129R
Firmicutes
KK228823.1
3
KAB29477.1
16031


1122
GCA_000641655.1
1422455
1280

Staphylococcus aureus VET0130R
VET0130R
Firmicutes
KK228852.1
3
KAB32012.1
16034


1123
GCA_000641675.1
1422456
1280

Staphylococcus aureus VET0132R
VET0132R
Firmicutes
KK228890.1
3
KAB33825.1
16037


1124
GCA_000641695.1
1422457
1280

Staphylococcus aureus VET0133R
VET0133R
Firmicutes
KK228932.1
3
KAB37793.1
16040


1125
GCA_000641715.1
1422458
1280

Staphylococcus aureus VET0134R
VET0134R
Firmicutes
KK228988.1
3
KAB38132.1
16043


1126
GCA_000641735.1
1422460
1280

Staphylococcus aureus VET0140R
VET0140R
Firmicutes
KK229019.1
3
KAB42667.1
16046


1127
GCA_000641755.1
1422462
1280

Staphylococcus aureus VET0148R
VET0148R
Firmicutes
KK229051.1
3
KAB46003.1
16049


1128
GCA_000641775.1
1422464
1280

Staphylococcus aureus VET0151R
VET0151R
Firmicutes
KK229081.1
3
KAB45741.1
16052


1129
GCA_000641795.1
1422465
1280

Staphylococcus aureus VET0152R
VET0152R
Firmicutes
KK229110.1
3
KAB51677.1
16055


1130
GCA_000641815.1
1422467
1280

Staphylococcus aureus VET0155R
VET0155R
Firmicutes
KK229172.1
3
KAB53193.1
16058


1131
GCA_000641835.1
1422468
1280

Staphylococcus aureus VET0156R
VET0156R
Firmicutes
KK229219.1
3
KAB55784.1
16061


1132
GCA_000641855.1
1422472
1280

Staphylococcus aureus VET0161R
VET0161R
Firmicutes
KK229266.1
3
KAB58082.1
16064


1133
GCA_000641875.1
1422473
1280

Staphylococcus aureus VET0162R
VET0162R
Firmicutes
KK229299.1
3
KAB59419.1
16067


1134
GCA_000641895.1
1422474
1280

Staphylococcus aureus VET0164R
VET0164R
Firmicutes
KK229332.1
3
KAB62993.1
16070


1135
GCA_000641915.1
1422475
1280

Staphylococcus aureus VET0165R
VET0165R
Firmicutes
KK229377.1
3
KAB66109.1
16073


1136
GCA_000641935.1
1422476
1280

Staphylococcus aureus VET0166R
VET0166R
Firmicutes
KK229442.1
3
KAB66874.1
16076


1137
GCA_000641955.1
1422477
1280

Staphylococcus aureus VET0167R
VET0167R
Firmicutes
KK229493.1
3
KAB70776.1
16079


1138
GCA_000641975.1
1422478
1280

Staphylococcus aureus VET0171R
VET0171R
Firmicutes
KK229539.1
3
KAB73064.1
16082


1139
GCA_000641995.1
1422479
1280

Staphylococcus aureus VET0176R
VET0176R
Firmicutes
KK229579.1
3
KAB75150.1
16085


1140
GCA_000642015.1
1422480
1280

Staphylococcus aureus VET0177R
VET0177R
Firmicutes
KK229612.1
3
KAB78038.1
16088


1141
GCA_000642035.1
1422481
1280

Staphylococcus aureus VET0178R
VET0178R
Firmicutes
KK229644.1
3
KAB81593.1
16091


1142
GCA_000642055.1
1422482
1280

Staphylococcus aureus VET0179R
VET0179R
Firmicutes
KK229686.1
3
KAB84387.1
16094


1143
GCA_000642075.1
1422483
1280

Staphylococcus aureus VET0180R
VET0180R
Firmicutes
KK229729.1
3
KAB84694.1
16097


1144
GCA_000642095.1
1422488
1280

Staphylococcus aureus VET0188R
VET0188R
Firmicutes
KK229754.1
3
KAB91416.1
16100


1145
GCA_000642115.1
1422489
1280

Staphylococcus aureus VET0189R
VET0189R
Firmicutes
KK229800.1
3
KAB92906.1
16103


1146
GCA_000642135.1
1422490
1280

Staphylococcus aureus VET0190R
VET0190R
Firmicutes
KK229842.1
3
KAB93617.1
16106


1147
GCA_000642155.1
1422492
1280

Staphylococcus aureus VET0192R
VET0192R
Firmicutes
KK229894.1
3
KAB98475.1
16109


1148
GCA_000642175.1
1422493
1280

Staphylococcus aureus VET0193R
VET0193R
Firmicutes
KK229956.1
3
KAB98436.1
16112


1149
GCA_000642195.1
1422494
1280

Staphylococcus aureus VET0194R
VET0194R
Firmicutes
KK230007.1
3
KAC00309.1
16115


1150
GCA_000642215.1
1422495
1280

Staphylococcus aureus VET0195R
VET0195R
Firmicutes
KK230044.1
3
KAC04037.1
16118


1151
GCA_000642235.1
1422498
1280

Staphylococcus aureus VET0198R
VET0198R
Firmicutes
KK230081.1
3
KAC08058.1
16121


1152
GCA_000642255.1
1422500
1280

Staphylococcus aureus VET0200R
VET0200R
Firmicutes
KK230124.1
3
KAC10255.1
16124


1153
GCA_000642275.1
1422508
1280

Staphylococcus aureus VET0212R
VET0212R
Firmicutes
KK230171.1
3
KAC11816.1
16127


1154
GCA_000642295.1
1422509
1280

Staphylococcus aureus VET0213R
VET0213R
Firmicutes
KK230206.1
3
KAC14781.1
16130


1155
GCA_000642315.1
1422510
1280

Staphylococcus aureus VET0214R
VET0214R
Firmicutes
KK230245.1
3
KAC17658.1
16133


1156
GCA_000642335.1
1422511
1280

Staphylococcus aureus VET0215R
VET0215R
Firmicutes
KK230294.1
3
KAC20377.1
16136


1157
GCA_000642355.1
1422512
1280

Staphylococcus aureus VET0216R
VET0216R
Firmicutes
KK230357.1
3
KAC21946.1
16139


1158
GCA_000642375.1
1422513
1280

Staphylococcus aureus VET0217R
VET0217R
Firmicutes
KK230406.1
3
KAC25278.1
16142


1159
GCA_000642395.1
1422514
1280

Staphylococcus aureus VET0218R
VET0218R
Firmicutes
KK230455.1
3
KAC29151.1
16145


1160
GCA_000642415.1
1422516
1280

Staphylococcus aureus VET0221R
VET0221R
Firmicutes
KK230491.1
3
KAC33554.1
16148


1161
GCA_000642435.1
1422517
1280

Staphylococcus aureus VET0222R
VET0222R
Firmicutes
KK230550.1
3
KAC34157.1
16151


1162
GCA_000642455.1
1422518
1280

Staphylococcus aureus VET0224R
VET0224R
Firmicutes
KK230611.1
3
KAC33241.1
16154


1163
GCA_000642475.1
1422519
1280

Staphylococcus aureus VET0227R
VET0227R
Firmicutes
KK230635.1
3
KAC37672.1
16157


1164
GCA_000642495.1
1422520
1280

Staphylococcus aureus VET0228R
VET0228R
Firmicutes
KK230680.1
3
KAC40880.1
16160


1165
GCA_000642515.1
1422522
1280

Staphylococcus aureus VET0230R
VET0230R
Firmicutes
KK230709.1
3
KAC45126.1
16163


1166
GCA_000642535.1
1422525
1280

Staphylococcus aureus VET0236R
VET0236R
Firmicutes
KK230757.1
3
KAC44749.1
16166


1167
GCA_000642555.1
1422526
1280

Staphylococcus aureus VET0237R
VET0237R
Firmicutes
KK230781.1
3
KAC51539.1
16169


1168
GCA_000642575.1
1422527
1280

Staphylococcus aureus VET0241R
VET0241R
Firmicutes
KK230828.1
3
KAC50575.1
16172


1169
GCA_000642595.1
1422528
1280

Staphylococcus aureus VET0243R
VET0243R
Firmicutes
KK230863.1
3
KAC52444.1
16175


1170
GCA_000642615.1
1422530
1280

Staphylococcus aureus VET0247R
VET0247R
Firmicutes
KK230896.1
3
KAC57903.1
16178


1171
GCA_000642635.1
1422531
1280

Staphylococcus aureus VET0249R
VET0249R
Firmicutes
KK230930.1
3
KAC59267.1
16181


1172
GCA_000642655.1
1422533
1280

Staphylococcus aureus VET0252R
VET0252R
Firmicutes
KK230956.1
3
KAC64902.1
16184


1173
GCA_000642675.1
1422534
1280

Staphylococcus aureus VET0253R
VET0253R
Firmicutes
KK231012.1
3
KAC65216.1
16187


1174
GCA_000642695.1
1422535
1280

Staphylococcus aureus VET0254R
VET0254R
Firmicutes
KK231053.1
3
KAC66579.1
16190


1175
GCA_000642715.1
1422536
1280

Staphylococcus aureus VET0256R
VET0256R
Firmicutes
KK231074.1
3
KAC76251.1
16193


1176
GCA_000642735.1
1422537
1280

Staphylococcus aureus VET0259R
VET0259R
Firmicutes
KK231155.1
3
KAC70676.1
16196


1177
GCA_000642755.1
1422538
1280

Staphylococcus aureus VET0260R
VET0260R
Firmicutes
KK231188.1
3
KAC73890.1
16199


1178
GCA_000642775.1
1422539
1280

Staphylococcus aureus VET0261R
VET0261R
Firmicutes
KK231221.1
3
KAC78737.1
16202


1179
GCA_000642795.1
1422540
1280

Staphylococcus aureus VET0263R
VET0263R
Firmicutes
KK231265.1
3
KAC82512.1
16205


1180
GCA_000642815.1
1422541
1280

Staphylococcus aureus VET0267R
VET0267R
Firmicutes
KK231317.1
3
KAC80332.1
16208


1181
GCA_000642835.1
1422542
1280

Staphylococcus aureus VET0268R
VET0268R
Firmicutes
KK231348.1
3
KAC86159.1
16211


1182
GCA_000642855.1
1422543
1280

Staphylococcus aureus VET0269R
VET0269R
Firmicutes
KK231386.1
3
KAC89254.1
16214


1183
GCA_000642875.1
1422544
1280

Staphylococcus aureus VET0270R
VET0270R
Firmicutes
KK231435.1
3
KAC89181.1
16217


1184
GCA_000642895.1
1422545
1280

Staphylococcus aureus VET0271R
VET0271R
Firmicutes
KK231470.1
3
KAC93844.1
16220


1185
GCA_000642915.1
1422546
1280

Staphylococcus aureus VET0275R
VET0275R
Firmicutes
KK231503.1
3
KAC96630.1
16223


1186
GCA_000642935.1
1422547
1280

Staphylococcus aureus VET0278R
VET0278R
Firmicutes
KK231552.1
3
KAC97653.1
16226


1187
GCA_000642955.1
1422548
1280

Staphylococcus aureus VET0279R
VET0279R
Firmicutes
KK231605.1
3
KAD00064.1
16229


1188
GCA_000642975.1
1422549
1280

Staphylococcus aureus VET0280R
VET0280R
Firmicutes
KK231633.1
3
KAD04306.1
16232


1189
GCA_000642995.1
1422550
1280

Staphylococcus aureus VET0282R
VET0282R
Firmicutes
KK231663.1
3
KAD08152.1
16235


1190
GCA_000643015.1
1422551
1280

Staphylococcus aureus VET0283R
VET0283R
Firmicutes
KK231710.1
3
KAD07875.1
16238


1191
GCA_000643035.1
1422552
1280

Staphylococcus aureus VET0284R
VET0284R
Firmicutes
KK231759.1
3
KAD11428.1
16241


1192
GCA_000643055.1
1422553
1280

Staphylococcus aureus VET0286R
VET0286R
Firmicutes
KK231797.1
3
KAD14196.1
16244


1193
GCA_000643075.1
1422554
1280

Staphylococcus aureus VET0287R
VET0287R
Firmicutes
KK231839.1
3
KAD16933.1
16247


1194
GCA_000643095.1
1422555
1280

Staphylococcus aureus VET0288R
VET0288R
Firmicutes
KK231877.1
3
KAD20112.1
16250


1195
GCA_000643115.1
1422556
1280

Staphylococcus aureus VET0289R
VET0289R
Firmicutes
KK231905.1
3
KAD22452.1
16253


1196
GCA_000643135.1
1422557
1280

Staphylococcus aureus VET0290R
VET0290R
Firmicutes
KK231934.1
3
KAD23853.1
16256


1197
GCA_000643155.1
1422558
1280

Staphylococcus aureus VET0291R
VET0291R
Firmicutes
KK231957.1
3
KAD27442.1
16259


1198
GCA_000643175.1
1422559
1280

Staphylococcus aureus VET0292R
VET0292R
Firmicutes
KK231982.1
3
KAD29135.1
16262


1199
GCA_000643195.1
1422561
1280

Staphylococcus aureus VET0294R
VET0294R
Firmicutes
KK232006.1
3
KAD33183.1
16265


1200
GCA_000643215.1
1422562
1280

Staphylococcus aureus VET0295R
VET0295R
Firmicutes
KK232044.1
3
KAD35158.1
16268


1201
GCA_000643235.1
1422563
1280

Staphylococcus aureus VET0296R
VET0296R
Firmicutes
KK232071.1
3
KAD41139.1
16271


1202
GCA_000643255.1
1422564
1280

Staphylococcus aureus VET0297R
VET0297R
Firmicutes
KK232123.1
3
KAD37497.1
16274


1203
GCA_000643275.1
1422566
1280

Staphylococcus aureus VET0299R
VET0299R
Firmicutes
KK232151.1
3
KAD41938.1
16277


1204
GCA_000643295.1
1422567
1280

Staphylococcus aureus VET0300R
VET0300R
Firmicutes
KK232180.1
3
KAD44775.1
16280


1205
GCA_000643315.1
1422569
1280

Staphylococcus aureus VET0302R
VET0302R
Firmicutes
KK232221.1
3
KAD49432.1
16283


1206
GCA_000643335.1
1422570
1280

Staphylococcus aureus VET0303R
VET0303R
Firmicutes
KK232282.1
3
KAD48763.1
16286


1207
GCA_000643355.1
1422571
1280

Staphylococcus aureus VET0304R
VET0304R
Firmicutes
KK232321.1
3
KAD53925.1
16289


1208
GCA_000643375.1
1422572
1280

Staphylococcus aureus VET0305R
VET0305R
Firmicutes
KK232371.1
3
KAD57265.1
16292


1209
GCA_000643395.1
1422574
1280

Staphylococcus aureus VET0307R
VET0307R
Firmicutes
KK232424.1
3
KAD59398.1
16295


1210
GCA_000643415.1
1422575
1280

Staphylococcus aureus VET0308R
VET0308R
Firmicutes
KK232479.1
3
KAD59590.1
16298


1211
GCA_000643435.1
1422576
1280

Staphylococcus aureus VET0309R
VET0309R
Firmicutes
KK232506.1
3
KAD64095.1
16301


1212
GCA_000643455.1
1422577
1280

Staphylococcus aureus VET0312R
VET0312R
Firmicutes
KK232547.1
3
KAD64971.1
16304


1213
GCA_000643475.1
1422578
1280

Staphylococcus aureus VET0313R
VET0313R
Firmicutes
KK232579.1
3
KAD71132.1
16307


1214
GCA_000643495.1
1422579
1280

Staphylococcus aureus VET0314R
VET0314R
Firmicutes
KK232626.1
3
KAD76144.1
16310


1215
GCA_000643515.1
1422580
1280

Staphylococcus aureus VET0315R
VET0315R
Firmicutes
KK232671.1
3
KAD70469.1
16313


1216
GCA_000643535.1
1422581
1280

Staphylococcus aureus VET0316R
VET0316R
Firmicutes
KK232698.1
3
KAD78845.1
16316


1217
GCA_000643555.1
1422582
1280

Staphylococcus aureus VET0317R
VET0317R
Firmicutes
KK232759.1
3
KAD77330.1
16319


1218
GCA_000643575.1
1422583
1280

Staphylococcus aureus VET0318R
VET0318R
Firmicutes
KK232802.1
3
KAD80657.1
16322


1219
GCA_000643595.1
1422585
1280

Staphylococcus aureus VET0320R
VET0320R
Firmicutes
KK232846.1
3
KAD85222.1
16325


1220
GCA_000643615.1
1422586
1280

Staphylococcus aureus VET0322R
VET0322R
Firmicutes
KK232899.1
3
KAD85662.1
16328


1221
GCA_000643635.1
1422587
1280

Staphylococcus aureus VET0323R
VET0323R
Firmicutes
KK232949.1
3
KAD90247.1
16331


1222
GCA_000643655.1
1422588
1280

Staphylococcus aureus VET0325R
VET0325R
Firmicutes
KK233004.1
3
KAD93694.1
16334


1223
GCA_000643675.1
1422589
1280

Staphylococcus aureus VET0326R
VET0326R
Firmicutes
KK233060.1
3
KAD94381.1
16337


1224
GCA_000643695.1
1422590
1280

Staphylococcus aureus VET0329R
VET0329R
Firmicutes
KK233107.1
3
KAD99176.1
16340


1225
GCA_000643715.1
1422591
1280

Staphylococcus aureus VET0331R
VET0331R
Firmicutes
KK233161.1
3
KAD98842.1
16343


1226
GCA_000643735.1
1422593
1280

Staphylococcus aureus VET0333R
VET0333R
Firmicutes
KK233217.1
3
KAD99163.1
16346


1227
GCA_000643755.1
1422594
1280

Staphylococcus aureus VET0335R
VET0335R
Firmicutes
KK233273.1
3
KAE03357.1
16349


1228
GCA_000643775.1
1422595
1280

Staphylococcus aureus VET0336R
VET0336R
Firmicutes
KK233293.1
3
KAE06091.1
16352


1229
GCA_000643795.1
1422596
1280

Staphylococcus aureus VET0337R
VET0337R
Firmicutes
KK233320.1
3
KAE10343.1
16355


1230
GCA_000643815.1
1422597
1280

Staphylococcus aureus VET0338R
VET0338R
Firmicutes
KK233365.1
3
KAE11832.1
16358


1231
GCA_000643835.1
1422598
1280

Staphylococcus aureus VET0339R
VET0339R
Firmicutes
KK233392.1
3
KAE16058.1
16361


1232
GCA_000643855.1
1422599
1280

Staphylococcus aureus VET0340R
VET0340R
Firmicutes
KK233439.1
3
KAE17680.1
16364


1233
GCA_000643875.1
1422600
1280

Staphylococcus aureus VET0341R
VET0341R
Firmicutes
KK233484.1
3
KAE21314.1
16367


1234
GCA_000643895.1
1422603
1280

Staphylococcus aureus VET0352R
VET0352R
Firmicutes
KK233526.1
3
KAE22706.1
16370


1235
GCA_000643915.1
1422605
1280

Staphylococcus aureus VET0354R
VET0354R
Firmicutes
KK233565.1
3
KAE26218.1
16373


1236
GCA_000643935.1
1422606
1280

Staphylococcus aureus VET0357R
VET0357R
Firmicutes
KK233602.1
3
KAE28381.1
16376


1237
GCA_000643955.1
1422608
1280

Staphylococcus aureus VET0359R
VET0359R
Firmicutes
KK233637.1
3
KAE30967.1
16379


1238
GCA_000643975.1
1422609
1280

Staphylococcus aureus VET0360R
VET0360R
Firmicutes
KK233668.1
3
KAE34716.1
16382


1239
GCA_000643995.1
1422611
1280

Staphylococcus aureus VET0363R
VET0363R
Firmicutes
KK233714.1
3
KAE36917.1
16385


1240
GCA_000644015.1
1422613
1280

Staphylococcus aureus VET0366R
VET0366R
Firmicutes
KK233762.1
3
KAE38769.1
16388


1241
GCA_000644035.1
1422614
1280

Staphylococcus aureus VET0367R
VET0367R
Firmicutes
KK233806.1
3
KAE42476.1
16391


1242
GCA_000644055.1
1422616
1280

Staphylococcus aureus VET0369R
VET0369R
Firmicutes
KK233856.1
3
KAE45135.1
16394


1243
GCA_000644075.1
1422617
1280

Staphylococcus aureus VET0373R
VET0373R
Firmicutes
KK233916.1
3
KAE45866.1
16397


1244
GCA_000644095.1
1422618
1280

Staphylococcus aureus VET0376R
VET0376R
Firmicutes
KK233953.1
3
KAE50291.1
16400


1245
GCA_000644115.1
1422619
1280

Staphylococcus aureus VET0382R
VET0382R
Firmicutes
KK233998.1
3
KAE51871.1
16403


1246
GCA_000644135.1
1422620
1280

Staphylococcus aureus VET0383R
VET0383R
Firmicutes
KK234034.1
3
KAE56033.1
16406


1247
GCA_000644155.1
1422621
1280

Staphylococcus aureus VET0384R
VET0384R
Firmicutes
KK234091.1
3
KAE58619.1
16409


1248
GCA_000644175.1
1422622
1280

Staphylococcus aureus VET0387R
VET0387R
Firmicutes
KK234154.1
3
KAE60715.1
16412


1249
GCA_000644195.1
1422623
1280

Staphylococcus aureus VET0388R
VET0388R
Firmicutes
KK234207.1
3
KAE63797.1
16415


1250
GCA_000644215.1
1422624
1280

Staphylococcus aureus VET0389R
VET0389R
Firmicutes
KK234244.1
3
KAE63594.1
16418


1251
GCA_000644235.1
1422625
1280

Staphylococcus aureus VET0390R
VET0390R
Firmicutes
KK234279.1
3
KAE68676.1
16421


1252
GCA_000644255.1
1422626
1280

Staphylococcus aureus VET0393R
VET0393R
Firmicutes
KK234337.1
3
KAE69670.1
16424


1253
GCA_000644275.1
1422627
1280

Staphylococcus aureus VET0394R
VET0394R
Firmicutes
KK234392.1
3
KAE72491.1
16427


1254
GCA_000644295.1
1422628
1280

Staphylococcus aureus VET0395R
VET0395R
Firmicutes
KK234444.1
3
KAE78484.1
16430


1255
GCA_000644315.1
1422629
1280

Staphylococcus aureus VET0396R
VET0396R
Firmicutes
KK234517.1
3
KAE76736.1
16433


1256
GCA_000644335.1
1422630
1280

Staphylococcus aureus VET0399R
VET0399R
Firmicutes
KK234558.1
3
KAE81551.1
16436


1257
GCA_000644355.1
1422632
1280

Staphylococcus aureus VET0401R
VET0401R
Firmicutes
KK234614.1
3
KAE84897.1
16439


1258
GCA_000644375.1
1422633
1280

Staphylococcus aureus VET0402R
VET0402R
Firmicutes
KK234667.1
3
KAE84991.1
16442


1259
GCA_000644395.1
1422634
1280

Staphylococcus aureus VET0403R
VET0403R
Firmicutes
KK234707.1
3
KAE89404.1
16445


1260
GCA_000644415.1
1422635
1280

Staphylococcus aureus VET0406R
VET0406R
Firmicutes
KK234760.1
3
KAE90296.1
16448


1261
GCA_000644435.1
1422636
1280

Staphylococcus aureus VET0407R
VET0407R
Firmicutes
KK234801.1
3
KAE93402.1
16451


1262
GCA_000644455.1
1422637
1280

Staphylococcus aureus VET0410R
VET0410R
Firmicutes
KK234843.1
3
KAE97233.1
16454


1263
GCA_000644475.1
1422638
1280

Staphylococcus aureus VET0411R
VET0411R
Firmicutes
KK234874.1
3
KAE99814.1
16457


1264
GCA_000644495.1
1422639
1280

Staphylococcus aureus VET0412R
VET0412R
Firmicutes
KK234915.1
3
KAE99887.1
16460


1265
GCA_000644515.1
1422640
1280

Staphylococcus aureus VET0413R
VET0413R
Firmicutes
KK234944.1
3
KAF04816.1
16463


1266
GCA_000644535.1
1422642
1280

Staphylococcus aureus VET0415R
VET0415R
Firmicutes
KK234978.1
3
KAF09789.1
16466


1267
GCA_000644555.1
1422643
1280

Staphylococcus aureus VET0417R
VET0417R
Firmicutes
KK235031.1
3
KAF06948.1
16469


1268
GCA_000644575.1
1422644
1280

Staphylococcus aureus VET0418R
VET0418R
Firmicutes
KK235067.1
3
KAF12149.1
16472


1269
GCA_000644595.1
1422645
1280

Staphylococcus aureus VET0421R
VET0421R
Firmicutes
KK235112.1
3
KAF14362.1
16475


1270
GCA_000644615.1
1422647
1280

Staphylococcus aureus VET0423R
VET0423R
Firmicutes
KK235151.1
3
KAF17950.1
16478


1271
GCA_000644635.1
1422649
1280

Staphylococcus aureus VET0425R
VET0425R
Firmicutes
KK235201.1
3
KAF21049.1
16481


1272
GCA_000644655.1
1422651
1280

Staphylococcus aureus VET0427R
VET0427R
Firmicutes
KK235253.1
3
KAF20976.1
16484


1273
GCA_000644675.1
1422652
1280

Staphylococcus aureus VET0428R
VET0428R
Firmicutes
KK235284.1
3
KAF25643.1
16487


1274
GCA_000644695.1
1422653
1280

Staphylococcus aureus VET0431R
VET0431R
Firmicutes
KK235319.1
3
KAF31108.1
16490


1275
GCA_000644715.1
1422654
1280

Staphylococcus aureus VET0432R
VET0432R
Firmicutes
KK235373.1
3
KAF28014.1
16493


1276
GCA_000644735.1
1422655
1280

Staphylococcus aureus VET0433R
VET0433R
Firmicutes
KK235408.1
3
KAF33774.1
16496


1277
GCA_000644755.1
1422656
1280

Staphylococcus aureus VET0434R
VET0434R
Firmicutes
KK235447.1
3
KAF35730.1
16499


1278
GCA_000644775.1
1422657
1280

Staphylococcus aureus VET0435R
VET0435R
Firmicutes
KK235486.1
3
KAF38655.1
16502


1279
GCA_000644795.1
1422660
1280

Staphylococcus aureus VET0438R
VET0438R
Firmicutes
KK235526.1
3
KAF42882.1
16505


1280
GCA_000644815.1
1422661
1280

Staphylococcus aureus VET0439R
VET0439R
Firmicutes
KK235571.1
3
KAF42846.1
16508


1281
GCA_000644835.1
1422662
1280

Staphylococcus aureus VET0440R
VET0440R
Firmicutes
KK235606.1
3
KAF46909.1
16511


1282
GCA_000644855.1
1422663
1280

Staphylococcus aureus VET0442R
VET0442R
Firmicutes
KK235649.1
3
KAF47443.1
16514


1283
GCA_000644875.1
1422664
1280

Staphylococcus aureus VET0443R
VET0443R
Firmicutes
KK235707.1
3
KAF48000.1
16517


1284
GCA_000644895.1
1422665
1280

Staphylococcus aureus VET0444R
VET0444R
Firmicutes
KK235727.1
3
KAF54049.1
16520


1285
GCA_000644915.1
1422666
1280

Staphylococcus aureus VET0446R
VET0446R
Firmicutes
KK235765.1
3
KAF54414.1
16523


1286
GCA_000644935.1
1422667
1280

Staphylococcus aureus VET0451R
VET0451R
Firmicutes
KK235791.1
3
KAF60186.1
16526


1287
GCA_000644955.1
1422668
1280

Staphylococcus aureus VET0452R
VET0452R
Firmicutes
KK235845.1
3
KAF62547.1
16529


1288
GCA_000644975.1
1422669
1280

Staphylococcus aureus VET0454R
VET0454R
Firmicutes
KK235896.1
3
KAF64112.1
16532


1289
GCA_000644995.1
1422670
1280

Staphylococcus aureus VET0455R
VET0455R
Firmicutes
KK235952.1
3
KAF67904.1
16535


1290
GCA_000645015.1
1422671
1280

Staphylococcus aureus VET0456R
VET0456R
Firmicutes
KK235994.1
3
KAF70713.1
16538


1291
GCA_000645035.1
1422672
1280

Staphylococcus aureus VET0459R
VET0459R
Firmicutes
KK236040.1
3
KAF71815.1
16541


1292
GCA_000645055.1
1422673
1280

Staphylococcus aureus VET0460R
VET0460R
Firmicutes
KK236088.1
3
KAF75590.1
16544


1293
GCA_000645075.1
1422674
1280

Staphylococcus aureus VET0462R
VET0462R
Firmicutes
KK236132.1
3
KAF76891.1
16547


1294
GCA_000645095.1
1422675
1280

Staphylococcus aureus VET0463R
VET0463R
Firmicutes
KK236171.1
3
KAF80459.1
16550


1295
GCA_000645115.1
1422676
1280

Staphylococcus aureus VET0464R
VET0464R
Firmicutes
KK236208.1
3
KAF84648.1
16553


1296
GCA_000645155.1
1422679
1280

Staphylococcus aureus VET0468R
VET0468R
Firmicutes
KK236266.1
3
KAF88486.1
16556


1297
GCA_000645175.1
1422681
1280

Staphylococcus aureus VET0470R
VET0470R
Firmicutes
KK236311.1
3
KAF92874.1
16559


1298
GCA_000645195.1
1422685
1280

Staphylococcus aureus VET0478R
VET0478R
Firmicutes
KK236370.1
3
KAF91778.1
16562


1299
GCA_000645215.1
1422686
1280

Staphylococcus aureus VET0481R
VET0481R
Firmicutes
KK236396.1
3
KAG01061.1
16565


1300
GCA_000645235.1
1422687
1280

Staphylococcus aureus VET0485R
VET0485R
Firmicutes
KK236455.1
3
KAF98702.1
16568


1301
GCA_000645255.1
1422688
1280

Staphylococcus aureus VET0486R
VET0486R
Firmicutes
KK236493.1
3
KAF97456.1
16571


1302
GCA_000645275.1
1422689
1280

Staphylococcus aureus VET0488R
VET0488R
Firmicutes
KK236523.1
3
KAG04155.1
16574


1303
GCA_000645295.1
1422752
1280

Staphylococcus aureus VET0519S
VET0519S
Firmicutes
KK236567.1
3
KAG04820.1
16577


1304
GCA_000645315.1
1422691
1280

Staphylococcus aureus VET0596R
VET0596R
Firmicutes
KK236596.1
3
KAG08556.1
16580


1305
GCA_000645355.1
1422755
1280

Staphylococcus aureus VET0645S
VET0645S
Firmicutes
KK236705.1
3
KAG10681.1
16583


1306
GCA_000645375.1
1422756
1280

Staphylococcus aureus VET0657S
VET0657S
Firmicutes
KK236725.1
3
KAG16001.1
16586


1307
GCA_000645435.1
1422760
1280

Staphylococcus aureus VET0779S
VET0779S
Firmicutes
KK236834.1
3
KAG21726.1
16589


1308
GCA_000645475.1
1422763
1280

Staphylococcus aureus VET0809S
VET0809S
Firmicutes
KK236898.1
3
KAG29030.1
16592


1309
GCA_000645495.1
1422764
1280

Staphylococcus aureus VET0810S
VET0810S
Firmicutes
KK236944.1
3
KAG32270.1
16595


1310
GCA_000645535.1
1422766
1280

Staphylococcus aureus VET0919S
VET0919S
Firmicutes
KK237057.1
3
KAG34711.1
16598


1311
GCA_000645555.1
1422767
1280

Staphylococcus aureus VET0920S
VET0920S
Firmicutes
KK237082.1
3
KAG37987.1
16601


1312
GCA_000645655.1
1422772
1280

Staphylococcus aureus VET1035S
VET1035S
Firmicutes
KK237308.1
3
KAG51662.1
16604


1313
GCA_000645675.1
1422773
1280

Staphylococcus aureus VET1048S
VET1048S
Firmicutes
KK237351.1
3
KAG55493.1
16607


1314
GCA_000645695.1
1422774
1280

Staphylococcus aureus VET1052S
VET1052S
Firmicutes
KK237399.1
3
KAG59146.1
16610


1315
GCA_000645715.1
1422775
1280

Staphylococcus aureus VET1054S
VET1054S
Firmicutes
KK237441.1
3
KAG59708.1
16613


1316
GCA_000645735.1
1422777
1280

Staphylococcus aureus VET1068S
VET1068S
Firmicutes
KK237467.1
3
KAG65359.1
16616


1317
GCA_000645755.1
1422778
1280

Staphylococcus aureus VET1088S
VET1088S
Firmicutes
KK237500.1
3
KAG67528.1
16619


1318
GCA_000645775.1
1422780
1280

Staphylococcus aureus VET1104S
VET1104S
Firmicutes
KK237537.1
3
KAG68215.1
16622


1319
GCA_000645795.1
1422781
1280

Staphylococcus aureus VET1168S
VET1168S
Firmicutes
KK237569.1
3
KAG69693.1
16625


1320
GCA_000645815.1
1422782
1280

Staphylococcus aureus VET1181S
VET1181S
Firmicutes
KK237594.1
3
KAG74736.1
16628


1321
GCA_000645835.1
1422783
1280

Staphylococcus aureus VET1245S
VET1245S
Firmicutes
KK237651.1
3
KAG76839.1
16631


1322
GCA_000645855.1
1422786
1280

Staphylococcus aureus VET1411S
VET1411S
Firmicutes
KK237699.1
3
KAG76108.1
16634


1323
GCA_000645875.1
1422789
1280

Staphylococcus aureus VET1434S
VET1434S
Firmicutes
KK237730.1
3
KAG81176.1
16637


1324
GCA_000645895.1
1422790
1280

Staphylococcus aureus VET1468S
VET1468S
Firmicutes
KK237767.1
3
KAG82430.1
16640


1325
GCA_000645915.1
1422791
1280

Staphylococcus aureus VET1495S
VET1495S
Firmicutes
KK237796.1
3
KAG84392.1
16643


1326
GCA_000645935.1
1422792
1280

Staphylococcus aureus VET1499S
VET1499S
Firmicutes
KK237828.1
3
KAG88853.1
16646


1327
GCA_000645975.1
1422795
1280

Staphylococcus aureus VET1519S
VET1519S
Firmicutes
KK237920.1
3
KAG92816.1
16649


1328
GCA_000645995.1
1422796
1280

Staphylococcus aureus VET1526S
VET1526S
Firmicutes
KK237967.1
3
KAG95315.1
16652


1329
GCA_000646055.1
1422799
1280

Staphylococcus aureus VET1727S
VET1727S
Firmicutes
KK238084.1
3
KAH01283.1
16655


1330
GCA_000646075.1
1422800
1280

Staphylococcus aureus VET1738S
VET1738S
Firmicutes
KK238117.1
3
KAH06869.1
16658


1331
GCA_000646115.1
1422802
1280

Staphylococcus aureus VET1816S
VET1816S
Firmicutes
KK238213.1
3
KAH07514.1
16661


1332
GCA_000646135.1
1422803
1280

Staphylococcus aureus VET1817S
VET1817S
Firmicutes
KK238232.1
3
KAH16053.1
16664


1333
GCA_000646155.1
1422804
1280

Staphylococcus aureus VET1822S
VET1822S
Firmicutes
KK238270.1
3
KAH15238.1
16667


1334
GCA_000646195.1
1422693
1280

Staphylococcus aureus VET1832R
VET1832R
Firmicutes
KK238379.1
3
KAH19617.1
16670


1335
GCA_000646215.1
1422695
1280

Staphylococcus aureus VET1834R
VET1834R
Firmicutes
KK238417.1
3
KAH24557.1
16673


1336
GCA_000646235.1
1422696
1280

Staphylococcus aureus VET1835R
VET1835R
Firmicutes
KK238465.1
3
KAH28158.1
16676


1337
GCA_000646255.1
1422697
1280

Staphylococcus aureus VET1838R
VET1838R
Firmicutes
KK238513.1
3
KAH29215.1
16679


1338
GCA_000646275.1
1422698
1280

Staphylococcus aureus VET1839R
VET1839R
Firmicutes
KK238556.1
3
KAH33224.1
16682


1339
GCA_000646295.1
1422700
1280

Staphylococcus aureus VET1843R
VET1843R
Firmicutes
KK238600.1
3
KAH35673.1
16685


1340
GCA_000646315.1
1422701
1280

Staphylococcus aureus VET1844R
VET1844R
Firmicutes
KK238654.1
3
KAH37682.1
16688


1341
GCA_000646335.1
1422702
1280

Staphylococcus aureus VET1845R
VET1845R
Firmicutes
KK238712.1
3
KAH40130.1
16691


1342
GCA_000646355.1
1422703
1280

Staphylococcus aureus VET1846R
VET1846R
Firmicutes
KK238762.1
3
KAH41312.1
16694


1343
GCA_000646375.1
1422704
1280

Staphylococcus aureus VET1848R
VET1848R
Firmicutes
KK238790.1
3
KAH45888.1
16697


1344
GCA_000646395.1
1422705
1280

Staphylococcus aureus VET1849R
VET1849R
Firmicutes
KK238827.1
3
KAH47354.1
16700


1345
GCA_000646415.1
1422706
1280

Staphylococcus aureus VET1850R
VET1850R
Firmicutes
KK238862.1
3
KAH50036.1
16703


1346
GCA_000646435.1
1422707
1280

Staphylococcus aureus VET1851R
VET1851R
Firmicutes
KK238898.1
3
KAH53958.1
16706


1347
GCA_000646455.1
1422708
1280

Staphylococcus aureus VET1852R
VET1852R
Firmicutes
KK238957.1
3
KAH55298.1
16709


1348
GCA_000646475.1
1422709
1280

Staphylococcus aureus VET1853R
VET1853R
Firmicutes
KK239008.1
3
KAH59147.1
16712


1349
GCA_000646495.1
1422710
1280

Staphylococcus aureus VET1854R
VET1854R
Firmicutes
KK239060.1
3
KAH62179.1
16715


1350
GCA_000646515.1
1422711
1280

Staphylococcus aureus VET1855R
VET1855R
Firmicutes
KK239111.1
3
KAH64795.1
16718


1351
GCA_000646535.1
1422712
1280

Staphylococcus aureus VET1856R
VET1856R
Firmicutes
KK239165.1
3
KAH67715.1
16721


1352
GCA_000646555.1
1422714
1280

Staphylococcus aureus VET1859R
VET1859R
Firmicutes
KK239222.1
3
KAH70236.1
16724


1353
GCA_000646575.1
1422715
1280

Staphylococcus aureus VET1860R
VET1860R
Firmicutes
KK239279.1
3
KAH70953.1
16727


1354
GCA_000646595.1
1422716
1280

Staphylococcus aureus VET1861R
VET1861R
Firmicutes
KK239317.1
3
KAH74942.1
16730


1355
GCA_000646615.1
1422717
1280

Staphylococcus aureus VET1865R
VET1865R
Firmicutes
KK239359.1
3
KAH77221.1
16733


1356
GCA_000646635.1
1422718
1280

Staphylococcus aureus VET1866R
VET1866R
Firmicutes
KK239396.1
3
KAH77148.1
16736


1357
GCA_000646655.1
1422719
1280

Staphylococcus aureus VET1867R
VET1867R
Firmicutes
KK239416.1
3
KAH82036.1
16739


1358
GCA_000646675.1
1422720
1280

Staphylococcus aureus VET1868R
VET1868R
Firmicutes
KK239446.1
3
KAH85417.1
16742


1359
GCA_000646695.1
1422722
1280

Staphylococcus aureus VET1871R
VET1871R
Firmicutes
KK239489.1
3
KAH87605.1
16745


1360
GCA_000646715.1
1422723
1280

Staphylococcus aureus VET1872R
VET1872R
Firmicutes
KK239544.1
3
KAH91094.1
16748


1361
GCA_000646735.1
1422724
1280

Staphylococcus aureus VET1873R
VET1873R
Firmicutes
KK239596.1
3
KAH91685.1
16751


1362
GCA_000646755.1
1422725
1280

Staphylococcus aureus VET1875R
VET1875R
Firmicutes
KK239632.1
3
KAH96192.1
16754


1363
GCA_000646775.1
1422727
1280

Staphylococcus aureus VET1877R
VET1877R
Firmicutes
KK239680.1
3
KAH96017.1
16757


1364
GCA_000646795.1
1422728
1280

Staphylococcus aureus VET1880R
VET1880R
Firmicutes
KK239707.1
3
KAI00778.1
16760


1365
GCA_000646815.1
1422729
1280

Staphylococcus aureus VET1884R
VET1884R
Firmicutes
KK239758.1
3
KAI04126.1
16763


1366
GCA_000646835.1
1422730
1280

Staphylococcus aureus VET1886R
VET1886R
Firmicutes
KK239796.1
3
KAI02997.1
16766


1367
GCA_000646855.1
1422731
1280

Staphylococcus aureus VET1890R
VET1890R
Firmicutes
KK239825.1
3
KAI08748.1
16769


1368
GCA_000646875.1
1422732
1280

Staphylococcus aureus VET1892R
VET1892R
Firmicutes
KK239862.1
3
KAI10610.1
16772


1369
GCA_000646895.1
1422733
1280

Staphylococcus aureus VET1893R
VET1893R
Firmicutes
KK239901.1
3
KAI13050.1
16775


1370
GCA_000646915.1
1422734
1280

Staphylococcus aureus VET1895R
VET1895R
Firmicutes
KK239942.1
3
KAI15462.1
16778


1371
GCA_000646935.1
1422736
1280

Staphylococcus aureus VET1897R
VET1897R
Firmicutes
KK239986.1
3
KAI16289.1
16781


1372
GCA_000646955.1
1422738
1280

Staphylococcus aureus VET1899R
VET1899R
Firmicutes
KK240031.1
3
KAI19041.1
16784


1373
GCA_000646975.1
1422739
1280

Staphylococcus aureus VET1901R
VET1901R
Firmicutes
KK240053.1
3
KAI22534.1
16787


1374
GCA_000646995.1
1422740
1280

Staphylococcus aureus VET1904R
VET1904R
Firmicutes
KK240086.1
3
KAI26859.1
16790


1375
GCA_000647015.1
1422741
1280

Staphylococcus aureus VET1905R
VET1905R
Firmicutes
KK240125.1
3
KAI29886.1
16793


1376
GCA_000647035.1
1422742
1280

Staphylococcus aureus VET1906R
VET1906R
Firmicutes
KK240163.1
3
KAI31280.1
16796


1377
GCA_000647055.1
1422744
1280

Staphylococcus aureus VET1908R
VET1908R
Firmicutes
KK240210.1
3
KAI34386.1
16799


1378
GCA_000647075.1
1422745
1280

Staphylococcus aureus VET1909R
VET1909R
Firmicutes
KK240248.1
3
KAI37686.1
16802


1379
GCA_000647095.1
1422747
1280

Staphylococcus aureus VET1911R
VET1911R
Firmicutes
KK240284.1
3
KAI38933.1
16805


1380
GCA_000647115.1
1422748
1280

Staphylococcus aureus VET1912R
VET1912R
Firmicutes
KK240323.1
3
KAI42594.1
16808


1381
GCA_000647135.1
1422749
1280

Staphylococcus aureus VET1913R
VET1913R
Firmicutes
KK240355.1
3
KAI44808.1
16811


1382
GCA_000647155.1
1422750
1280

Staphylococcus aureus VET1914R
VET1914R
Firmicutes
KK240383.1
3
KAI46182.1
16814


1383
GCA_000647175.1
1422805
1280

Staphylococcus aureus VET1917S
VET1917S
Firmicutes
KK240411.1
3
KAI50314.1
16817


1384
GCA_000647195.1
1422807
1280

Staphylococcus aureus VET1923S
VET1923S
Firmicutes
KK240446.1
3
KAI52601.1
16820


1385
GCA_000647215.1
1422809
1280

Staphylococcus aureus VET1949S
VET1949S
Firmicutes
KK240494.1
3
KAI51895.1
16823


1386
GCA_000647235.1
1422810
1280

Staphylococcus aureus VET1950S
VET1950S
Firmicutes
KK240520.1
3
KAI58512.1
16826


1387
GCA_000647255.1
1422812
1280

Staphylococcus aureus VET1956S
VET1956S
Firmicutes
KK240554.1
3
KAI59070.1
16829


1388
GCA_000647275.1
1422813
1280

Staphylococcus aureus VET1959S
VET1959S
Firmicutes
KK240580.1
3
KAI62095.1
16832


1389
GCA_000647295.1
1413576
1280

Staphylococcus aureus ZTA09/
ZTA09/
Firmicutes
KK240619.1
3
KAI65038.1
16835






03576-8HST
03576-8HST


1390
GCA_000647315.1
1413582
1280

Staphylococcus aureus ZTA09/
ZTA09/
Firmicutes
KK240655.1
3
KAI67117.1
16838






03734-9HSA
03734-9HSA


1391
GCA_000647335.1
1413584
1280

Staphylococcus aureus ZTA09/
ZTA09/
Firmicutes
KK240683.1
3
KAI71118.1
16841






03745-9HSA
03745-9HSA


1392
GCA_000647355.1
1413570
1280

Staphylococcus aureus ZTA10/
ZTA10/
Firmicutes
KK240724.1
3
KAI72298.1
16844






00045-9HST
00045-9HST


1393
GCA_000647375.1
1413574
1280

Staphylococcus aureus ZTA10/
ZTA10/
Firmicutes
KK240757.1
3
KAI76028.1
16847






00047-8HST
00047-8HST


1394
GCA_000647395.1
1413572
1280

Staphylococcus aureus ZTA10/
ZTA10/
Firmicutes
KK240801.1
3
KAI77491.1
16850






00058-8HST
00058-8HST


1395
GCA_000647415.1
1413581
1280

Staphylococcus aureus ZTA10/
ZTA10/
Firmicutes
KK240836.1
3
KAI79407.1
16853






02412-8HSA
02412-8HSA


1396
GCA_000647435.1
1413585
1280

Staphylococcus aureus ZTA11/
ZTA11/
Firmicutes
KK240874.1
3
KAI83421.1
16856






00189-8HSA
00189-8HSA


1397
GCA_000645135.1
1422677
1280

Staphylococcus aureus VET0465R
VET0465R
Firmicutes
KK328149.1
3
KAF82852.1
16859


1398
GCA_000725445.1
1502784
1502784

Pseudomonas sp. AAC
AAC
Proteobacteria
KL647094.1
3
KES25284.1
16862


1399
GCA_000969845.1
1078087
1078087

Parabacteroides sp. HGS0025
HGS0025
Bacteroidetes
KQ033902.1
3
KKB51170.1
16865


1400
GCA_000969845.1
1078087
1078087

Parabacteroides sp. HGS0025
HGS0025
Bacteroidetes
KQ033903.1
3
KKB46310.1
16868


1401
GCA_001032775.1
573
573

Klebsiella pneumoniae

CHS201
Proteobacteria
KQ088951.1
2
KME80490.1
16871


1402
GCA_001034405.1
615
615

Serratia marcescens

UCI88
Proteobacteria
KQ089789.1
2
KMJ04347.1
16873


1403
GCA_001457055.1
1414648
1414648

Bacillus sp. SGD-V-76
SGD-V-76
Firmicutes
KQ758727.1
2
KSU86125.1
16875


1404
GCA_001519055.1
1739114
1739114

Novosphingobium sp. Fuku2-ISO-50
Fuku2-ISO-50
Proteobacteria
KQ954285.1
4
KUR80453.1
16877


1405
GCA_001578705.1
1303
1303

Streptococcus oralis

DD05
Firmicutes
KQ969038.1
2
KXT60079.1
16881


1406
GCA_000956765.1
61645
61645

Enterobacter asburiae

33838
Proteobacteria
LAAP01000054.1
3
KJP12011.1
16883


1407
GCA_000987705.1
1639
1639

Listeria monocytogenes

DPC6895
Firmicutes
LABG01000005.1
2
KK042008.1
16886


1408
GCA_001044655.1
1396
1396

Bacillus cereus

INRA A3
Firmicutes
LABH01000008.1
2
KMQ31911.1
16888


1409
GCA_001044655.1
1396
1396

Bacillus cereus

INRA A3
Firmicutes
LABH01000014.1
2
KMQ31454.1
16890


1410
GCA_001044655.1
1396
1396

Bacillus cereus

INRA A3
Firmicutes
LABH01000016.1
2
KMQ31339.1
16892


1411
GCA_001044855.1
1396
1396

Bacillus cereus

RIVM BC 934
Firmicutes
LABP01000126.1
2
KMQ07576.1
16894


1412
GCA_000963235.1
29290
29290

Candidatus Magnetobacterium bavaricum


Nitrospirae
LACI01000945.1
2
KJU85605.1
16896


1413
GCA_000961765.1
1629719
1629719

Clostridiaceae bacterium BRH_c20a

Firmicutes
LADT01000090.1
3
KJS18752.1
16898


1414
GCA_001010195.1
562
562

Escherichia coli

M17-1
Proteobacteria
LBDD01000010.1
2
KLD44466.1
16901


1415
GCA_001007525.1
670
670

Vibrio parahaemolyticus

MAVP-E
Proteobacteria
LBHP01000003.1
3
KKZ08483.1
16903


1416
GCA_001005805.1
1590
1590

Lactobacillus plantarum

PS128
Firmicutes
LBHS01000003.1
2
KKX43503.1
16906


1417
GCA_000981945.1
1409947
1352

Enterococcus faecium MRSN 3418
MRSN 3418
Firmicutes
LBIM01000096.1
3
KKJ66889.1
16908


1418
GCA_000996715.1
1618997
1618997

Candidatus Uhrbacteria bacterium



Candidatus

LCAU01000021.1
3
KKR96940.1
16911






GW2011_GWF2_41_16

Uhrbacteria


1419
GCA_001007555.1
615
615

Serratia marcescens

90-166
Proteobacteria
LCWI01000023.1
2
KKZ15776.1
16914


1420
GCA_001008595.1
1396
1396

Bacillus cereus

B4080
Firmicutes
LCYK01000007.1
2
KLA35044.1
16916


1421
GCA_001008665.1
1396
1396

Bacillus cereus

B4158
Firmicutes
LCYP01000035.1
2
KLA36292.1
16918


1422
GCA_001011775.1
550
550

Enterobacter cloacae

GN02032
Proteobacteria
LDCC01000090.1
2
KLF79538.1
16920


1423
GCA_001011075.1
1656220
1656220

Serratia sp. TEL
TEL
Proteobacteria
LDEG01000009.1
2
KLE38479.1
16922


1424
GCA_001043655.1
1396
1396

Bacillus cereus

LK9
Firmicutes
LDUP01000008.1
2
KMN72583.1
16924


1425
GCA_001043705.1
1628212
1628212

Chromobacterium sp. LK11
LK11
Proteobacteria
LDUR01000028.1
4
KMN78963.1
16926


1426
GCA_001276465.1
61645
61645

Enterobacter asburiae

C7
Proteobacteria
LDVX01000157.1
3
KOQ86134.1
16930


1427
GCA_001276515.1
1661745
1661745

Haemophilus sp. C1
C1
Proteobacteria
LDVZ01000018.1
3
KOQ96629.1
16933


1428
GCA_001580555.1
1609637
1609637

Stenotrophomonas sp. DDT-1
DDT-1
Proteobacteria
LEKR01000030.1
3
KXU94746.1
16936


1429
GCA_001051865.1
211759
615

Serratia marcescens subsp. marcescens
AH0650_Sm1
Proteobacteria
LFJS01000014.1
2
KMU49983.1
16939


1430
GCA_001184405.1
1090471
1090471

Candidatus Burkholderia humilis

UZHbot5
Proteobacteria
LFMX01000038.1
3
KMZ12177.1
16941


1431
GCA_001183595.1
648
648

Aeromonas caviae

A23
Proteobacteria
LFX001000113.1
4
KMY27377.1
16944


1432
GCA_001270215.1
670
670

Vibrio parahaemolyticus

S487-4
Proteobacteria
LFZE01000076.1
3
KOF39297.1
16948


1433
GCA_001298135.1
405946
405946

Oceanobacillus caeni

HM6
Firmicutes
LGTK01000035.1
3
KPH74233.1
16951


1434
GCA_001297125.1
1690247
1690247

Pseudomonas sp. RIT-PI-q
RIT-PI-q
Proteobacteria
LHPC01000026.1
3
KPG99048.1
16954


1435
GCA_001483145.1
172045
172045

Elizabethkingia miricola

EM_CHUV
Bacteroidetes
LIQC01000017.1
4
KUG12361.1
16957


1436
GCA_001317205.1
211759
615

Serratia marcescens subsp. marcescens
945154301
Proteobacteria
LJEV01000097.1
4
KPS74519.1
16961


1437
GCA_001317425.1
211759
615

Serratia marcescens subsp. marcescens
945174350
Proteobacteria
LJEX01000059.1
4
KPS95936.1
16965


1438
GCA_001295775.1
1523428
1523428
beta proteobacterium AAP99
AAP99
Proteobacteria
LJIA01000001.1
2
KPF70566.1
16969


1439
GCA_001411765.1
1255
1255

Pediococcus pentosaceus

wikim20
Firmicutes
LJIU01000002.1
2
KQB82200.1
16971


1440
GCA_001420605.1
1712029
1712029

Bacillus sp. FJAT-25509
FJAT-25509
Firmicutes
LJIZ01000033.1
2
KQL33557.1
16973


1441
GCA_001401315.1
129140
251699

Pseudomonas syringae pv. tagetis
ICMP4091
Proteobacteria
LJRM01000029.1
4
KPY89108.1
16975


1442
GCA_001243675.1
1507977
1507977

Vibrio sp. J2-4
J2-4
Proteobacteria
LK933622.1
3
CDT62308.1
16979


1443
GCA_001262155.1
1507978
1507978

Vibrio sp. J2-26
J2-26
Proteobacteria
LK934170.1
3
CDT49142.1
16982


1444
GCA_001467105.1
1208100
317

Pseudomonas syringae ICMP 19498
ICMP 19498
Proteobacteria
LKCH01000127.1
2
KTC51736.1
16985


1445
GCA_001466905.1
716914
716914

Pseudomonas sp. ICMP 3272
ICMP 3272
Proteobacteria
LKEK01000086.1
2
KTB70323.1
16987


1446
GCA_001466845.1
1198306
317

Pseudomonas syringae ICMP 11293
ICMP 11293
Proteobacteria
LKEP01000045.1
2
KTB90078.1
16989


1447
GCA_001467365.1
1198307
317

Pseudomonas syringae ICMP 11292
ICMP 11292
Proteobacteria
LKGU01000007.1
2
KTC03050.1
16991


1448
GCA_001429565.1
180957
554

Pectobacterium carotovorum subsp.
PcbHPI01
Proteobacteria
LKKQ01000034.1
2
KRF62306.1
16993







brasiliense



1449
GCA_001449735.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07184
Proteobacteria
LLM001000014.1
2
KSF14311.1
16995


1450
GCA_001450755.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07239
Proteobacteria
LLNK01000023.1
5
KSG00435.1
16997


1451
GCA_001452525.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07690
Proteobacteria
LLSK01000113.1
5
KSO26594.1
17002


1452
GCA_001453015.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07263
Proteobacteria
LLTV01000002.1
5
KSQ24404.1
17007


1453
GCA_001453015.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07263
Proteobacteria
LLTV01000014.1
3
KSQ18859.1
17012


1454
GCA_001425705.1
1736430
1736430

Pelomonas sp. Root1217
Root1217
Proteobacteria
LMDC01000012.1
2
KQV52821.1
17015


1455
GCA_001425835.1
1736436
1736436

Afipia sp. Root123D2
Rootl23D2
Proteobacteria
LMDP01000003.1
2
KQW19009.1
17017


1456
GCA_001421745.1
1735694
1735694

Sphingomonas sp. Leaf230
Leaf230
Proteobacteria
LMKW01000009.1
2
KQN02369.1
17019


1457
GCA_001424085.1
1736359
1736359

Rhizobium sp. Leaf386
Leaf386
Proteobacteria
LMQF01000024.1
3
KQS95552.1
17021


1458
GCA_001428335.1
1736401
1736401

Arthrobacter sp. Soil762
Soil762
Actinobacteria
LMSG01000001.1
2
KRE80987.1
17024


1459
GCA_000953375.1
40480
2095

Mycoplasma capricolum subsp. capripneumoniae
F38
Tenericutes
LN515398.1
2
CEA11436.1
17026


1460
GCA_000953235.1
40480
2095

Mycoplasma capricolum subsp. capripneumoniae
ILRI181
Tenericutes
LN515399.1
2
CEA10432.1
17028


1461
GCA_001460855.1
754345
715

Actinobacillus pleuropneumoniae serovar 8

Proteobacteria
LN908249.1
3
CUU52508.1
17030


1462
GCA_001463205.1
562
562

Escherichia coli

50639799
Proteobacteria
LNHQ01000124.1
2
KSX76371.1
17033


1463
GCA_001547355.1
1352
1352

Enterococcus faecium

U-1313438
Firmicutes
LNLE01000074.1
3
KWY00933.1
17035


1464
GCA_001545595.1
1352
1352

Enterococcus faecium

VRE-1300937
Firmicutes
LNLK01000231.1
3
KWY16707.1
17038


1465
GCA_001545605.1
1352
1352

Enterococcus faecium

VRE-1400408
Firmicutes
LNLP01000005.1
3
KWY36996.1
17041


1466
GCA_001547195.1
1352
1352

Enterococcus faecium

VRE-1401878
Firmicutes
LNLW01000317.1
2
KWY51064.1
17044


1467
GCA_001545785.1
1352
1352

Enterococcus faecium

VRE-1402215
Firmicutes
LNLZ01000131.1
2
KWY60248.1
17046


1468
GCA_001545675.1
1352
1352

Enterococcus faecium

VRE-1402258
Firmicutes
LNMC01000072.1
2
KWY71636.1
17048


1469
GCA_001547115.1
1352
1352

Enterococcus faecium

VRE-1402435
Firmicutes
LNME01000036.1
3
KWY79778.1
17050


1470
GCA_001547015.1
1352
1352

Enterococcus faecium

VRE-1402673
Firmicutes
LNMI01000065.1
2
KWY89823.1
17053


1471
GCA_001547025.1
1352
1352

Enterococcus faecium

VRE-1402991
Firmicutes
LNMJ01000050.1
3
KWY92722.1
17055


1472
GCA_001547045.1
1352
1352

Enterococcus faecium

VRE-1403299
Firmicutes
LNMK01000076.1
3
KWY92992.1
17058


1473
GCA_001547425.1
1352
1352

Enterococcus faecium

VRE-1403540
Firmicutes
LNMM01000174.1
3
KWY96007.1
17061


1474
GCA_001547445.1
1352
1352

Enterococcus faecium

VRE-1404192
Firmicutes
LNM001000097.1
3
KWZ06304.1
17064


1475
GCA_001455955.1
1280
1280

Staphylococcus aureus

SA7112
Firmicutes
LNTF01000010.1
3
KST54505.1
17067


1476
GCA_001467955.1
45072
45072

Legionella quateirensis

ATCC 49507
Proteobacteria
LNYR01000034.1
2
KTD46365.1
17070


1477
GCA_001515985.1
1734408
1734408

Sphingomonadales bacterium BRH_c3

Proteobacteria
LOET01000087.1
2
KUO54659.1
17072


1478
GCA_001583705.1
1396
1396

Bacillus cereus

FSL W8-0003
Firmicutes
LOMQ01000001.1
2
KXY14129.1
17074


1479
GCA_001575545.1
562
562

Escherichia coli

G213
Proteobacteria
LOOH01000120.1
2
KXQ35635.1
17076


1480
GCA_001562375.1
562
562

Escherichia coli

108191
Proteobacteria
LORE01000010.1
2
KXG66578.1
17078


1481
GCA_001527325.1
101571
101571

Burkholderia ubonensis

MSMB2054
Proteobacteria
LOZC01000019.1
4
KVM18168.1
17080


1482
GCA_001527345.1
101571
101571

Burkholderia ubonensis

MSMB2055
Proteobacteria
LOZD01000004.1
4
KVM22194.1
17084


1483
GCA_001527425.1
101571
101571

Burkholderia ubonensis

MSMB2061
Proteobacteria
LOZH01000020.1
4
KVM54441.1
17088


1484
GCA_001527955.1
101571
101571

Burkholderia ubonensis

MSMB1599WGS
Proteobacteria
LPAJ01000129.1
2
KVO16515.1
17092


1485
GCA_001529565.1
101571
101571

Burkholderia ubonensis

MSMB2022WGS
Proteobacteria
LPCI01000083.1
2
KVR44248.1
17094


1486
GCA_001528545.1
60552
60552

Burkholderia vietnamiensis

AU25340
Proteobacteria
LPCP01000011.1
3
KVR99614.1
17096


1487
GCA_001529645.1
60552
60552

Burkholderia vietnamiensis

HI3392
Proteobacteria
LPCS01000140.1
2
KVS07629.1
17099


1488
GCA_001529225.1
101571
101571

Burkholderia ubonensis

MSMB1221WGS
Proteobacteria
LPEK01000051.1
3
KVU94135.1
17101


1489
GCA_001531435.1
101571
101571

Burkholderia ubonensis

MSMB1508WGS
Proteobacteria
LPFT01000048.1
2
KVX54694.1
17104


1490
GCA_001531105.1
101571
101571

Burkholderia ubonensis

MSMB2092WGS
Proteobacteria
LPHE01000088.1
3
KWA77747.1
17106


1491
GCA_001531535.1
101571
101571

Burkholderia ubonensis

MSMB2093WGS
Proteobacteria
LPHF01000028.1
3
KWB32211.1
17109


1492
GCA_001532205.1
101571
101571

Burkholderia ubonensis

MSMB2110WGS
Proteobacteria
LPHP01000047.1
2
KWB80882.1
17112


1493
GCA_001472685.1
301102
158836

Enterobacter hormaechei subsp. oharae
SMART_723
Proteobacteria
LPPG01000028.1
3
KTI37619.1
17114


1494
GCA_001472055.1
301102
158836

Enterobacter hormaechei subsp. oharae
SMART_286
Proteobacteria
LPQM01000012.1
2
KTJ90670.1
17117


1495
GCA_001572345.1
562
562

Escherichia coli

CFSAN025116
Proteobacteria
LPYQ01000233.1
2
KXM51394.1
17119


1496
GCA_001572325.1
562
562

Escherichia coli

CFSAN025117
Proteobacteria
LPYR01000272.1
2
KXM54363.1
17121


1497
GCA_001572445.1
562
562

Escherichia coli

CFSAN025127
Proteobacteria
LPYZ01000244.1
2
KXM99995.1
17123


1498
GCA_001563205.1
1352
1352

Enterococcus faecium

805447/07
Firmicutes
LQRS01000049.1
3
KXH57776.1
17125


1499
GCA_001519675.1
562
562

Escherichia coli

GN02137
Proteobacteria
LQSE01000001.1
2
KUS35848.1
17128


1500
GCA_001521215.1
562
562

Escherichia coli

GN02289
Proteobacteria
LQSV01000130.1
2
KUT10059.1
17130


1501
GCA_001519835.1
562
562

Escherichia coli

GN02290
Proteobacteria
LQSW01000102.1
2
KUT23043.1
17132


1502
GCA_001521195.1
562
562

Escherichia coli

GN02314
Proteobacteria
LQSY01000192.1
2
KUT23265.1
17134


1503
GCA_001519855.1
562
562

Escherichia coli

GN02317
Proteobacteria
LQSZ01000228.1
2
KUT30718.1
17136


1504
GCA_001520275.1
562
562

Escherichia coli

GN02359
Proteobacteria
LQTG01000182.1
2
KUT68247.1
17138


1505
GCA_001520235.1
562
562

Escherichia coli

GN02514
Proteobacteria
LQUF01000113.1
2
KUU91589.1
17140


1506
GCA_001521115.1
562
562

Escherichia coli

GN03661
Proteobacteria
LQWC01000068.1
2
KUX27115.1
17142


1507
GCA_001518225.1
550
550

Enterobacter cloacae

GN04225
Proteobacteria
LRC001000001.1
2
KUQ77231.1
17144


1508
GCA_001518605.1
550
550

Enterobacter cloacae

GN04369
Proteobacteria
LRCT01000127.1
2
KUQ90476.1
17146


1509
GCA_001529365.1
56812
56812

Shewanella frigidimarina

Ag06-30
Proteobacteria
LRDC01000022.1
2
KVX01473.1
17148


1510
GCA_001524915.1
550
550

Enterobacter cloacae

SMART_1260
Proteobacteria
LRJW01000001.1
2
KVK22109.1
17150


1511
GCA_001604835.1
644
644

Aeromonas hydrophila

AL09-79
Proteobacteria
LRRV01000001.1
3
KYQ15613.1
17152


1512
GCA_001604855.1
644
644

Aeromonas hydrophila

AL10-121
Proteobacteria
LRRW01000002.1
3
KYQ10111.1
17155


1513
GCA_001604895.1
644
644

Aeromonas hydrophila

ML09-121
Proteobacteria
LRRX01000002.1
3
KYQ13516.1
17158


1514
GCA_001604905.1
644
644

Aeromonas hydrophila

ML09-122
Proteobacteria
LRRY01000003.1
3
KYQ20474.1
17161


1515
GCA_001548475.1
398518
103855

Bordetella hinzii LMG 13501
LMG 13501
Proteobacteria
LRUJ01000004.1
2
KXA74272.1
17164


1516
GCA_000018545.1
394
380

Sinorhizobium fredii NGR234
NGR234
Proteobacteria
U00090.2
2
AAB91631.1
17166


1517
GCA_000014225.1
342610
288

Pseudoalteromonas atlantica T6c
T6c
Proteobacteria
CP000388.1
2
ABG41254.1
17168


1518
GCA_000022305.1
535289
721785

Acidovorax ebreus TPSY
TPSY
Proteobacteria
CP001392.1
2
ACM32747.1
17170


1519
GCA_000146185.1
515620
39485
[Eubacterium] eligens ATCC 27750
ATCC 27750
Firmicutes
CP001104.1
2
ACR72776.1
17172


1520
GCA_000020605.1
515619
39491
[Eubacterium rectale] ATCC 33656
ATCC 33656
Firmicutes
CP001107.1
2
ACR74433.1
17174


1521
GCA_000190515.1
930170
1428

Bacillus thuringiensis serovar
YBT-020
Firmicutes
CP002509.1
2
ADY24842.1
17176







finitimus YBT-020


1522
GCA_000262385.1
1126211
1390

Bacillus amyloliquefaciens Y2
Y2
Firmicutes
CP003332.1
2
AFJ62119.1
17178


1523
GCA_000510285.1
1435044
76759

Pseudomona monteiliis SB3078
SB3078
Proteobacteria
CP006978.1
2
AHC83882.1
17180


1524
GCA_000510325.1
1435058
76759

Pseudomonas monteilii SB3101
SB3101
Proteobacteria
CP006979.1
2
AHC89253.1
17182


1525
GCA_000568815.1
1150621
66821

Sulfurospirillum multivorans DSM 12446
DSM 12446
Proteobacteria
CP007201.1
2
AHJ13792.1
17184


1526
GCA_000746525.1
237609
237609

Pseudomonas alkylphenolia

KL28
Proteobacteria
CP009048.1
2
AIL63104.1
17186


1527
GCA_000784875.3
1484158
1484158

Pantoea sp. PSNIH1
PSNIH1
Proteobacteria
CP009883.1
2
AIX52585.1
17188


1528
GCA_000784965.1
1484157
1484157

Pantoea sp. PSNIH2
PSNIH2
Proteobacteria
CP009869.1
2
AIX76375.1
17190


1529
GCA_000827045.1
1570330
1570330

Bacillus sp. BH072
BH072
Firmicutes
CP009938.1
2
AJE80313.1
17192


1530
GCA_001022195.1
571
571

Klebsiella oxytoca

CAV1374
Proteobacteria
CP011635.1
2
AKL33255.1
17194


1531
GCA_000009705.1
103690
103690

Nostoc sp. PCC 7120

Cyanobacteria
BA000019.2
2
BAB73898.1
17196


1532
GCA_000009125.1
267608
305

Ralstonia solanacearum GMI1000
GMI1000
Proteobacteria
AL646052.1
2
CAD16319.1
17198


1533
GCA_000196815.1
330214
330214

Nitrospira defluvii


Nitrospirae
FP929003.1
2
CBK39910.1
17200


1534
GCA_000284395.1
1155777
492670

Bacillus methylotrophicus YAU B9601-Y2
YAU B9601-Y2
Firmicutes
HE774679.1
2
CCG49955.1
17202


1535
GCA_000438055.1
1262843
1262843

Clostridium sp. CAG:813

Firmicutes
FR902242.1
2
CDE97488.1
17204


1536
GCA_000736655.1
1397851
40576

Xenorhabdus bovienii str. feltiae France
feltiae France
Proteobacteria
HG426714.1
2
CDG89550.1
17206


1537
GCA_000736675.1
1397852
40576

Xenorhabdus bovienii str. feltiae Florida
feltiae Florida
Proteobacteria
HG426895.1
2
CDG92165.1
17208


1538
GCA_000756695.1
1034943
1034943

Legionella massiliensis


Proteobacteria
CCSB01000001.1
2
CDZ76665.1
17210


1539
GCA_000756815.1
1034943
1034943

Legionella massiliensis

LegA
Proteobacteria
CCVW01000001.1
2
CEE12403.1
17212


1540
GCA_001299055.1
1806504
1806504

Achromobacter sp. 2789STDY5608606
2789STDY5608606
Proteobacteria
CYTI01000029.1
2
CUJ73685.1
17214


1541
GCA_001538585.1
615
615

Serratia marcescens

2880STDY5682979
Proteobacteria
FCLD01000012.1
2
CVH06624.1
17216


1542
GCA_001539465.1
615
615

Serratia marcescens

2880STDY5683000
Proteobacteria
FCMT01000016.1
2
CVH45990.1
17218


1543
GCA_900064365.1
446
446

Legionella pneumophila

2532STDY5467650
Proteobacteria
FJMH01000005.1
2
CZP78225.1
17220


1544
GCA_900064365.1
446
446

Legionella pneumophila

2532STDY5467650
Proteobacteria
FJMH01000026.1
2
CZQ07176.1
17222


1545
GCA_000152545.1
350703
287

Pseudomonas aeruginosa 2192
2192
Proteobacteria
CH482384.1
2
EAZ59087.1
17224


1546
GCA_000173435.1
547043
28026

Bifidobacterium pseudocatenulatum DSM 20438 =
DSM 20438
Actinobacteria
ABXX02000002.1
2
EEG71310.1
17226






JCM 1200 = LMG 10505


1547
GCA_000156535.1
536231
166486

Roseburia intestinalis L1-82
L1-82
Firmicutes
GG692752.1
2
EEU99049.1
17228


1548
GCA_000162755.2
658187
168933

Legionella drancourtii LLAP12
LLAP12
Proteobacteria
JH413795.1
2
EHL32738.1
17230


1549
GCA_000247895.1
883121
54291

Raoultella ornithinolytica 10-5246
10-5246
Proteobacteria
JH603146.1
2
EHT09458.1
17232


1550
GCA_000286415.1
1156919
72556

Achromobacter piechaudii HLE
HLE
Proteobacteria
AUE01000146.1
2
EJO27433.1
17234


1551
GCA_000310225.1
1234382
164400

Thauera phenylacetica B4P
B4P
Proteobacteria
AMXF01000005.1
2
ENO98788.1
17236


1552
GCA_000411195.1
883101
80866

Delftia acidovorans CCUG 274B
CCUG 274B
Proteobacteria
KE150279.1
2
EPD37371.1
17238


1553
GCA_000466385.1
649747
1391

Aneurinibacillus aneurinilyticus ATCC 12856
ATCC 12856
Firmicutes
KE952776.1
2
ERI11820.1
17240


1554
GCA_000481145.1
1402528
287

Pseudomonas aeruginosa BWHPSA028
BWHPSA028
Proteobacteria
KI518959.1
2
ERV92401.1
17242


1555
GCA_000486525.1
930772
28901

Salmonella enterica subsp. enterica
ATCC 43845
Proteobacteria
AOXX01000056.1
2
ESF54845.1
17244






serovar Senftenberg str. ATCC 43845


1556
GCA_000492715.1
1329844
550

Enterobacter cloacae BWH 29
BWH 29
Proteobacteria
KI535567.1
2
ESM46331.1
17246


1557
GCA_000534175.1
1400151
550

Enterobacter cloacae UCI 36
UCI 36
Proteobacteria
KI973125.1
2
EUL65865.1
17248


1558
GCA_000534195.1
1400150
550

Enterobacter cloacae UCI 35
UCI 35
Proteobacteria
KI973132.1
2
EUL69873.1
17250


1559
GCA_000307775.2
1218352
316

Pseudomonas stutzeri KOS6
KOS6
Proteobacteria
KK020676.1
2
EWC39936.1
17252


1560
GCA_000588875.1
1461752
1461752

Sphingobium sp. Ant17
Ant17
Proteobacteria
JEMV01000093.1
2
EXS68251.1
17254


1561
GCA_000715205.1
1178540
1178540

Bacillus sp. DW5-4
DW5-4
Firmicutes
JOTP01000043.1
2
KEP24867.1
17256


1562
GCA_000735105.1
421072
421072

Epilithonimonas lactis

LMG 24401
Bacteroidetes
JPLY01000003.1
2
KFC21766.1
17258


1563
GCA_000740715.1
1423
1423

Bacillus subtilis

NKYL29
Firmicutes
JPYY01000008.1
2
KFI14244.1
17260


1564
GCA_000741685.1
547043
28026

Bifidobacterium pseudocatenulatum DSM
LMG 10505
Actinobacteria
JGZF01000003.1
2
KFI74923.1
17262






20438 = JCM 1200 = LMG 10505


1565
GCA_000798515.1
562
562

Escherichia coli

CVM N33561PS
Proteobacteria
JUDN01000122.1
2
KHJ15951.1
17264


1566
GCA_000935285.1
54291
54291

Raoultella ornithinolytica

BAL286
Proteobacteria
JXXF01000284.1
2
KIZ39818.1
17266


1567
GCA_000937505.2
546
546

Citrobacter freundii

MRSN 12115
Proteobacteria
JYFZ02000010.1
2
KJB99792.1
17268


1568
GCA_000957025.1
1619245
1619245

Enterobacter sp. 35666
35666
Proteobacteria
JZZC01000021.1
2
KJN38560.1
17270


1569
GCA_000964095.1
756892
756892

Acinetobacter indicus

KM7
Proteobacteria
JZRF01000069.1
2
KJV39508.1
17272


1570
GCA_001038915.1
293386
293386

Bacillus stratosphericus

LK23
Firmicutes
LDWL01000010.1
2
KML18487.1
17274


1571
GCA_001038775.1
293386
293386

Bacillus stratosphericus

LK33
Firmicutes
LDWU01000014.1
2
KML62012.1
17276


1572
GCA_001043535.1
293386
293386

Bacillus stratosphericus

LK5
Firmicutes
LDUH01000019.1
2
KMN31317.1
17278


1573
GCA_001043795.1
1628211
1628211

Bacillus sp. LK10
LK10
Firmicutes
LDUQ01000030.1
2
KMN70269.1
17280


1574
GCA_001267695.1
1390
1390

Bacillus amyloliquefaciens

KCTC 13012
Firmicutes
LHCC01000003.1
2
KOC82292.1
17282


1575
GCA_001280655.1
670
670

Vibrio parahaemolyticus

S372-5
Proteobacteria
LIRQ01000039.1
2
KOY23385.1
17284


1576
GCA_001423425.1
1736330
1736330

Rhizobium sp. Leaf306
Leaf306
Proteobacteria
LMNX01000001.1
2
KQQ38326.1
17286


1577
GCA_001431585.1
40324
40324

Stenotrophomonas maltophilia

JCM9942
Proteobacteria
LLXS01000084.1
2
KRG37251.1
17288


1578
GCA_001431425.1
83617
83617

Stenotrophomonas nitritireducens

DSM 12575
Proteobacteria
LDJG01000008.1
2
KRG58645.1
17290


1579
GCA_001449175.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07074
Proteobacteria
LLLA01000001.1
2
KSC65530.1
17292


1580
GCA_001452965.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07260
Proteobacteria
LLTT01000003.1
2
KSQ38235.1
17294


1581
GCA_001461845.1
1740805
1740805

Bacillus sp. NRRL B-4257
NRRL B-4257
Firmicutes
LLZB01000026.1
2
KSV97269.1
17296


1582
GCA_001461825.1
1740803
1740803

Bacillus sp. NRRL B-41580
NRRL B-41580
Firmicutes
LLZC01000021.1
2
KSV97837.1
17298


1583
GCA_001469685.1
1390
1390

Bacillus amyloliquefaciens

Jxnuwx-1
Firmicutes
LMAT01000001.1
2
KTF62015.1
17300


1584
GCA_001507425.1
1742859
1742859

Flavobacteriaceae bacterium CRH
CRH
Bacteroidetes
LMAJ01000029.1
2
KUJ59693.1
17302


1585
GCA_001519075.1
1117702
1117702

Novosphingobium fuchskuhlense

FNE08-7
Proteobacteria
KQ954244.1
2
KUR72680.1
17304


1586
GCA_001526365.1
1637876
1637876

Burkholderia sp. MSMB1835
MSMB1835
Proteobacteria
LOYP01000005.1
2
KVL39772.1
17306


1587
GCA_001593025.1
1671366
1671366

Ruminococcus sp. DSM 100440
DSM 100440
Firmicutes
LFIL01000002.1
2
KYG88423.1
17308


1588
GCA_000013305.1
362663
562

Escherichia coli 536
536
Proteobacteria
CP000247.1
2
ABG69918.1
17310


1589
GCA_000333215.1
316435
562

Escherichia coli Nissle 1917
Nissle 1917
Proteobacteria
CAPM01000056.1
2
CCQ05514.1
17312


1590
GCA_000627095.1
1444274
562

Escherichia coli 1-182-04_S4_C3
1-182-04_S4_C3
Proteobacteria
JJLH01000028.1
2
EZJ21710.1
17314


1591
GCA_000627215.1
1444245
562

Escherichia coli 1-182-04_S4_C2
1-182-04_S4_C2
Proteobacteria
JJLM01000058.1
2
EZJ42018.1
17316


1592
GCA_000627175.1
1444217
562

Escherichia coli 1-182-04_S4_C1
1-182-04_S4_C1
Proteobacteria
JJLP01000024.1
2
EZJ61189.1
17318


1593
GCA_000711455.1
1444214
562

Escherichia coli 8-415-05_S4_C1
8-415-05_S4_C1
Proteobacteria
JOMT01000106.1
2
KEJ12238.1
17320


1594
GCA_000711365.1
1444242
562

Escherichia coli 8-415-05_S4_C2
8-415-05_S4_C2
Proteobacteria
JOMU01000094.1
2
KEJ13626.1
17322


1595
GCA_000711435.1
1444271
562

Escherichia coli 8-415-05_S4_C3
8-415-05_S4_C3
Proteobacteria
JOMV01000018.1
2
KEJ33279.1
17324


1596
GCA_000713455.1
1444189
562

Escherichia coli 8-415-05_S3_C3
8-415-05_S3_C3
Proteobacteria
JOSA01000022.1
2
KEN34070.1
17326


1597
GCA_000713495.1
1444131
562

Escherichia coli 8-415-05_S3_C1
8-415-05_S3_C1
Proteobacteria
JOSB01000027.1
2
KEN41712.1
17328


1598
GCA_000713585.1
1444159
562

Escherichia coli 8-415-05_S3_C2
8-415-05_S3_C2
Proteobacteria
JOSI01000106.1
2
KEN74069.1
17330


1599
GCA_000194475.2
869685
562

Escherichia coli 9.1649
9.1649
Proteobacteria
AEZY02000025.1
2
KKA60260.1
17332


1600
GCA_000015425.1
400667
470

Acinetobacter baumannii ATCC 17978
ATCC 17978
Proteobacteria
CP000521.1
2
AB013066.2
17334


1601
GCA_000410575.1
1331671
303

Pseudomonas putida H8234
H8234
Proteobacteria
CP005976.1
2
AGN81863.1
17336


1602
GCA_000972745.1
339
339

Xanthomonas campestris

17
Proteobacteria
CP011256.1
2
AKC78200.1
17338


1603
GCA_001587155.1
305
305

Ralstonia solanacearum

IBSBF1503
Proteobacteria
CP012943.1
2
AMP74179.1
17340


1604
GCA_000369305.1
1217628
470

Acinetobacter baumannii NIPH 70
NIPH 70
Proteobacteria
KB849921.1
2
ENW63934.1
17342


1605
GCA_000967945.1
294
294

Pseudomonas fluorescens

C1
Proteobacteria
LACE01000014.1
2
KJZ35756.1
17344


1606
GCA_001452415.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07681
Proteobacteria
LLSB01000045.1
2
KSM97145.1
17346


1607
GCA_001593425.1
470
470

Acinetobacter baumannii

ATCC 17978
Proteobacteria
LOIA01000001.1
2
KWX65128.1
17348


1608
GCA_000965905.1
550
550

Enterobacter cloacae

CIDEIMsCOL14
Proteobacteria
JZKY01000004.1
2
KJX33869.1
17350


1609
GCA_000250075.2
868184
562

Escherichia coli DEC10E
DEC10E
Proteobacteria
AIGT01000041.1
2
EHW83928.1
17352


1610
GCA_000250475.2
868204
562

Escherichia coli DEC14D
DEC14D
Proteobacteria
AIHN01000055.1
2
EHX90142.1
17354


1611
GCA_000408605.1
1182702
562

Escherichia coli KTE103
KTE103
Proteobacteria
KE137186.1
2
EOW20700.1
17356


1612
GCA_000458935.1
1281121
562

Escherichia coli HVH 194
HVH 194
Proteobacteria
KE700788.1
2
EQT99520.1
17358






(4-2356805)
(4-2356805)


1613
GCA_000488795.1
1269010
562

Escherichia coli 910096-2
910096-2
Proteobacteria
KI534966.1
2
ESE28058.1
17360


1614
GCA_000687105.1
1444147
562

Escherichia coli 2-005-03_S3_C2
2-005-03_S3_C2
Proteobacteria
JMGT01000049.1
2
KDA72414.1
17362


1615
GCA_000711415.1
1444071
562

Escherichia coli 2-316-03_S1_C2
2-316-03_S1_C2
Proteobacteria
JOMX01000122.1
2
KEJ24822.1
17364


1616
GCA_000711475.1
1444042
562

Escherichia coli 2-316-03_S1_C1
2-316-03_S1_C1
Proteobacteria
JOMW01000161.1
2
KEJ23493.1
17366


1617
GCA_000714105.1
1444239
562

Escherichia coli 5-172-05_S4_C2
5-172-05_S4_C2
Proteobacteria
JOQN01000018.1
2
KEL24738.1
17368


1618
GCA_000714145.1
1444211
562

Escherichia coli 5-172-05_S4_C1
5-172-05_S4_C1
Proteobacteria
JOQP01000002.1
2
KEL41024.1
17370


1619
GCA_000714225.1
1444269
562

Escherichia coli 5-172-05_S4_C3
5-172-05_S4_C3
Proteobacteria
JOQT01000008.1
2
KEL61646.1
17372


1620
GCA_000818965.1
1010817
562

Escherichia coli C691-71 (14b)
C691-71 (14b)
Proteobacteria
JXBV01000029.1
2
KIG27435.1
17374


1621
GCA_001283365.1
562
562

Escherichia coli

503130_aEPEC
Proteobacteria
CYCS01000027.1
2
CTV70059.1
17376


1622
GCA_000492535.1
1328393
573

Klebsiella pneumoniae UCICRE 7
UCICRE 7
Proteobacteria
KI535498.1
2
ESL95857.1
17378


1623
GCA_000688175.1
1438809
573

Klebsiella pneumoniae UCI 64
UCI 64
Proteobacteria
JJNI01000059.1
2
EZR09256.1
17380


1624
GCA_001034055.1
573
573

Klebsiella pneumoniae

BIDMC89
Proteobacteria
KQ089634.1
2
KMI15680.1
17382


1625
GCA_000828775.1
1334564
615

Serratia marcescens SM39
SM39
Proteobacteria
AP013063.1
2
BAO34671.1
17384


1626
GCA_001086525.1
630
630

Yersinia enterocolitica

ERL08708
Proteobacteria
CPZT01000005.1
2
CNG20833.1
17386


1627
GCA_001125285.1
630
630

Yersinia enterocolitica

H1527/93
Proteobacteria
CQCE01000004.1
2
CNJ07176.1
17388


1628
GCA_001515115.1
666
666

Vibrio cholerae

M988
Proteobacteria
LQBX01000042.1
2
KUO23349.1
17390


1629
GCA_000965785.1
817
817

Bacteroides fragilis

BOB25
Bacteroidetes
CP011073.1
2
AKA50670.1
17392


1630
GCA_000307435.1
999417
823

Parabacteroides distasonis CL09T03C24
CL09T03C24
Bacteroidetes
JH976487.1
2
EKN28634.1
17394


1631
GCA_000156375.1
411464
901

Desulfovibrio piger ATCC 29098
ATCC 29098
Proteobacteria
DS996355.1
2
EEB34165.1
17396


1632
GCA_000013885.1
323097
912

Nitrobacter hamburgensis X14
X14
Proteobacteria
CP000319.1
2
ABE61672.1
17398


1633
GCA_000336555.1
883079
1034

Afipia clevelandensis ATCC 49720
ATCC 49720
Proteobacteria
KB375281.1
2
EKS39930.1
17400


1634
GCA_000756355.1
1429888
1245

Leuconostoc mesenteroides P45
P45
Firmicutes
JRGZ01000002.1
2
KGB50927.1
17402


1635
GCA_000146325.1
862514
1254

Pediococcus acidilactici DSM 20284
DSM 20284
Firmicutes
GL397067.1
2
EFL96228.1
17404


1636
GCA_000195025.1
888813
1305

Streptococcus sanguinis SK330
SK330
Firmicutes
GL878548.1
2
EGF16080.1
17406


1637
GCA_900059415.1
1307
1307

Streptococcus suis

LSS12
Firmicutes
FIFP01000007.1
2
CYU22313.1
17408


1638
GCA_900061375.1
1307
1307

Streptococcus suis

SS985
Firmicutes
FILR01000007.1
2
CYX44081.1
17410


1639
GCA_000339495.1
857115
1309

Streptococcus mutans NLML8
NLML8
Firmicutes
AHSV01000017.1
2
EMB57079.1
17412


1640
GCA_000339955.1
857125
1309

Streptococcus mutans N3209
N3209
Firmicutes
AHSL01000008.1
2
EMC13032.1
17414


1641
GCA_001558215.1
1309
1309

Streptococcus mutans

NG8
Firmicutes
CP013237.1
2
AMF85252.1
17416


1642
GCA_000186445.1
888745
1311

Streptococcus agalactiae ATCC 13813
ATCC 13813
Firmicutes
GL636070.1
2
EFV96552.1
17418


1643
GCA_000221325.2
876138
1311

Streptococcus agalactiae FSL S3-026
FSLS3-026
Firmicutes
AEXT01000002.1
2
EGS28536.1
17420


1644
GCA_000289795.1
1154788
1311

Streptococcus agalactiae FSL S3-501
FSLS3-501
Firmicutes
ALQE01000108.1
2
EPT39845.1
17422


1645
GCA_000310365.1
1154776
1311

Streptococcus agalactiae FSL S3-586
FSLS3-586
Firmicutes
ANCM01000071.1
2
EPV87467.1
17424


1646
GCA_000310425.1
1154786
1311

Streptococcus agalactiae FSL S3-251
FSLS3-251
Firmicutes
ANC001000045.1
2
EPV95019.1
17426


1647
GCA_001017995.1
1311
1311

Streptococcus agalactiae

DK-B-USS-155
Firmicutes
LBKI01000029.1
2
KLL29854.1
17428


1648
GCA_001018015.1
1311
1311

Streptococcus agalactiae

DK-B-USS-204
Firmicutes
LBKK01000069.1
2
KLL34442.1
17430


1649
GCA_001018055.1
1311
1311

Streptococcus agalactiae

DK-B-USS-215
Firmicutes
LBKL01000103.1
2
KLL34969.1
17432


1650
GCA_000975495.1
1450185
1349

Streptococcus uberis C8329
C8329
Firmicutes
JATG01000003.1
2
KKF49829.1
17434


1651
GCA_000205205.1
749517
1351

Enterococcus faecalis TX1467
TX1467
Firmicutes
GL884006.1
2
EGG58909.1
17436


1652
GCA_000393495.1
1169246
1351

Enterococcus faecalis EnGen0327
A-3-1
Firmicutes
KB944973.1
2
EOL13670.1
17438


1653
GCA_000393535.1
1169248
1351

Enterococcus faecalis EnGen0329
Merz192
Firmicutes
KB945004.1
2
EOK19568.1
17440


1654
GCA_000395285.1
1158677
1351

Enterococcus faecalis EnGen0289
DS16
Firmicutes
KB947440.1
2
EOJ40184.1
17442


1655
GCA_000395305.1
1158678
1351

Enterococcus faecalis EnGen0285
RC73
Firmicutes
KB947448.1
2
EOJ44767.1
17444


1656
GCA_000415225.1
1258582
1351

Enterococcus faecalis 20.SD.W.06
20.SD.W.06
Firmicutes
KE351746.1
2
EPI04163.1
17446


1657
GCA_000519485.1
1391473
1351

Enterococcus faecalis EnGen0403
EnGen0403
Firmicutes
KI912960.1
2
ETT98569.1
17448


1658
GCA_000519505.1
1391474
1351

Enterococcus faecalis EnGen0404
EnGen0404
Firmicutes
KI912968.1
2
ETU01533.1
17450


1659
GCA_000519525.1
1391475
1351

Enterococcus faecalis EnGen0405
EnGen0405
Firmicutes
KI912974.1
2
ETU06238.1
17452


1660
GCA_000519545.1
1391476
1351

Enterococcus faecalis EnGen0406
EnGen0406
Firmicutes
KI912979.1
2
ETU10204.1
17454


1661
GCA_000519585.1
1391478
1351

Enterococcus faecalis EnGen0408
EnGen0408
Firmicutes
KI912990.1
2
ETU16615.1
17456


1662
GCA_000519625.1
1391480
1351

Enterococcus faecalis EnGen0410
EnGen0410
Firmicutes
KI913001.1
2
ETU21340.1
17458


1663
GCA_000519665.1
1391482
1351

Enterococcus faecalis EnGen0412
EnGen0412
Firmicutes
KI913012.1
2
ETU24458.1
17460


1664
GCA_000519725.1
1391485
1351

Enterococcus faecalis EnGen0415
EnGen0415
Firmicutes
KI913026.1
2
ETU31995.1
17462


1665
GCA_000519785.1
1391488
1351

Enterococcus faecalis EnGen0418
EnGen0418
Firmicutes
KI913052.1
2
ETU40537.1
17464


1666
GCA_000519845.1
1391491
1351

Enterococcus faecalis EnGen0421
EnGen0421
Firmicutes
KI913064.1
2
ETU48375.1
17466


1667
GCA_000442845.1
1137134
1358

Lactococcus lactis subsp. lactis A12
A12
Firmicutes
CBLU010000009.1
2
CDG04462.1
17468


1668
GCA_001047375.1
1121307
1495

Clostridium cylindrosporum DSM 605
DSM 605
Firmicutes
LFVU01000026.1
2
KMT21891.1
17470


1669
GCA_001579785.1
1502
1502

Clostridium perfringens

JP838
Firmicutes
CP010994.1
2
AMN36763.1
17472


1670
GCA_001372515.1
1505
1505
[Clostridium] sordellii
W2922
Firmicutes
CELK01000014.1
2
CEQ11379.1
17474


1671
GCA_000493655.1
1349417
1515

Ruminiclostridium thermocellum BC1

Firmicutes
CBQ0010000050.1
2
CDG36276.1
17476


1672
GCA_000234155.1
742735
1531
[Clostridium] clostridioforme 2_1_49FAA
2_1_49FAA
Firmicutes
JH376870.1
2
EHG33946.1
17478


1673
GCA_000724405.2
1443118
1542

Clostridium novyi A str. GD211209
GD211209
Firmicutes
JENN01000006.1
2
KEH95234.1
17480


1674
GCA_000469365.1
649758
1580

Lactobacillus brevis ATCC 14869 = DSM 20054
ATCC 14869
Firmicutes
KI271248.1
2
ERK44588.1
17482


1675
GCA_001433855.1
649758
1580

Lactobacillus brevis ATCC 14869 = DSM 20054
DSM 20054
Firmicutes
AZCP01000001.1
2
KRK21385.1
17484


1676
GCA_000175315.3
562973
1656

Actinomyces viscosus C505
C505
Actinobacteria
KI391970.1
2
EGE38623.2
17486


1677
GCA_001602115.1
1748
1748

Propionibacterium acidipropionici

ATCC 55737
Actinobacteria
CP014352.1
2
AMS06949.1
17488


1678
GCA_000632085.1
13689
13689

Sphingomonas paucimobilis

EPA505
Proteobacteria
JFYY01000026.1
2
EZP69577.1
17490


1679
GCA_000955645.1
1347790
28131

Prevotella intermedia ZT
ZT
Bacteroidetes
ATMK01000029.1
2
KJJ86348.1
17492


1680
GCA_000011545.1
272560
28450

Burkholderia pseudomallei K96243
K96243
Proteobacteria
BX571965.1
2
CAH34734.1
17494


1681
GCA_000015925.1
357348
28450

Burkholderia pseudomallei 1106a
1106a
Proteobacteria
CP000572.1
2
ABN90934.1
17496


1682
GCA_000152345.1
331978
28450

Burkholderia pseudomallei Pasteur 52237
Pasteur 52237
Proteobacteria
CH899746.1
2
ED090949.1
17498


1683
GCA_000193455.1
320371
28450

Burkholderia pseudomallei 1710a
1710a
Proteobacteria
CM000832.1
2
EET07297.1
17500


1684
GCA_000193475.1
357347
28450

Burkholderia pseudomallei 1106b
1106b
Proteobacteria
CM000774.1
2
EES25793.1
17502


1685
GCA_000259755.1
1086032
28450

Burkholderia pseudomallei 1258a
1258a
Proteobacteria
AHJB01000130.1
2
EIF62858.1
17504


1686
GCA_000259775.1
1086033
28450

Burkholderia pseudomallei 1258b
1258b
Proteobacteria
AHJC01000129.1
2
EIF64459.1
17506


1687
GCA_000259795.1
1086036
28450

Burkholderia pseudomallei 354e
354e
Proteobacteria
AHJD01000107.1
2
EIF75597.1
17508


1688
GCA_000259815.1
1086034
28450

Burkholderia pseudomallei 354a
354a
Proteobacteria
AGVS01000297.1
2
EIF80279.1
17510


1689
GCA_000294635.1
1229785
28450

Burkholderia pseudomallei BPC006
BPC006
Proteobacteria
CP003781.1
2
AFR14682.1
17512


1690
GCA_000756125.1
28450
28450

Burkholderia pseudomallei

Mahidol-1106a
Proteobacteria
CP008781.1
2
AIO13383.1
17514


1691
GCA_000756145.1
28450
28450

Burkholderia pseudomallei

1106a
Proteobacteria
CP008758.1
2
AI091702.1
17516


1692
GCA_000757035.2
331978
28450

Burkholderia pseudomallei Pasteur 52237
Pasteur 52237
Proteobacteria
CP009899.1
2
AJX61451.1
17518


1693
GCA_000757185.1
28450
28450

Burkholderia pseudomallei

BGS
Proteobacteria
KN150946.1
2
KGC78979.1
17520


1694
GCA_000757255.1
28450
28450

Burkholderia pseudomallei

BGJ
Proteobacteria
KN150955.1
2
KGD17915.1
17522


1695
GCA_000763555.1
28450
28450

Burkholderia pseudomallei

BGK
Proteobacteria
CP008916.1
2
AIS47055.1
17524


1696
GCA_000770455.1
1439854
28450

Burkholderia pseudomallei B03
B03
Proteobacteria
CP009151.1
2
AIV91806.1
17526


1697
GCA_000770535.1
1439855
28450

Burkholderia pseudomallei A79A
A79A
Proteobacteria
CP009165.1
2
AIV95750.1
17528


1698
GCA_000775085.1
1439860
28450

Burkholderia pseudomallei TSV28
TSV28
Proteobacteria
JQHU01000150.1
2
KGX68805.1
17530


1699
GCA_000775675.1
1439856
28450

Burkholderia pseudomallei A79C
A79C
Proteobacteria
JQHQ01000114.1
2
KGY01694.1
17532


1700
GCA_000775685.1
1439857
28450

Burkholderia pseudomallei A79D
A79D
Proteobacteria
JQHR01000047.1
2
KGY04116.1
17534


1701
GCA_000932075.1
28450
28450

Burkholderia pseudomallei

QCMRI_BP07
Proteobacteria
JYBG01000039.1
2
KIX42366.1
17536


1702
GCA_000932145.1
28450
28450

Burkholderia pseudomallei

QCMRI_BP32
Proteobacteria
JYBK01000004.1
2
KIX63305.1
17538


1703
GCA_000953095.1
28450
28450

Burkholderia pseudomallei

3921
Proteobacteria
LK936442.1
2
CDU27413.1
17540


1704
GCA_000954175.1
28450
28450

Burkholderia pseudomallei

vgh07
Proteobacteria
CP010973.1
2
AJW52247.1
17542


1705
GCA_000959285.1
272560
28450

Burkholderia pseudomallei K96243
K96243
Proteobacteria
CP009538.1
2
AJX28157.1
17544


1706
GCA_001182265.1
28450
28450

Burkholderia pseudomallei

EY6
Proteobacteria
CWJD01000032.1
2
CRY48213.1
17546


1707
GCA_001191815.1
28450
28450

Burkholderia pseudomallei

C32
Proteobacteria
CSQC01000014.1
2
CPN90195.1
17548


1708
GCA_001192415.1
28450
28450

Burkholderia pseudomallei

C36
Proteobacteria
CSQF01000015.1
2
CP007168.1
17550


1709
GCA_001192815.1
28450
28450

Burkholderia pseudomallei

C58
Proteobacteria
CSOW01000015.1
2
CPM40570.1
17552


1710
GCA_001193035.1
28450
28450

Burkholderia pseudomallei

C30
Proteobacteria
CSSB01000014.1
2
CPQ62517.1
17554


1711
GCA_001193615.1
28450
28450

Burkholderia pseudomallei

C11
Proteobacteria
CSRL01000034.1
2
CPQ18530.1
17556


1712
GCA_001193655.1
28450
28450

Burkholderia pseudomallei

C54
Proteobacteria
CSLU01000014.1
2
CPI70802.1
17558


1713
GCA_001194765.1
28450
28450

Burkholderia pseudomallei

C52
Proteobacteria
CSN001000016.1
2
CPK88012.1
17560


1714
GCA_001196125.1
28450
28450

Burkholderia pseudomallei

C31
Proteobacteria
CSM001000014.1
2
CPJ40971.1
17562


1715
GCA_001196775.1
28450
28450

Burkholderia pseudomallei

C50
Proteobacteria
CSMS01000016.1
2
CPJ76825.1
17564


1716
GCA_001197015.1
28450
28450

Burkholderia pseudomallei

C17
Proteobacteria
CSMH01000029.1
2
CPJ85555.1
17566


1717
GCA_001197235.1
28450
28450

Burkholderia pseudomallei

6./96
Proteobacteria
CSLAO1000038.1
2
CPH77136.1
17568


1718
GCA_001197775.1
28450
28450

Burkholderia pseudomallei

C3
Proteobacteria
CSME01000015.1
2
CPJ25324.1
17570


1719
GCA_001197795.1
28450
28450

Burkholderia pseudomallei

C44
Proteobacteria
CSSV01000015.1
2
CPR02281.1
17572


1720
GCA_001199195.1
28450
28450

Burkholderia pseudomallei

C51
Proteobacteria
CSMB01000033.1
2
CPJ69674.1
17574


1721
GCA_001199695.1
28450
28450

Burkholderia pseudomallei

C68
Proteobacteria
CSNM01000014.1
2
CPK70853.1
17576


1722
GCA_001199815.1
28450
28450

Burkholderia pseudomallei

C28
Proteobacteria
CSRV01000015.1
2
CPQ22985.1
17578


1723
GCA_001200615.1
28450
28450

Burkholderia pseudomallei

C1
Proteobacteria
CSPL01000013.1
2
CPN03544.1
17580


1724
GCA_001200935.1
28450
28450

Burkholderia pseudomallei

504/96
Proteobacteria
CSLC01000034.1
2
CPH78827.1
17582


1725
GCA_001202415.1
28450
28450

Burkholderia pseudomallei

C48
Proteobacteria
CSLS01000014.1
2
CPI57651.1
17584


1726
GCA_001204515.1
28450
28450

Burkholderia pseudomallei

C69
Proteobacteria
CSPX01000005.1
2
CPN26697.1
17586


1727
GCA_001205935.1
28450
28450

Burkholderia pseudomallei

C22
Proteobacteria
CSNB01000034.1
2
CPK20311.1
17588


1728
GCA_001206495.1
28450
28450

Burkholderia pseudomallei

C70
Proteobacteria
CSOV01000015.1
2
CPM33011.1
17590


1729
GCA_001207675.1
28450
28450

Burkholderia pseudomallei

C66
Proteobacteria
CSQA01000015.1
2
CPN87629.1
17592


1730
GCA_001208545.1
28450
28450

Burkholderia pseudomallei

C13
Proteobacteria
CSSE01000014.1
2
CPQ68104.1
17594


1731
GCA_001209405.1
28450
28450

Burkholderia pseudomallei

C15
Proteobacteria
CSPA01000014.1
2
CPM53772.1
17596


1732
GCA_001209505.1
28450
28450

Burkholderia pseudomallei

C21
Proteobacteria
CSOU01000014.1
2
CPM10513.1
17598


1733
GCA_001210705.1
28450
28450

Burkholderia pseudomallei

C16
Proteobacteria
CSQP01000036.1
2
CPP09133.1
17600


1734
GCA_001210965.1
28450
28450

Burkholderia pseudomallei

C42
Proteobacteria
CSNW01000016.1
2
CPL40888.1
17602


1735
GCA_001211345.1
28450
28450

Burkholderia pseudomallei

C62
Proteobacteria
CSPM01000015.1
2
CPN14436.1
17604


1736
GCA_001211405.1
28450
28450

Burkholderia pseudomallei

C26
Proteobacteria
CSNQ01000016.1
2
CPK90390.1
17606


1737
GCA_001211505.1
28450
28450

Burkholderia pseudomallei

C53
Proteobacteria
CSRJ01000015.1
2
CPP68451.1
17608


1738
GCA_001211565.1
28450
28450

Burkholderia pseudomallei

C10
Proteobacteria
CSRH01000038.1
2
CPP97990.1
17610


1739
GCA_001211865.1
28450
28450

Burkholderia pseudomallei

C29
Proteobacteria
CSQB01000014.1
2
CPN87378.1
17612


1740
GCA_001212025.1
28450
28450

Burkholderia pseudomallei

C2
Proteobacteria
CSSW01000015.1
2
CPR00121.1
17614


1741
GCA_001212065.1
28450
28450

Burkholderia pseudomallei

P6
Proteobacteria
CSLI01000012.1
2
CPH39453.1
17616


1742
GCA_001212185.1
28450
28450

Burkholderia pseudomallei

21/96
Proteobacteria
CSKV01000012.1
2
CPG82753.1
17618


1743
GCA_001212325.1
28450
28450

Burkholderia pseudomallei

C25
Proteobacteria
CSOX01000015.1
2
CPM46611.1
17620


1744
GCA_001212405.1
28450
28450

Burkholderia pseudomallei

EY1
Proteobacteria
CSKM01000009.1
2
CPG38360.1
17622


1745
GCA_001212465.1
28450
28450

Burkholderia pseudomallei

2/96
Proteobacteria
CSKX01000014.1
2
CPH00885.1
17624


1746
GCA_001212705.1
28450
28450

Burkholderia pseudomallei

EY3
Proteobacteria
CSKP01000034.1
2
CPH42028.1
17626


1747
GCA_001277875.1
28450
28450

Burkholderia pseudomallei

vgh16R
Proteobacteria
CP012515.1
2
ALB92817.1
17628


1748
GCA_001277895.1
28450
28450

Burkholderia pseudomallei

vgh16W
Proteobacteria
CP012517.1
2
ALB98879.1
17630


1749
GCA_001277975.1
28450
28450

Burkholderia pseudomallei

982
Proteobacteria
CP012576.1
2
ALC58207.1
17632


1750
GCA_001320215.1
28450
28450

Burkholderia pseudomallei

6
Proteobacteria
CGEV01000013.1
2
CFT55154.1
17634


1751
GCA_001320825.1
28450
28450

Burkholderia pseudomallei

C37
Proteobacteria
CIHR01000013.1
2
CPQ86668.1
17636


1752
GCA_001320865.1
28450
28450

Burkholderia pseudomallei

C61
Proteobacteria
CFZT01000014.1
2
CFP14331.1
17638


1753
GCA_001320905.1
28450
28450

Burkholderia pseudomallei

C6
Proteobacteria
CGFU01000014.1
2
CFU67050.1
17640


1754
GCA_001320945.1
28450
28450

Burkholderia pseudomallei

C4
Proteobacteria
CFXK01000014.1
2
CFM98899.1
17642


1755
GCA_001320985.1
28450
28450

Burkholderia pseudomallei

C9
Proteobacteria
CFXG01000012.1
2
CFM81858.1
17644


1756
GCA_001321015.1
28450
28450

Burkholderia pseudomallei

C7
Proteobacteria
CIJT01000014.1
2
CPM85720.1
17646


1757
GCA_001321045.1
28450
28450

Burkholderia pseudomallei

C8
Proteobacteria
CIGV01000033.1
2
CPL97294.1
17648


1758
GCA_001321065.1
28450
28450

Burkholderia pseudomallei

C12
Proteobacteria
CFZL01000037.1
2
CFO92224.1
17650


1759
GCA_001321085.1
28450
28450

Burkholderia pseudomallei

C46
Proteobacteria
CFXP01000015.1
2
CFN19260.1
17652


1760
GCA_001321105.1
28450
28450

Burkholderia pseudomallei

C45
Proteobacteria
CIGX01000033.1
2
CPL11643.1
17654


1761
GCA_001321125.1
28450
28450

Burkholderia pseudomallei

C43
Proteobacteria
CIBE01000017.1
2
CPN25051.1
17656


1762
GCA_001321145.1
28450
28450

Burkholderia pseudomallei

C47
Proteobacteria
CIKM01000030.1
2
CPO46736.1
17658


1763
GCA_001321165.1
28450
28450

Burkholderia pseudomallei

C27
Proteobacteria
CFWL01000014.1
2
CFL99481.1
17660


1764
GCA_001321185.1
28450
28450

Burkholderia pseudomallei

C24
Proteobacteria
CIJQ01000014.1
2
CP089903.1
17662


1765
GCA_001321205.1
28450
28450

Burkholderia pseudomallei

C23
Proteobacteria
CGHT01000014.1
2
CFW49159.1
17664


1766
GCA_001321225.1
28450
28450

Burkholderia pseudomallei

C64
Proteobacteria
CFWQ01000015.1
2
CFM22755.1
17666


1767
GCA_001321245.1
28450
28450

Burkholderia pseudomallei

C63
Proteobacteria
CIBB01000014.1
2
CPK84415.1
17668


1768
GCA_001321265.1
28450
28450

Burkholderia pseudomallei

C65
Proteobacteria
CFZI01000014.1
2
CFO79487.1
17670


1769
GCA_001321285.1
28450
28450

Burkholderia pseudomallei

C67
Proteobacteria
CGFW01000014.1
2
CFU75863.1
17672


1770
GCA_001321305.1
28450
28450

Burkholderia pseudomallei

C14
Proteobacteria
CGFJ01000015.1
2
CFU18823.1
17674


1771
GCA_001321325.1
28450
28450

Burkholderia pseudomallei

C18
Proteobacteria
CFXB01000030.1
2
CFM67594.1
17676


1772
GCA_001321345.1
28450
28450

Burkholderia pseudomallei

C20
Proteobacteria
CGIB01000015.1
2
CFW79173.1
17678


1773
GCA_001321365.1
28450
28450

Burkholderia pseudomallei

C19
Proteobacteria
CFZB01000015.1
2
CFO54185.1
17680


1774
GCA_001321385.1
28450
28450

Burkholderia pseudomallei

C49
Proteobacteria
CFXU01000016.1
2
CFN47247.1
17682


1775
GCA_001321405.1
28450
28450

Burkholderia pseudomallei

C57
Proteobacteria
CGFL01000014.1
2
CFU32908.1
17684


1776
GCA_001321425.1
28450
28450

Burkholderia pseudomallei

C59
Proteobacteria
CFZV01000014.1
2
CFP26209.1
17686


1777
GCA_001321445.1
28450
28450

Burkholderia pseudomallei

C60
Proteobacteria
CIBL01000035.1
2
CPP85431.1
17688


1778
GCA_001321465.1
28450
28450

Burkholderia pseudomallei

C41
Proteobacteria
CFWT01000016.1
2
CFM37245.1
17690


1779
GCA_001321485.1
28450
28450

Burkholderia pseudomallei

C56
Proteobacteria
CIBF01000030.1
2
CPQ63811.1
17692


1780
GCA_001321505.1
28450
28450

Burkholderia pseudomallei

C39
Proteobacteria
CFYP01000014.1
2
CF010819.1
17694


1781
GCA_001321525.1
28450
28450

Burkholderia pseudomallei

C40
Proteobacteria
CIGS01000014.1
2
CPL75788.1
17696


1782
GCA_001321545.1
28450
28450

Burkholderia pseudomallei

C38
Proteobacteria
CFXD01000034.1
2
CFM72557.1
17698


1783
GCA_001321565.1
28450
28450

Burkholderia pseudomallei

C35
Proteobacteria
CIJK01000015.1
2
CPK97832.1
17700


1784
GCA_001321585.1
28450
28450

Burkholderia pseudomallei

C33
Proteobacteria
CHKY01000034.1
2
CPN81614.1
17702


1785
GCA_001321605.1
28450
28450

Burkholderia pseudomallei

C34
Proteobacteria
CGHK01000004.1
2
CFW09147.1
17704


1786
GCA_001321625.1
28450
28450

Burkholderia pseudomallei

C55
Proteobacteria
CGFR01000015.1
2
CFU54707.1
17706


1787
GCA_001326895.1
28450
28450

Burkholderia pseudomallei

2746b
Proteobacteria
CFVL01000010.1
2
CFK50101.1
17708


1788
GCA_001326935.1
28450
28450

Burkholderia pseudomallei

EY4
Proteobacteria
CHFD01000017.1
2
CPG83473.1
17710


1789
GCA_001327035.1
28450
28450

Burkholderia pseudomallei

DB30729/00
Proteobacteria
CGEZ01000012.1
2
CFT72113.1
17712


1790
GCA_001327075.1
28450
28450

Burkholderia pseudomallei

497/96
Proteobacteria
CFVV01000013.1
2
CFL13092.1
17714


1791
GCA_001327155.1
28450
28450

Burkholderia pseudomallei

35/96
Proteobacteria
CFWJ01000011.1
2
CFL88486.1
17716


1792
GCA_001327395.1
28450
28450

Burkholderia pseudomallei

708a
Proteobacteria
CIAY01000003.1
2
CPE71818.1
17718


1793
GCA_001327415.1
28450
28450

Burkholderia pseudomallei

BRI
Proteobacteria
CGFB01000038.1
2
CFT96170.1
17720


1794
GCA_001327435.1
28450
28450

Burkholderia pseudomallei

E8
Proteobacteria
CGFC01000007.1
2
CFT85447.1
17722


1795
GCA_001327495.1
28450
28450

Burkholderia pseudomallei

TRF661
Proteobacteria
CFWE01000007.1
2
CFL56334.1
17724


1796
GCA_001327555.1
28450
28450

Burkholderia pseudomallei

E0387
Proteobacteria
CHFI01000014.1
2
CPI51234.1
17726


1797
GCA_000486815.1
997333
28901

Salmonella enterica subsp.
0250
Proteobacteria
AOYM01000072.1
2
ESG20657.1
17728







enterica serovar Oranienburg






str. 0250


1798
GCA_000940895.1
1454592
28901

Salmonella enterica subsp.
CDC 06-0532
Proteobacteria
CP007211.1
2
AJQ64506.1
17730







enterica serovar Anatum str.






CDC 06-0532


1799
GCA_000963535.1
1454590
28901

Salmonella enterica subsp.
USDA-ARS-
Proteobacteria
CP007483.1
2
AJZ80320.1
17732







enterica serovar Anatum str.
USMARC-1175






USDA-ARS-USMARC-1175


1800
GCA_001217125.1
36809
36809

Mycobacterium abscessus

PAP090
Actinobacteria
CSWS01000008.1
2
CPW02861.1
17734


1801
GCA_000332975.1
1220583
36820

Gordonia aichiensis NBRC 108223
NBRC 108223
Actinobacteria
BANR01000007.1
2
GAC48719.1
17736


1802
GCA_000014925.1
290340
43663

Paenarthrobacter aurescens TC1
TC1; ATCC
Actinobacteria
CP000474.1
2
ABM09581.1
17738







BAA-1386


1803
GCA_000473915.1
1219013
43767

Rhodococcus equi NBRC 101255 = C 7
C 7
Actinobacteria
APJC01000016.1
2
ERN46351.1
17740


1804
GCA_001467645.1
45065
45065

Legionella geestiana

ATCC 49504
Proteobacteria
LNYC01000024.1
2
KTD01946.1
17742


1805
GCA_000967915.1
61635
61635

Acholeplasma brassicae

O502
Tenericutes
FO681348.1
2
CCV65562.1
17744


1806
GCA_001038235.1
61647
61647

Pluralibacter gergoviae

DS82E24
Proteobacteria
LDZG01000031.1
2
KMK02865.1
17746


1807
GCA_000568815.1
1150621
66821

Sulfurospirillum multivorans DSM 12446
DSM 12446
Proteobacteria
CP007201.1
2
AHJ12534.1
17748


1808
GCA_001509475.1
68262
68262

Streptomyces regalis

NRRL 3151
Actinobacteria
LLZG01000047.1
2
KUL42778.1
17750


1809
GCA_000257785.1
1095730
76860

Streptococcus constellatus subsp.
SK53
Firmicutes
AICQ01000008.1
2
EID21980.1
17752







constellatus SK53


1810
GCA_000474075.1
1095730
76860

Streptococcus constellatus subsp.
SK53
Firmicutes
BASU01000001.1
2
GAD37767.1
17754







constellatus SK53


1811
GCA_001434855.1
1423788
83526

Lactobacillus paralimentarius DSM 19674
DSM 19674
Firmicutes
AZDY01000037.1
2
KRK83038.1
17756


1812
GCA_000186185.1
562971
85698

Achromobacter xylosoxidans C54
C54
Proteobacteria
GL636034.1
2
EFV85442.1
17758


1813
GCA_000364225.1
1235802
97253

Eubacterium plexicaudatum ASF492
ASF492
Firmicutes
KB822499.1
2
EMZ26178.1
17760


1814
GCA_000317595.1
698759
103232

Streptomyces ipomoeae 91-03
91-03
Actinobacteria
AEJC01000486.1
2
EKX62822.1
17762


1815
GCA_000017145.1
366394
110321

Sinorhizobium medicae WSM419
WSM419
Proteobacteria
CP000740.1
2
ABR64200.1
17764


1816
GCA_001188555.1
121719
121719

Pannonibacter phragmitetus

CGMCC9175
Proteobacteria
LGSQ01000007.1
2
KND18807.1
17766


1817
GCA_000092505.1
762051
136609

Leuconostoc kimchii IMSNU 11154
IMSNU 11154
Firmicutes
CP001758.1
2
ADG41466.1
17768


1818
GCA_000156215.1
445975
147206

Collinsella stercoris DSM 13279
DSM 13279
Actinobacteria
DS995474.1
2
EEA91362.1
17770


1819
GCA_000235505.1
742737
154046

Hungatella hathewayi WAL-18680
WAL-18680
Firmicutes
JH379027.1
2
EHI61152.1
17772


1820
GCA_000178255.1
702450
154288

Turicibacter sanguinis PC909
PC909
Firmicutes
ADMN01000123.1
2
EFF62517.1
17774


1821
GCA_001465255.1
162209
162209

Paenibacillus naphthalenovorans

32O-Y
Firmicutes
CP013652.1
2
ALS25374.1
17776


1822
GCA_000767835.1
176090
176090

Streptococcus sinensis

HKU4
Firmicutes
JPEN01000062.1
2
KGM37271.1
17778


1823
GCA_000568075.1
314330
314330

Enterobacter sp. DC1
DC1
Proteobacteria
AZUA01000002.1
2
EWG70341.1
17780


1824
GCA_001050135.1
320787
320787

Cyclobacterium amurskyense

KCTC 12363
Bacteroidetes
CP012040.1
2
AKP49793.1
17782


1825
GCA_000964065.1
332411
332411

Aquitalea magnusonii

SM6
Proteobacteria
JZRC01000020.1
2
KJV29339.1
17784


1826
GCA_000264295.1
1163407
347483

Rhodanobacter spathiphylli B39
B39
Proteobacteria
AJXT01000055.1
2
EIL89963.1
17786


1827
GCA_000737685.1
362418
362418

Flavobacterium reichenbachii

LMG 25512
Bacteroidetes
JPRL01000001.1
2
KFF05553.1
17788


1828
GCA_001405815.1
388408
388408

Labrenzia alexandrii

CECT 5112
Proteobacteria
CXWD01000013.1
2
CTQ72905.1
17790


1829
GCA_001444505.1
554343
554343

Psychrobacter piscatorii

LQ58
Proteobacteria
LNDJ01000085.1
2
KRU21991.1
17792


1830
GCA_000956505.1
582680
582680

Microbacterium azadirachtae

ARN176
Actinobacteria
JYIX01000037.1
2
KJL32259.1
17794


1831
GCA_000245715.1
1050222
1050222

Paenibacillus sp. Aloe-11
Aloe-11
Firmicutes
JH601082.1
2
EHS54840.1
17796


1832
GCA_000282055.1
1144313
1144313

Flavobacterium sp. CF136
CF136
Bacteroidetes
AKJZ01000027.1
2
EJL63880.1
17798


1833
GCA_000282675.1
1144320
1144320

Pantoea sp. GM01
GM01
Proteobacteria
AKIU01000064.1
2
EJL84705.1
17800


1834
GCA_000260835.1
946077
1165090

Imtechella halotolerans K1
K1
Bacteroidetes
AJJU01000017.1
2
EID73851.1
17802


1835
GCA_001532035.1
1207504
1207504

Burkholderia pseudomultivorans

MSMB368WGS
Proteobacteria
LPJR01000094.1
2
KWF17574.1
17804


1836
GCA_000466565.1
1226324
1226324

Blautia sp. KLE 1732
KLE 1732
Firmicutes
KE993386.1
2
ERI96811.1
17806


1837
GCA_000403295.2
1235792
1235792

Lachnospiraceae bacterium M18-1
M18-1
Firmicutes
KE159609.1
2
EOS38323.1
17808


1838
GCA_000403335.2
1235793
1235793

Lachnospiraceae bacterium COE1
COE1
Firmicutes
KE159632.1
2
EOS41468.1
17810


1839
GCA_000438215.1
1263066
1263066

Clostridium clostridioforme CAG:511

Firmicutes
FR903693.1
2
CDF26098.1
17812


1840
GCA_000768755.1
1537504
1537504

Porphyromonas sp. COT-108 OH1349
COT-108
Bacteroidetes
JRAH01000034.1
2
KGN67552.1
17814







OH1349


1841
GCA_001508375.1
1635262
1635262

Desulfotomaculum sp. 46_296

Firmicutes
LGFZ01000024.1
2
KUK53685.1
17816


1842
GCA_000988325.1
1643451
1643451

Sphingobacterium sp. Ag1
Ag1
Bacteroidetes
LBGU01000044.1
2
KKO89442.1
17818


1843
GCA_001187905.1
1681195
1681195

Pantoea sp. RIT-PI-b
RIT-PI-b
Proteobacteria
LGIS01000026.1
2
KNC08320.1
17820


1844
GCA_001422575.1
1736224
1736224

Serratia sp. Leaf51
Leaf51
Proteobacteria
LMU01000057.1
2
KQN48064.1
17822


1845
GCA_000979175.1
2209
2209

Methanosarcina mazei

1.H.A.1A.3
Euryarchaeota
JJQH01000125.1
2
KKH38512.1
17824


1846
GCA_000979195.1
2209
2209

Methanosarcina mazei

1.H.A.2.3
Euryarchaeota
JJQM01000126.1
2
KKH53104.1
17826


1847
GCA_000979205.1
2209
2209

Methanosarcina mazei

1.H.A.2.7
Euryarchaeota
JJQ001000047.1
2
KKH68857.1
17828


1848
GCA_000979255.1
2209
2209

Methanosarcina mazei

1.H.M.1A.2
Euryarchaeota
JJQS01000129.1
2
KKH71868.1
17830


1849
GCA_000979275.1
2209
2209

Methanosarcina mazei

1.H.M.2.2
Euryarchaeota
JJQV01000133.1
2
KKH80640.1
17832


1850
GCA_000979335.1
2209
2209

Methanosarcina mazei

2.F.A.2.3
Euryarchaeota
JJOR01000174.1
2
KKF98496.1
17834


1851
GCA_000979925.1
2209
2209

Methanosarcina mazei

1.H.A.1A.6
Euryarchaeota
JJQJ01000061.1
2
KKH51286.1
17836


1852
GCA_000980005.1
2209
2209

Methanosarcina mazei

1.H.A.2.8
Euryarchaeota
JJQP01000201.1
2
KKH64073.1
17838


1853
GCA_000980055.1
2209
2209

Methanosarcina mazei

1.H.M.1A.1
Euryarchaeota
JJQR01000061.1
2
KKH76320.1
17840


1854
GCA_000980075.1
2209
2209

Methanosarcina mazei

1.H.M.2.3
Euryarchaeota
JJQW01000059.1
2
KKH88481.1
17842


1855
GCA_000980085.1
2209
2209

Methanosarcina mazei

1.H.M.1A.3
Euryarchaeota
JJQT01000187.1
2
KKH75119.1
17844


1856
GCA_000980105.1
2209
2209

Methanosarcina mazei

1.H.M.2.4
Euryarchaeota
JJQX01000190.1
2
KKH91069.1
17846


1857
GCA_000980135.1
2209
2209

Methanosarcina mazei

1.H.T.2.1
Euryarchaeota
JJQZ01000005.1
2
KKI00020.1
17848


1858
GCA_000980155.1
2209
2209

Methanosarcina mazei

1.H.T.2.3
Euryarchaeota
JJRA01000002.1
2
KKI06936.1
17850


1859
GCA_000980175.1
2209
2209

Methanosarcina mazei

1.H.T.2.5
Euryarchaeota
JJRB01000041.1
2
KKI04817.1
17852


1860
GCA_000465655.1
1390372
1390

Bacillus amyloliquefaciens EGD-AQ14
EGD-AQ14
Firmicutes
AVQH01000001.1
2
ERH59124.1
17854


1861
GCA_000092605.1
75379
926

Thiomonas intermedia K12
K12
Proteobacteria
CP002021.1
3
ADG31357.1
17856


1862
GCA_001263815.1
837
837

Porphyromonas gingivalis

A7436
Bacteroidetes
CP011995.1
3
AKV63928.1
17859


1863
GCA_000436435.1
1263050
1263050

Bacteroides ovatus CAG:22

Bacteroidetes
FR885648.1
3
CDB59852.1
17862


1864
GCA_000154245.1
411489
411489

Clostridium sp. L2-50
L2-50
Firmicutes
DS480312.1
3
ED056710.1
17865


1865
GCA_000768935.1
1515615
1515615

Porphyromonas sp. COT-290 OH860
COT-290
Bacteroidetes
JRAR01000072.1
3
KGN82593.1
17868







OH860


1866
GCA_001183745.1
438
438

Acetobacter pasteurianus

Ab 3
Proteobacteria
CP012111.1
3
AKR49340.1
17871


1867
GCA_000496775.1
1399146
550

Enterobacter cloacae S611
S611
Proteobacteria
AXOM01000048.1
3
ESS57310.1
17874


1868
GCA_000007445.1
199310
562

Escherichia coli CFT073
CFT073
Proteobacteria
AE014075.1
3
AAN80859.1
17877


1869
GCA_000164295.1
749528
562

Escherichia coli MS 45-1
MS 45-1
Proteobacteria
GG772205.1
3
EFJ93881.1
17880


1870
GCA_000164415.1
749536
562

Escherichia coli MS 110-3
MS 110-3
Proteobacteria
GG773033.1
3
EFU46133.1
17883


1871
GCA_000164435.1
749541
562

Escherichia coli MS 153-1
MS 153-1
Proteobacteria
GG773212.1
3
EFU49595.1
17886


1872
GCA_000164535.1
749550
562

Escherichia coli MS 200-1
MS 200-1
Proteobacteria
GG773863.1
3
EFJ59502.1
17889


1873
GCA_000164595.1
749530
562

Escherichia coli MS 60-1
MS 60-1
Proteobacteria
GG774357.1
3
EGB82665.1
17892


1874
GCA_000179795.1
753642
562

Escherichia coli NC101
NC101
Proteobacteria
AEFA01000016.1
3
EFM52806.1
17895


1875
GCA_000190915.1
656390
562

Escherichia coli H263
H263
Proteobacteria
GL871979.1
3
EGB52118.1
17898


1876
GCA_000233875.1
885276
562

Escherichia coli str. ‘clone D i2’
clone D i2
Proteobacteria
CP002211.1
3
AER84780.1
17901


1877
GCA_000233895.1
885275
562

Escherichia coli str. ‘clone D i14’
clone D i14
Proteobacteria
CP002212.1
3
AER89699.1
17904


1878
GCA_000241975.1
656398
562

Escherichia coli H397
H397
Proteobacteria
JH590471.1
3
EH002519.1
17907


1879
GCA_000295775.2
1206108
562

Escherichia coli J96
J96
Proteobacteria
ALIN02000009.1
3
ELL42848.1
17910


1880
GCA_000326165.1
1169374
562

Escherichia coli KTE106
KTE106
Proteobacteria
ANXN01000036.1
3
ELI13536.1
17913


1881
GCA_000326225.1
1169381
562

Escherichia coli KTE124
KTE124
Proteobacteria
ANXU01000045.1
3
ELI43906.1
17916


1882
GCA_000326285.1
1169385
562

Escherichia coli KTE131
KTE131
Proteobacteria
ANXY01000031.1
3
ELI67626.1
17919


1883
GCA_000326305.1
1169386
562

Escherichia coli KTE133
KTE133
Proteobacteria
ANXZ01000016.1
3
ELI72589.1
17922


1884
GCA_000326325.1
1169387
562

Escherichia coli KTE137
KTE137
Proteobacteria
ANYA01000031.1
3
ELI75960.1
17925


1885
GCA_000326385.1
1169393
562

Escherichia coli KTE153
KTE153
Proteobacteria
ANYG01000025.1
3
EU03561.1
17928


1886
GCA_000326405.1
1169395
562

Escherichia coli KTE160
KTE160
Proteobacteria
ANYI01000026.1
3
EU14334.1
17931


1887
GCA_000326605.1
1169400
562

Escherichia coli KTE174
KTE174
Proteobacteria
ANYN01000054.1
3
EU38405.1
17934


1888
GCA_000326625.1
1169366
562

Escherichia coli KTE88
KTE88
Proteobacteria
ANYV01000037.1
3
EU71313.1
17937


1889
GCA_000326705.1
1169390
562

Escherichia coli KTE145
KTE145
Proteobacteria
ANYD01000026.1
3
ELI89432.1
17940


1890
GCA_000326905.1
1169398
562

Escherichia coli KTE167
KTE167
Proteobacteria
KB731668.1
3
EU28710.1
17943


1891
GCA_000350745.1
1169334
562

Escherichia coli KTE15
KTE15
Proteobacteria
KB732276.1
3
ELC30031.1
17946


1892
GCA_000350985.1
1181735
562

Escherichia coli KTE189
KTE189
Proteobacteria
KB732437.1
3
ELC84584.1
17949


1893
GCA_000351005.1
1181737
562

Escherichia coli KTE191
KTE191
Proteobacteria
KB732446.1
3
ELC89744.1
17952


1894
GCA_000351045.1
1181747
562

Escherichia coli KTE201
KTE201
Proteobacteria
KB732482.1
3
ELC99568.1
17955


1895
GCA_000351105.1
1181752
562

Escherichia coli KTE206
KTE206
Proteobacteria
KB732494.1
3
ELD14727.1
17958


1896
GCA_000351245.1
1181766
562

Escherichia coli KTE220
KTE220
Proteobacteria
KB733367.1
3
ELD50500.1
17961


1897
GCA_000351485.1
1182660
562

Escherichia coli KTE53
KTE53
Proteobacteria
KB732687.1
3
ELE05785.1
17964


1898
GCA_000351545.1
1182664
562

Escherichia coli KTE57
KTE57
Proteobacteria
KB732714.1
3
ELE19657.1
17967


1899
GCA_000351565.1
1182665
562

Escherichia coli KTE58
KTE58
Proteobacteria
KB732739.1
3
ELE23560.1
17970


1900
GCA_000351665.1
1182679
562

Escherichia coli KTE72
KTE72
Proteobacteria
KB733397.1
3
ELE50401.1
17973


1901
GCA_000351805.1
1182691
562

Escherichia coli KTE86
KTE86
Proteobacteria
KB732872.1
3
ELE80392.1
17976


1902
GCA_000351825.1
1182692
562

Escherichia coli KTE87
KTE87
Proteobacteria
KB732881.1
3
ELE90662.1
17979


1903
GCA_000351845.1
1182696
562

Escherichia coli KTE93
KTE93
Proteobacteria
KB732897.1
3
ELE91478.1
17982


1904
GCA_000352085.1
1169328
562

Escherichia coli KTE8
KTE8
Proteobacteria
KB732984.1
3
ELF50405.1
17985


1905
GCA_000352265.1
1169341
562

Escherichia coli KTE22
KTE22
Proteobacteria
KB733023.1
3
ELF92090.1
17988


1906
GCA_000352365.1
1182666
562

Escherichia coli KTE59
KTE59
Proteobacteria
KB733042.1
3
ELG14338.1
17991


1907
GCA_000352385.1
1182670
562

Escherichia coli KTE63
KTE63
Proteobacteria
KB733049.1
3
ELG17003.1
17994


1908
GCA_000352405.1
1182672
562

Escherichia coli KTE65
KTE65
Proteobacteria
KB733066.1
3
ELG24591.1
17997


1909
GCA_000352545.1
1182709
562

Escherichia coli KTE118
KTE118
Proteobacteria
KB733111.1
3
ELG54538.1
18000


1910
GCA_000352565.1
1182712
562

Escherichia coli KTE123
KTE123
Proteobacteria
KB733071.1
3
ELG58278.1
18003


1911
GCA_000352905.1
1181729
562

Escherichia coli KTE183
KTE183
Proteobacteria
KB733173.1
3
ELH44356.1
18006


1912
GCA_000353005.1
1181753
562

Escherichia coli KTE207
KTE207
Proteobacteria
KB733196.1
3
ELH62529.1
18009


1913
GCA_000353025.1
1181755
562

Escherichia coli KTE209
KTE209
Proteobacteria
KB733361.1
3
ELH59268.1
18012


1914
GCA_000353065.1
1181761
562

Escherichia coli KTE215
KTE215
Proteobacteria
KB733208.1
3
ELH80077.1
18015


1915
GCA_000353105.1
1181764
562

Escherichia coli KTE218
KTE218
Proteobacteria
KB733215.1
3
ELH85630.1
18018


1916
GCA_000353125.1
1181769
562

Escherichia coli KTE223
KTE223
Proteobacteria
KB733352.1
3
ELH88471.1
18021


1917
GCA_000353185.1
1169372
562

Escherichia coli KTE104
KTE104
Proteobacteria
KB733272.1
3
ELI08747.1
18024


1918
GCA_000401755.1
1322345
562

Escherichia coli ATCC 25922
ATCC 25922
Proteobacteria
ASHD01000045.1
3
EOR52540.1
18027


1919
GCA_000408125.1
1181741
562

Escherichia coli KTE195
KTE195
Proteobacteria
KE136905.1
3
EOV07668.1
18030


1920
GCA_000408285.1
1181772
562

Escherichia coli KTE226
KTE226
Proteobacteria
KE136996.1
3
EOX10652.1
18033


1921
GCA_000408505.1
1182693
562

Escherichia coli KTE89
KTE89
Proteobacteria
KE137142.1
3
EOV94186.1
18036


1922
GCA_000456005.1
1280956
562

Escherichia coli HVH 1 (4-6876161)
HVH 1 (4-6876161)
Proteobacteria
KE698776.1
3
EQN11053.1
18039


1923
GCA_000456065.1
1280959
562

Escherichia coli HVH 4 (4-7276109)
HVH 4 (4-7276109)
Proteobacteria
KE698831.1
3
EQN19685.1
18042


1924
GCA_000456125.1
1280962
562

Escherichia coli HVH 7 (4-7315031)
HVH 7 (4-7315031)
Proteobacteria
KE698877.1
3
EQN35019.1
18045


1925
GCA_000456205.1
1280967
562

Escherichia coli HVH 16 (4-7649002)
HVH 16 (4-7649002)
Proteobacteria
KE698922.1
3
EQN48989.1
18048


1926
GCA_000456285.1
1280971
562

Escherichia coli HVH 20 (4-5865042)
HVH 20 (4-5865042)
Proteobacteria
KE699006.1
3
EQN62516.1
18051


1927
GCA_000456305.1
1280972
562

Escherichia coli HVH 21 (4-4517873)
HVH 21 (4-4517873)
Proteobacteria
KE699022.1
3
EQN79331.1
18054


1928
GCA_000456385.1
1280977
562

Escherichia coli HVH 26 (4-5703913)
HVH 26 (4-5703913)
Proteobacteria
KE699069.1
3
EQN86135.1
18057


1929
GCA_000456405.1
1280978
562

Escherichia coli HVH 27 (4-7449267)
HVH 27 (4-7449267)
Proteobacteria
KE699090.1
3
EQN96595.1
18060


1930
GCA_000456425.1
1280979
562

Escherichia coli HVH 28 (4-0907367)
HVH 28 (4-0907367)
Proteobacteria
KE699097.1
3
EQO12273.1
18063


1931
GCA_000456465.1
1280981
562

Escherichia coli HVH 30 (4-2661829)
HVH 30 (4-2661829)
Proteobacteria
KE699120.1
3
EQO16638.1
18066


1932
GCA_000456485.1
1280982
562

Escherichia coli HVH 31 (4-2602156)
HVH 31 (4-2602156)
Proteobacteria
KE699127.1
3
EQO18515.1
18069


1933
GCA_000456545.1
1280985
562

Escherichia coli HVH 35 (4-2962667)
HVH 35 (4-2962667)
Proteobacteria
KE699157.1
3
EQO32111.1
18072


1934
GCA_000456565.1
1280987
562

Escherichia coli HVH 37 (4-2773848)
HVH 37 (4-2773848)
Proteobacteria
KE699170.1
3
EQO40647.1
18075


1935
GCA_000456625.1
1280990
562

Escherichia coli HVH 40 (4-1219782)
HVH 40 (4-1219782)
Proteobacteria
KE699214.1
3
EQO47387.1
18078


1936
GCA_000456765.1
1280997
562

Escherichia coli HVH 48 (4-2658593)
HVH 48 (4-2658593)
Proteobacteria
KE699294.1
3
EQO84680.1
18081


1937
GCA_000456785.1
1280999
562

Escherichia coli HVH 51 (4-2172526)
HVH 51 (4-2172526)
Proteobacteria
KE699304.1
3
EQO93036.1
18084


1938
GCA_000456825.1
1281002
562

Escherichia coli HVH 55 (4-2646161)
HVH 55 (4-2646161)
Proteobacteria
KE699321.1
3
EQP00513.1
18087


1939
GCA_000456845.1
1281003
562

Escherichia coli HVH 56 (4-2153033)
HVH 56 (4-2153033)
Proteobacteria
KE699325.1
3
EQP09250.1
18090


1940
GCA_000456865.1
1281004
562

Escherichia coli HVH 58 (4-2839709)
HVH 58 (4-2839709)
Proteobacteria
KE699335.1
3
EQP11538.1
18093


1941
GCA_000456905.1
1281006
562

Escherichia coli HVH 61 (4-2736020)
HVH 61 (4-2736020)
Proteobacteria
KE699360.1
3
EQP21163.1
18096


1942
GCA_000456965.1
1281009
562

Escherichia coli HVH 68 (4-0888028)
HVH 68 (4-0888028)
Proteobacteria
KE699393.1
3
EQP38130.1
18099


1943
GCA_000457005.1
1281011
562

Escherichia coli HVH 70 (4-2963531)
HVH 70 (4-2963531)
Proteobacteria
KE699425.1
3
EQP55415.1
18102


1944
GCA_000457045.1
1281013
562

Escherichia coli HVH 74 (4-1034782)
HVH 74 (4-1034782)
Proteobacteria
KE699452.1
3
EQP53333.1
18105


1945
GCA_000457065.1
1281014
562

Escherichia coli HVH 76 (4-2538717)
HVH 76 (4-2538717)
Proteobacteria
KE699459.1
3
EQP61514.1
18108


1946
GCA_000457085.1
1281015
562

Escherichia coli HVH 77 (4-2605759)
HVH 77 (4-2605759)
Proteobacteria
KE699520.1
3
EQP73530.1
18111


1947
GCA_000457105.1
1281016
562

Escherichia coli HVH 78 (4-2735946)
HVH 78 (4-2735946)
Proteobacteria
KE699531.1
3
EQP70429.1
18114


1948
GCA_000457265.1
1281026
562

Escherichia coli HVH 89 (4-5885604)
HVH 89 (4-5885604)
Proteobacteria
KE699634.1
3
EQQ06480.1
18117


1949
GCA_000457325.1
1281029
562

Escherichia coli HVH 92 (4-5930790)
HVH 92 (4-5930790)
Proteobacteria
KE705250.1
3
EQQ25252.1
18120


1950
GCA_000457345.1
1281031
562

Escherichia coli HVH 95 (4-6074464)
HVH 95 (4-6074464)
Proteobacteria
KE699681.1
3
EQQ27933.1
18123


1951
GCA_000457385.1
1281032
562

Escherichia coli HVH 96 (4-5934869)
HVH 96 (4-5934869)
Proteobacteria
KE699694.1
3
EQQ41432.1
18126


1952
GCA_000457405.1
1281036
562

Escherichia coli HVH 100 (4-2850729)
HVH 100 (4-2850729)
Proteobacteria
KE699702.1
3
EQQ33647.1
18129


1953
GCA_000457435.1
1281039
562

Escherichia coli HVH 103 (4-5904188)
HVH 103 (4-5904188)
Proteobacteria
KE699715.1
3
EQQ53134.1
18132


1954
GCA_000457515.1
1281045
562

Escherichia coli HVH 109 (4-6977162)
HVH 109 (4-6977162)
Proteobacteria
KE699785.1
3
EQQ74422.1
18135


1955
GCA_000457555.1
1281047
562

Escherichia coli HVH 111 (4-7039018)
HVH 111 (4-7039018)
Proteobacteria
KE699806.1
3
EQQ75981.1
18138


1956
GCA_000457575.1
1281048
562

Escherichia coli HVH 112 (4-5987253)
HVH 112 (4-5987253)
Proteobacteria
KE699821.1
3
EQQ88668.1
18141


1957
GCA_000457615.1
1281050
562

Escherichia coli HVH 114 (4-7037740)
HVH 114 (4-7037740)
Proteobacteria
KE699847.1
3
EQQ90545.1
18144


1958
GCA_000457675.1
1281053
562

Escherichia coli HVH 116 (4-6879942)
HVH 116 (4-6879942)
Proteobacteria
KE699890.1
3
EQR07410.1
18147


1959
GCA_000457695.1
1281054
562

Escherichia coli HVH 117 (4-6857191)
HVH 117(4-6857191)
Proteobacteria
KE699912.1
3
EQR15138.1
18150


1960
GCA_000457715.1
1281055
562

Escherichia coli HVH 118 (4-7345399)
HVH 118 (4-7345399)
Proteobacteria
KE699926.1
3
EQR19371.1
18153


1961
GCA_000457755.1
1281057
562

Escherichia coli HVH 120 (4-6978681)
HVH 120 (4-6978681)
Proteobacteria
KE699947.1
3
EQR28930.1
18156


1962
GCA_000457915.1
1281065
562

Escherichia coli HVH 132 (4-6876862)
HVH 132 (4-6876862)
Proteobacteria
KE700080.1
3
EQR67054.1
18159


1963
GCA_000457995.1
1281070
562

Escherichia coli HVH 137 (4-2124971)
HVH 137(4-2124971)
Proteobacteria
KE700110.1
3
EQR88164.1
18162


1964
GCA_000458015.1
1281071
562

Escherichia coli HVH 138 (4-6066704)
HVH 138 (4-6066704)
Proteobacteria
KE700120.1
3
EQR94358.1
18165


1965
GCA_000458095.1
1281075
562

Escherichia coli HVH 142 (4-5627451)
HVH 142 (4-5627451)
Proteobacteria
KE700203.1
3
EQS19450.1
18168


1966
GCA_000458115.1
1281076
562

Escherichia coli HVH 143 (4-5674999)
HVH 143 (4-5674999)
Proteobacteria
KE700210.1
3
EQS13124.1
18171


1967
GCA_000458135.1
1281077
562

Escherichia coli HVH 144 (4-4451937)
HVH 144 (4-4451937)
Proteobacteria
KE700223.1
3
EQS20959.1
18174


1968
GCA_000458215.1
1281082
562

Escherichia coli HVH 149 (4-4451880)
HVH 149 (4-4451880)
Proteobacteria
KE700251.1
3
EQS40214.1
18177


1969
GCA_000458355.1
1281090
562

Escherichia coli HVH 157 (4-3406229)
HVH 157 (4-3406229)
Proteobacteria
KE700382.1
3
ERA75001.1
18180


1970
GCA_000458375.1
1281091
562

Escherichia coli HVH 158 (4-3224287)
HVH 158 (4-3224287)
Proteobacteria
KE700388.1
3
EQS62808.1
18183


1971
GCA_000458395.1
1281092
562

Escherichia coli HVH 159 (4-5818141)
HVH 159 (4-5818141)
Proteobacteria
KE700400.1
3
ERA80457.1
18186


1972
GCA_000458415.1
1281093
562

Escherichia coli HVH 160 (4-5695937)
HVH 160 (4-5695937)
Proteobacteria
KE700412.1
3
ERA86693.1
18189


1973
GCA_000458435.1
1281094
562

Escherichia coli HVH 161 (4-3119890)
HVH 161 (4-3119890)
Proteobacteria
KE700429.1
3
EQS67056.1
18192


1974
GCA_000458535.1
1281099
562

Escherichia coli HVH 169 (4-1075578)
HVH 169 (4-1075578)
Proteobacteria
KE700489.1
3
EQS96897.1
18195


1975
GCA_000458575.1
1281101
562

Escherichia coli HVH 171 (4-3191958)
HVH 171 (4-3191958)
Proteobacteria
KE700518.1
3
EQT00426.1
18198


1976
GCA_000458605.1
1281102
562

Escherichia coli HVH 172 (4-3248542)
HVH 172 (4-3248542)
Proteobacteria
KE700534.1
3
EQT14974.1
18201


1977
GCA_000458645.1
1281104
562

Escherichia coli HVH 175 (4-3405184)
HVH 175 (4-3405184)
Proteobacteria
KE700564.1
3
EQT25531.1
18204


1978
GCA_000458745.1
1281111
562

Escherichia coli HVH 184 (4-3343286)
HVH 184 (4-3343286)
Proteobacteria
KE700641.1
3
EQT45492.1
18207


1979
GCA_000458765.1
1281112
562

Escherichia coli HVH 185 (4-2876639)
HVH 185 (4-2876639)
Proteobacteria
KE700651.1
3
EQT50681.1
18210


1980
GCA_000458895.1
1281119
562

Escherichia coli HVH 192 (4-3054470)
HVH 192 (4-3054470)
Proteobacteria
KE700778.1
3
EQT83221.1
18213


1981
GCA_000458935.1
1281121
562

Escherichia coli HVH 194 (4-2356805)
HVH 194 (4-2356805)
Proteobacteria
KE700789.1
3
EQT95718.1
18216


1982
GCA_000458995.1
1281124
562

Escherichia coli HVH 197 (4-4466217)
HVH 197 (4-4466217)
Proteobacteria
KE700810.1
3
EQU21869.1
18219


1983
GCA_000459035.1
1281126
562

Escherichia coli HVH 199 (4-5670322)
HVH 199 (4-5670322)
Proteobacteria
KE700830.1
3
EQU12098.1
18222


1984
GCA_000459255.1
1281137
562

Escherichia coli HVH 210 (4-3042480)
HVH 210 (4-3042480)
Proteobacteria
KE700929.1
3
ERA90778.1
18225


1985
GCA_000459275.1
1281138
562

Escherichia coli HVH 211 (4-3041891)
HVH 211 (4-3041891)
Proteobacteria
KE700944.1
3
EQU70206.1
18228


1986
GCA_000459295.1
1281139
562

Escherichia coli HVH 212 (3-9305343)
HVH 212 (3-9305343)
Proteobacteria
KE700966.1
3
EQU77946.1
18231


1987
GCA_000459355.1
1281143
562

Escherichia coli HVH 216 (4-3042952)
HVH 216 (4-3042952)
Proteobacteria
KE701004.1
3
EQU95026.1
18234


1988
GCA_000459395.1
1281145
562

Escherichia coli HVH 218 (4-4500903)
HVH 218 (4-4500903)
Proteobacteria
KE701041.1
3
EQV01575.1
18237


1989
GCA_000459415.1
1281146
562

Escherichia coli HVH 220 (4-5876842)
HVH 220 (4-5876842)
Proteobacteria
KE701064.1
3
EQV09456.1
18240


1990
GCA_000459515.1
1281151
562

Escherichia coli HVH 227 (4-2277670)
HVH 227 (4-2277670)
Proteobacteria
KE701157.1
3
EQV27904.1
18243


1991
GCA_000459535.1
1281152
562

Escherichia coli HVH 228 (4-7787030)
HVH 228 (4-7787030)
Proteobacteria
KE701167.1
3
ERA94628.1
18246


1992
GCA_000459595.1
1281155
562

Escherichia coli KOEGE 10 (25a)
KOEGE 10 (25a)
Proteobacteria
KE701219.1
3
ERB07224.1
18249


1993
GCA_000459615.1
1281156
562

Escherichia coli KOEGE 30 (63a)
KOEGE 30 (63a)
Proteobacteria
KE701229.1
3
EQV33722.1
18252


1994
GCA_000459755.1
1281163
562

Escherichia coli KOEGE 58 (171a)
KOEGE 58 (171a)
Proteobacteria
KE701333.1
3
EQV70972.1
18255


1995
GCA_000459835.1
1281167
562

Escherichia coli KOEGE 70 (185a)
KOEGE 70 (185a)
Proteobacteria
KE701373.1
3
EQV84934.1
18258


1996
GCA_000460055.1
1281178
562

Escherichia coli UMEA 3053-1
UMEA 3053-1
Proteobacteria
KE701486.1
3
EQW43215.1
18261


1997
GCA_000460175.1
1281184
562

Escherichia coli UMEA 3113-1
UMEA 3113-1
Proteobacteria
KE701574.1
3
EQW70393.1
18264


1998
GCA_000460215.1
1281186
562

Escherichia coli UMEA 3121-1
UMEA 3121-1
Proteobacteria
KE701594.1
3
EQW80283.1
18267


1999
GCA_000460235.1
1281187
562

Escherichia coli UMEA 3122-1
UMEA 3122-1
Proteobacteria
KE701612.1
3
EQW87486.1
18270


2000
GCA_000460415.1
1281197
562

Escherichia coli UMEA 3159-1
UMEA 3159-1
Proteobacteria
KE701731.1
3
EQX12316.1
18273


2001
GCA_000460515.1
1281202
562

Escherichia coli UMEA 3172-1
UMEA 3172-1
Proteobacteria
KE701794.1
3
EQX35785.1
18276


2002
GCA_000460575.1
1281205
562

Escherichia coli UMEA 3175-1
UMEA 3175-1
Proteobacteria
KE701853.1
3
EQX43608.1
18279


2003
GCA_000460655.1
1281209
562

Escherichia coli UMEA 3185-1
UMEA 3185-1
Proteobacteria
KE701908.1
3
EQX66169.1
18282


2004
GCA_000460695.1
1281211
562

Escherichia coli UMEA 3193-1
UMEA 3193-1
Proteobacteria
KE701963.1
3
EQX76187.1
18285


2005
GCA_000460875.1
1281220
562

Escherichia coli UMEA 3216-1
UMEA 3216-1
Proteobacteria
KE702085.1
3
EQY22299.1
18288


2006
GCA_000460915.1
1281222
562

Escherichia coli UMEA 3220-1
UMEA 3220-1
Proteobacteria
KE702109.1
3
EQY33196.1
18291


2007
GCA_000460955.1
1281224
562

Escherichia coli UMEA 3222-1
UMEA 3222-1
Proteobacteria
KE702144.1
3
EQY45032.1
18294


2008
GCA_000461035.1
1281228
562

Escherichia coli UMEA 3244-1
UMEA 3244-1
Proteobacteria
KE702194.1
3
EQY55714.1
18297


2009
GCA_000461055.1
1281230
562

Escherichia coli UMEA 3257-1
UMEA 3257-1
Proteobacteria
KE702215.1
3
EQY72171.1
18300


2010
GCA_000461335.1
1281248
562

Escherichia coli UMEA 3391-1
UMEA 3391-1
Proteobacteria
KE702394.1
3
EQZ19658.1
18303


2011
GCA_000461375.1
1281252
562

Escherichia coli UMEA 3585-1
UMEA 3585-1
Proteobacteria
KE702412.1
3
EQZ26675.1
18306


2012
GCA_000461435.1
1281255
562

Escherichia coli UMEA 3617-1
UMEA 3617-1
Proteobacteria
KE702447.1
3
EQZ41390.1
18309


2013
GCA_000461655.1
1281268
562

Escherichia coli UMEA 3707-1
UMEA 3707-1
Proteobacteria
KE702569.1
3
EQZ91637.1
18312


2014
GCA_000461815.1
1281276
562

Escherichia coli UMEA 3955-1
UMEA 3955-1
Proteobacteria
KE702703.1
3
ERA32823.1
18315


2015
GCA_000461835.1
1281277
562

Escherichia coli UMEA 4075-1
UMEA 4075-1
Proteobacteria
KE702710.1
3
ERA36348.1
18318


2016
GCA_000463605.1
1281257
562

Escherichia coli UMEA 3652-1
UMEA 3652-1
Proteobacteria
KE705271.1
3
ERF54134.1
18321


2017
GCA_000488075.1
1281249
562

Escherichia coli UMEA 3426-1
UMEA 3426-1
Proteobacteria
KI530636.1
3
ESK18132.1
18324


2018
GCA_000488095.1
1281234
562

Escherichia coli UMEA 3290-1
UMEA 3290-1
Proteobacteria
KI530644.1
3
ESK18554.1
18327


2019
GCA_000488115.1
1281263
562

Escherichia coli UMEA 3693-1
UMEA 3693-1
Proteobacteria
KI530660.1
3
ESK29586.1
18330


2020
GCA_000488315.1
1268980
562

Escherichia coli 907391
907391
Proteobacteria
KI530980.1
3
ESC95631.1
18333


2021
GCA_000488475.1
1268990
562

Escherichia coli 907892
907892
Proteobacteria
KI532243.1
3
ESD43645.1
18336


2022
GCA_000488795.1
1269010
562

Escherichia coli 910096-2
910096-2
Proteobacteria
KI534866.1
3
ESE27410.1
18339


2023
GCA_000488815.1
1269008
562

Escherichia coli A25922R
A25922R
Proteobacteria
KI535058.1
3
ESE32327.1
18342


2024
GCA_000488835.1
1269009
562

Escherichia coli A35218R
A35218R
Proteobacteria
KI535180.1
3
ESE38128.1
18345


2025
GCA_000494975.1
1281023
562

Escherichia coli HVH 86 (4-7026218)
HVH 86 (4-7026218)
Proteobacteria
KI538693.1
3
ESP10882.1
18348


2026
GCA_000494975.1
1281023
562

Escherichia coli HVH 86 (4-7026218)
HVH 86 (4-7026218)
Proteobacteria
KI538695.1
3
ESP23171.1
18351


2027
GCA_000506445.2
1389417
562

Escherichia coli LAU-EC6
LAU-EC6
Proteobacteria
AYNF01000074.1
3
ETE11169.1
18354


2028
GCA_000507685.1
1281250
562

Escherichia coli UMEA 3489-1
UMEA 3489-1
Proteobacteria
KI669372.1
3
ETF35984.1
18357


2029
GCA_000633655.1
1445863
562

Escherichia coli BIDMC 83
BIDMC 83
Proteobacteria
KK214043.1
3
EZQ63564.1
18360


2030
GCA_000692475.1
1438673
562

Escherichia coli BIDMC 65
BIDMC 65
Proteobacteria
KK736329.1
3
KDG03094.1
18363


2031
GCA_000696545.1
562
562

Escherichia coli

2009-46
Proteobacteria
JJNT01000018.1
3
KD090448.1
18366


2032
GCA_000714595.1
316435
562

Escherichia coli Nissle 1917
Nissle 1917
Proteobacteria
CP007799.1
3
AID79061.1
18369


2033
GCA_000743255.1
1322345
562

Escherichia coli ATCC 25922
ATCC 25922
Proteobacteria
CP009072.1
3
AIL16531.1
18372


2034
GCA_001030285.1
562
562

Escherichia coli

BWH59
Proteobacteria
KQ087625.1
3
KLX17105.1
18375


2035
GCA_001030435.1
562
562

Escherichia coli

MGH122
Proteobacteria
KQ087876.1
3
KLX44352.1
18378


2036
GCA_001030445.1
562
562

Escherichia coli

BIDMC97
Proteobacteria
KQ087859.1
3
KLX45653.1
18381


2037
GCA_001280385.1
562
562

Escherichia coli

SF-166
Proteobacteria
CP012633.1
3
ALD34922.1
18384


2038
GCA_001463115.1
562
562

Escherichia coli

50664179
Proteobacteria
LNHU01000095.1
3
KSY02659.1
18387


2039
GCA_001518355.1
562
562

Escherichia coli

GN02748
Proteobacteria
LQZV01000057.1
3
KUR38256.1
18390


2040
GCA_001519115.1
562
562

Escherichia coli

GN02007
Proteobacteria
LQRW01000143.1
3
KUR81832.1
18393


2041
GCA_001519125.1
562
562

Escherichia coli

GN02009
Proteobacteria
LQRX01000141.1
3
KUR94071.1
18396


2042
GCA_001519215.1
562
562

Escherichia coli

GN02045
Proteobacteria
LQRY01000066.1
3
KUR99612.1
18399


2043
GCA_001519315.1
562
562

Escherichia coli

GN02183
Proteobacteria
LQSM01000041.1
3
KUS68705.1
18402


2044
GCA_001519365.1
562
562

Escherichia coli

GN02175
Proteobacteria
LQSL01000095.1
3
KUS65754.1
18405


2045
GCA_001519435.1
562
562

Escherichia coli

GN02050
Proteobacteria
LQRZ01000151.1
3
KUS06588.1
18408


2046
GCA_001519485.1
562
562

Escherichia coli

GN03398
Proteobacteria
LQVU01000143.1
3
KUW86271.1
18411


2047
GCA_001519595.1
562
562

Escherichia coli

GN02323
Proteobacteria
LQTA01000215.1
3
KUT33561.1
18414


2048
GCA_001519645.1
562
562

Escherichia coli

GN02639
Proteobacteria
LQUW01000126.1
3
KUV71918.1
18417


2049
GCA_001519895.1
562
562

Escherichia coli

GN02345
Proteobacteria
LQTD01000025.1
3
KUT65775.1
18420


2050
GCA_001520055.1
562
562

Escherichia coli

GN02392
Proteobacteria
LQTM01000161.1
3
KUT92654.1
18423


2051
GCA_001520195.1
562
562

Escherichia coli

GN02627
Proteobacteria
LQUU01000218.1
3
KUV55766.1
18426


2052
GCA_001520215.1
562
562

Escherichia coli

GN02529
Proteobacteria
LQUG01000209.1
3
KUU92987.1
18429


2053
GCA_001520555.1
562
562

Escherichia coli

GN02590
Proteobacteria
LQUP01000306.1
3
KUV32574.1
18432


2054
GCA_001520715.1
562
562

Escherichia coli

GN03545
Proteobacteria
LQVY01000168.1
3
KUX05523.1
18435


2055
GCA_001520735.1
562
562

Escherichia coli

GN03496
Proteobacteria
LQVX01000201.1
3
KUX02162.1
18438


2056
GCA_001520815.1
562
562

Escherichia coli

GN02766
Proteobacteria
LQVG01000173.1
3
KUW18188.1
18441


2057
GCA_001520895.1
562
562

Escherichia coli

GN02411
Proteobacteria
LQTP01000196.1
3
KUU04902.1
18444


2058
GCA_001521015.1
562
562

Escherichia coli

GN02867
Proteobacteria
LQVL01000165.1
3
KUW44250.1
18447


2059
GCA_001521155.1
562
562

Escherichia coli

GN02787
Proteobacteria
LQVJ01000229.1
3
KUW29415.1
18450


2060
GCA_001521225.1
562
562

Escherichia coli

GN02350
Proteobacteria
LQTE01000122.1
3
KUT58679.1
18453


2061
GCA_001521315.1
562
562

Escherichia coli

GN03786
Proteobacteria
LQWD01000068.1
3
KUX37210.1
18456


2062
GCA_001521355.1
562
562

Escherichia coli

GN02547
Proteobacteria
LQUL01000230.1
3
KUV14410.1
18459


2063
GCA_001521455.1
562
562

Escherichia coli

GN04262
Proteobacteria
LQWM01000080.1
3
KUX73639.1
18462


2064
GCA_001521575.1
562
562

Escherichia coli

GN03324
Proteobacteria
LQVT01000030.1
3
KUW86783.1
18465


2065
GCA_001521635.1
562
562

Escherichia coli

GN04153
Proteobacteria
LQWI01000317.1
3
KUX51102.1
18468


2066
GCA_001524885.1
562
562

Escherichia coli

GN02609
Proteobacteria
LRA001000013.1
3
KVI42424.1
18471


2067
GCA_001524905.1
562
562

Escherichia coli

GN02487
Proteobacteria
LRAN01000026.1
3
KVI22808.1
18474


2068
GCA_001562835.1
562
562

Escherichia coli

JPH264
Proteobacteria
KQ961179.1
3
KXG92284.1
18477


2069
GCA_001571575.1
562
562

Escherichia coli

UM131
Proteobacteria
LRX001000021.1
3
KXL04869.1
18480


2070
GCA_001571585.1
562
562

Escherichia coli

UM149
Proteobacteria
LRXN01000040.1
3
KXL27378.1
18483


2071
GCA_001571645.1
562
562

Escherichia coli

CD44
Proteobacteria
LRXP01000062.1
3
KXL05683.1
18486


2072
GCA_001571725.1
562
562

Escherichia coli

UM128
Proteobacteria
LRXU01000008.1
3
KXL13115.1
18489


2073
GCA_001471755.1
564
564

Escherichia fergusonii

FDAARGOS_170
Proteobacteria
LORS01000001.1
3
KTK75705.1
18492


2074
GCA_000415405.1
1244143
1351

Enterococcus faecalis VC1B-1
VC1B-1
Firmicutes
KE352639.1
3
EPI32466.1
18495


2075
GCA_000519685.1
1391483
1351

Enterococcus faecalis EnGen0413
EnGen0413
Firmicutes
KI913017.1
3
ETU24520.1
18498


2076
GCA_000322325.1
1138929
1352

Enterococcus faecium EnGen0048
E4215
Firmicutes
KB030000.1
3
ELB67022.1
18501


2077
GCA_000371505.1
999408
1531
[Clostridium] clostridioforme 90A8
90A8
Firmicutes
KB850978.1
3
ENZ13057.1
18504


2078
GCA_000487575.2
984211
28901

Salmonella enterica subsp.
ATCC BAA-1592
Proteobacteria
CP007531.1
3
AHW13890.1
18507







enterica serovar Anatum str.






ATCC BAA-1592


2079
GCA_000495295.1
1321366
28901

Salmonella enterica subsp.
S-70
Proteobacteria
AQQN01000068.1
3
ESP72121.1
18510







enterica serovar Saintpaul






str. S-70


2080
GCA_000495315.1
1323580
28901

Salmonella enterica subsp.
S-76
Proteobacteria
AROZ01000126.1
3
ESP76604.1
18513







enterica serovar Oranienburg






str. S-76


2081
GCA_000748865.1
1173435
28901

Salmonella enterica subsp.
CFSAN000207
Proteobacteria
JRDQ01000027.1
3
KFT73591.1
18516







enterica serovar Bareilly






str. CFSAN000207


2082
GCA_000806625.1
59201
28901

Salmonella enterica subsp.
CFSAN024764
Proteobacteria
JWQO01000015.1
3
KHP33099.1
18519







enterica



2083
GCA_000806925.1
59201
28901

Salmonella enterica subsp.
CFSAN024763
Proteobacteria
JWQP01000009.1
3
KHP34815.1
18522







enterica



2084
GCA_000988525.1
1454585
28901

Salmonella enterica subsp.
USDA-ARS-
Proteobacteria
CP007584.1
3
AKF88465.1
18525







enterica serovar Anatum
USMARC-1735






str. USDA-ARS-USMARC-1735


2085
GCA_001241205.1
58712
28901

Salmonella enterica subsp.
CVM N44698
Proteobacteria
LHFG01000018.1
3
KNK74744.1
18528







enterica serovar Anatum


2086
GCA_001247355.1
58712
28901

Salmonella enterica subsp.
CVM N51307
Proteobacteria
LHON01000003.1
3
KNW86449.1
18531







enterica serovar Anatum


2087
GCA_001447095.1
58712
28901

Salmonella enterica subsp.
GT-38
Proteobacteria
CP013226.1
3
ALO88020.1
18534







enterica serovar Anatum


2088
GCA_001475375.1
28901
28901

Salmonella enterica

CVM 43842
Proteobacteria
JYTH01000003.1
3
KTQ21993.1
18537


2089
GCA_001478355.1
58712
28901

Salmonella enterica subsp.
CVM N38876
Proteobacteria
JYXM01000005.1
3
KUB19293.1
18540







enterica serovar Anatum


2090
GCA_001479145.1
58712
28901

Salmonella enterica subsp.
CVM N31410
Proteobacteria
JYVK01000019.1
3
KTY61367.1
18543







enterica serovar Anatum


2091
GCA_001479905.1
192955
28901

Salmonella enterica subsp.
CVM N38870
Proteobacteria
JYXJ01000004.1
3
KUB06249.1
18546







enterica serovar Kentucky


2092
GCA_001481105.1
58712
28901

Salmonella enterica subsp.
CVM N42473
Proteobacteria
JYZV01000014.1
3
KUD94944.1
18549







enterica serovar Anatum


2093
GCA_001569785.1
28901
28901

Salmonella enterica

NGUA13
Proteobacteria
BCOL01000077.1
3
GAR53165.1
18552


2094
GCA_000154805.1
428126
29348
[Clostridium] spiroforme
DSM 1552
Firmicutes
DS562851.1
3
EDS74761.1
18555






DSM 1552


2095
GCA_001483145.1
172045
172045

Elizabethkingia miricola

EM_CHUV
Bacteroidetes
LIQC01000001.1
3
KUG13796.1
18558


2096
GCA_000273015.1
997874
246787

Bacteroides cellulosilyticus

CL02T12C19
Bacteroidetes
JH724089.1
3
EIY23905.1
18561






CL02T12C19


2097
GCA_000403255.2
397288
397288

Lachnospiraceae bacterium 3-1
3-1
Firmicutes
KE159581.1
3
EOS20511.1
18564


2098
GCA_000157115.2
469598
469598

Escherichia sp. 3_2_53FAA
3_2_53FAA
Proteobacteria
KQ235746.1
3
EEH86957.1
18567


2099
GCA_000437535.1
1263103
1263103

Prevotella stercorea CAG:629

Bacteroidetes
FR899171.1
3
CDE34946.1
18570


2100
GCA_000486445.2
938141
28901

Salmonella enterica subsp.
ATCC 15791
Proteobacteria
CP012349.1
4
AKW15253.1
18573







enterica serovar Sloterdijk






str. ATCC 15791










(Part B)























L



P



T



X




ThsA



ThsB (i)



ThsB (ii)



ThsB (iii)



K
protein
M
N
O
protein
Q
R
S
protein
U
V
W
protein



DNA SEQ
length
ThsB (i)
PRT SEQ
DNA SEQ
length
ThsB (ii)
PRT SEQ
DNA SEQ
length
ThsB (iii)
PRT SEQ
DNA SEQ
length


1
ID NO:
(aa)
protein_accession
ID NO:
ID NO:
(aa)
protein_accession
ID NO:
ID NO:
(aa)
protein_accession
ID NO:
ID NO:
(aa)





2
18577
478
EAN10000.1
13221
18578
161
EAN09998.1
13222
18579
283


3
18580
477
EAZ85482.1
13224
18581
226


4
18582
478
EFF33949.1
13226
18583
161
EFF33951.1
13227
18584
283


5
18585
478
EFF30625.1
13229
18586
161
EFF30623.1
13230
18587
283


6
18588
461
EFA90643.1
13232
18589
165


7
18590
474
EFM65151.1
13234
18591
165


8
18592
471
EFF51767.1
13236
18593
182
EFF51769.1
13237
18594
203


9
18595
500
AAP11367.1
13239
18596
206


10
18597
473
EFM08815.1
13241
18598
166
EFM08816.1
13242
18599
203


11
18600
466
KND82315.1
13244
18601
160
KND82316.1
13245
18602
214


12
18603
466
KOE55211.1
13247
18604
160
KOE55212.1
13248
18605
214


13
18606
478
EHM35988.1
13250
18607
161
EHM35990.1
13251
18608
283


14
18609
473
EPE98430.1
13253
18610
162


15
18611
217
EGV07223.1
13255
18612
208
EGV07230.1
13256
18613
164


16
18614
469
EHD29826.1
13258
18615
206
EHD29828.1
13259
18616
310


17
18617
375
EHM75406.1
13261
18618
202
EHM75402.1
13262
18619
308


18
18620
466
EHK91560.1
13264
18621
69
EHK91561.1
13265
18622
214


19
18623
489
EOR48147.1
13267
18624
202
EOR48148.1
13268
18625
344


20
18626
470
EID19241.1
13270
18627
206
EID19242.1
13271
18628
388


21
18629
381
EIA14314.1
13273
18630
202
EIA14315.1
13274
18631
344


22
18632
159
EIC95415.1
13276
18633
122


23
18634
476
EKS70340.1
13278
18635
162


24
18636
466
KOE52659.1
13280
18637
214
KOE52660.1
13281
18638
160


25
18639
466
KOE56125.1
13283
18640
214
KOE56126.1
13284
18641
160


26
18642
465
EIJ69684.1
13286
18643
164
EIJ69602.1
13287
18644
208


27
18645
208
EIL59627.1
13289
18646
155


28
18647
477
EJH65284.1
13291
18648
97


29
18649
473
EPV35488.1
13293
18650
165


30
18651
499
CAN93963.1
13295
18652
956


31
18653
483
CAQ50580.1
13297
18654
202
CAQ50581.1
13298
18655
308


32
18656
482
EKF39861.1
13300
18657
162
EKF39859.1
13301
18658
184


33
18659
477
ETE93553.1
13303
18660
226


34
18661
477
ETE97367.1
13305
18662
226


35
18663
479
EPC81227.1
13307
18664
210


36
18665
478
ELI26318.1
13309
18666
203


37
18667
478
ELJ29819.1
13311
18668
203


38
18669
472
EME14865.1
13313
18670
160
EME14867.1
13314
18671
194


39
18672
484
EMF02810.1
13316
18673
163


40
18674
484
BAO35115.1
13318
18675
163


41
18676
560
BAO91364.1
13320
18677
485


42
18678
482
BAQ74701.1
13322
18679
158
BAQ74699.1
13323
18680
134
BAQ74700.1
13324
18681
177


43
18683
480
ENZ83251.1
13327
18684
163
ENZ83249.1
13328
18685
194


44
18686
480
EQB07553.1
13330
18687
155


45
18688
476
EPJ82188.1
13332
18689
160


46
18690
480
EPR14529.1
13334
18691
155


47
18692
483
EQM91606.1
13336
18693
202
EQM91605.1
13337
18694
344


48
18695
483
EPZ04958.1
13339
18696
202
EPZ04959.1
13340
18697
344


49
18698
483
EPZ06673.1
13342
18699
202
EPZ06672.1
13343
18700
344


50
18701
375
EPZ03689.1
13345
18702
202
EPZ03688.1
13346
18703
344


51
18704
375
EPZ11498.1
13348
18705
202
EPZ11497.1
13349
18706
308


52
18707
231
EQC60102.1
13351
18708
165


53
18709
473
EQG20076.1
13353
18710
141


54
18711
473
EQK23002.1
13355
18712
165


55
18713
482
ETR95050.1
13357
18714
164
ETR94961.1
13358
18715
385
ETR95013.1
13359
18716
111


56
18719
481
EQL89246.1
13363
18720
104
EQL89247.1
13364
18721
191


57
18722
484
ERH73217.1
13366
18723
163


58
18724
473
ERT62591.1
13368
18725
165


59
18726
487
ERT61533.1
13370
18727
163
ERT61545.1
13371
18728
376


60
18729
473
ERT58461.1
13373
18730
165


61
18731
482
ERT19167.1
13375
18732
158
ERT19165.1
13376
18733
179
ERT19166.1
13377
18734
183


62
18736
487
ESR69981.1
13380
18737
167
ESR69983.1
13381
18738
183


63
18739
480
KAJ84752.1
13383
18740
141
KAJ84753.1
13384
18741
206


64
18742
479
KAJ82224.1
13386
18743
206


65
18744
474
ETD82033.1
13388
18745
165


66
18746
489
ESZ88709.1
13390
18747
168
ESZ88707.1
13391
18748
184


67
18749
478
ETJ99317.1
13393
18750
203


68
18751
221
KYK73941.1
13395
18752
160
KYK73942.1
13396
18753
214


69
18754
468
ETO98875.1
13398
18755
166


70
18756
456
GAE27471.1
13400
18757
161


71
18758
451
GAM02794.1
13402
18759
143
GAM02793.1
13403
18760
186


72
18761
477
CAE30981.1
13405
18762
193
CAE30983.1
13406
18763
165


73
18764
477
CCP18524.1
13408
18765
146
CCP18522.1
13409
18766
307


74
18767
480
CDZ53066.1
13411
18768
159


75
18769
468
CEF52296.1
13413
18770
153


76
18771
237
CJD59502.1
13415
18772
248


77
18773
500
EEL09526.1
13417
18774
206


78
18775
476
EEL84781.1
13419
18776
192
EEL84783.1
13420
18777
139


79
18778
476
EEL90115.1
13422
18779
192
EEL90113.1
13423
18780
139


80
18781
473
EFH92718.1
13425
18782
165


81
18783
486
EFR92172.1
13427
18784
202


82
18785
487
EIK62341.1
13429
18786
167
EIK59131.1
13430
18787
192


83
18788
481
ABB40970.1
13432
18789
146
ABB40968.1
13433
18790
180
ABB40962.1
13434
18791
262


84
18792
480
ABD68806.1
13436
18793
157


85
18794
479
ABR91779.1
13438
18795
163
ABR91881.1
13439
18796
197


86
18797
477
ABI42032.1
13441
18798
164
ABI42037.1
13442
18799
160


87
18800
466
ABN74272.1
13444
18801
165
ABN74273.1
13445
18802
214


88
18803
549
ABO35463.1
13447
18804
171


89
18805
484
ABP73210.1
13449
18806
165
ABP73208.1
13450
18807
183


90
18808
478
ABR34953.1
13452
18809
229
ABR34957.1
13453
18810
202
ABR34959.1
13454
18811
166


91
18813
1197
ABR65054.1
13457
18814
641


92
18815
482
ACA73844.1
13459
18816
158
ACA73842.1
13460
18817
179
ACA73843.1
13461
18818
183


93
18820
476
ACB66893.1
13464
18821
135
ACB66892.1
13465
18822
197


94
18823
342
ACX81592.1
13467
18824
214
ACX81593.1
13468
18825
160


95
18826
479
ACZ11006.1
13470
18827
202


96
18828
325
ADB76072.1
13472
18829
421
ADB76078.1
13473
18830
793


97
18831
481
ADY67728.1
13475
18832
162
ADY67726.1
13476
18833
130
ADY67729.1
13477
18834
465


98
18835
293
ADP84994.1
13479
18836
535


99
18837
345
AEB29796.1
13481
18838
182
AEB29798.1
13482
18839
194


100
18840
482
AEA61150.1
13484
18841
161
AEA61151.1
13485
18842
193
AEA61157.1
13486
18843
155


101
18846
381
AFH70384.1
13490
18847
202
AFH70385.1
13491
18848
344


102
18849
466
AEW76522.1
13493
18850
214
AEW76523.1
13494
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357
19406
473
CRW38422.1
14050
19407
165


358
19408
473
CRW56682.1
14052
19409
165


359
19410
473
CRW57506.1
14054
19411
165


360
19412
473
CRW51171.1
14056
19413
165


361
19414
473
CRW56053.1
14058
19415
165


362
19416
473
CRW51028.1
14060
19417
165


363
19418
473
CRW62438.1
14062
19419
165


364
19420
473
CRW52653.1
14064
19421
165


365
19422
473
CRW57935.1
14066
19423
165


366
19424
473
CRW58504.1
14068
19425
165


367
19426
473
CRW59077.1
14070
19427
165


368
19428
473
CRW78808.1
14072
19429
165


369
19430
473
CRW72028.1
14074
19431
165


370
19432
473
CRW79987.1
14076
19433
165


371
19434
473
CRW76327.1
14078
19435
165


372
19436
473
CRW80128.1
14080
19437
165


373
19438
473
CRW66999.1
14082
19439
165


374
19440
473
CRW70540.1
14084
19441
165


375
19442
473
CRW76747.1
14086
19443
165


376
19444
473
CRW76878.1
14088
19445
165


377
19446
473
CRW80962.1
14090
19447
165


378
19448
473
CRW81686.1
14092
19449
165


379
19450
473
CRW77668.1
14094
19451
165


380
19452
473
CRW79793.1
14096
19453
165


381
19454
473
CRW80957.1
14098
19455
165


382
19456
481
CTT29891.1
14100
19457
155


383
19458
481
CTZ05317.1
14102
19459
155


384
19460
491
CUB16901.1
14104
19461
165


385
19462
482
CUI41016.1
14106
19463
161
CUI41048.1
14107
19464
193
CUI41311.1
14108
19465
155


386
19467
473
CUK22711.1
14111
19468
146
CUK22702.1
14112
19469
113


387
19470
486
CUK50737.1
14114
19471
202


388
19472
486
CUK61278.1
14116
19473
202


389
19474
486
CUK91822.1
14118
19475
202


390
19476
461
EDM51054.1
14120
19477
203
EDM51056.1
14121
19478
188
EDM51058.1
14122
19479
282


391
19480
484
CUY08443.1
14124
19481
163


392
19482
484
CUZ68596.1
14126
19483
163


393
19484
484
CUZ82333.1
14128
19485
163


394
19486
484
CUZ53179.1
14130
19487
163


395
19488
484
CVA27418.1
14132
19489
163


396
19490
484
CUZ41313.1
14134
19491
163


397
19492
484
CVA08079.1
14136
19493
163


398
19494
484
CUZ42337.1
14138
19495
163


399
19496
484
CVA28833.1
14140
19497
163


400
19498
484
CUZ16090.1
14142
19499
163


401
19500
484
CUZ61026.1
14144
19501
163


402
19502
484
CUZ90983.1
14146
19503
163


403
19504
484
CUZ73356.1
14148
19505
163


404
19506
484
CVA13520.1
14150
19507
163


405
19508
484
CVA22984.1
14152
19509
163


406
19510
484
CUY16507.1
14154
19511
163


407
19512
484
CUZ58687.1
14156
19513
163


408
19514
484
CUZ73597.1
14158
19515
163


409
19516
484
CUZ84806.1
14160
19517
163


410
19518
484
CUZ51268.1
14162
19519
163


411
19520
484
CVA06067.1
14164
19521
163


412
19522
484
CUZ66217.1
14166
19523
163


413
19524
484
CUZ96361.1
14168
19525
163


414
19526
484
CUZ56063.1
14170
19527
163


415
19528
484
CUZ47666.1
14172
19529
163


416
19530
306
CUZ65482.1
14174
19531
163


417
19532
484
CUZ64434.1
14176
19533
163


418
19534
484
CUZ76056.1
14178
19535
163


419
19536
484
CVA13481.1
14180
19537
163


420
19538
484
CVA27120.1
14182
19539
163


421
19540
484
CVA15846.1
14184
19541
163


422
19542
484
CUZ46999.1
14186
19543
163


423
19544
484
CUZ30986.1
14188
19545
163


424
19546
484
CUZ02657.1
14190
19547
163


425
19548
484
CUZ51348.1
14192
19549
163


426
19550
484
CUZ55112.1
14194
19551
163


427
19552
484
CVA20234.1
14196
19553
163


428
19554
484
CUZ69722.1
14198
19555
163


429
19556
306
CUZ82685.1
14200
19557
163


430
19558
484
CUZ92253.1
14202
19559
163


431
19560
484
CUZ80137.1
14204
19561
163


432
19562
306
CUZ43160.1
14206
19563
163


433
19564
484
CVA39205.1
14208
19565
163


434
19566
484
CVA66680.1
14210
19567
163


435
19568
484
CUZ78128.1
14212
19569
163


436
19570
484
CUZ53811.1
14214
19571
163


437
19572
484
CVA07157.1
14216
19573
163


438
19574
484
CUZ96160.1
14218
19575
163


439
19576
484
CVA63355.1
14220
19577
163


440
19578
484
CVB19765.1
14222
19579
163


441
19580
484
CVB15307.1
14224
19581
163


442
19582
484
CVB18610.1
14226
19583
163


443
19584
484
CVC33373.1
14228
19585
163


444
19586
484
CVC43459.1
14230
19587
163


445
19588
484
CVB44154.1
14232
19589
163


446
19590
484
CVC13577.1
14234
19591
163


447
19592
306
CVB24202.1
14236
19593
163


448
19594
484
CVB63328.1
14238
19595
163


449
19596
484
CVB58992.1
14240
19597
163


450
19598
306
CVB73390.1
14242
19599
163


451
19600
306
CVA22542.1
14244
19601
163


452
19602
484
CVC54883.1
14246
19603
163


453
19604
484
CVC47662.1
14248
19605
163


454
19606
484
CVC16868.1
14250
19607
163


455
19608
484
CVA94551.1
14252
19609
163


456
19610
484
CVB98061.1
14254
19611
163


457
19612
484
CVB27563.1
14256
19613
163


458
19614
484
CVC12710.1
14258
19615
163


459
19616
484
CVB94236.1
14260
19617
163


460
19618
484
CVC34514.1
14262
19619
163


461
19620
484
CVC37237.1
14264
19621
163


462
19622
484
CVC09959.1
14266
19623
163


463
19624
484
CVB51982.1
14268
19625
163


464
19626
484
CVB83683.1
14270
19627
163


465
19628
484
CVB86104.1
14272
19629
163


466
19630
484
CVC63999.1
14274
19631
163


467
19632
306
CVB86034.1
14276
19633
163


468
19634
484
CVC85541.1
14278
19635
163


469
19636
484
CVC33606.1
14280
19637
163


470
19638
484
CVC91020.1
14282
19639
163


471
19640
484
CVC23340.1
14284
19641
163


472
19642
484
CVC01465.1
14286
19643
163


473
19644
484
CVC17896.1
14288
19645
163


474
19646
484
CVC49253.1
14290
19647
163


475
19648
306
CVD13477.1
14292
19649
163


476
19650
484
CVC16333.1
14294
19651
163


477
19652
484
CVC38388.1
14296
19653
163


478
19654
484
CVC81405.1
14298
19655
163


479
19656
484
CVC81576.1
14300
19657
163


480
19658
484
CVC86607.1
14302
19659
163


481
19660
484
CVC98763.1
14304
19661
163


482
19662
484
CVC91159.1
14306
19663
163


483
19664
484
CVC94687.1
14308
19665
163


484
19666
484
CVC52230.1
14310
19667
163


485
19668
484
CVC98236.1
14312
19669
163


486
19670
484
CVB21750.1
14314
19671
163


487
19672
484
CVC48200.1
14316
19673
163


488
19674
484
CVC71583.1
14318
19675
163


489
19676
484
CVC84184.1
14320
19677
163


490
19678
306
CVC59774.1
14322
19679
163


491
19680
484
CVE09079.1
14324
19681
163


492
19682
484
CVD69880.1
14326
19683
163


493
19684
484
CVD52024.1
14328
19685
163


494
19686
484
CVD94582.1
14330
19687
163


495
19688
484
CVD41050.1
14332
19689
163


496
19690
306
CVD28932.1
14334
19691
163


497
19692
484
CVC37080.1
14336
19693
163


498
19694
484
CVE33508.1
14338
19695
163


499
19696
306
CVC40354.1
14340
19697
163


500
19698
306
CVE27819.1
14342
19699
163


501
19700
484
CVE60700.1
14344
19701
163


502
19702
306
CVE69177.1
14346
19703
163


503
19704
484
CVE06156.1
14348
19705
163


504
19706
484
CVE70674.1
14350
19707
163


505
19708
484
CVD68135.1
14352
19709
163


506
19710
484
CVE19607.1
14354
19711
163


507
19712
484
CVE94911.1
14356
19713
163


508
19714
484
CVE74015.1
14358
19715
163


509
19716
484
CVE69277.1
14360
19717
163


510
19718
484
CVD84064.1
14362
19719
163


511
19720
484
CVE29091.1
14364
19721
163


512
19722
484
CVD89467.1
14366
19723
163


513
19724
306
CVE62900.1
14368
19725
163


514
19726
484
CVE95691.1
14370
19727
163


515
19728
484
CVF11375.1
14372
19729
163


516
19730
484
CVF28649.1
14374
19731
163


517
19732
484
CVC97390.1
14376
19733
163


518
19734
484
CVD52643.1
14378
19735
163


519
19736
484
CVE22758.1
14380
19737
163


520
19738
484
CVE97454.1
14382
19739
163


521
19740
484
CVF28158.1
14384
19741
163


522
19742
484
CVE60533.1
14386
19743
163


523
19744
484
CVE66058.1
14388
19745
163


524
19746
484
CVF01477.1
14390
19747
163


525
19748
484
CVE93253.1
14392
19749
163


526
19750
484
CVF50134.1
14394
19751
163


527
19752
306
CVF09910.1
14396
19753
163


528
19754
484
CVE63411.1
14398
19755
163


529
19756
484
CVE05444.1
14400
19757
163


530
19758
484
CVE67662.1
14402
19759
163


531
19760
484
CVE73566.1
14404
19761
163


532
19762
484
CVF13064.1
14406
19763
163


533
19764
484
CVE92994.1
14408
19765
163


534
19766
484
CVF15667.1
14410
19767
163


535
19768
484
CVE70361.1
14412
19769
163


536
19770
484
CVF77810.1
14414
19771
163


537
19772
484
CVF08046.1
14416
19773
163


538
19774
484
CVF84133.1
14418
19775
163


539
19776
484
CVF82137.1
14420
19777
163


540
19778
484
CVG26701.1
14422
19779
163


541
19780
484
CVG63887.1
14424
19781
163


542
19782
484
CVG49433.1
14426
19783
163


543
19784
484
CVF96091.1
14428
19785
163


544
19786
484
CVG60811.1
14430
19787
163


545
19788
484
CVG18576.1
14432
19789
163


546
19790
484
CVG60263.1
14434
19791
163


547
19792
484
CVG00271.1
14436
19793
163


548
19794
484
CVG18115.1
14438
19795
163


549
19796
484
CVG66394.1
14440
19797
163


550
19798
306
CVF82722.1
14442
19799
163


551
19800
484
CVG27190.1
14444
19801
163


552
19802
484
CVH08322.1
14446
19803
163


553
19804
306
CVG82345.1
14448
19805
163


554
19806
484
CVG89971.1
14450
19807
163


555
19808
484
CVG75193.1
14452
19809
163


556
19810
484
CVG91902.1
14454
19811
163


557
19812
484
CVG61740.1
14456
19813
163


558
19814
484
CVG55691.1
14458
19815
163


559
19816
484
CVG99595.1
14460
19817
163


560
19818
484
CVG85863.1
14462
19819
163


561
19820
484
CVH13264.1
14464
19821
163


562
19822
484
CVH22072.1
14466
19823
163


563
19824
484
CVG79637.1
14468
19825
163


564
19826
484
CVH31713.1
14470
19827
163


565
19828
484
CVG61487.1
14472
19829
163


566
19830
484
CVF47762.1
14474
19831
163


567
19832
484
CVH23246.1
14476
19833
163


568
19834
484
CVG86968.1
14478
19835
163


569
19836
484
CVG92546.1
14480
19837
163


570
19838
484
CVH34063.1
14482
19839
163


571
19840
465
CVG73755.1
14484
19841
163


572
19842
484
CVH31045.1
14486
19843
163


573
19844
484
CVH30700.1
14488
19845
163


574
19846
484
CVG97923.1
14490
19847
163


575
19848
484
CVH42939.1
14492
19849
163


576
19850
484
CVH11711.1
14494
19851
163


577
19852
484
CVH39720.1
14496
19853
163


578
19854
484
CVH33846.1
14498
19855
163


579
19856
484
CVG91297.1
14500
19857
163


580
19858
484
CVH37749.1
14502
19859
163


581
19860
484
CVH21011.1
14504
19861
163


582
19862
484
CVG01680.1
14506
19863
163


583
19864
484
CVH35255.1
14508
19865
163


584
19866
484
CVH07271.1
14510
19867
163


585
19868
484
CVH30938.1
14512
19869
163


586
19870
484
CVH50697.1
14514
19871
163


587
19872
484
CVH40526.1
14516
19873
163


588
19874
484
CVH64630.1
14518
19875
163


589
19876
484
CVH70543.1
14520
19877
163


590
19878
484
CVH72213.1
14522
19879
163


591
19880
484
CVH65593.1
14524
19881
163


592
19882
593
CVJ13862.1
14526
19883
505


593
19884
479
CVJ11186.1
14528
19885
166
CVJ11217.1
14529
19886
257


594
19887
335
CVJ34976.1
14531
19888
293


595
19889
486
CWV39708.1
14533
19890
202


596
19891
486
CWW37521.1
14535
19892
202


597
19893
469
CYO51346.1
14537
19894
206
CYO51297.1
14538
19895
388


598
19896
468
CYT98226.1
14540
19897
156


599
19898
469
CZB11023.1
14542
19899
206
CZB10962.1
14543
19900
382


600
19901
469
CZB35760.1
14545
19902
206
CZB35774.1
14546
19903
382


601
19904
125
CZD24096.1
14548
19905
184


602
19906
125
CZC77665.1
14550
19907
184


603
19908
125
CZD72514.1
14552
19909
184


604
19910
125
CZE23710.1
14554
19911
184


605
19912
473
CAW93166.1
14556
19913
165


606
19914
345
CBK94113.1
14558
19915
260


607
19916
483
CCE59806.1
14560
19917
202
CCE59807.1
14561
19918
362


608
19919
472
CDD80087.1
14563
19920
166
CDD80084.1
14564
19921
196


609
19922
472
EEG72545.1
14566
19923
203


610
19924
424
EEP27314.1
14568
19925
163
EEP27315.1
14569
19926
189
EEP27316.1
14570
19927
376


611
19928
475
EEI83076.1
14572
19929
205


612
19930
478
EEV44994.1
14574
19931
161
EEV44996.1
14575
19932
283


613
19933
485
EES71590.1
14577
19934
227


614
19935
471
EEY94493.1
14579
19936
231
EEY94495.1
14580
19937
194


615
19938
478
EFS10289.1
14582
19939
161
EFS10291.1
14583
19940
283


616
19941
478
EGF19708.1
14585
19942
206
EGF19710.1
14586
19943
388


617
19944
476
EGK00062.1
14588
19945
203
EGK00061.1
14589
19946
191


618
19947
1379
CCH29380.1
14591
19948
404


619
19949
473
CCN04568.1
14593
19950
146


620
19951
484
CDG13495.1
14595
19952
144


621
19953
485
CDH26047.1
14597
19954
196


622
19955
478
EZP94705.1
14599
19956
161
EZP94707.1
14600
19957
283


623
19958
478
EZP99084.1
14602
19959
161
EZP99086.1
14603
19960
283


624
19961
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21959
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16603
21960
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1312
21961
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KAG51660.1
16605
21962
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KAG51661.1
16606
21963
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1313
21964
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21965
202
KAG55492.1
16609
21966
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1314
21967
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KAG59144.1
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21968
202
KAG59145.1
16612
21969
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1315
21970
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KAG59706.1
16614
21971
202
KAG59707.1
16615
21972
308


1316
21973
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KAG65357.1
16617
21974
202
KAG65358.1
16618
21975
308


1317
21976
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16620
21977
202
KAG67527.1
16621
21978
308


1318
21979
483
KAG68213.1
16623
21980
202
KAG68214.1
16624
21981
308


1319
21982
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KAG69691.1
16626
21983
202
KAG69692.1
16627
21984
308


1320
21985
483
KAG74734.1
16629
21986
202
KAG74735.1
16630
21987
308


1321
21988
483
KAG76837.1
16632
21989
202
KAG76838.1
16633
21990
308


1322
21991
483
KAG76106.1
16635
21992
202
KAG76107.1
16636
21993
308


1323
21994
483
KAG81174.1
16638
21995
202
KAG81175.1
16639
21996
308


1324
21997
483
KAG82428.1
16641
21998
202
KAG82429.1
16642
21999
308


1325
22000
483
KAG84390.1
16644
22001
202
KAG84391.1
16645
22002
308


1326
22003
483
KAG88851.1
16647
22004
202
KAG88852.1
16648
22005
308


1327
22006
483
KAG92814.1
16650
22007
202
KAG92815.1
16651
22008
308


1328
22009
483
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16653
22010
202
KAG95314.1
16654
22011
308


1329
22012
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16656
22013
202
KAH01282.1
16657
22014
308


1330
22015
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16659
22016
202
KAH06868.1
16660
22017
308


1331
22018
483
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16662
22019
202
KAH07513.1
16663
22020
308


1332
22021
483
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16665
22022
202
KAH16052.1
16666
22023
308


1333
22024
483
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16668
22025
202
KAH15237.1
16669
22026
308


1334
22027
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16671
22028
202
KAH19616.1
16672
22029
308


1335
22030
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16674
22031
202
KAH24556.1
16675
22032
308


1336
22033
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16677
22034
202
KAH28157.1
16678
22035
308


1337
22036
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16680
22037
202
KAH29214.1
16681
22038
308


1338
22039
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22040
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22041
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1339
22042
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22043
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16687
22044
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1340
22045
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16689
22046
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16690
22047
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1341
22048
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16692
22049
202
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16693
22050
308


1342
22051
483
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16695
22052
202
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16696
22053
308


1343
22054
483
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16698
22055
202
KAH45887.1
16699
22056
308


1344
22057
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KAH47352.1
16701
22058
202
KAH47353.1
16702
22059
308


1345
22060
483
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16704
22061
202
KAH50035.1
16705
22062
308


1346
22063
483
KAH53956.1
16707
22064
202
KAH53957.1
16708
22065
308


1347
22066
483
KAH55296.1
16710
22067
202
KAH55297.1
16711
22068
308


1348
22069
483
KAH59145.1
16713
22070
202
KAH59146.1
16714
22071
308


1349
22072
483
KAH62177.1
16716
22073
202
KAH62178.1
16717
22074
308


1350
22075
483
KAH64793.1
16719
22076
202
KAH64794.1
16720
22077
308


1351
22078
483
KAH67713.1
16722
22079
202
KAH67714.1
16723
22080
308


1352
22081
483
KAH70234.1
16725
22082
202
KAH70235.1
16726
22083
308


1353
22084
483
KAH70951.1
16728
22085
202
KAH70952.1
16729
22086
308


1354
22087
483
KAH74940.1
16731
22088
202
KAH74941.1
16732
22089
308


1355
22090
483
KAH77219.1
16734
22091
202
KAH77220.1
16735
22092
308


1356
22093
483
KAH77146.1
16737
22094
202
KAH77147.1
16738
22095
308


1357
22096
483
KAH82034.1
16740
22097
202
KAH82035.1
16741
22098
308


1358
22099
131
KAH85415.1
16743
22100
202
KAH85416.1
16744
22101
308


1359
22102
483
KAH87603.1
16746
22103
202
KAH87604.1
16747
22104
308


1360
22105
483
KAH91092.1
16749
22106
202
KAH91093.1
16750
22107
308


1361
22108
483
KAH91683.1
16752
22109
202
KAH91684.1
16753
22110
308


1362
22111
483
KAH96190.1
16755
22112
202
KAH96191.1
16756
22113
308


1363
22114
483
KAH96015.1
16758
22115
202
KAH96016.1
16759
22116
308


1364
22117
483
KAI00776.1
16761
22118
202
KAI00777.1
16762
22119
308


1365
22120
483
KAI04124.1
16764
22121
202
KAI04125.1
16765
22122
308


1366
22123
483
KAI02995.1
16767
22124
202
KAI02996.1
16768
22125
308


1367
22126
483
KAI08746.1
16770
22127
202
KAI08747.1
16771
22128
308


1368
22129
483
KAI10608.1
16773
22130
202
KAI10609.1
16774
22131
308


1369
22132
483
KAI13048.1
16776
22133
202
KAI13049.1
16777
22134
308


1370
22135
483
KAI15460.1
16779
22136
202
KAI15461.1
16780
22137
308


1371
22138
375
KAI16286.1
16782
22139
202
KAI16287.1
16783
22140
308


1372
22141
483
KAI19039.1
16785
22142
202
KAI19040.1
16786
22143
308


1373
22144
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KAI22532.1
16788
22145
202
KAI22533.1
16789
22146
308


1374
22147
375
KAI26856.1
16791
22148
202
KAI26857.1
16792
22149
308


1375
22150
375
KAI29883.1
16794
22151
202
KAI29884.1
16795
22152
308


1376
22153
483
KAI31278.1
16797
22154
202
KAI31279.1
16798
22155
308


1377
22156
483
KAI34384.1
16800
22157
202
KAI34385.1
16801
22158
308


1378
22159
483
KAI37684.1
16803
22160
202
KAI37685.1
16804
22161
308


1379
22162
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KAI38931.1
16806
22163
202
KAI38932.1
16807
22164
308


1380
22165
483
KAI42592.1
16809
22166
202
KAI42593.1
16810
22167
308


1381
22168
483
KAI44806.1
16812
22169
202
KAI44807.1
16813
22170
308


1382
22171
483
KAI46180.1
16815
22172
202
KAI46181.1
16816
22173
308


1383
22174
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KAI50312.1
16818
22175
202
KAI50313.1
16819
22176
308


1384
22177
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KAI52599.1
16821
22178
202
KAI52600.1
16822
22179
308


1385
22180
483
KAI51893.1
16824
22181
202
KAI51894.1
16825
22182
308


1386
22183
483
KAI58510.1
16827
22184
202
KAI58511.1
16828
22185
308


1387
22186
483
KAI59068.1
16830
22187
202
KAI59069.1
16831
22188
308


1388
22189
375
KAI62092.1
16833
22190
202
KAI62093.1
16834
22191
308


1389
22192
483
KAI65036.1
16836
22193
202
KAI65037.1
16837
22194
308


1390
22195
483
KAI67114.1
16839
22196
202
KAI67115.1
16840
22197
72


1391
22198
483
KAI71115.1
16842
22199
202
KAI71116.1
16843
22200
72


1392
22201
483
KAI72296.1
16845
22202
202
KAI72297.1
16846
22203
308


1393
22204
483
KAI76026.1
16848
22205
202
KAI76027.1
16849
22206
308


1394
22207
483
KAI77489.1
16851
22208
202
KAI77490.1
16852
22209
308


1395
22210
483
KAI79405.1
16854
22211
202
KAI79406.1
16855
22212
308


1396
22213
483
KAI83419.1
16857
22214
202
KAI83420.1
16858
22215
308


1397
22216
483
KAF82850.1
16860
22217
202
KAF82851.1
16861
22218
308


1398
22219
487
KES25285.1
16863
22220
167
KES25283.1
16864
22221
183


1399
22222
487
KKB51169.1
16866
22223
160
KKB51171.1
16867
22224
186


1400
22225
481
KKB46311.1
16869
22226
163
KKB46308.1
16870
22227
181


1401
22228
478
KME80491.1
16872
22229
203


1402
22230
484
KMJ04348.1
16874
22231
163


1403
22232
480
KSU86124.1
16876
22233
202


1404
22234
484
KUR80454.1
16878
22235
165
KUR80452.1
16879
22236
184
KUR80451.1
16880
22237
259


1405
22238
476
KXT60078.1
16882
22239
207


1406
22240
477
KJP12012.1
16884
22241
146
KJP12010.1
16885
22242
161


1407
22243
486
KKO42007.1
16887
22244
202


1408
22245
480
KMQ31910.1
16889
22246
202


1409
22247
480
KMQ31455.1
16891
22248
202


1410
22249
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KMQ31338.1
16893
22250
202


1411
22251
477
KMQ07577.1
16895
22252
226


1412
22253
488
KJU85604.1
16897
22254
162


1413
22255
475
KJS18753.1
16899
22256
160
KJS18754.1
16900
22257
228


1414
22258
478
KLD44467.1
16902
22259
203


1415
22260
481
KKZ08482.1
16904
22261
200
KKZ08481.1
16905
22262
191


1416
22263
479
KKX43504.1
16907
22264
209


1417
22265
478
KKJ66888.1
16909
22266
161
KKJ66890.1
16910
22267
283


1418
22268
480
KKR96939.1
16912
22269
168
KKR96941.1
16913
22270
393


1419
22271
484
KKZ15777.1
16915
22272
163


1420
22273
586
KLA35046.1
16917
22274
325


1421
22275
477
KLA36291.1
16919
22276
226


1422
22277
481
KLF79288.1
16921
22278
155


1423
22279
484
KLE38478.1
16923
22280
163


1424
22281
481
KMN72582.1
16925
22282
202


1425
22283
481
KMN78964.1
16927
22284
155
KMN78968.1
16928
22285
155
KMN78965.1
16929
22286
190


1426
22287
477
KOQ86135.1
16931
22288
146
KOQ86133.1
16932
22289
161


1427
22290
479
KOQ96627.1
16934
22291
205
KOQ96628.1
16935
22292
165


1428
22293
487
KXU94745.1
16937
22294
167
KXU94712.1
16938
22295
183


1429
22296
484
KMU49984.1
16940
22297
163


1430
22298
269
KMZ12178.1
16942
22299
103
KMZ12179.1
16943
22300
174


1431
22301
477
KMY27374.1
16945
22302
155
KMY27378.1
16946
22303
147
KMY27376.1
16947
22304
165


1432
22305
481
KOF39298.1
16949
22306
200
KOF39299.1
16950
22307
191


1433
22308
492
KPH74234.1
16952
22309
161
KPH74237.1
16953
22310
175


1434
22311
487
KPG99047.1
16955
22312
167
KPG99049.1
16956
22313
183


1435
22314
486
KUG12362.1
16958
22315
163
KUG12363.1
16959
22316
235
KUG12375.1
16960
22317
178


1436
22318
477
KPS74517.1
16962
22319
200
KPS74518.1
16963
22320
146
KPS74516.1
16964
22321
395


1437
22322
477
KPS95937.1
16966
22323
146
KPS95938.1
16967
22324
200
KPS95939.1
16968
22325
395


1438
22326
487
KPF70567.1
16970
22327
165


1439
22328
477
KQB82199.1
16972
22329
202


1440
22330
474
KQL33556.1
16974
22331
222


1441
22332
477
KPY89191.1
16976
22333
147
KPY89133.1
16977
22334
167
KPY89165.1
16978
22335
276


1442
22336
482
CDT62295.1
16980
22337
166
CDT62262.1
16981
22338
228


1443
22339
482
CDT49130.1
16983
22340
166
CDT49099.1
16984
22341
228


1444
22342
475
KTC51735.1
16986
22343
160


1445
22344
475
KTB70324.1
16988
22345
160


1446
22346
494
KTB90115.1
16990
22347
312


1447
22348
388
KTC03052.1
16992
22349
231


1448
22350
474
KRF62305.1
16994
22351
200


1449
22352
474
KSF14310.1
16996
22353
163


1450
22354
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KSG00434.1
16998
22355
158
KSG00432.1
16999
22356
179
KSG00433.1
17000
22357
183


1451
22359
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KSO26595.1
17003
22360
158
KSO26596.1
17004
22361
183
KSO26597.1
17005
22362
179


1452
22364
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KSQ24405.1
17008
22365
158
KSQ24406.1
17009
22366
183
KSQ24407.1
17010
22367
179


1453
22369
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KSQ18858.1
17013
22370
167
KSQ18860.1
17014
22371
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1454
22372
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KQV52822.1
17016
22373
158


1455
22374
596
KQW19001.1
17018
22375
370


1456
22376
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KQN02370.1
17020
22377
158


1457
22378
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KQS95551.1
17022
22379
205
KQS95550.1
17023
22380
174


1458
22381
334
KRE80989.1
17025
22382
318


1459
22383
240
CEA11437.1
17027
22384
156


1460
22385
240
CEA10433.1
17029
22386
156


1461
22387
307
CUU52510.1
17031
22388
165
CUU52511.1
17032
22389
214


1462
22390
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KSX76370.1
17034
22391
166


1463
22392
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KWY00932.1
17036
22393
161
KWY00934.1
17037
22394
283


1464
22395
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KWY16708.1
17039
22396
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KWY16706.1
17040
22397
283


1465
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KWY36997.1
17042
22399
161
KWY36995.1
17043
22400
283


1466
22401
329
KWY51063.1
17045
22402
161


1467
22403
314
KWY60249.1
17047
22404
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1468
22405
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KWY71635.1
17049
22406
161


1469
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KWY79779.1
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22408
161
KWY79777.1
17052
22409
283


1470
22410
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KWY89824.1
17054
22411
114


1471
22412
478
KWY92723.1
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22413
161
KWY92721.1
17057
22414
283


1472
22415
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KWY92991.1
17059
22416
161
KWY92993.1
17060
22417
283


1473
22418
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KWY96006.1
17062
22419
161
KWY96008.1
17063
22420
283


1474
22421
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KWZ06303.1
17065
22422
161
KWZ06305.1
17066
22423
283


1475
22424
489
KST54507.1
17068
22425
202
KST54506.1
17069
22426
344


1476
22427
477
KTD46364.1
17071
22428
163


1477
22429
479
KUO54663.1
17073
22430
155


1478
22431
500
KXY14128.1
17075
22432
206


1479
22433
126
KXQ35633.1
17077
22434
155


1480
22435
126
KXG66577.1
17079
22436
155


1481
22437
476
KVM18169.1
17081
22438
160
KVM18174.1
17082
22439
155
KVM18170.1
17083
22440
197


1482
22441
476
KVM22188.1
17085
22442
155
KVM22193.1
17086
22443
160
KVM22192.1
17087
22444
197


1483
22445
476
KVM54442.1
17089
22446
160
KVM54448.1
17090
22447
155
KVM54443.1
17091
22448
197


1484
22449
476
KVO16516.1
17093
22450
146


1485
22451
536
KVR44247.1
17095
22452
315


1486
22453
484
KVR99615.1
17097
22454
189
KVR99752.1
17098
22455
129


1487
22456
477
KVS07628.1
17100
22457
203


1488
22458
484
KVU94134.1
17102
22459
189
KVU94209.1
17103
22460
129


1489
22461
476
KVX54695.1
17105
22462
160


1490
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493
KWA77748.1
17107
22464
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1758
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1759
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1760
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1761
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1762
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1763
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1764
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CPO89917.1
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1765
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CFW49157.1
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23022
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1766
23023
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CFM22758.1
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1767
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1768
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CFO79489.1
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1769
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CFU75865.1
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1770
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1771
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1772
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1773
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263
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1774
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1775
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1776
23043
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1777
23045
263
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23046
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1778
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1779
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1780
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1781
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273
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1782
23055
273
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1783
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CPK97857.1
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1784
23059
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CPN81591.1
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1785
23061
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1786
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1787
23065
263
CFK50093.1
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1788
23067
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CPG83454.1
17711
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1789
23069
273
CFT72111.1
17713
23070
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1790
23071
273
CFL13096.1
17715
23072
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1791
23073
273
CFL88482.1
17717
23074
185


1792
23075
263
CPE71771.1
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23076
185


1793
23077
273
CFT96164.1
17721
23078
185


1794
23079
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CFT85443.1
17723
23080
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1795
23081
263
CFL56340.1
17725
23082
185


1796
23083
263
CPI51266.1
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23084
185


1797
23085
249
ESG20658.1
17729
23086
295


1798
23087
278
AJQ64507.1
17731
23088
303


1799
23089
278
AJZ80319.1
17733
23090
303


1800
23091
234
CPW02870.1
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170


1801
23093
279
GAC48718.1
17737
23094
171


1802
23095
258
ABM10182.1
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169


1803
23097
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ERN46352.1
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169


1804
23099
230
KTD01947.1
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1805
23101
297
CCV65563.1
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23102
162


1806
23103
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KMK02864.1
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1807
23105
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AHJ12535.1
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1808
23107
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KUL42777.1
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1809
23109
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EID21941.1
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1810
23111
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GAD37766.1
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1811
23113
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KRK83039.1
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1812
23115
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EFV85441.1
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1813
23117
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EMZ26177.1
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1814
23119
290
EKX62814.1
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23120
410


1815
23121
293
ABR64201.1
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1816
23123
292
KND18806.1
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23124
166


1817
23125
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ADG41467.1
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166


1818
23127
290
EEA91363.1
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1819
23129
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EHI61154.1
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23130
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1820
23131
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EFF62518.1
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23132
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1821
23133
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ALS25373.1
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1822
23135
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KGM37270.1
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1823
23137
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EWG70340.1
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1824
23139
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AKP49794.1
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1825
23141
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KJV29336.1
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23142
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1826
23143
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EIL89964.1
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23144
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1827
23145
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KFF05552.1
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1828
23147
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CTQ72907.1
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1829
23149
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KRU21992.1
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1830
23151
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KJL32260.1
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1831
23153
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EHS54841.1
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1832
23155
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EJL63881.1
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1833
23157
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EJL84706.1
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1834
23159
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EID73850.1
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1835
23161
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KWF17575.1
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1836
23163
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ERI96810.1
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215


1837
23165
319
EOS38322.1
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23166
166


1838
23167
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EOS41469.1
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23168
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1839
23169
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CDF26097.1
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23170
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1840
23171
317
KGN67553.1
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23172
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1841
23173
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KUK53686.1
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1842
23175
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KKO89197.1
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1843
23177
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KNC08319.1
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1844
23179
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KQN47926.1
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23180
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1845
23181
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KKH38513.1
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1846
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1847
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1848
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1849
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KKH80639.1
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1850
23191
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1851
23193
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KKH51285.1
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1852
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1853
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1854
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193


1855
23201
276
KKH75120.1
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1856
23203
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KKH91068.1
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193


1857
23205
276
KKI00019.1
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193


1858
23207
276
KKI06937.1
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193


1859
23209
276
KKI04816.1
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23210
193


1860
23211
255
ERH59125.1
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23212
190


1861
23213
279
ADG31356.1
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23214
187
ADG31358.1
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23215
186


1862
23216
273
AKV63927.1
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23217
188
AKV63929.1
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23218
231


1863
23219
281
CDB59853.1
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23220
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CDB59854.1
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23221
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1864
23222
297
EDO56708.1
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23223
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EDO56706.1
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23224
184


1865
23225
271
KGN82594.1
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23226
187
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23227
224


1866
23228
277
AKR49339.1
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AKR49342.1
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1867
23231
292
ESS57196.1
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23232
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ESS57523.1
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1868
23234
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AAN80857.1
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1869
23237
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EFJ93883.1
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1870
23240
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1871
23243
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1872
23246
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1873
23249
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1874
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1875
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EGB52116.1
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1876
23258
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1877
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1878
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EHO02521.1
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1879
23267
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ELL42846.1
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169


1880
23270
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1881
23273
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1882
23276
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1883
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1884
23282
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1885
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1886
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278
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ELJ14333.1
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169


1887
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ELJ38403.1
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1888
23294
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ELJ71311.1
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23295
307
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17939
23296
169


1889
23297
278
ELI89430.1
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307
ELI89431.1
17942
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169


1890
23300
278
ELJ28708.1
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17945
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169


1891
23303
278
ELC30029.1
17947
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169


1892
23306
278
ELC84582.1
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1893
23309
278
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1894
23312
278
ELC99566.1
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ELC99567.1
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1895
23315
278
ELD14725.1
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23316
307
ELD14726.1
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169


1896
23318
278
ELD50498.1
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307
ELD50499.1
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169


1897
23321
278
ELE05783.1
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23322
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ELE05784.1
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169


1898
23324
278
ELE19655.1
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307
ELE19656.1
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169


1899
23327
278
ELE23558.1
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23328
307
ELE23559.1
17972
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169


1900
23330
278
ELE50399.1
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23331
307
ELE50400.1
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23332
169


1901
23333
278
ELE80390.1
17977
23334
307
ELE80391.1
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169


1902
23336
278
ELE90660.1
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23337
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ELE90661.1
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169


1903
23339
278
ELE91476.1
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307
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1904
23342
278
ELF50403.1
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169


1905
23345
278
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307
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169


1906
23348
278
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1907
23351
278
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1908
23354
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1909
23357
278
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169


1910
23360
278
ELG58276.1
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307
ELG58277.1
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169


1911
23363
278
ELH44354.1
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307
ELH44355.1
18008
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169


1912
23366
278
ELH62527.1
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307
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18011
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169


1913
23369
278
ELH59266.1
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307
ELH59267.1
18014
23371
169


1914
23372
278
ELH80075.1
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307
ELH80076.1
18017
23374
169


1915
23375
278
ELH85628.1
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307
ELH85629.1
18020
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169


1916
23378
278
ELH88469.1
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307
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18023
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169


1917
23381
278
ELI08745.1
18025
23382
307
ELI08746.1
18026
23383
169


1918
23384
278
EOR52538.1
18028
23385
307
EOR52539.1
18029
23386
169


1919
23387
278
EOV07666.1
18031
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307
EOV07667.1
18032
23389
169


1920
23390
278
EOX10650.1
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307
EOX10651.1
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169


1921
23393
278
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18037
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307
EOV94185.1
18038
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169


1922
23396
278
EQN11055.1
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23397
307
EQN11054.1
18041
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169


1923
23399
278
EQN19683.1
18043
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307
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18044
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169


1924
23402
278
EQN35017.1
18046
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307
EQN35018.1
18047
23404
140


1925
23405
278
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307
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18050
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169


1926
23408
278
EQN62514.1
18052
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307
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18053
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169


1927
23411
278
EQN79329.1
18055
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307
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18056
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169


1928
23414
278
EQN86133.1
18058
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307
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18059
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169


1929
23417
278
EQN96593.1
18061
23418
307
EQN96594.1
18062
23419
169


1930
23420
278
EQO12275.1
18064
23421
307
EQO12274.1
18065
23422
169


1931
23423
278
EQO16636.1
18067
23424
307
EQO16637.1
18068
23425
169


1932
23426
278
EQO18513.1
18070
23427
307
EQO18514.1
18071
23428
169


1933
23429
278
EQO32109.1
18073
23430
307
EQO32110.1
18074
23431
169


1934
23432
278
EQO40645.1
18076
23433
307
EQO40646.1
18077
23434
169


1935
23435
278
EQO47385.1
18079
23436
307
EQO47386.1
18080
23437
169


1936
23438
278
EQO84678.1
18082
23439
307
EQO84679.1
18083
23440
169


1937
23441
278
EQO93034.1
18085
23442
307
EQO93035.1
18086
23443
169


1938
23444
278
EQO00511.1
18088
23445
307
EQP00512.1
18089
23446
169


1939
23447
278
EQP09248.1
18091
23448
307
EQP09249.1
18092
23449
169


1940
23450
278
EQP11536.1
18094
23451
307
EQP11537.1
18095
23452
169


1941
23453
278
EQP21161.1
18097
23454
307
EQP21162.1
18098
23455
169


1942
23456
278
EQP38128.1
18100
23457
307
EQP38129.1
18101
23458
169


1943
23459
278
EQP55411.1
18103
23460
307
EQP55412.1
18104
23461
169


1944
23462
278
EQP53331.1
18106
23463
307
EQP53332.1
18107
23464
169


1945
23465
278
EQP61512.1
18109
23466
307
EQP61513.1
18110
23467
169


1946
23468
278
EQP73528.1
18112
23469
307
EQP73529.1
18113
23470
169


1947
23471
278
EQP70427.1
18115
23472
307
EQP70428.1
18116
23473
169


1948
23474
278
EQQ06478.1
18118
23475
307
EQQ06479.1
18119
23476
169


1949
23477
278
EQQ25250.1
18121
23478
307
EQQ25251.1
18122
23479
169


1950
23480
278
EQQ27931.1
18124
23481
307
EQQ27932.1
18125
23482
169


1951
23483
278
EQQ41430.1
18127
23484
307
EQQ41431.1
18128
23485
169


1952
23486
278
EQQ33645.1
18130
23487
307
EQQ33646.1
18131
23488
169


1953
23489
278
EQQ53132.1
18133
23490
307
EQQ53133.1
18134
23491
169


1954
23492
278
EQQ74420.1
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23493
307
EQQ74421.1
18137
23494
169


1955
23495
278
EQQ75979.1
18139
23496
307
EQQ75980.1
18140
23497
169


1956
23498
278
EQQ88666.1
18142
23499
307
EQQ88667.1
18143
23500
169


1957
23501
278
EQQ90543.1
18145
23502
307
EQQ90544.1
18146
23503
169


1958
23504
278
EQR07408.1
18148
23505
307
EQR07409.1
18149
23506
169


1959
23507
278
EQR15136.1
18151
23508
307
EQR15137.1
18152
23509
169


1960
23510
278
EQR19369.1
18154
23511
307
EQR19370.1
18155
23512
169


1961
23513
278
EQR28928.1
18157
23514
307
EQR28929.1
18158
23515
169


1962
23516
278
EQR67052.1
18160
23517
307
EQR67053.1
18161
23518
169


1963
23519
278
EQR88162.1
18163
23520
307
EQR88163.1
18164
23521
169


1964
23522
278
EQR94356.1
18166
23523
307
EQR94357.1
18167
23524
169


1965
23525
278
EQS19448.1
18169
23526
307
EQS19449.1
18170
23527
169


1966
23528
278
EQS13122.1
18172
23529
307
EQS13123.1
18173
23530
169


1967
23531
278
EQS20957.1
18175
23532
307
EQS20958.1
18176
23533
169


1968
23534
278
EQS40212.1
18178
23535
307
EQS40213.1
18179
23536
169


1969
23537
278
ERA74999.1
18181
23538
307
ERA75000.1
18182
23539
169


1970
23540
278
EQS62806.1
18184
23541
307
EQS62807.1
18185
23542
169


1971
23543
278
ERA80455.1
18187
23544
307
ERA80456.1
18188
23545
169


1972
23546
278
ERA86691.1
18190
23547
307
ERA86692.1
18191
23548
169


1973
23549
278
EQS67054.1
18193
23550
307
EQS67055.1
18194
23551
169


1974
23552
278
EQS96895.1
18196
23553
307
EQS96896.1
18197
23554
169


1975
23555
278
EQT00424.1
18199
23556
307
EQT00425.1
18200
23557
169


1976
23558
278
EQT14972.1
18202
23559
307
EQT14973.1
18203
23560
169


1977
23561
278
EQT25529.1
18205
23562
307
EQT25530.1
18206
23563
169


1978
23564
278
EQT45490.1
18208
23565
307
EQT45491.1
18209
23566
169


1979
23567
278
EQT50679.1
18211
23568
307
EQT50680.1
18212
23569
169


1980
23570
278
EQT83219.1
18214
23571
307
EQT83220.1
18215
23572
169


1981
23573
249
EQT95716.1
18217
23574
307
EQT95717.1
18218
23575
169


1982
23576
278
EQU21867.1
18220
23577
307
EQU21868.1
18221
23578
169


1983
23579
278
EQU12096.1
18223
23580
307
EQU12097.1
18224
23581
169


1984
23582
278
ERA90776.1
18226
23583
307
ERA90777.1
18227
23584
169


1985
23585
278
EQU70204.1
18229
23586
307
EQU70205.1
18230
23587
169


1986
23588
278
EQU77944.1
18232
23589
307
EQU77945.1
18233
23590
169


1987
23591
278
EQU95024.1
18235
23592
307
EQU95025.1
18236
23593
169


1988
23594
278
EQV01573.1
18238
23595
307
EQV01574.1
18239
23596
169


1989
23597
278
EQV09454.1
18241
23598
307
EQV09455.1
18242
23599
169


1990
23600
278
EQV27902.1
18244
23601
307
EQV27903.1
18245
23602
169


1991
23603
278
ERA94626.1
18247
23604
307
ERA94627.1
18248
23605
169


1992
23606
278
ERB07222.1
18250
23607
307
ERB07223.1
18251
23608
169


1993
23609
278
EQV33720.1
18253
23610
307
EQV33721.1
18254
23611
169


1994
23612
278
EQV70970.1
18256
23613
307
EQV70971.1
18257
23614
169


1995
23615
278
EQV84932.1
18259
23616
307
EQV84933.1
18260
23617
169


1996
23618
278
EQW43213.1
18262
23619
307
EQW43214.1
18263
23620
169


1997
23621
278
EQW70391.1
18265
23622
307
EQW70392.1
18266
23623
169


1998
23624
278
EQW80281.1
18268
23625
307
EQW80282.1
18269
23626
169


1999
23627
278
EQW87484.1
18271
23628
307
EQW87485.1
18272
23629
169


2000
23630
278
EQX12314.1
18274
23631
307
EQX12315.1
18275
23632
169


2001
23633
278
EQX35783.1
18277
23634
307
EQX35784.1
18278
23635
169


2002
23636
278
EQX43606.1
18280
23637
307
EQX43607.1
18281
23638
169


2003
23639
278
EQX66167.1
18283
23640
307
EQX66168.1
18284
23641
169


2004
23642
278
EQX76185.1
18286
23643
307
EQX76186.1
18287
23644
169


2005
23645
278
EQY22297.1
18289
23646
307
EQY22298.1
18290
23647
169


2006
23648
278
EQY33194.1
18292
23649
307
EQY33195.1
18293
23650
169


2007
23651
278
EQY45030.1
18295
23652
307
EQY45031.1
18296
23653
169


2008
23654
278
EQY55712.1
18298
23655
307
EQY55713.1
18299
23656
169


2009
23657
278
EQY72169.1
18301
23658
307
EQY72170.1
18302
23659
169


2010
23660
278
EQZ19656.1
18304
23661
307
EQZ19657.1
18305
23662
169


2011
23663
278
EQZ26677.1
18307
23664
307
EQZ26676.1
18308
23665
169


2012
23666
278
EQZ41388.1
18310
23667
307
EQZ41389.1
18311
23668
169


2013
23669
278
EQZ91635.1
18313
23670
307
EQZ91636.1
18314
23671
169


2014
23672
278
ERA32821.1
18316
23673
307
ERA32822.1
18317
23674
169


2015
23675
278
ERA36346.1
18319
23676
307
ERA36347.1
18320
23677
169


2016
23678
278
ERF54132.1
18322
23679
307
ERF54133.1
18323
23680
169


2017
23681
278
ESK18130.1
18325
23682
307
ESK18131.1
18326
23683
169


2018
23684
278
ESK18552.1
18328
23685
307
ESK18553.1
18329
23686
169


2019
23687
278
ESK29584.1
18331
23688
307
ESK29585.1
18332
23689
169


2020
23690
278
ESC95629.1
18334
23691
307
ESC95630.1
18335
23692
169


2021
23693
278
ESD43647.1
18337
23694
81
ESD43646.1
18338
23695
169


2022
23696
278
ESE27408.1
18340
23697
307
ESE27409.1
18341
23698
169


2023
23699
278
ESE32329.1
18343
23700
307
ESE32328.1
18344
23701
169


2024
23702
278
ESE38126.1
18346
23703
307
ESE38127.1
18347
23704
169


2025
23705
278
ESP10884.1
18349
23706
307
ESP10883.1
18350
23707
169


2026
23708
278
ESP23169.1
18352
23709
307
ESP23170.1
18353
23710
169


2027
23711
278
ETE11167.1
18355
23712
307
ETE11168.1
18356
23713
169


2028
23714
278
ETF35982.1
18358
23715
307
ETF35983.1
18359
23716
169


2029
23717
278
EZQ63562.1
18361
23718
307
EZQ63563.1
18362
23719
169


2030
23720
278
KDG03092.1
18364
23721
307
KDG03093.1
18365
23722
169


2031
23723
278
KDO90446.1
18367
23724
307
KDO90447.1
18368
23725
169


2032
23726
278
AID79059.1
18370
23727
307
AID79060.1
18371
23728
169


2033
23729
278
AIL14919.1
18373
23730
307
AIL14831.1
18374
23731
169


2034
23732
278
KLX17103.1
18376
23733
307
KLX17104.1
18377
23734
169


2035
23735
278
KLX44350.1
18379
23736
307
KLX44351.1
18380
23737
169


2036
23738
278
KLX45651.1
18382
23739
307
KLX45652.1
18383
23740
169


2037
23741
278
ALD37596.1
18385
23742
287
ALD34923.1
18386
23743
169


2038
23744
278
KSY03096.1
18388
23745
287
KSY02660.1
18389
23746
169


2039
23747
278
KUR38293.1
18391
23748
287
KUR38255.1
18392
23749
169


2040
23750
278
KUR81992.1
18394
23751
287
KUR81833.1
18395
23752
169


2041
23753
278
KUR94139.1
18397
23754
287
KUR94070.1
18398
23755
169


2042
23756
278
KUR99652.1
18400
23757
287
KUR99611.1
18401
23758
169


2043
23759
278
KUS68975.1
18403
23760
287
KUS68706.1
18404
23761
169


2044
23762
278
KUS65771.1
18406
23763
287
KUS65753.1
18407
23764
169


2045
23765
278
KUS06605.1
18409
23766
287
KUS06587.1
18410
23767
169


2046
23768
278
KUW86276.1
18412
23769
287
KUW86272.1
18413
23770
169


2047
23771
278
KUT33564.1
18415
23772
287
KUT33560.1
18416
23773
169


2048
23774
278
KUV71943.1
18418
23775
287
KUV71917.1
18419
23776
169


2049
23777
278
KUT65778.1
18421
23778
287
KUT65774.1
18422
23779
169


2050
23780
278
KUT92675.1
18424
23781
287
KUT92653.1
18425
23782
169


2051
23783
278
KUV55803.1
18427
23784
287
KUV55765.1
18428
23785
169


2052
23786
278
KUU93006.1
18430
23787
287
KUU92986.1
18431
23788
169


2053
23789
278
KUV32585.1
18433
23790
287
KUV32575.1
18434
23791
169


2054
23792
278
KUX05541.1
18436
23793
287
KUX05522.1
18437
23794
169


2055
23795
278
KUX02226.1
18439
23796
287
KUX02163.1
18440
23797
169


2056
23798
278
KUW18250.1
18442
23799
287
KUW18189.1
18443
23800
169


2057
23801
278
KUU04918.1
18445
23802
287
KUU04901.1
18446
23803
169


2058
23804
278
KUW44263.1
18448
23805
287
KUW44251.1
18449
23806
169


2059
23807
278
KUW29429.1
18451
23808
287
KUW29414.1
18452
23809
169


2060
23810
278
KUT58705.1
18454
23811
287
KUT58680.1
18455
23812
169


2061
23813
278
KUX37247.1
18457
23814
287
KUX37209.1
18458
23815
169


2062
23816
278
KUV14431.1
18460
23817
287
KUV14409.1
18461
23818
169


2063
23819
278
KUX73675.1
18463
23820
287
KUX73638.1
18464
23821
169


2064
23822
278
KUW86808.1
18466
23823
287
KUW86784.1
18467
23824
169


2065
23825
278
KUX51137.1
18469
23826
287
KUX51101.1
18470
23827
169


2066
23828
278
KVI42459.1
18472
23829
287
KVI42423.1
18473
23830
169


2067
23831
278
KVI22812.1
18475
23832
287
KVI22807.1
18476
23833
169


2068
23834
278
KXG92286.1
18478
23835
307
KXG92285.1
18479
23836
169


2069
23837
278
KXL04892.1
18481
23838
287
KXL04868.1
18482
23839
169


2070
23840
278
KXL27416.1
18484
23841
287
KXL27377.1
18485
23842
169


2071
23843
278
KXL05688.1
18487
23844
287
KXL05684.1
18488
23845
169


2072
23846
278
KXL13376.1
18490
23847
287
KXL13116.1
18491
23848
169


2073
23849
278
KTK78308.1
18493
23850
287
KTK75706.1
18494
23851
169


2074
23852
285
EPI32469.1
18496
23853
474
EPI32467.1
18497
23854
153


2075
23855
283
ETU24521.1
18499
23856
281
ETU24519.1
18500
23857
173


2076
23858
281
ELB67023.1
18502
23859
277
ELB67021.1
18503
23860
166


2077
23861
271
ENZ13054.1
18505
23862
98
ENZ13056.1
18506
23863
134


2078
23864
278
AHW13888.1
18508
23865
294
AHW13889.1
18509
23866
169


2079
23867
278
ESP72123.1
18511
23868
295
ESP72122.1
18512
23869
169


2080
23870
278
ESP76606.1
18514
23871
295
ESP76605.1
18515
23872
169


2081
23873
278
KFT73589.1
18517
23874
303
KFT73590.1
18518
23875
169


2082
23876
278
KHP33250.1
18520
23877
287
KHP33098.1
18521
23878
169


2083
23879
278
KHP35541.1
18523
23880
287
KHP34816.1
18524
23881
169


2084
23882
278
AKF88466.1
18526
23883
303
AMQ08961.1
18527
23884
169


2085
23885
278
KNK74746.1
18529
23886
303
KNK74745.1
18530
23887
169


2086
23888
278
KNW86451.1
18532
23889
303
KNW86450.1
18533
23890
169


2087
23891
277
ALO88018.1
18535
23892
303
ALO88019.1
18536
23893
169


2088
23894
278
KTQ22862.1
18538
23895
287
KTQ21994.1
18539
23896
169


2089
23897
278
KUB19504.1
18541
23898
287
KUB19292.1
18542
23899
169


2090
23900
278
KTY61531.1
18544
23901
287
KTY61368.1
18545
23902
169


2091
23903
278
KUB06355.1
18547
23904
287
KUB06250.1
18548
23905
169


2092
23906
278
KUD95102.1
18550
23907
287
KUD94943.1
18551
23908
169


2093
23909
278
GAR53163.1
18553
23910
303
GAR53164.1
18554
23911
169


2094
23912
282
EDS74763.1
18556
23913
284
EDS74762.1
18557
23914
217


2095
23915
291
KUG13795.1
18559
23916
284
KUG13797.1
18560
23917
168


2096
23918
278
EIY23904.1
18562
23919
176
EIY23906.1
18563
23920
176


2097
23921
297
EOS20512.1
18565
23922
280
EOS20510.1
18566
23923
154


2098
23924
278
EEH86955.2
18568
23925
307
EEH86956.1
18569
23926
169


2099
23927
293
CDE34945.1
18571
23928
266
CDE34947.1
18572
23929
185


2100
23930
278
AKW15255.1
18574
23931
303
AKW15260.1
18575
23932
291
AKW15254.1
18576
23933
169










(Part C)






















AB



AF






Y
Z
AA
ThsB (iv)
AC
AD
AE
ThsB (v)
AG
AH



ThsB (iv)
PRT SEQ
DNA SEQ
protein
ThsB (v)
PRT SEQ
DNA SEQ
protein
Genomic
Genomic
AI


1
protein_accession
ID NO:
ID NO:
length (aa)
protein_accession
ID NO:
ID NO:
length (aa)
Start Point
End Point
comments





2








18199
21006


3








629
2777


4








5626
8433


5








22562
25369


6








51158
53041


7








972
2894


8








7781
10368


9








4395990
4398131


10








72122
74690


11








36696
39253


12








36738
39295


13








12931
15738


14








26929
28839


15








168640
171278
Additional ThsA homolog EGV07143.1


16








117544
120507


17








6436
9650
Additional ThsA homolog EHM75397.1


18








29271
31828


19








13966
17199


20








5865
9078


21








89212
92444
Additional ThsA homolog EIA14316.1


22








52056
55538
Additional ThsA homolog EIC95445.1 and EIC95416.1


23








1081676
1083596


24








66368
68925


25








66447
69004


26








17507
20048


27








86
1182


28








11678
13703


29








329879
331798


30








5296579
5302199


31








2271775
2274990


32








5587
8095


33








7411
9563


34








7716
9868


35








166
2264


36








331145
333209


37








416875
418939


38








9843
12589


39








137838
139780


40








3230645
3232587


41








214042
218633


42
BAQ74698.1
13325
18682
282




3398464
3402455


43








222931
225520


44








46820
51171


45








29183
31097


46








46863
51213


47








6531
9746


48








58762
61977


49








29869
33084


50








6530
9744
Additional ThsA homolog EPZ03687.1


51








29869
33083
Additional ThsA homolog EPZ11496.1


52








1186644
1187914


53








4035
5954


54








4032
5951


55
ETR95047.1
13360
18717
392
ETR95035.1
13361
18718
258
57073
63348


56








102852
105529


57








68333
70275


58








29849
31768


59








10611
13921


60








38796
40715


61
ERT19164.1
13378
18735
284




47778
51812


62








13859
16441


63








12425
15043


64








4783
6845


65








15034
16957


66








140001
142539


67








28373
30424


68








1
1825


69








64004
65911


70








166
2021


71








6080
8527


72








515442
517994


73








674
3536


74








139546
141467


75








41136
43033


76








13018
14436


77








4125512
4127653


78








5228544
5231702


79








5761473
5764631


80








1756503
1758422


81








257376
259446


82








3144948
3147551


83








416071
423425


84








1137270
1142967


85








3070609
3073154


86








1196726
1201628


87








1362278
1364836


88








1106775
1110408


89








6843
9373


90
ABR34956.1
13455
18812
397




3262303
3271086


91








193025
201754


92
ACA73841.1
13462
18819
284




3700507
3704541


93








1522479
1525210


94








159043
161228


95








26150
28218


96








3660129
3669571


97








30739
34915


98








8582744
8587380


99








1144241
1146856


100
AEA61153.1
13487
18844
185
AEA61148.1
13488
18845
380
2903631
2911620


101








2114555
2117787
Additional ThsA homolog AFH70386.1


102








463662
466219


103








4207854
4209995


104








2480783
2484341


105








3773861
3775803


106








2704998
2706901


107








587283
590090


108








3506208
3510086


109








2181958
2185173


110








5998143
6005265


111








3932979
3934921


112








1794531
1800432
Additional ThsA homolog AHZ68659.1


113








3384959
3385740


114








10892
12978


115








3875996
3877938


116








1315665
1318348


117
AIU01467.1
13536
18893
397




3262298
3271081


118








4055767
4058527


119








77843
79615
Additional ThsA homolog AJK51070.1


120








333850
336261


121








329400
331811


122








347430
349849


123








347423
349980


124








3945969
3949326


125








4205818
4210073


126








1170644
1172700


127








2330122
2333479


128








1113818
1116217


129








882751
885296


130








2831462
2835547


131








311495
313453


132








6039155
6041758


133








79256
82956


134








1727530
1732447


135








1268306
1270321


136








3178713
3180655


137








2230390
2233379


138








2056187
2058744


139








1551820
1554323


140








1705326
1706706


141








2176463
2179695


142








2168129
2171362


143








2280993
2284226


144








3915939
3920392


145








1704217
1705597


146








2183524
2186331


147








1361260
1364863
Additional ThsA homolog AMJ40915.1


148








1163503
1166716


149








5251680
5253446


150








4624
9364


151








123406
125800


152








414
2808


153








4336
6730


154








112666
114575


155
CQJ38345.1
13644
19001
395




119502
126440


156








170171
175125


157








22084
24292


158








15713
17632


159








97
2016


160








3516
5435


161








86
2005


162








126
2045


163








86
2005


164








86504
88423


165








126
2045


166








3572
5491


167








86
2005


168








86
2005


169








86
2005


170








3523
5442


171








86
2005


172








15712
17631


173








15714
17633


174








15715
17634


175








15715
17634


176








17014
18933


177








86
2005


178








15715
17634


179








16634
18553


180








17014
18933


181








15714
17633


182








86
2005


183








86
2005


184








86
2005


185








15916
17835


186








86
2005


187








86
2005


188








86
2005


189








86
2005


190








17014
18933


191








16688
18607


192








86
2005


193








86
2005


194








86
2005


195








15714
17633


196








86
2005


197








15712
17631


198








15707
17626


199








15715
17634


200








16688
18607


201








86
2005


202








15713
17632


203








86
2005


204








86
2005


205








86
2005


206








15727
17646


207








86
2005


208








19604
21523


209








15675
17594


210








86
2005


211








86
2005


212








103
2022


213








86
2005


214








15667
17586


215








86
2005


216








86
2005


217








86
2005


218








86
2005


219








111
2030


220








86
2005


221








86
2005


222








86
2005


223








15714
17633


224








20763
22682


225








15715
17634


226








90
2009


227








86
2005


228








86
2005


229








86
2005


230








15715
17634


231








86
2005


232








90
2009


233








126
2045


234








93
2012


235








86
2005


236








86
2005


237








15713
17632


238








86
2005


239








15711
17630


240








15713
17632


241








86
2005


242








9021
10940


243








86
2005


244








86
2005


245








86
2005


246








85
2004


247








86
2005


248








86
2005


249








19605
21524


250








15916
17835


251








15715
17634


252








15916
17835


253








15916
17835


254








86
2005


255








85
2004


256








86
2005


257








86
2005


258








86
2005


259








3523
5442


260








15715
17634


261








15715
17634


262








15715
17634


263








86
2005


264








86
2005


265








86
2005


266








86
2005


267








86
2005


268








15916
17835


269








86
2005


270








86
2005


271








86
2005


272








15916
17835


273








15916
17835


274








15916
17835


275








15713
17632


276








15715
17634


277








85
2004


278








20706
22625


279








85
2004


280








85
2004


281








86
2005


282








86
2005


283








90
2009


284








86
2005


285








15714
17633


286








15719
17638


287








15710
17629


288








15726
17645


289








3523
5442


290








15715
17634


291








15915
17834


292








86
2005


293








86
2005


294








86
2005


295








86
2005


296








86
2005


297








86
2005


298








15715
17634


299








86
2005


300








86
2005


301








86
2005


302








86
2005


303








86
2005


304








86
2005


305








86
2005


306








86
2005


307








86
2005


308








86
2005


309








86
2005


310








3520
5439


311








86
2005


312








86
2005


313








86
2005


314








86
2005


315








15715
17634


316








85
2004


317








19612
21531


318








15715
17634


319








15712
17631


320








15715
17634


321








19605
21524


322








86
2005


323








15714
17633


324








15715
17634


325








85
2004


326








15715
17634


327








19605
21524


328








85
2004


329








86
2005


330








86
2005


331








15714
17633


332








15713
17632


333








3523
5442


334








15715
17634


335








19605
21524


336








86
2005


337








86
2005


338








57301
59220


339








16030
17949


340








86
2005


341








86
2005


342








86
2005


343








15714
17633


344








15715
17634


345








86
2005


346








90
2009


347








85
2004


348








86
2005


349








21322
23241


350








86
2005


351








86
2005


352








86
2005


353








86
2005


354








86
2005


355








84
2003


356








86
2005


357








86
2005


358








86
2005


359








86
2005


360








57
1976


361








86
2005


362








90
2009


363








86
2005


364








126
2045


365








90
2009


366








86
2005


367








86
2005


368








86
2005


369








3523
5442


370








86
2005


371








86
2005


372








86
2005


373








86
2005


374








86
2005


375








86
2005


376








86
2005


377








3523
5442


378








3523
5442


379








86
2005


380








86
2005


381








86
2005


382








20582
22497


383








69792
71707


384








473455
475428


385
CUI40923.1
14109
19466
380




61503
69491


386








29199
31433


387








91096
93166


388








13294
15364


389








91096
93166


390








208463
212572


391








52908
54850


392








205694
207636


393








51817
53759


394








52565
54507


395








40795
42737


396








208781
210723


397








416502
418444


398








52868
54810


399








205143
207085


400








205136
207078


401








52762
54704


402








48586
50528


403








205291
207233


404








227349
229291


405








54635
56577


406








205150
207092


407








52282
54224


408








98754
100696


409








459698
461640


410








1072447
1074389


411








52866
54808


412








52771
54713


413








53129
55071


414








52821
54763


415








381639
383581


416








251604
253547
Additional ThsA homolog CUZ65536.1


417








227335
229277


418








215912
217854


419








170621
172563


420








54612
56554


421








259463
261405


422








52769
54711


423








215028
216970


424








55119
57061


425








145344
147286


426








51538
53480


427








54675
56617


428








52756
54698


429








247802
249745
Additional ThsA homolog CUZ82852.1


430








468965
470907


431








52873
54815


432








58418
60361
Additional ThsA homolog CUZ43256.1


433








52608
54550


434








98756
100698


435








51815
53757


436








48717
50659


437








378607
380549


438








259489
261431


439








259461
261403


440








53320
55262


441








52797
54739


442








259463
261405


443








71559
73501


444








71562
73504


445








205150
207092


446








54661
56603


447








2774448
2776391
Additional ThsA homolog CVB24107.1


448








474999
476941


449








205287
207229


450








54153
56096
Additional ThsA homolog CVB73330.1


451








287703
289646
Additional ThsA homolog CVA22598.1


452








205297
207239


453








54674
56616


454








227325
229267


455








259463
261405


456








52811
54753


457








259443
261385


458








259454
261396


459








52807
54749


460








54610
56552


461








54003
55945


462








52860
54802


463








555244
557186


464








205101
207043


465








259463
261405


466








55632
57574


467








469398
471341
Additional ThsA homolog CVB85980.1


468








52988
54930


469








53025
54967


470








52986
54928


471








245145
247087


472








228659
230601


473








259502
261444


474








72560
74502


475








54144
56087
Additional ThsA homolog CVD13385.1


476








53587
55529


477








205145
207087


478








259537
261479


479








52763
54705


480








204839
206781


481








250690
252632


482








52792
54734


483








52806
54748


484








259463
261405


485








53587
55529


486








54693
56635


487








381593
383535


488








259463
261405


489








53129
55071


490








229979
231922
Additional ThsA homolog CVC59825.1


491








40797
42739


492








53318
55260


493








474325
476267


494








276598
278540


495








205145
207087


496








56080
58023
Additional ThsA homolog CVD28877.1


497








203403
205345


498








205188
207130


499








100253
102196
Additional ThsA homolog CVC40444.1


500








54152
56095
Additional ThsA homolog CVE27748.1


501








52837
54779


502








287741
289684
Additional ThsA homolog CVE69273.1


503








250718
252660


504








53129
55071


505








409590
411532


506








225217
227159


507








55828
57770


508








52615
54557


509








259463
261405


510








85596
87538


511








40786
42728


512








51813
53755


513








331093
333036
Additional ThsA homolog CVE63008.1


514








205143
207085


515








246483
248425


516








55632
57574


517








203360
205302


518








203361
205303


519








53129
55071


520








302434
304376


521








205143
207085


522








250747
252689


523








51815
53757


524








52610
54552


525








218394
220336


526








204804
206746


527








56080
58023
Additional ThsA homolog CVF09827.1


528








225215
227157


529








380827
382769


530








507350
509292


531








205145
207087


532








205180
207122


533








468279
470221


534








204811
206753


535








2911354
2913296


536








204806
206748


537








48895
50837


538








250731
252673


539








250678
252620


540








209597
211539


541








205292
207234


542








218370
220312


543








204799
206741


544








259507
261449


545








98756
100698


546








52831
54773


547








229166
231108


548








229192
231134


549








52862
54804


550








469390
471333
Additional ThsA homolog CVF82665.1


551








205176
207118


552








86294
88236


553








195844
197787
Additional ThsA homolog CVG82395.1


554








259485
261427


555








52838
54780


556








259463
261405


557








205143
207085


558








204848
206790


559








52908
54850


560








48895
50837


561








204800
206742


562








205105
207047


563








52761
54703


564








205143
207085


565








804248
806190


566








42050
43992


567








259463
261405


568








98758
100700


569








205139
207081


570








203358
205300


571








245017
246902


572








244655
246597


573








204808
206750


574








55294
57236


575








40785
42727


576








146358
148300


577








203356
205298


578








213928
215870


579








53145
55087


580








302444
304386


581








205171
207113


582








86298
88240


583








225285
227227


584








2489848
2491790


585








48902
50844


586








205139
207081


587








52816
54758


588








48889
50831


589








259463
261405


590








276608
278550


591








52823
54765


592








219855
224432


593








665752
668658


594








10795
15202
Additional ThsA homolog CVJ34926.1


595








91413
93483


596








91412
93482


597








145450
148647


598








170139
172016


599








147107
150314


600








5221
8428


601








27175
28106


602








89207
90138


603








56578
57509


604








2764
3695


605








755402
757321


606








2281482
2283690
Additional ThsA homolog CBK94115.1


607








2147940
2151155


608








5550
8081


609








216318
218740


610








381949
385460


611








5760
7808


612








300284
303091


613








49142
51298


614








1929426
1932118


615








14797
17604


616








684310
687507


617








127257
129883


618








2141168
2149732


619








3041325
3043214


620








3085346
3087231


621








553
2600


622








10886
13693


623








14764
17571


624








10882
13689


625








34164
36837


626








58272
62622


627








7752
11008
Additional ThsA homolog EWC94486.1


628








270
5901


629








3054
11860


630
EXE88613.1
14621
19978
405
EXE88615.1
14622
19979
261
264895
270729


631








55048
58095


632








95834
100666


633








284960
286849


634








509807
511734


635








2108537
2115530


636








708642
710850


637








599550
602414


638








83092
84822


639








176458
181638


640








177762
182743


641








207
2134


642








251026
252953


643








4590
6517


644








2641819
2643746


645








442583
444510


646








430783
432710


647








251121
253048


648








205694
207650


649








4337287
4339430


650








154987
158145


651








19805
21921


652








417
3971


653








13781
16588


654








7847
10654


655








4608
7415


656








10909
13716


657








36794
39601


658








10909
13716


659








36880
39687


660








42693
45500


661








42768
45575


662








42629
45436


663








13781
16588


664








2627330
2629968


665








166982
169811


666








1603
3518


667








23156
26372


668








58886
62101


669








58887
62102


670








58821
62036


671








58821
62036


672








58887
62102


673








58887
62102


674








2720
5935


675








11491
14706


676








58887
62102


677








58887
61046


678








58887
62102


679








58887
62102


680








3137
6352


681








58887
62102


682








58887
62102


683








58887
62102


684








58887
62102


685








89236
92451


686








58887
62102


687








58881
62096


688








58887
62102


689








89217
92431
Additional ThsA homolog EZR97100.1


690








58887
62102


691








89217
92432


692








58653
61868


693








58887
62102


694








11494
14709


695








89253
92468


696








17149
20364


697








58886
62101


698








89215
92430


699








58887
62102


700








58887
62102


701








51382
54597


702








58887
62102


703








58887
62102


704








58887
62102


705








27394
30609


706








11491
14706


707








58887
62102


708








89217
92432


709








58887
62102


710








89087
92302


711








58821
62036


712








58821
62036


713








89168
92383


714








102659
105874


715








58887
62102


716








56011
59226


717








58887
62102


718








58887
62102


719








58887
62101


720








58887
62102


721








13914
17129


722








58887
62102


723








58887
62102


724








58887
62102


725








58887
62102


726








58886
62101


727








58887
62102


728








58887
62102


729








35404
38619


730








58887
62102


731








20381
23596


732








58887
62102


733








58887
62102


734








58887
62102


735








11491
14706


736








86075
89290


737








58887
62102


738








58887
62101


739








58887
62102


740








58830
62045


741








59025
62239
Additional ThsA homolog EZT27374.1


742








58887
62102


743








58887
62102


744








58887
62102


745








58821
62036


746








89258
92473


747








58692
61907


748








58887
62101
Additional ThsA homolog EZT47450.1


749








89211
92425
Additional ThsA homolog EZT50535.1


750








58886
62101


751








58887
62102


752








58887
62102


753








89173
92388


754








85365
88580


755








58887
62102


756








58887
62102


757








58896
62111


758








58887
62102


759








58887
62102


760








58887
62102


761








5927
9142


762








58887
62102


763








58887
62102


764








58653
61868


765








58821
62036


766








58888
62103


767








58887
62102


768








58887
62102


769








58887
62102


770








58887
62102


771








1635
3550


772








1609
3524


773








135764
138293


774








1226749
1227659


775








107019
109625


776








92321
94908


777








101172
103087


778








24694
33804


779








261749
270859


780








11963
13878


781








11673
14353


782








11661
14339


783








37
2714


784








11671
14348


785








1494
4171


786








10184
12273


787








51656
53785


788








368690
371206


789








20762
22677


790








408
2323


791








57709
59078


792








852
2259


793








402013
404602
Additional ThsA homolog KEQ37438.1


794








534537
537500


795








54006
55948


796








268
2210


797
KFF62087.1
15092
20449
278




278870
286182


798








13328
15398


799








29271
31828


800








1177641
1180423


801








796009
798073


802








25866
35282


803








14362
17169


804








43124
45703


805








1357
3279


806








14786
17593


807








80211
82768
Additional ThsA homolog KIE90699.1 and KIE90686.1


808








80286
82844
Additional ThsA homolog KIE90603.1


809








80290
82848
Additional ThsA homolog KIE97286.1


810








25818
28376
Additional ThsA homolog KIE97673.1


811








25803
28361
Additional ThsA homolog KIE96200.1


812








80213
82771
Additional ThsA homolog KIE90358.1


813
KHN56275.1
15137
20494
183




212601
218790


814








89226
92441


815








548602
550666


816








791385
792765


817








4381185
4383127


818








79011
80966


819








79815
81770


820








57400
59342


821








343540
345493


822








303729
307800


823








268769
271576


824








540414
543221


825








119577
122384


826








551887
554694


827








743854
746661


828








119853
122660


829








28372
37080


830








1890562
1892626


831








923150
925214


832








766850
768914


833








2675060
2675910


834








979222
981286


835








1470124
1472188


836








93913
98742
Additional ThsA homolog ENU62563.1


837








97812
100703


838








1497967
1506125


839








170794
174348
Additional ThsA homolog ENX27879.1


840








676899
679468


841








1866683
1870168


842








214685
217492


843








121299
124106


844








1399298
1402105


845








123919
126726


846








122496
125303


847








122329
125136


848








448160
450967


849








575596
578403


850








401264
404071


851








254055
256166


852








800671
802590


853








253248
255167


854








476
3696


855








212236
214349


856








1791824
1793888


857








773643
775707


858








434828
436769


859








397991
399932


860








449083
451024


861








95
2309


862








1377455
1381181


863








2693429
2697155


864








737416
740613


865








1907694
1910501


866








1393914
1395856


867








103489
105607


868








53375
55317


869








89124
92339


870








58887
62102


871








88416
91631


872








58887
62102


873








58887
62102


874








58887
62102


875








89258
92473


876








59082
62297


877








88152
91367


878








58887
62102


879








89302
92517


880








59082
62297


881








3860
7075


882








58887
62102


883








2496
5711


884








58887
62102


885








89302
92517


886








88596
91811


887








2217
5432


888








89258
92473


889








58887
62102


890








59471
62686


891








76731
79946


892








36126
39341


893








89173
92388


894








89173
92388


895








89124
92339


896








58887
62102


897








89258
92472
Additional ThsA homolog EZV09968.1


898








58887
62102


899








79669
82884


900








89302
92517


901








58475
61690


902








58887
62102


903








58887
62102


904








89192
92407


905








58887
62102


906








89155
92370


907








64585
67800


908








89258
92473


909








88340
91555


910








89192
92407


911








58821
62036


912








58887
62102


913








3860
7075


914








58765
61980


915








58887
62101
Additional ThsA homolog EZV68413.1


916








88570
91785


917








89253
92468


918








58887
62102


919








58887
62102


920








59048
62263


921








35074
38289


922








64681
67896


923








58887
62102


924








88826
92041


925








88334
91549


926








3114
6329


927








58887
62102


928








58887
62102


929








59079
62294


930








3091
6306


931








3091
6306


932








58887
62102


933








59099
62314


934








58653
61868


935








58887
62102


936








89173
92388


937








89168
92383


938








58887
62102


939








89258
92473


940








89258
92473


941








58887
62102


942








58887
62102


943








58887
62102


944








58887
62102


945








58653
61868


946








89028
92243


947








3800
7015


948








87505
90720


949








59081
62296


950








58655
61870


951








89301
92515


952








58887
62102


953








58887
62102


954








58887
62102


955








3114
6329


956








58887
62102


957








89302
92517


958








51851
55066


959








89258
92473


960








58887
62102


961








58887
62102


962








59503
62718


963








58887
62102


964








40472
43687


965








58887
62102


966








58907
62122


967








26695
29910


968








58887
62102


969








89798
93013


970








58887
62102


971








58887
62102


972








89301
92515
Additional ThsA homolog EZX30780.1


973








58653
61867
Additional ThsA homolog EZX33811.1


974








89253
92467
Additional ThsA homolog EZX38407.1


975








89258
92473


976








6173
9387


977








58887
62101


978








85412
88627


979








58887
62102


980








58887
62102


981








58887
62101
Additional ThsA homolog EZX53549.1


982








89302
92517


983








59081
62296


984








58887
62102


985








63625
66839
Additional ThsA homolog EZX64344.1


986








58887
62102


987








58821
62036


988








58887
62102


989








8858
12073


990








89257
92472


991








89302
92517


992








58887
62102


993








63857
67072


994








87357
90572


995








89258
92473


996








58887
62102


997








89214
92429


998








89253
91325


999








89168
92383


1000








58887
62102


1001








48320
51535


1002








89302
92517


1003








29770
32985


1004








89304
92521


1005








58887
62102


1006








89253
92468


1007








58887
62102


1008








89253
91412


1009








2625
5840


1010








88832
92047


1011








89302
92517


1012








89302
92517


1013








58887
62102


1014








89216
92431


1015








58887
62102


1016








64320
67534
Additional ThsA homolog EZY44866.1


1017








58887
62102


1018








58887
62102


1019








58887
62101
Additional ThsA homolog EZY52188.1


1020








58887
62101
Additional ThsA homolog EZY54363.1


1021








4154
7368
Additional ThsA homolog EZY58963.1


1022








58887
62102


1023








58887
62102


1024








89258
92473


1025








58887
62102


1026








58887
62102


1027








89302
92517


1028








58887
62102


1029








58821
62036


1030








58831
62046


1031








89253
92468


1032








14360
17575


1033








86376
89591


1034








89253
92468


1035








58887
61350


1036








58821
62036


1037








58887
61350


1038








3244
6459


1039








58887
62101
Additional ThsA homolog EZZ07027.1


1040








3860
7075


1041








89258
92474


1042








58887
62102


1043








58887
62101


1044








89028
92243


1045








57669
60884


1046








58887
62102


1047








57242
60457


1048








11497
14712


1049








58887
62102


1050








89603
92818


1051








14572
17787


1052








58887
62102


1053








58887
62102


1054








88413
91628


1055








59194
62409


1056








58887
62102


1057








89186
92401


1058








58887
62102


1059








89001
92216


1060








58887
62101
Additional ThsA homolog EZZ66975.1


1061








58887
62102


1062








89304
92519


1063








58887
62102


1064








89160
92375


1065








58830
62045


1066








89217
92432


1067








58887
62102


1068








58821
62036


1069








58821
62036


1070








58887
62102


1071








86561
89776


1072








58887
62102


1073








89302
92517


1074








58887
62102


1075








86128
89343


1076








58886
62101


1077








72244
75459


1078








58887
62102


1079








89253
92468


1080








58828
62043


1081








58887
62102


1082








58887
62102


1083








58887
62102


1084








58887
62102


1085








89217
92432


1086








89168
92383


1087








89216
92431


1088








58821
62036


1089








58887
62102


1090








58887
62102


1091








58821
62036


1092








58887
62101


1093








1088
4303


1094








89302
92517


1095








89258
92473


1096








58887
62102


1097








58886
62101


1098








58886
62101


1099








89236
92451


1100








58887
62102


1101








58887
62102


1102








58887
62102


1103








58887
62102


1104








11491
14706


1105








73114
76329


1106








58821
62036


1107








58887
62102


1108








27936
31151


1109








58887
62102


1110








58887
62102


1111








89217
92432


1112








86600
89815


1113








58887
62102


1114








58821
62036


1115








58887
62102


1116








58821
62036


1117








58821
62036


1118








58887
62102


1119








58887
62102


1120








90149
93364


1121








89243
92458


1122








58887
62102


1123








58887
62102


1124








58886
62101


1125








89302
92517


1126








86097
89312


1127








89258
92473


1128








58887
62102


1129








89253
92468


1130








58887
62102


1131








23191
26406


1132








58887
62102


1133








58887
62102


1134








58887
61046


1135








58887
62102


1136








28112
30271


1137








58886
62101


1138








58821
62036


1139








58886
62101


1140








58887
62102


1141








89302
92517


1142








58887
62102


1143








58887
62102


1144








89258
92473


1145








89302
92517


1146








89258
92473


1147








26639
29854


1148








58821
62036


1149








14243
17458


1150








58887
62102


1151








58887
62102


1152








89217
92432


1153








58886
62101


1154








89303
92518


1155








58886
62101


1156








58887
61046


1157








7935
11150


1158








7491
10706


1159








58887
62102


1160








89302
92517


1161








89283
92498


1162








3990
6149


1163








58887
62102


1164








3990
6149


1165








89302
92517


1166








89173
92388


1167








89167
92382


1168








58887
62102


1169








29744
32959


1170








58821
62036


1171








86117
89332


1172








89302
92517


1173








58887
62102


1174








58887
62102


1175








59150
62365


1176








89257
92472


1177








58887
61046


1178








89303
91462


1179








58887
62102


1180








58887
62102


1181








58831
62046


1182








58887
62102


1183








58887
62102


1184








59012
62227


1185








58887
62102


1186








42602
45817


1187








58821
62036


1188








58821
62036


1189








86600
89815


1190








58887
62102


1191








14572
17787


1192








58887
62102


1193








88664
91879


1194








58887
62102


1195








89172
92386


1196








87289
90503


1197








89172
92386


1198








58821
62036


1199








89216
92430


1200








58887
62101


1201








2720
5935


1202








58887
62101


1203








58887
62101


1204








58888
62103


1205








58887
62102


1206








89173
92388


1207








86562
89777


1208








89257
92472


1209








2720
5935


1210








58886
62101


1211








87715
90930


1212








17386
20601


1213








58887
62102


1214








89253
92468


1215








89302
92517


1216








58764
61979


1217








58652
61867


1218








58886
62101


1219








58887
62102


1220








58887
62102


1221








58887
62102


1222








58887
62102


1223








58887
62102


1224








11769
14984


1225








58877
62092


1226








329
2488


1227








329
2488


1228








89258
92473


1229








73104
76319


1230








11491
14706


1231








58887
62102


1232








58887
62102


1233








29744
32959


1234








58887
62102


1235








58887
62102


1236








58887
62102


1237








58821
62036


1238








58829
62044


1239








58821
62036


1240








58887
62102


1241








58887
62102


1242








58887
62102


1243








58887
61046


1244








89302
91461


1245








58887
62102


1246








58887
62102


1247








89302
92517


1248








58887
62102


1249








65904
69119


1250








58887
62102


1251








58887
62102


1252








58887
62102


1253








14572
17787


1254








89217
92432


1255








58887
62102


1256








58764
61979


1257








86241
89456


1258








58887
62102


1259








58887
62102


1260








58887
62102


1261








58887
62102


1262








58821
62036


1263








89303
92518


1264








58821
62036


1265








58887
62102


1266








58887
62102


1267








58887
62102


1268








58887
62102


1269








58887
62101
Additional ThsA homolog KAF14361.1


1270








58886
62101


1271








58887
62102


1272








89302
92517


1273








29744
32959


1274








89302
92517


1275








58821
62036


1276








58887
62102


1277








58831
62046


1278








58887
62102


1279








73077
76292


1280








73866
77081


1281








58530
61745


1282








58887
62102


1283








329
2488


1284








58821
62036


1285








89173
92388


1286








58887
62102


1287








58887
62102


1288








58887
62102


1289








58887
62102


1290








58887
62102


1291








58829
62044


1292








58829
62044


1293








58887
62102


1294








58831
62046


1295








2720
5935


1296








58887
62102


1297








89168
92383


1298








58887
62102


1299








89253
92468


1300








89258
91417


1301








89302
91461


1302








52248
55463


1303








58821
62036


1304








58887
62102


1305








7905
11120


1306








35425
38640


1307








89142
92357


1308








35344
38559


1309








58887
62102


1310








7905
11120


1311








7905
11120


1312








58887
62102


1313








58887
62102


1314








17266
20481


1315








89142
92357


1316








89180
92395


1317








89217
92432


1318








58887
62102


1319








58887
62102


1320








89216
92431


1321








87144
90359


1322








58887
62102


1323








11773
14988


1324








89258
92473


1325








59129
62344


1326








58887
62102


1327








89301
92516


1328








58887
62102


1329








58887
62102


1330








58887
62102


1331








58887
62102


1332








89302
92517


1333








58831
62046


1334








3137
6352


1335








58887
62102


1336








58887
62102


1337








58887
62102


1338








50208
53423


1339








88375
91590


1340








58887
62102


1341








58887
62102


1342








58887
62101


1343








58888
62103


1344








58888
62103


1345








58821
62036


1346








58887
62102


1347








58764
61979


1348








58887
62102


1349








58887
62102


1350








58887
62102


1351








89258
92473


1352








58887
62102


1353








89302
92517


1354








58887
62102


1355








58890
62105


1356








58887
62102


1357








58887
62102


1358








58887
61046


1359








58887
62102


1360








15133
18348


1361








58887
62102


1362








58887
62102


1363








58887
62102


1364








58887
62102


1365








58887
62102


1366








58887
62102


1367








89215
92430


1368








89173
92388


1369








58887
62102


1370








58887
62102


1371








11492
14706
Additional ThsA homolog KAI16288.1


1372








2720
5935


1373








58887
62102


1374








58887
62101
Additional ThsA homolog KAI26858.1


1375








58887
62101
Additional ThsA homolog KAI29885.1


1376








58887
62102


1377








58887
62102


1378








58887
62102


1379








89266
92481


1380








58887
62102


1381








89181
92396


1382








89181
92396


1383








58887
62102


1384








5826
9041


1385








58821
62036


1386








59195
62410


1387








17302
20517


1388








58887
62101
Additional ThsA homolog KAI62094.1


1389








58887
62102


1390








89257
92472


1391








23094
26309


1392








89302
92517


1393








58887
62102


1394








58887
62102


1395








58887
62102


1396








58887
62102


1397








2720
5935


1398








605684
608266


1399








2378987
2381503


1400








310640
313504


1401








1255726
1257790


1402








3826893
3828835


1403








1485
3579


1404








639688
643130


1405








94340
96396


1406








1102
3496


1407








13655
15725


1408








20332
22454


1409








974
3096


1410








374357
376479


1411








74618
76770


1412








1153
3114


1413








41277
43918


1414








69089
71153


1415








179848
182525


1416








11882
13968


1417








12651
15458


1418








3676
7033


1419








8280
10222


1420








2504
6185


1421








7387
9539


1422








47043
48958


1423








241192
243134


1424








1908
3989


1425








37118
42808


1426








1106
3500


1427








163
2785


1428








15686
18266


1429








46608
48550


1430








1044
3541


1431








8558
14045


1432








364692
367369


1433








28016
30521


1434








69058
71661


1435








123469
126673


1436








2503
6286


1437








10631
14414


1438








507977
509953


1439








259469
261537


1440








93299
100962
Additional ThsA homolog KQL33554.1


1441








244173
247473


1442








145624
150941


1443








184894
190211


1444








4452
6364


1445








128226
130138


1446








298909
301699


1447








4866
10841


1448








204433
206473


1449








16453
18427


1450
KSG00431.1
17001
22358
284




2213
6247


1451
KSO26598.1
17006
22363
284




124680
128714


1452
KSQ24408.1
17011
22368
284




62982
67016


1453








49733
52315


1454








282217
284200


1455








208592
217300


1456








41760
43858


1457








156668
159376


1458








733755
736830


1459








77736
79508
Additional ThsA homolog CEA11435.1


1460








77793
79565
Additional ThsA homolog CEA10431.1


1461








1337272
1339830
Additional ThsA homolog CUU52509.1


1462








87151
89092


1463








746
3553


1464








1614
4421


1465








2106
4913


1466








131
1607


1467








1
1432


1468








8
1931


1469








1077
3884


1470








295
2073


1471








2520
5327


1472








14947
17754


1473








131
2938


1474








4405
7212


1475








30227
33460


1476








244740
246667


1477








1617
5976


1478








445956
448097


1479








102
952


1480








450
1300


1481








55284
63357


1482








42235
50308


1483








55284
63357


1484








981
2861


1485








2598
11358


1486








7069
9713


1487








132958
135057


1488








8547
11191


1489








55235
57150


1490








935
3606


1491








935
3606


1492








2598
11358


1493








81585
84446


1494








155366
164406


1495








80319
82234


1496








7669
9584


1497








7624
9539


1498








10977
13784


1499








32084
34025


1500








16664
18605


1501








9359
11274


1502








5128
7069


1503








5113
7054


1504








38647
40562


1505








9513
11428


1506








15944
17885


1507








124218
126133


1508








17640
19555


1509








2202
4082


1510








229143
231058


1511








2404458
2405838


1512








817577
818957


1513








615084
616464


1514








152013
153393


1515








195157
198738


1516








10904
18356


1517








3334527
3335974


1518








1341773
1343206


1519








1844605
1846063


1520








584164
585641


1521








134834
136244


1522








2071675
2073130


1523








3926192
3927625


1524








3874800
3876233


1525








2458217
2461483


1526








4332366
4333799


1527








232808
234255


1528








160530
161977


1529








2481111
2482500


1530








273049
274496


1531








2639516
2640982


1532








2812522
2813955


1533








97573
99025


1534








2075549
2077004


1535








26
1071


1536








2133
3628


1537








84
1579


1538








1084123
1085545


1539








1084123
1085545


1540








11228
12661


1541








33036
34488


1542








29409
30859


1543








224969
226401


1544








235
1667


1545








2635439
2636872


1546








428631
430077


1547








25772
27249


1548








914
2336


1549








2463639
2465086


1550








1
862


1551








26558
27991


1552








34236
35669


1553








3765
5175


1554








1734329
1735762


1555








3509
4956


1556








2790710
2792159


1557








157503
158952


1558








1926980
1928429


1559








2177471
2178599


1560








1830
3263


1561








11498
12911


1562








1519
2929


1563








76033
77422


1564








112479
113937


1565








11530
12977


1566








2365
3812


1567








2349
3796


1568








10610
12057


1569








1347
2737


1570








61132
62524


1571








88884
90276


1572








89055
90447


1573








25772
27164


1574








51881
53291


1575








190051
191475


1576








977432
978898


1577








33964
35397


1578








207130
208563


1579








308501
309935


1580








124638
126071


1581








75914
77369


1582








88200
89655


1583








76300
77755


1584








25517
26932


1585








1192816
1194306


1586








150195
151627


1587








132737
134160


1588








1955978
1958455


1589








485658
488135


1590








278588
281125


1591








83713
86250


1592








279549
282086


1593








505157
507634


1594








505059
507536


1595








467434
469911


1596








505205
507682


1597








467455
469932


1598








467255
469732


1599








485332
487809


1600








3065568
3066757


1601








2559672
2561088


1602








1235298
1236673


1603








1860855
1862226


1604








348719
350085


1605








251369
252744


1606








33638
35013


1607








696957
698323


1608








90011
91494


1609








167083
168566


1610








190234
191717


1611








421379
422862


1612








1485164
1486647


1613








41076
42559


1614








68604
70087


1615








68623
70106


1616








115692
117175


1617








23055
24538


1618








22088
23571


1619








195988
197471


1620








8031
9514


1621








22905
24388


1622








655324
656726


1623








184
1586


1624








378494
379896


1625








2737817
2739300


1626








188075
189558


1627








217136
218619


1628








4679
6125


1629








618232
619597


1630








58857
60199


1631








25138
26419


1632








878549
880212


1633








1017795
1019207


1634








970449
971790


1635








279792
281124


1636








234529
235862


1637








43541
44877


1638








24580
25916


1639








26348
27675


1640








4106
5433


1641








432088
433415


1642








2015511
2016838


1643








198483
199621


1644








12987
14314


1645








10816
11954


1646








1
738


1647








45207
46534


1648








15185
16512


1649








11095
12233


1650








16291
17618


1651








922
2380


1652








80649
82053


1653








98527
99931


1654








80649
82053


1655








79320
80724


1656








5485
6910


1657








2391314
2392718


1658








98697
100101


1659








1629344
1630748


1660








1587489
1588893


1661








1758391
1759795


1662








1761238
1762642


1663








168103
169507


1664








98697
100101


1665








394942
396346


1666








80649
82053


1667








63660
64995


1668








157063
158363


1669








3080200
3081662


1670








73291
74729


1671








15431
16773


1672








367310
368729


1673








1719
3138


1674








86400
87735


1675








17508
18843


1676








552979
555192


1677








537536
538890


1678








50209
51614


1679








18293
19811


1680








855094
856495


1681








790419
791775


1682








151715
153071


1683








1035215
1036571


1684








61907
63263


1685








52334
53516


1686








51361
52543


1687








16395
17577


1688








15348
16530


1689








774460
775816


1690








951413
952763


1691








3133822
3135172


1692








1666481
1667831


1693








1054353
1055733


1694








3639547
3640897


1695








763489
764869


1696








4111
5512


1697








3956631
3958032


1698








10999
12349


1699








51317
52718


1700








51317
52718


1701








163388
164744


1702








207731
209087


1703








834005
835406


1704








825117
826473


1705








848376
849726


1706








51424
52804


1707








4446
5796


1708








4446
5796


1709








182936
184286


1710








179243
180593


1711








4446
5796


1712








4446
5796


1713








4417
5797


1714








179237
180587


1715








179433
180783


1716








4412
5762


1717








2681
4031


1718








181925
183305


1719








4443
5823


1720








51272
52652


1721








179390
180770


1722








4412
5762


1723








179263
180613


1724








53137
54487


1725








182219
183599


1726








347718
349068


1727








4443
5823


1728








179226
180606


1729








179431
180781


1730








4446
5796


1731








4446
5826


1732








181022
182402


1733








4446
5826


1734








179425
180775


1735








181377
182727


1736








4443
5793


1737








179233
180613


1738








4446
5826


1739








179233
180613


1740








4442
5792


1741








201348
202728


1742








179317
180667


1743








143710
145060


1744








56633
58013


1745








2681
4061


1746








2680
4060


1747








837068
838424


1748








837352
838708


1749








3604904
3606260


1750








2690
4070


1751








4446
5826


1752








179438
180788


1753








179224
180604


1754








4441
5791


1755








179249
180599


1756








4446
5826


1757








51372
52722


1758








4446
5826


1759








4425
5775


1760








4446
5796


1761








4446
5826


1762








4446
5796


1763








4425
5775


1764








179241
180591


1765








4412
5762


1766








179408
180788


1767








4441
5821


1768








179422
180772


1769








179114
180494


1770








179207
180587


1771








52653
54033


1772








4378
5758


1773








4437
5787


1774








179117
180467


1775








179226
180606


1776








179442
180792


1777








4414
5764


1778








179412
180792


1779








4446
5826


1780








180295
181645


1781








179423
180803


1782








51342
52722


1783








179412
180792


1784








4443
5793


1785








347708
349088


1786








4433
5783


1787








2676
4026


1788








2664
4044


1789








2671
4051


1790








179328
180708


1791








2675
4055


1792








247106
248456


1793








2662
4042


1794








137298
138678


1795








179122
180472


1796








181161
182511


1797








24097
26600


1798








1774206
1776730


1799








2995200
2997724


1800








215678
217047


1801








11
1365


1802








433369
434723


1803








116084
117447


1804








134
1383


1805








614798
616228


1806








2913
4396


1807








1236162
1237611


1808








52273
54418


1809








103276
104603


1810








103269
104596


1811








230894
232214


1812








32976
34498


1813








142644
144066


1814








2712
4835


1815








399088
400472


1816








239679
241054


1817








1893650
1894991


1818








392918
394286


1819








845508
848346
Additional ThsA homolog EHI61161.1 and EHI61160.1


1820








8273
9663


1821








5106952
5108412


1822








67402
68729


1823








385610
386991


1824








391196
392625


1825








10416
11602


1826








1
1463


1827








1773192
1774570


1828








93771
95197


1829








52979
54377


1830








169073
170436


1831








111454
112853


1832








295
1674


1833








52811
54295


1834








22017
23446


1835








46093
47494


1836








10780
12281


1837








578586
580026


1838








18949
20411


1839








1720
3139


1840








402136
403598


1841








17069
18543


1842








778829
780278


1843








239846
241330


1844








8796
9991


1845








8027
9442


1846








10583
11998


1847








10583
11998


1848








101221
102636


1849








108258
109673


1850








73923
75338


1851








9557
10972


1852








8731
10146


1853








10583
11998


1854








9409
10824


1855








3016
4431


1856








9405
10820


1857








10583
11998


1858








73814
75229


1859








10583
11998


1860








75727
77531
Additional ThsA homolog ERH59123.1


1861








2134919
2137041


1862








794273
796356


1863








27958
29914


1864








58581
61165


1865








25655
27734


1866








2276956
2281580


1867








214397
218349


1868








2202763
2205300


1869








72963
75500


1870








72753
75290


1871








335401
337938


1872








73026
75563


1873








96286
98823


1874








78963
81500


1875








626450
628927


1876








2144499
2147036


1877








2144499
2147036


1878








857876
860413


1879








190277
192754


1880








292755
295292


1881








332657
335194


1882








333878
336415


1883








294681
297218


1884








115649
118186


1885








332547
335084


1886








315968
318505


1887








299437
301974


1888








294697
297234


1889








415578
418115


1890








299437
301974


1891








919475
922012


1892








751819
754356


1893








414378
416915


1894








430384
432921


1895








1711734
1714271


1896








1827507
1830044


1897








807551
810088


1898








722094
724631


1899








2570589
2573126


1900








771268
773805


1901








769990
772527


1902








1718201
1720738


1903








763807
766344


1904








745301
747838


1905








1739780
1742317


1906








1808916
1811453


1907








1830255
1832792


1908








637302
639839


1909








2820435
2822972


1910








4138023
4140560


1911








952621
955158


1912








424893
427430


1913








4840540
4843077


1914








415549
418086


1915








2733635
2736172


1916








949017
951554


1917








328880
331417


1918








390295
392832


1919








977582
980119


1920








1830964
1833501


1921








767420
769957


1922








1643560
1646097


1923








1378858
1381395


1924








755487
758023


1925








881168
883705


1926








1825551
1828088


1927








738544
741081


1928








142767
145304


1929








964862
967399


1930








776235
778772


1931








655024
657561


1932








1874434
1876971


1933








624797
627334


1934








128934
131471


1935








136721
139258


1936








1726846
1729383


1937








823627
826164


1938








1937935
1940472


1939








1944646
1947183


1940








993314
995851


1941








821085
823622


1942








651372
653909


1943








958507
962380


1944








1037695
1040232


1945








2023087
2025624


1946








413025
415562


1947








925402
927939


1948








1824339
1826876


1949








1963306
1965843


1950








1723817
1726354


1951








1061869
1064406


1952








455375
457912


1953








99107
101644


1954








134788
137325


1955








415169
417706


1956








411378
413915


1957








1723198
1725735


1958








969440
971977


1959








119038
121575


1960








779299
781836


1961








837980
840517


1962








957690
960227


1963








647128
649665


1964








1304387
1306924


1965








118566
121103


1966








964548
967085


1967








1037220
1039757


1968








1765512
1768049


1969








959782
962319


1970








1631617
1634154


1971








955226
957763


1972








1051957
1054494


1973








404789
407326


1974








994327
996864


1975








422844
425381


1976








1057307
1059844


1977








752850
755387


1978








435581
438118


1979








415671
418208


1980








593893
596430


1981








2084900
2087438


1982








945151
947688


1983








699363
701900


1984








696094
698631


1985








1817777
1820314


1986








844786
847323


1987








140683
143220


1988








849733
852270


1989








840414
842951


1990








949044
951581


1991








415164
417701


1992








863928
866465


1993








415572
418109


1994








747799
750336


1995








418408
420945


1996








961748
964285


1997








419569
422106


1998








1015638
1018175


1999








889676
892213


2000








948468
951005


2001








1885183
1887720


2002








966038
968575


2003








960076
962613


2004








122404
124941


2005








1681006
1683543


2006








993136
995673


2007








998786
1001323


2008








423592
426129


2009








119049
121586


2010








967343
969880


2011








777273
779810


2012








333878
336415


2013








135104
137641


2014








414973
417510


2015








415129
417666


2016








953263
955800


2017








413367
415904


2018








422253
424790


2019








414879
417416


2020








332578
335115


2021








72684
74543


2022








991
3528


2023








72684
75221


2024








204036
206573


2025








51535
54072


2026








70748
73285


2027








166520
169057


2028








1268434
1270971


2029








327480
330017


2030








1970301
1972838


2031








6539
9076


2032








2178487
2181024


2033








3086900
3089437


2034








1764944
1767481


2035








892818
895355


2036








724298
726835


2037








2073702
2076179


2038








16866
19343


2039








11451
13928


2040








14738
17215


2041








22974
25451


2042








163601
166078


2043








55002
57479


2044








2345
4822


2045








1414
3891


2046








36221
38698


2047








11452
13929


2048








11452
13929


2049








11452
13929


2050








11455
13932


2051








11448
13925


2052








11452
13929


2053








4703
7180


2054








11452
13929


2055








56836
59313


2056








54998
57475


2057








11567
14044


2058








18041
20518


2059








11452
13929


2060








36219
38696


2061








11452
13929


2062








11450
13927


2063








120924
123401


2064








36218
38695


2065








11448
13925


2066








11452
13929


2067








11452
13929


2068








12006
14543


2069








117483
119960


2070








6719
9196


2071








9656
12133


2072








94488
96965


2073








2528497
2530974


2074








1447
5265


2075








307506
309710


2076








445336
447510


2077








197601
199542


2078








1343346
1345843


2079








1895
4396


2080








4806
7307


2081








19162
21686


2082








185651
188127


2083








166065
168541


2084








1030001
1032525


2085








158687
161211


2086








664126
666650


2087








1383218
1385739


2088








247534
250011


2089








19324
21800


2090








3794
6270


2091








205986
208462


2092








163830
166306


2093








17595
20119


2094








127282
129675


2095








140059
142319


2096








607545
609474


2097








17857
20090


2098








811700
814237


2099








571
3852
Additional ThsA homolog CDE34944.1


2100








1837917
1847352









The TIR domain gene, thsB, has a strong tendency (35%) to appear in multiple copies clustered around the thsA gene (FIG. 5A). Such duplication is typical to specificity-conferring genes in defense systems (such as the S subunit in type I R-M systems), where duplication followed by diversification serves for multiple specificities of the system. It is therefore possible that the TIR domain gene is responsible for identification of specific phage patterns, with multiple TIR domain genes serving for recognition of different phage components. Under this hypothesis, it is tempting to suggest that Thoeris is the prokaryotic ancestral form of pathogen-associated molecular pattern (PAMP) receptors.


A recent study showed that TIR domains can have enzymatic NAD+ hydrolase activities. In animal neurons, NAD+ hydrolase activity of the SARM1 TIR domain-containing gene leads to NAD+ depletion and generation of ADP-ribose and cyclic ADP-ribose that form signaling molecules regulating axonal degeneration. An E99A point mutation in the B. amyloliquefaciens Y2 KwaB protein, which aligns with the catalytic residue in the SARM1 NAD-cleaving TIR domain (FIG. 5E) abolished the protective activity of Thoeris (FIG. 5C). Moreover, point mutations in the ThsA NAD binding site predicted to abolish NAD binding also resulted in system inactivation (ThsA:N112A and ThsA:D100A/N115A for the B. cereus and B. amyloliquefaciens systems, respectively). These results mark NAD+ binding and hydrolysis as essential for the anti-phage activity of the Thoeris system.


Example 6
Genomic Identification and Analysis of the Druantia System

Objective:


Identify the candidate defense system based on the enrichment of the anchor COG1205.


Methods:


As above


Results:


Another system worthwhile of a brief discussion is the Druantia system (named after a deity from the Gallic mythology). This system is characterized by a very large protein (˜1800-2100aa) containing a DUF1998 (a domain of unknown function), as well as a helicase signature and a Walker A/B motif suggestive of ATP utilization. This polypeptide, named DruE, is encoded by a very large gene, named druE.


The druE gene is typically preceded by a set of highly variable genes with no recognizable domains or function prediction—either 3 genes sized 350-600aa each (Type I; druB, druC, and drub), or two genes sized 700aa-900aa (Type II; druX, druY), or a single large gene of 1000-1200aa (Type III; druF) (FIGS. 6A and 6B). The system is in some cases also preceded by a gene druA, annotated as DUF4338, comprising yet another domain of unknown function; and Type II systems are also associated with a cytosine methylase (FIG. 6A). In at least one instance, druA was downstream (3′) of the druE gene. (FIG. 6A—second embodiment of a Type I Druantia system)


A Type I system (FIG. 6B) cloned from E. coli UMEA 4076-1 into E. coli MG1655 rendered the engineered strain resistant against 4 of the 6 phages tested, and by serially deleting each of the 4 genes in this system, it was verified that all 4 are essential for its activity (FIG. 6C). Notably, DUF1998-containing genes are among the components of the recently reported DISARM and Dpd defense systems, where their function is also unknown. The sheer size of the Druantia system (12 kb of genomic DNA) was unexpected and surprising, suggesting a complex function, and the near-complete absence of recognizable domains in its encoded polypeptides is suggestive of a new mode of defense not shared by prokaryotic defense systems whose mechanism are currently understood.


Elements of the Druantia system (Types I, II, and III, are presented in Table 10.









TABLE 10





The Druantia Defense System and Components Thereof


This table is presented in landscape orientation. Due to the number of columns, the table


has been split into parts. Part A includes the first set of columns and therefore should


be place to the left of subsequent parts (Part B and where relevant Part C). To avoid any


doubt, the rows of the table in each part line up once the tables are placed together.







(Part A)

























I



A
B
C
D
E
F
G
H
#genes


1
assembly_accession
taxid
species_taxid
organism_name
infraspecific_name
phylum
genomic_accession
Type
identified





2
GCA_001372455.1
1505
1505
[Clostridium] sordellii
R26833
Firmicutes
CELG01000003.1
I
4


3
GCA_001516615.1
1765683
1765683

Acidibacillus ferrooxidans

ITV01
Firmicutes
LPVJ01000027.1
I
5


4
GCA_000367505.1
1315967
33934

Anoxybacillus flavithermus NBRC 109594
NBRC 109594
Firmicutes
BARH01000005.1
I
4


5
GCA_001425485.1
1736375
1736375

Aureimonas sp. Leaf427
Leaf427
Proteobacteria
LMQW01000021.1
I
3


6
GCA_001425525.1
1736384
1736384

Aureimonas sp. Leaf460
Leaf460
Proteobacteria
LMQY01000066.1
I
3


7
GCA_001043655.1
1396
1396

Bacillus cereus

LK9
Firmicutes
LDUP01000008.1
I
4


8
GCA_000291115.1
1053212
1396

Bacillus cereus HuB5-5
HuB5-5
Firmicutes
JH792120.1
I
4


9
GCA_001048695.1
1499688
1499688

Bacillus sp. LF1
LF1
Firmicutes
CVRB01000003.1
I
4


10
GCA_000708005.1
1454376
28026

Bifidobacterium pseudocatenulatum IPLA36007
IPLA36007
Actinobacteria
JEOD01000003.1
I
3


11
GCA_000513015.1
1161409
1161409

Bifidobacterium sp. MSTE12
MSTE12
Actinobacteria
AZYA01000034.1
I
3


12
GCA_001402875.1
1079
1079

Blastochloris viridis

ATCC 19567
Proteobacteria
CP012946.1
I
3


13
GCA_001459775.1
1079
1079

Blastochloris viridis


Proteobacteria
LN907867.1
I
3


14
GCA_000757095.1
28450
28450

Burkholderia pseudomallei

BDE
Proteobacteria
KN150937.1
I
4


15
GCA_000774465.1
1434201
28450

Burkholderia pseudomallei MSHR4299
MSHR4299
Proteobacteria
KN323020.1
I
3


16
GCA_000152345.1
331978
28450

Burkholderia pseudomallei Pasteur 52237
Pasteur 52237
Proteobacteria
CH899741.1
I
3


17
GCA_000757035.2
331978
28450

Burkholderia pseudomallei Pasteur 52237
Pasteur 52237
Proteobacteria
CP009899.1
I
4


18
GCA_000808035.2
57975
57975

Burkholderia thailandensis

2003015869
Proteobacteria
CP008914.2
I
3


19
GCA_001527035.1
101571
101571

Burkholderia ubonensis

MSMB1607WGS
Proteobacteria
LPAR01000085.1
I
4


20
GCA_001528155.1
101571
101571

Burkholderia ubonensis

MSMB1633WGS
Proteobacteria
LPAU01000139.1
I
3


21
GCA_001051235.2
1400863
1400862

Candidatus Competibacter denitrificans Run_A_D11
Run_A_D11
Proteobacteria
CBTJ020000108.1
I
3


22
GCA_001292585.1
1509431
1509431

Candidatus Magnetomorum sp. HK-1

Proteobacteria
JPDT01002867.1
I
4


23
GCA_000785145.1
1003181
1003181

Candidatus Thiomargarita nelsonii


Proteobacteria
JSZA01001556.1
I
3


24
GCA_000952105.1
536
536

Chromobacterium violaceum

L_1B5_1
Proteobacteria
JYGI01000049.1
I
5


25
GCA_000577895.1
1216932
1216932

Clostridium bornimense

type strain: M2/40
Firmicutes
HG917869.1
I
4


26
GCA_000724245.2
1443123
1542

Clostridium novyi B str. ATCC 27606
ATCC 27606
Firmicutes
JENW01000064.1
I
3


27
GCA_000190355.1
556261
556261

Clostridium sp. D5
D5
Firmicutes
GL870812.1
I
3


28
GCA_000021925.1
272564
49338

Desulfitobacterium hafniense DCB-2
DCB-2
Firmicutes
CP001336.1
I
3


29
GCA_000024205.1
485916
58138

Desulfotomaculum acetoxidans DSM 771
DSM 771
Firmicutes
CP001720.1
I
3


30
GCA_001545095.1
1514105
1514105

Erysipelothrix sp. LV19
LV19
Firmicutes
CP013213.1
I
3


31
GCA_000797815.1
562
562

Escherichia coli

CVM N41556PS
Proteobacteria
JUBQ01000038.1
I
5


32
GCA_000797835.1
562
562

Escherichia coli

CVM N33804PS
Proteobacteria
JUDE01000009.1
I
5


33
GCA_000797855.1
562
562

Escherichia coli

CVM N33806PS
Proteobacteria
JUDD01000028.1
I
3


34
GCA_000798155.1
562
562

Escherichia coli

CVM N34077PS
Proteobacteria
JUCZ01000011.1
I
5


35
GCA_000798415.1
562
562

Escherichia coli

CVM N34557PS
Proteobacteria
JUCU01000008.1
I
4


36
GCA_001077875.1
562
562

Escherichia coli

KIC-2
Proteobacteria
LFJZ01000059.1
I
5


37
GCA_001420165.1
562
562

Escherichia coli

449
Proteobacteria
LIVL01000002.1
I
5


38
GCA_001442495.1
562
562

Escherichia coli

YD786
Proteobacteria
CP013112.1
I
5


39
GCA_001463535.1
562
562

Escherichia coli

50673720
Proteobacteria
LNHW01000058.1
I
5


40
GCA_001576545.1
562
562

Escherichia coli

G76
Proteobacteria
LOPR01000035.1
I
5


41
GCA_000194295.2
869676
562

Escherichia coli 97.0264
97.0264
Proteobacteria
AEZP02000004.1
I
5


42
GCA_000458275.1
1281086
562

Escherichia coli HVH 153 (3-9344314)
HVH 153 (3-9344314)
Proteobacteria
KE700289.1
I
5


43
GCA_000456745.1
1280996
562

Escherichia coli HVH 46 (4-2758776)
HVH 46 (4-2758776)
Proteobacteria
KE699287.1
I
5


44
GCA_000456745.1
1280996
562

Escherichia coli HVH 46 (4-2758776)
HVH 46 (4-2758776)
Proteobacteria
KE699283.1
I
5


45
GCA_000607285.1
1409786
562

Escherichia coli K02
K02
Proteobacteria
KK097723.1
I
5


46
GCA_000459655.1
1281158
562

Escherichia coli KOEGE 33 (68a)
KOEGE 33 (68a)
Proteobacteria
KE701247.1
I
5


47
GCA_000350745.1
1169334
562

Escherichia coli KTE15
KTE15
Proteobacteria
KB732282.1
I
5


48
GCA_000352905.1
1181729
562

Escherichia coli KTE183
KTE183
Proteobacteria
KB733173.1
I
5


49
GCA_000407945.1
1169352
562

Escherichia coli KTE34
KTE34
Proteobacteria
KE136741.1
I
5


50
GCA_000407745.1
1169320
562

Escherichia coli KTE35
KTE35
Proteobacteria
KE136604.1
I
5


51
GCA_000351665.1
1182679
562

Escherichia coli KTE72
KTE72
Proteobacteria
KB733389.1
I
5


52
GCA_000351805.1
1182691
562

Escherichia coli KTE86
KTE86
Proteobacteria
KB732864.1
I
5


53
GCA_000326625.1
1169366
562

Escherichia coli KTE88
KTE88
Proteobacteria
ANYV01000069.1
I
5


54
GCA_000408505.1
1182693
562

Escherichia coli KTE89
KTE89
Proteobacteria
KE137143.1
I
5


55
GCA_000351845.1
1182696
562

Escherichia coli KTE93
KTE93
Proteobacteria
KB732902.1
I
5


56
GCA_000576655.1
1314835
562

Escherichia coli MP1
MP1
Proteobacteria
JEMI01000044.1
I
5


57
GCA_000179175.1
679207
562

Escherichia coli MS 107-1
MS 107-1
Proteobacteria
ADWV01000005.1
I
5


58
GCA_000179095.1
796392
562

Escherichia coli MS 79-10
MS 79-10
Proteobacteria
ADWR01000035.1
I
3


59
GCA_000364305.1
1235805
562

Escherichia coli SWW33
SWW33
Proteobacteria
KB822527.1
I
5


60
GCA_000176635.2
656443
562

Escherichia coli TA271
TA271
Proteobacteria
GL884297.1
I
4


61
GCA_000460495.1
1281201
562

Escherichia coli UMEA 3163-1
UMEA 3163-1
Proteobacteria
KE701783.1
I
5


62
GCA_000461335.1
1281248
562

Escherichia coli UMEA 3391-1
UMEA 3391-1
Proteobacteria
KE702395.1
I
5


63
GCA_000461855.1
1281278
562

Escherichia coli UMEA 4076-1
UMEA 4076-1
Proteobacteria
KE702725.1
I
5


64
GCA_000434955.1
1262994
1262994

Firmicutes bacterium CAG:65

Firmicutes
FR882409.1
I
4


65
GCA_000750005.1
1430331
1430331

Geobacillus icigianus

G1w1
Firmicutes
JPYA01000201.1
I
4


66
GCA_001587475.1
1586290
1586290

Geobacillus sp. B4113_201601
B4113_201601
Firmicutes
LQYX01000099.1
I
4


67
GCA_001025095.1
1659191
1659191

Geobacillus sp. T6
T6
Firmicutes
LDNZ01000120.1
I
3


68
GCA_000174795.2
550542
550542

Geobacillus sp. Y412MC52
Y412MC52
Firmicutes
CP002442.1
I
4


69
GCA_000024705.1
544556
544556

Geobacillus sp. Y412MC61
Y412MC61
Firmicutes
CP001794.1
I
4


70
GCA_000743495.1
1422
1422

Geobacillus stearothermophilus

22
Firmicutes
JQCS01000005.1
I
4


71
GCA_000749985.1
1422
1422

Geobacillus stearothermophilus

53
Firmicutes
JPYV01000046.1
I
4


72
GCA_000154705.2
411684
244596

Hoeflea phototrophica DFL-43
DFL-43
Proteobacteria
CM002917.1
I
3


73
GCA_001428625.1
1736490
1736490

Hydrogenophaga sp. Root209
Root209
Proteobacteria
LMIE01000033.1
I
3


74
GCA_000230975.3
670307
53399

Hyphomicrobium denitrificans 1NES1
1NES1
Proteobacteria
CP005587.1
I
3


75
GCA_001078195.1
883119
571

Klebsiella oxytoca 10-5244
10-5244
Proteobacteria
KQ235774.1
I
5


76
GCA_000492915.1
1328370
573

Klebsiella pneumoniae MGH 32
MGH 32
Proteobacteria
KI535619.1
I
4


77
GCA_000018685.1
357809
66219

Lachnoclostridium phytofermentans ISDg
ISDg
Firmicutes
CP000885.1
I
3


78
GCA_000403475.2
1235799
1235799
Lachnospiraceae bacterium 3-2
3-2
Firmicutes
KE159795.1
I
4


79
GCA_000170755.1
313628
256847

Lentisphaera araneosa HTCC2155
HTCC2155
Lentisphaerae
ABCK01000024.1
I
3


80
GCA_000502535.1
1287273
1287273

Mesorhizobium sp. LNJC391B00
LNJC391B00
Proteobacteria
AYWI01000025.1
I
3


81
GCA_001508455.1
1641382
1641382

Methanocalculus sp. 52_23

Euryarchaeota
LGGJ01000025.1
I
4


82
GCA_000243255.1
937775
2315

Methanoplanus limicola DSM 2279
DSM 2279
Euryarchaeota
CM001436.1
I
4


83
GCA_000979685.1
2209
2209

Methanosarcina mazei

3.H.A.2.4
Euryarchaeota
JJPP01000022.1
I
4


84
GCA_000455825.1
1333857
300020

Microbacterium maritypicum MF109
MF109
Actinobacteria
ATAO01000002.1
I
3


85
GCA_001314225.1
1714373
1714373

Microbacterium sp. No. 7
No. 7
Actinobacteria
CP012697.1
I
3


86
GCA_000509385.1
1344956
1344956

Microbacteriumsp. TS-1
TS-1
Actinobacteria
BASQ01000001.1
I
3


87
GCA_000143085.1
105559
473531

Nitrosococcus watsonii C-113
C-113
Proteobacteria
CP002087.1
I
3


88
GCA_001044495.1
1628279
1628279

Nitrospina sp. SCGC_AAA799_C22

Nitrospinae
JZKJ01000047.1
I
3


89
GCA_000225995.2
1003237
28077

Nitrospirillum amazonense Y2
Y2
Proteobacteria
AFBX01000767.1
I
3


90
GCA_000442555.1
1117108
44250

Paenibacillus alvei TS-15
TS-15
Firmicutes
ATMT01000002.1
I
4


91
GCA_000024685.1
481743
481743

Paenibacillus sp. Y412MC10
Y412MC10
Firmicutes
CP001793.1
I
4


92
GCA_000803315.1
1507808
554

Pectobacterium carotovorum subsp. actinidiae
KKH3
Proteobacteria
JRMH01000001.1
I
5


93
GCA_000754765.1
78398
554

Pectobacterium carotovorum subsp. odoriferum
NCPPB 3839
Proteobacteria
JQOG01000013.1
I
3


94
GCA_000271665.2
1192197
365349

Pelosinus fermentans JBW45
JBW45
Firmicutes
CP010978.1
I
4


95
GCA_001298735.1
1677858
1677858

Propionispora sp. Iso2/2

Firmicutes
CYSP01000005.1
I
4


96
GCA_001450755.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07239
Proteobacteria
LLNK01000035.1
I
4


97
GCA_001451905.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07508
Proteobacteria
LLQO01000185.1
I
3


98
GCA_001452525.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07690
Proteobacteria
LLSK01000268.1
I
4


99
GCA_001548135.1
287
287

Pseudomonas aeruginosa

8380
Proteobacteria
AP014839.2
I
5


100
GCA_000647595.1
1339263
287

Pseudomonas aeruginosa 148
148
Proteobacteria
ATAJ01000067.1
I
4


101
GCA_000359505.1
1280938
287

Pseudomonas aeruginosa B136-33
B136-33
Proteobacteria
CP004061.1
I
3


102
GCA_000480905.1
1402553
287

Pseudomonas aeruginosa BL12
BL12
Proteobacteria
KI518868.1
I
5


103
GCA_000629605.1
1418235
287

Pseudomonas aeruginosa BWH049
BWH049
Proteobacteria
KK213281.1
I
5


104
GCA_000481145.1
1402528
287

Pseudomonas aeruginosa BWHPSA028
BWHPSA028
Proteobacteria
KI518960.1
I
5


105
GCA_000455705.1
1333855
287

Pseudomonas aeruginosa WC55
WC55
Proteobacteria
ATAQ01000308.1
I
4


106
GCA_000934565.1
294
294

Pseudomonas fluorescens

PCL1751
Proteobacteria
CP010896.1
I
5


107
GCA_000497385.1
1399145
303

Pseudomonas putida S610
S610
Proteobacteria
AYJQ01000058.1
I
5


108
GCA_000367825.1
1227924
303

Pseudomonas putida TRO1
TRO1
Proteobacteria
APBQ01000198.1
I
5


109
GCA_000812405.1
1582493
1582493

Pseudomonas sp. PI1
PI1
Proteobacteria
JWMC01000074.1
I
3


110
GCA_000737225.1
317
317

Pseudomonas syringae

UB0390
Proteobacteria
JPQV01000021.1
I
5


111
GCA_001587135.1
305
305

Ralstonia solanacearum

UW163
Proteobacteria
CP012941.1
I
5


112
GCA_001423045.1
1736327
1736327

Rathayibacter sp. Leaf296
Leaf296
Actinobacteria
LMNR01000001.1
I
3


113
GCA_001425345.1
1736357
1736357

Rhizobium sp. Leaf383
Leaf383
Proteobacteria
LMQD01000012.1
I
3


114
GCA_001424065.1
1736358
1736358

Rhizobium sp. Leaf384
Leaf384
Proteobacteria
LMQE01000005.1
I
3


115
GCA_000982715.1
191292
191292

Rhodococcus aetherivorans

IcdP1
Actinobacteria
CP011341.1
I
3


116
GCA_000341815.1
1278077
334542

Rhodococcus qingshengii BKS 20-40
BKS 20-40
Actinobacteria
AODN01000014.1
I
3


117
GCA_000824945.1
1830
1830

Rhodococcus ruber


Actinobacteria
CCSD01000049.1
I
4


118
GCA_000508185.1
1207055
1207055

Sphingobium sp. C100
C100
Proteobacteria
AYOY01000167.1
I
3


119
GCA_000158915.1
457427
998084

Streptomyces himastatinicus ATCC 53653
ATCC 53653
Actinobacteria
GG657754.1
I
3


120
GCA_000227705.3
717605
377615

Thermobacillus composti KWC4
KWC4
Firmicutes
CP003255.1
I
3


121
GCA_000176455.1
675809
666

Vibrio cholerae CT 5369-93
CT 5369-93
Proteobacteria
ADAL01000217.1
I
5


122
GCA_000746665.1
672
672

Vibrio vulnificus

93U204
Proteobacteria
CP009261.1
I
5


123
GCA_001116865.1
631
631

Yersinia intermedia

58735
Proteobacteria
CQER01000007.1
I
5


124
GCA_001299035.1
1806494
1806494

Achromobacter sp. 2789STDY5608612
2789STDY5608612
Proteobacteria
CYTE01000002.1
II
4


125
GCA_001509495.1
135947
135946

Actinoplanes awajinensis subsp. mycoplanecinus
NRRL B-16712
Actinobacteria
LLZH01000223.1
II
3


126
GCA_000389965.1
649831
649831

Actinoplanes sp. N902-109
N902-109
Actinobacteria
CP005929.1
II
3


127
GCA_000219665.2
1050720
358

Agrobacterium tumefaciens F2
F2
Proteobacteria
AFSD01000008.1
II
4


128
GCA_000018325.1
350688
461876

Alkaliphilus oremlandii OhILAs
OhILAs
Firmicutes
CP000853.1
II
3


129
GCA_001443605.1
1307839
1307839
bacterium L21-Spi-D4
L21-Spi-D4
Bacteroidetes
CP013118.1
II
3


130
GCA_000244935.1
319003
319003

Bradyrhizobium sp. WSM1253
WSM1253
Proteobacteria
JH600073.1
II
4


131
GCA_000144605.1
633149
74313

Brevundimonas subvibrioides ATCC 15264
ATCC 15264
Proteobacteria
CP002102.1
II
4


132
GCA_000182255.1
513051
87883

Burkholderia multivorans CGD1
CGD1
Proteobacteria
ACFB01000002.1
II
3


133
GCA_001532035.1
1207504
1207504

Burkholderia pseudomultivorans

MSMB368WGS
Proteobacteria
LPJR01000034.1
II
4


134
GCA_001424345.1
1736287
1736287

Burkholderia sp. Leaf177
Leaf177
Proteobacteria
LMPF01000022.1
II
4


135
GCA_001526735.1
101571
101571

Burkholderia ubonensis

MSMB1601WGS
Proteobacteria
LPAL01000127.1
II
3


136
GCA_001526945.1
101571
101571

Burkholderia ubonensis

MSMB1791WGS
Proteobacteria
LPAY01000146.1
II
3


137
GCA_001529895.1
101571
101571

Burkholderia ubonensis

MSMB1216WGS
Proteobacteria
LPEG01000082.1
II
4


138
GCA_001531945.1
101571
101571

Burkholderia ubonensis

MSMB609WGS
Proteobacteria
LPKF01000002.1
II
4


139
GCA_001534345.1
101571
101571

Burkholderia ubonensis

MSMB1466WGS
Proteobacteria
LPMV01000059.1
II
3


140
GCA_001426725.1
1736459
1736459

Cellulomonas sp. Root137
Root137
Actinobacteria
LMFG01000005.1
II
3


141
GCA_000016085.1
290318
1094

Chlorobium phaeovibrioides DSM 265
DSM 265
Chlorobi
CP000607.1
II
3


142
GCA_001563495.1
267125
267125

Chryseobacterium kwangjuense

KJ1R5
Bacteroidetes
LPUR01000001.1
II
3


143
GCA_001281005.1
546
546

Citrobacter freundii

P10159
Proteobacteria
CP012554.1
II
4


144
GCA_000158355.2
469595
469595

Citrobacter sp. 30_2
30_2
Proteobacteria
KI391991.1
II
4


145
GCA_000759755.1
1114921
67827

Citrobacter werkmanii NBRC 105721
NBRC 105721
Proteobacteria
BBMW01000007.1
II
4


146
GCA_001515955.1
1734399
1734399

Clostridia bacterium BRH_c25

Firmicutes
LOES01000090.1
II
3


147
GCA_001584185.1
279113
279113

Collimonas pratensis

Ter91
Proteobacteria
CP013234.1
II
4


148
GCA_000725405.1
1274
1274

Dermacoccus nishinomiyaensis

M25
Actinobacteria
CP008889.1
II
3


149
GCA_000023565.1
561229
556

Dickeya chrysanthemi Ech1591
Ech1591
Proteobacteria
CP001655.1
II
4


150
GCA_001011625.1
548
548

Enterobacter aerogenes

GN02761
Proteobacteria
LDBO01000027.1
II
4


151
GCA_001518055.1
548
548

Enterobacter aerogenes

GN02761
Proteobacteria
LRCC01000127.1
II
4


152
GCA_001518435.1
548
548

Enterobacter aerogenes

GN05782
Proteobacteria
LRCY01000101.1
II
4


153
GCA_001011955.1
61645
61645

Enterobacter asburiae

GN02208
Proteobacteria
LDCK01000014.1
II
3


154
GCA_000958325.1
550
550

Enterobacter cloacae

44517
Proteobacteria
JZXX01000013.1
II
4


155
GCA_000958345.1
550
550

Enterobacter cloacae

44524
Proteobacteria
JZXW01000013.1
II
4


156
GCA_000958385.1
550
550

Enterobacter cloacae

44541
Proteobacteria
JZXU01000010.1
II
4


157
GCA_000965895.1
550
550

Enterobacter cloacae

CIDEIMsCOL13
Proteobacteria
JZKX01000010.1
II
4


158
GCA_000965925.1
550
550

Enterobacter cloacae

CIDEIMsCOL16
Proteobacteria
JZLA01000009.1
II
4


159
GCA_000965975.1
550
550

Enterobacter cloacae

CIDEIMsCOL18
Proteobacteria
JZLC01000004.1
II
4


160
GCA_000965985.1
550
550

Enterobacter cloacae

CIDEIMsCOL19
Proteobacteria
JZLD01000016.1
II
4


161
GCA_000966045.1
550
550

Enterobacter cloacae

CIDEIMsCOL6
Proteobacteria
JZKQ01000011.1
II
4


162
GCA_000966055.1
550
550

Enterobacter cloacae

CIDEIMsCOL7
Proteobacteria
JZKR01000007.1
II
4


163
GCA_000966085.1
550
550

Enterobacter cloacae

CIDEIMsCOL8
Proteobacteria
JZKS01000009.1
II
4


164
GCA_000966125.1
550
550

Enterobacter cloacae

CIDEIMsCOL11
Proteobacteria
JZKV01000018.1
II
4


165
GCA_000968675.1
550
550

Enterobacter cloacae

CIDEIMsCOL15
Proteobacteria
JZKZ01000021.1
II
4


166
GCA_000235765.3
1104326
550

Enterobacter cloacae subsp. dissolvens SDM
SDM
Proteobacteria
CP003678.1
II
4


167
GCA_001472385.1
299766
158836

Enterobacter hormaechei subsp. steigerwaltii
SMART_539
Proteobacteria
LPPV01000001.1
II
4


168
GCA_001473115.1
299766
158836

Enterobacter hormaechei subsp. steigerwaltii
SMART_1078
Proteobacteria
LPOL01000074.1
II
4


169
GCA_000568075.1
314330
314330

Enterobacter sp. DC1
DC1
Proteobacteria
AZUA01000002.1
II
4


170
GCA_000010305.1
379066
173480

Gemmatimonas aurantiaca T-27
T-27
Gemmatimonadetes
AP009153.1
II
4


171
GCA_000298195.1
1108045
83341

Gordonia rhizosphera NBRC 16068
NBRC 16068
Actinobacteria
BAHC01000188.1
II
3


172
GCA_001275395.1
1704290
1704290

Hapalosiphon sp. MRB220
MRB220
Cyanobacteria
LIRN01000101.1
II
3


173
GCA_000567145.1
1400164
573

Klebsiella pneumoniae BIDMC 46b
BIDMC 46b
Proteobacteria
KK036716.1
II
4


174
GCA_000529775.1
1379689
573

Klebsiella pneumoniae subsp. pneumoniae T69
T69
Proteobacteria
HG518478.1
II
4


175
GCA_000169115.1
247639
247639
marine gamma proteobacterium HTCC2080
HTCC2080
Proteobacteria
AAVV01000004.1
II
3


176
GCA_001424165.1
1736272
1736272

Massilia sp. Leaf139
Leaf139
Proteobacteria
LMOJ01000003.1
II
4


177
GCA_000970225.1
1434114
2209

Methanosarcina mazei LYC
LYC
Euryarchaeota
CP009513.1
II
3


178
GCA_000757795.1
693986
334852

Methylobacterium oryzae CBMB2C
CBMB20
Proteobacteria
CP003811.1
II
4


179
GCA_001542815.1
925818
925818

Methylobacterium sp. AMS5
AMS5
Proteobacteria
CP006992.1
II
4


180
GCA_000834175.1
1587523
1587523

Microbacterium sp. MEJ108Y
MEJ108Y
Actinobacteria
JXQX01000022.1
II
3


181
GCA_000568915.1
457406
457406

Micromonospora sp. M42
M42
Actinobacteria
KK037233.1
II
3


182
GCA_000306785.1
477641
477641

Modestobacter marinus

BC501
Actinobacteria
FO203431.1
II
3


183
GCA_000307755.2
1239989
582

Morganella morganii SC01
SC01
Proteobacteria
AMWL02000021.1
II
4


184
GCA_001570445.1
228230
228230

Mycobacterium canariasense

JCM15298
Actinobacteria
BCSY01000069.1
II
3


185
GCA_001307545.1
1766
1766

Mycobacterium fortuitum

CT6
Actinobacteria
CP011269.1
II
3


186
GCA_001187505.1
134601
134601

Mycobacterium goodii

X7B
Actinobacteria
CP012150.1
II
3


187
GCA_001570485.1
59813
59813

Mycobacterium novocastrense

JCM18114
Actinobacteria
BCTA01000023.1
II
3


188
GCA_000024365.1
479431
53461

Nakamurella multipartita DSM 44233
DSM 44233
Actinobacteria
CP001737.1
II
3


189
GCA_000963985.1
1628190
1628190

Pantoea sp. BL1
BL1
Proteobacteria
JZRH01000052.1
II
4


190
GCA_001447385.1
1745182
1745182

Paracoccussp. MKU1
MKU1
Proteobacteria
LLWQ01000019.1
II
3


191
GCA_000808515.1
555
554

Pectobacterium carotovorum subsp. carotovorum
BC T5
Proteobacteria
JUJS01000001.1
II
4


192
GCA_000294535.1
1218933
554

Pectobacterium carotovorum subsp. carotovorum PCC21
PCC21
Proteobacteria
CP003776.1
II
4


193
GCA_001026985.1
82985
82985

Pragia fontium

24613
Proteobacteria
CP010423.1
II
4


194
GCA_000829255.1
287
287

Pseudomonas aeruginosa

NCGM 1984
Proteobacteria
AP014646.1
II
3


195
GCA_000829275.1
287
287

Pseudomonas aeruginosa

NCGM 1900
Proteobacteria
AP014622.1
II
3


196
GCA_001449645.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07177
Proteobacteria
LLMG01000101.1
II
3


197
GCA_001449765.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07186
Proteobacteria
LLMQ01000093.1
II
3


198
GCA_001450265.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07378
Proteobacteria
LLOC01000126.1
II
4


199
GCA_001450505.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07170
Proteobacteria
LLLZ01000038.1
II
4


200
GCA_001450545.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07176
Proteobacteria
LLMF01000085.1
II
3


201
GCA_001450995.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07387
Proteobacteria
LLOL01000018.1
II
4


202
GCA_001451125.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07406
Proteobacteria
LLOT01000015.1
II
4


203
GCA_001451485.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07425
Proteobacteria
LLPM01000023.1
II
4


204
GCA_001451605.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07486
Proteobacteria
LLPSO1000097.1
II
4


205
GCA_001451625.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07487
Proteobacteria
LLPTO1000056.1
II
4


206
GCA_001451815.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07498
Proteobacteria
LLQE01000017.1
II
4


207
GCA_001451885.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07504
Proteobacteria
LLQK01000005.1
II
4


208
GCA_001451985.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07622
Proteobacteria
LLQT01000086.1
II
4


209
GCA_001452025.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07626
Proteobacteria
LLQX01000033.1
II
4


210
GCA_001452045.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07627
Proteobacteria
LLQY01000018.1
II
4


211
GCA_001452305.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07645
Proteobacteria
LLRQ01000036.1
II
4


212
GCA_001452325.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07647
Proteobacteria
LLRS01000111.1
II
3


213
GCA_001452575.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07694
Proteobacteria
LLSO01000025.1
II
4


214
GCA_001452675.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07703
Proteobacteria
LLSX01000034.1
II
4


215
GCA_001453345.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07624
Proteobacteria
LLQV01000015.1
II
4


216
GCA_001453365.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07625
Proteobacteria
LLQW01000076.1
II
4


217
GCA_001453415.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07632
Proteobacteria
LLRD01000075.1
II
3


218
GCA_001453485.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07646
Proteobacteria
LLRR01000027.1
II
4


219
GCA_001453565.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07679
Proteobacteria
LLRZ01000123.1
II
4


220
GCA_001453595.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07683
Proteobacteria
LLSD01000091.1
II
4


221
GCA_001454045.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07276
Proteobacteria
LLUCO1000021.1
II
4


222
GCA_001454305.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07309
Proteobacteria
LLUY01000055.1
II
4


223
GCA_001454595.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07268
Proteobacteria
LLTZ01000033.1
II
4


224
GCA_000148745.1
798130
287

Pseudomonas aeruginosa 39016
39016
Proteobacteria
CM001020.1
II
3


225
GCA_000481745.1
1402498
287

Pseudomonas aeruginosa 6077
6077
Proteobacteria
KI519216.1
II
4


226
GCA_000480985.1
1402549
287

Pseudomonas aeruginosa BL08
BL08
Proteobacteria
KI518899.1
II
4


227
GCA_000480865.1
1402555
287

Pseudomonas aeruginosa BL14
BL14
Proteobacteria
KI518844.1
II
4


228
GCA_000480805.1
1402558
287

Pseudomonas aeruginosa BL17
BL17
Proteobacteria
KI518822.1
II
4


229
GCA_000629125.1
1447538
287

Pseudomonas aeruginosa BWH030
BWH030
Proteobacteria
KK212308.1
II
4


230
GCA_000629585.1
1418236
287

Pseudomonas aeruginosa BWH050
BWH050
Proteobacteria
KK213277.1
II
4


231
GCA_000481585.1
1402506
287

Pseudomonas aeruginosa BWHPSA006
BWHPSA006
Proteobacteria
KI519145.1
II
4


232
GCA_000480435.1
1402576
287

Pseudomonas aeruginosa C48
C48
Proteobacteria
KI518703.1
II
4


233
GCA_000481805.1
1402495
287

Pseudomonas aeruginosa JJ692
JJ692
Proteobacteria
KI519252.1
II
4


234
GCA_000513235.1
1306165
287

Pseudomonas aeruginosa MH27
MH27
Proteobacteria
CBTR010000015.1
II
3


235
GCA_000284555.1
1089456
287

Pseudomonas aeruginosa NCGM2.S1
NCGM2.S1
Proteobacteria
AP012280.1
II
3


236
GCA_000481785.1
1402496
287

Pseudomonas aeruginosa U2504
U2504
Proteobacteria
KI519240.1
II
4


237
GCA_000786485.1
1341645
287

Pseudomonas aeruginosa WS394
WS394
Proteobacteria
CBYA010000116.1
II
4


238
GCA_000012265.1
220664
380021

Pseudomonas protegens Pf-5
Pf-5
Proteobacteria
CP000076.1
II
4


239
GCA_000334035.1
1204471
317

Pseudomonas syringae BRIP34876
BRIP34876
Proteobacteria
KB316468.1
II
4


240
GCA_000334055.1
1205751
317

Pseudomonas syringae BRIP34881
BRIP34881
Proteobacteria
KB316535.1
II
4


241
GCA_000765305.1
323
251701

Pseudomonas syringae pv. tomato
NYS-T1
Proteobacteria
KN265560.1
II
4


242
GCA_001518465.1
323
251701

Pseudomonas syringae pv. tomato
A9
Proteobacteria
LNKY01000101.1
II
4


243
GCA_001518695.1
323
251701

Pseudomonas syringae pv. tomato
407
Proteobacteria
LNKZ01000069.1
II
4


244
GCA_000172895.1
546231
251701

Pseudomonas syringae pv. tomato T1
T1
Proteobacteria
ABSM01000016.1
II
4


245
GCA_000471625.1
1354303
248452

Psychrobacter aquaticus CMS 56
CMS 56
Proteobacteria
AUSW01000035.1
II
3


246
GCA_001297245.1
1538158
1538158

Rhizobium acidisoli

FH23
Proteobacteria
LJSR01000033.1
II
4


247
GCA_001425345.1
1736357
1736357

Rhizobium sp. Leaf383
Leaf383
Proteobacteria
LMQD01000026.1
II
3


248
GCA_001507595.1
1685379
1685379

Ruegeria sp. ZGT118
ZGT118
Proteobacteria
LQBQ01000001.1
II
3


249
GCA_001474275.1
28901
28901

Salmonella enterica

CVM 43767
Proteobacteria
JYQK01000006.1
II
4


250
GCA_001569645.1
28901
28901

Salmonella enterica

NGUA06
Proteobacteria
BCOE01000051.1
II
4


251
GCA_001569685.1
28901
28901

Salmonella enterica

NGUA08
Proteobacteria
BCOG01000098.1
II
4


252
GCA_001569765.1
28901
28901

Salmonella enterica

NGUA12
Proteobacteria
BCOK01000075.1
II
4


253
GCA_001569785.1
28901
28901

Salmonella enterica

NGUA13
Proteobacteria
BCOL01000051.1
II
4


254
GCA_001569865.1
28901
28901

Salmonella enterica

NGUA17
Proteobacteria
BCOP01000026.1
II
4


255
GCA_001569905.1
28901
28901

Salmonella enterica

NGUA19
Proteobacteria
BCOR01000051.1
II
4


256
GCA_001570025.1
28901
28901

Salmonella enterica

NGUA25
Proteobacteria
BCOX01000056.1
II
4


257
GCA_001570065.1
28901
28901

Salmonella enterica

NGUA27
Proteobacteria
BCOZ01000088.1
II
4


258
GCA_001570105.1
28901
28901

Salmonella enterica

NGUA29
Proteobacteria
BCPB01000051.1
II
4


259
GCA_001570145.1
28901
28901

Salmonella enterica

NGUA31
Proteobacteria
BCPD01000090.1
II
4


260
GCA_001570205.1
28901
28901

Salmonella enterica

NGUA34
Proteobacteria
BCPG01000042.1
II
4


261
GCA_001448925.1
1245396
28901

Salmonella enterica subsp. arizonae serovar 62:z36:- str. 5335/86
5335/86
Proteobacteria
LHTK01000001.1
II
4


262
GCA_000756465.1
1386967
28901

Salmonella enterica subsp. arizonae serovar 62:z36:- str.
RKS2983
Proteobacteria
CP006693.1
II
4






RKS2983


263
GCA_000748945.1
1173471
28901

Salmonella enterica subsp.enterica serovar Bareilly str.
CFSAN000235
Proteobacteria
JRCT01000004.1
II
4






CFSAN000235


264
GCA_000748965.1
1173472
28901

Salmonella enterica subsp. enterica serovar Bareilly str.
CFSAN000236
Proteobacteria
JRCS01000009.1
II
3






CFSAN000236


265
GCA_000749105.1
1182179
28901

Salmonella enterica subsp. enterica serovar Bareilly str.
CFSAN000754
Proteobacteria
JRCL01000011.1
II
4






CFSAN000754


266
GCA_000504705.2
1192560
28901

Salmonella enterica subsp. enterica serovar Cubana str. 76814
76814
Proteobacteria
KI635640.1
II
4


267
GCA_000430125.1
1271863
28901

Salmonella enterica subsp. enterica serovar Cubana str.
CFSAN002050
Proteobacteria
CP006055.1
II
4






CFSAN002050


268
GCA_000500025.1
1314885
28901

Salmonella enterica subsp. enterica serovar Cubana str.
CVM42234
Proteobacteria
ATEU01000012.1
II
4






CVM42234


269
GCA_000487835.1
1194151
28901

Salmonella enterica subsp. enterica serovar Norwich str.
CFSAN001077
Proteobacteria
APAM01000054.1
II
4






CFSAN001077


270
GCA_000486285.1
984254
28901

Salmonella enterica subsp. enterica serovar Virchow str. ATCC
ATCC 51955
Proteobacteria
AOXL01000118.1
II
4






51955


271
GCA_000171535.2
465517
28901

Salmonella enterica subsp. enterica serovar Virchow str. SL491
SL491
Proteobacteria
ABFH02000001.1
II
3


272
GCA_000516855.1
1249525
28901

Salmonella enterica subsp. enterica serovar Virchow str. SVQ1
SVQ1
Proteobacteria
KI911915.1
II
4


273
GCA_001409135.1
57743
28901

Salmonella enterica subsp. enterica serovar Weltevreden
2511STDY5462388
Proteobacteria
LN890518.1
II
4


274
GCA_001409155.1
57743
28901

Salmonella enterica subsp. enterica serovar Weltevreden
2511STDY5712384
Proteobacteria
LN890522.1
II
4


275
GCA_001409175.1
57743
28901

Salmonella enterica subsp. enterica serovar Weltevreden
2511STDY5712385
Proteobacteria
LN890524.1
II
4


276
GCA_001409195.1
57743
28901

Salmonella enterica subsp. enterica serovar Weltevreden
2511STDY5462413
Proteobacteria
LN890520.1
II
4


277
GCA_000230505.1
936157
28901

Salmonella enterica subsp. enterica serovar Weltevreden str.
2007-60-3289-1
Proteobacteria
FR775246.1
II
4






2007-60-3289-1


278
GCA_000171495.1
465518
28901

Salmonella enterica subsp. enterica serovar Weltevreden str.
HI_N05-537
Proteobacteria
ABFF01000011.1
II
4






HI_N05-537


279
GCA_001188155.1
59205
28901

Salmonella enterica subsp. houtenae
01-0133
Proteobacteria
JWSP01000004.1
II
4


280
GCA_000486245.1
1173948
28901

Salmonella enterica subsp. houtenae serovar 50:g, z51:- str. 01-
01-0133
Proteobacteria
AOXJ01000080.1
II
3






0133


281
GCA_000521925.1
1400186
615

Serratia marcescens BIDMC 44
BIDMC 44
Proteobacteria
KI929263.1
II
4


282
GCA_000633695.1
1445865
615

Serratia marcescens BIDMC 81
BIDMC 81
Proteobacteria
KK214290.1
II
4


283
GCA_000006965.1
266834
382

Sinorhizobium meliloti 1021
1021
Proteobacteria
AL591688.1
II
3


284
GCA_000346065.1
1286640
382

Sinorhizobium meliloti 2011
2011
Proteobacteria
CP004140.1
II
3


285
GCA_001461685.1
1358418
1358418

Sinorhizobium sp. GL28
GL28
Proteobacteria
AUSZ01000302.1
II
4


286
GCA_000280865.1
1160718
114687

Streptomyces auratus AGR0001
AGR0001
Actinobacteria
JH725387.1
II
3


287
GCA_001188955.1
1894
1894

Streptomyces aureofaciens

ATCC 10762
Actinobacteria
KQ257755.1
II
3


288
GCA_000222625.2
1051645
29497

Vibrio splendidus ATCC 33789
ATCC 33789
Proteobacteria
AFWG01000006.1
II
3


289
GCA_001139945.1
29483
29483

Yersinia aldovae

IP08791
Proteobacteria
CQEH01000010.1
II
4


290
GCA_001104645.1
631
631

Yersinia intermedia

FCF335
Proteobacteria
CQCT01000008.1
II
4


291
GCA_001144105.1
633
633

Yersinia pseudotuberculosis

N912
Proteobacteria
CQDI01000025.1
II
4


292
GCA_001166025.1
633
633

Yersinia pseudotuberculosis

OK5586
Proteobacteria
CQEB01000011.1
II
4


293
GCA_001319685.1
633
633

Yersinia pseudotuberculosis

IP32921
Proteobacteria
CIFM01000002.1
II
4


294
GCA_000834455.1
29485
29485

Yersinia rohdei

YRA
Proteobacteria
CP009787.1
II
4


295
GCA_000173775.1
527004
29485

Yersinia rohdei ATCC 43380
ATCC 43380
Proteobacteria
ACCD01000010.1
II
4


296
GCA_001581075.1
178900
178900

Acetobacter cerevisiae

LMG 1608
Proteobacteria
LHZY01000057.1
III
2


297
GCA_001077655.1
470
470

Acinetobacter baumannii

Ab04-mff
Proteobacteria
CP012006.1
III
2


298
GCA_001276085.1
470
470

Acinetobacter baumannii

5021_13
Proteobacteria
LGYV01000089.1
III
2


299
GCA_001441545.1
470
470

Acinetobacter baumannii

MRSN15038
Proteobacteria
LMZX01000006.1
III
2


300
GCA_001441555.1
470
470

Acinetobacter baumannii

MRSN20315
Proteobacteria
LMZV01000012.1
III
2


301
GCA_001441565.1
470
470

Acinetobacter baumannii

MRSN15084
Proteobacteria
LMZW01000004.1
III
2


302
GCA_001441625.1
470
470

Acinetobacter baumannii

MRSN20755
Proteobacteria
LMYO01000010.1
III
2


303
GCA_001441645.1
470
470

Acinetobacter baumannii

MRSN7081
Proteobacteria
LMZY01000005.1
III
2


304
GCA_000581835.1
1310681
470

Acinetobacter baumannii 1542444
1542444
Proteobacteria
JEYA01000001.1
III
2


305
GCA_000581295.1
1310630
470

Acinetobacter baumannii 99063
99063
Proteobacteria
JEXJ01000065.1
III
2


306
GCA_000335595.1
903937
470

Acinetobacter baumannii AA-014
AA-014
Proteobacteria
AMGA01000013.1
III
2


307
GCA_000369165.1
1217630
470

Acinetobacter baumannii NIPH 201
NIPH 201
Proteobacteria
KB849843.1
III
2


308
GCA_000369205.1
1217633
470

Acinetobacter baumannii NIPH 335
NIPH 335
Proteobacteria
KB849885.1
III
2


309
GCA_000369265.1
1217627
470

Acinetobacter baumannii NIPH 67
NIPH 67
Proteobacteria
KB849903.1
III
2


310
GCA_000309235.1
903926
470

Acinetobacter baumannii OIFC035
OIFC035
Proteobacteria
AMTB01000008.1
III
2


311
GCA_000305235.1
903902
470

Acinetobacter baumannii OIFC098
OIFC098
Proteobacteria
AMDF01000045.1
III
2


312
GCA_000368485.1
1217656
106649

Acinetobacter guillouiae NIPH 991
NIPH 991
Proteobacteria
KB849456.1
III
2


313
GCA_000369685.1
1144665
1144665

Acinetobacter sp. CIP 102136
CIP 102136
Proteobacteria
KB850142.1
III
2


314
GCA_000368425.1
1144669
1144669

Acinetobacter sp. CIP 102637
CIP 102637
Proteobacteria
KB849435.1
III
2


315
GCA_000154465.1
445970
28117

Alistipes putredinis DSM 17216
DSM 17216
Bacteroidetes
DS499580.1
III
2


316
GCA_001578515.1
28108
28108

Alteromonas macleodii

HOT1A3
Proteobacteria
CP012202.1
III
2


317
GCA_000300175.1
1004787
28108

Alteromonas macleodii str. ‘Balearic Sea AD45’
Balearic Sea AD45
Proteobacteria
CP003873.1
III
2


318
GCA_000204015.1
715226
76891

Asticcacaulis biprosthecum C19
C19
Proteobacteria
GL883078.1
III
2


319
GCA_000495835.1
1282361
1282361

Asticcacaulis sp. AC402
AC402
Proteobacteria
AWGC01000023.1
III
2


320
GCA_000061505.1
62928
62928

Azoarcus sp. BH72
BH72
Proteobacteria
AM406670.1
III
2


321
GCA_000817975.1
1328314
353

Azotobacter chroococcum NCIMB 8003
NCIMB 8003
Proteobacteria
CP010421.1
III
2


322
GCA_001286525.1
817
817

Bacteroides fragilis

BE1
Bacteroidetes
LN877293.1
III
2


323
GCA_000210835.1
862962
817

Bacteroides fragilis 638R
638R
Bacteroidetes
FQ312004.1
III
2


324
GCA_000598705.1
1339297
817

Bacteroides fragilis str. 1009-4-F #10
1009-4-F #10
Bacteroidetes
JGED01000021.1
III
2


325
GCA_000599285.2
1339296
817

Bacteroides fragilis str. 1009-4-F #7
1009-4-F #7
Bacteroidetes
JGEE01000031.1
III
2


326
GCA_000598325.1
1339309
817

Bacteroides fragilis str. 3783N1-2
3783N1-2
Bacteroidetes
JGCS01000280.1
III
2


327
GCA_000599065.2
1339310
817

Bacteroides fragilis str. 3783N1-6
3783N1-6
Bacteroidetes
JGEU01000034.1
III
2


328
GCA_000598605.1
1339311
817

Bacteroides fragilis str. 3783N1-8
3783N1-8
Bacteroidetes
JGDR01000052.1
III
2


329
GCA_000598345.1
1339312
817

Bacteroides fragilis str. 3783N2-1
3783N2-1
Bacteroidetes
JGCT01000263.1
III
2


330
GCA_000598165.1
1339313
817

Bacteroides fragilis str. 3976T7
3976T7
Bacteroidetes
JGCU01000310.1
III
2


331
GCA_000154525.1
449673
46506

Bacteroides stercoris ATCC 43183
ATCC 43183
Bacteroidetes
DS499662.1
III
2


332
GCA_001578555.1
820
820

Bacteroides uniformis

KLE1607
Bacteroidetes
KQ968311.1
III
2


333
GCA_000224655.1
693988
693988

Bilophila sp. 4_1_30
4_1_30
Proteobacteria
JH114233.1
III
2


334
GCA_000173575.1
516466
516466

Burkholderia sp. H160
H160
Proteobacteria
ABYL01000008.1
III
2


335
GCA_001527325.1
101571
101571

Burkholderia ubonensis

MSMB2054
Proteobacteria
LOZC01000078.1
III
2


336
GCA_001527345.1
101571
101571

Burkholderia ubonensis

MSMB2055
Proteobacteria
LOZD01000059.1
III
2


337
GCA_001527425.1
101571
101571

Burkholderia ubonensis

MSMB2061
Proteobacteria
LOZH01000090.1
III
2


338
GCA_001529135.1
101571
101571

Burkholderia ubonensis

MSMB1212WGS
Proteobacteria
LPED01000119.1
III
2


339
GCA_001531435.1
101571
101571

Burkholderia ubonensis

MSMB1508WGS
Proteobacteria
LPFT01000065.1
III
2


340
GCA_000531125.1
1400861
1400860

Candidatus Contendobacter odensis Run_B_J11
Run_B_J11
Proteobacteria
CBTK010000022.1
III
2


341
GCA_001292585.1
1509431
1509431

Candidatus Magnetomorum sp. HK-1

Proteobacteria
JPDT01000292.1
III
2


342
GCA_000477035.2
1348585
76594

Cellulophaga baltica NN016038
NN016038
Bacteroidetes
CP009887.1
III
2


343
GCA_000601485.1
1192034
51

Chondromyces apiculatus DSM 436
DSM 436
Proteobacteria
ASRX01000002.1
III
2


344
GCA_001421435.1
1735672
1735672

Chryseobacterium sp. Leaf201
Leaf201
Bacteroidetes
LMKA01000095.1
III
2


345
GCA_001281005.1
546
546

Citrobacter freundii

P10159
Proteobacteria
CP012554.1
III
2


346
GCA_001316675.1
546
546

Citrobacter freundii

ST62:944112508
Proteobacteria
LJEB01000070.1
III
2


347
GCA_001034465.1
1686377
1686377

Citrobacter sp. MGH100
MGH100
Proteobacteria
KQ089800.1
III
2


348
GCA_001037515.1
1686383
1686383

Citrobacter sp. MGH110
MGH110
Proteobacteria
KQ089830.1
III
2


349
GCA_000828895.1
1458425
1458425
Comamonadaceae bacterium A1
A1
Proteobacteria
AP014568.1
III
2


350
GCA_001277275.1
28141
28141

Cronobacter sakazakii

NCTC 8155
Proteobacteria
CP012253.1
III
2


351
GCA_000339015.1
956149
28141

Cronobacter sakazakii SP291
Sp291
Proteobacteria
CP004091.1
III
2


352
GCA_000961725.1
1629713
1629713
Desulfobulbaceae bacterium BRH_c16a

Proteobacteria
LADS01000053.1
III
2


353
GCA_001011305.1
548
548

Enterobacter aerogenes

GN02420
Proteobacteria
LDBI01000017.1
III
2


354
GCA_001011595.1
548
548

Enterobacter aerogenes

GN03959
Proteobacteria
LDBV01000046.1
III
2


355
GCA_001030055.1
548
548

Enterobacter aerogenes

UCI98
Proteobacteria
LESY01000010.1
III
2


356
GCA_001030185.1
548
548

Enterobacter aerogenes

UCI97
Proteobacteria
KQ087587.1
III
2


357
GCA_001022755.1
61645
61645

Enterobacter asburiae

GN02692
Proteobacteria
LEDI01000011.1
III
2


358
GCA_000952375.1
550
550

Enterobacter cloacae

MNCRE12
Proteobacteria
JYME01000006.1
III
2


359
GCA_001022875.1
550
550

Enterobacter cloacae

GN02773
Proteobacteria
LEDE01000006.1
III
2


360
GCA_001030145.1
550
550

Enterobacter cloacae

UCI86
Proteobacteria
KQ087579.1
III
2


361
GCA_001030195.1
550
550

Enterobacter cloacae

UCI85
Proteobacteria
KQ087593.1
III
2


362
GCA_001518245.1
550
550

Enterobacter cloacae

GN03848
Proteobacteria
LRCM01000015.1
III
2


363
GCA_001518625.1
550
550

Enterobacter cloacae

GN04311
Proteobacteria
LRCQ01000112.1
III
2


364
GCA_001317055.1
336306
550

Enterobacter cloacae subsp. cloacae
ST433:953102574
Proteobacteria
LJE001000030.1
III
2


365
GCA_000492435.1
1329856
550

Enterobacter cloacae UCICRE 12
UCICRE 12
Proteobacteria
KI535461.1
III
2


366
GCA_001037885.1
1686400
1686400

Enterobacter sp. BIDMC109
BIDMC109
Proteobacteria
KQ090002.1
III
2


367
GCA_000735105.1
421072
421072

Epilithonimonas lactis

LMG 24401
Bacteroidetes
JPLY01000004.1
III
2


368
GCA_001077815.1
1648404
1648404

Erythrobacter sp. s21-N3
s21-N3
Proteobacteria
CP011310.1
III
2


369
GCA_000181515.1
161528
161528

Erythrobacter sp. SD-21
SD-21
Proteobacteria
ABCG01000002.1
III
2


370
GCA_000695175.1
562
562

Escherichia coli

MI10-01
Proteobacteria
JHEZ01000002.1
III
2


371
GCA_000731455.1
562
562

Escherichia coli

D6-117_07.11
Proteobacteria
HG976958.1
III
2


372
GCA_000797755.1
562
562

Escherichia coli

CVM N33443PS
Proteobacteria
JUDP01000006.1
III
2


373
GCA_000797775.1
562
562

Escherichia coli

CVM N34322PS
Proteobacteria
JUCY01000038.1
III
2


374
GCA_000797995.1
562
562

Escherichia coli

CVM N36613PS
Proteobacteria
JUCH01000028.1
III
2


375
GCA_000798215.1
562
562

Escherichia coli

CVM N36620PS
Proteobacteria
JUCG01000047.1
III
2


376
GCA_000798415.1
562
562

Escherichia coli

CVM N34557PS
Proteobacteria
JUCU01000037.1
III
2


377
GCA_000798575.1
562
562

Escherichia coli

CVM N36404PS
Proteobacteria
JUCJ01000011.1
III
2


378
GCA_000819265.1
562
562

Escherichia coli

CVM N38428PS
Proteobacteria
JWYX01000074.1
III
2


379
GCA_000819645.1
562
562

Escherichia coli


Proteobacteria
CP010315.1
III
2


380
GCA_000934865.1
562
562

Escherichia coli

ATCC 35150
Proteobacteria
JXUS01000117.1
III
2


381
GCA_000935075.1
562
562

Escherichia coli

ATCC 35150 NalR
Proteobacteria
JYIO01000082.1
III
2


382
GCA_000953765.1
562
562

Escherichia coli

MCI_507
Proteobacteria
JZSD01000085.1
III
2


383
GCA_000965565.1
562
562

Escherichia coli

St. Olav172
Proteobacteria
JZDY01000017.1
III
2


384
GCA_000965655.1
562
562

Escherichia coli

St. Olav173
Proteobacteria
JZDZ01000061.1
III
2


385
GCA_001012075.1
562
562

Escherichia coli

CFSAN026805
Proteobacteria
LDCU01000029.1
III
2


386
GCA_001030405.1
562
562

Escherichia coli

MGH108
Proteobacteria
KQ087687.1
III
2


387
GCA_001191125.1
562
562

Escherichia coli

CFSAN026804
Proteobacteria
LGZD01000035.1
III
2


388
GCA_001191185.1
562
562

Escherichia coli

CFSAN026847
Proteobacteria
LGZE01000020.1
III
2


389
GCA_001191195.1
562
562

Escherichia coli

CFSAN026846
Proteobacteria
LGZI01000146.1
III
2


390
GCA_001191525.1
562
562

Escherichia coli

CFSAN026848
Proteobacteria
LHAB01000019.1
III
2


391
GCA_001263735.1
562
562

Escherichia coli

INSLA289
Proteobacteria
LHAT01000022.1
III
2


392
GCA_001281685.1
562
562

Escherichia coli

STEC 771
Proteobacteria
LGAZ01000005.1
III
2


393
GCA_001281725.1
562
562

Escherichia coli

STEC 2868
Proteobacteria
LGBJ01000009.1
III
2


394
GCA_001281755.1
562
562

Escherichia coli

E09/224
Proteobacteria
LGBP01000024.1
III
2


395
GCA_001281775.1
562
562

Escherichia coli

STEC 989
Proteobacteria
LGBA01000013.1
III
2


396
GCA_001281795.1
562
562

Escherichia coli

STEC 994
Proteobacteria
LGBB01000045.1
III
2


397
GCA_001281815.1
562
562

Escherichia coli

STEC 1109
Proteobacteria
LGBC01000012.1
III
2


398
GCA_001281845.1
562
562

Escherichia coli

STEC 2075
Proteobacteria
LGBD01000011.1
III
2


399
GCA_001281855.1
562
562

Escherichia coli

STEC 2112
Proteobacteria
LGBE01000001.1
III
2


400
GCA_001281885.1
562
562

Escherichia coli

STEC 2257
Proteobacteria
LGBF01000023.1
III
2


401
GCA_001281905.1
562
562

Escherichia coli

STEC 2410
Proteobacteria
LGBG01000006.1
III
2


402
GCA_001281915.1
562
562

Escherichia coli

STEC 2821
Proteobacteria
LGBI01000140.1
III
2


403
GCA_001281925.1
562
562

Escherichia coli

STEC 2667
Proteobacteria
LGBH01000007.1
III
2


404
GCA_001281965.1
562
562

Escherichia coli

E09/10
Proteobacteria
LGBK01000008.1
III
2


405
GCA_001281985.1
562
562

Escherichia coli

EPEC 287
Proteobacteria
LGBL01000025.1
III
2


406
GCA_001281995.1
562
562

Escherichia coli

EPEC 393
Proteobacteria
LGBM01000019.1
III
2


407
GCA_001282025.1
562
562

Escherichia coli

EPEC 1572
Proteobacteria
LGBN01000001.1
III
2


408
GCA_001282035.1
562
562

Escherichia coli

EPEC 1669
Proteobacteria
LGBO01000067.1
III
2


409
GCA_001282065.1
562
562

Escherichia coli

STEC 2820
Proteobacteria
LGBQ01000003.1
III
2


410
GCA_001284665.1
562
562

Escherichia coli

503459_aEPEC
Proteobacteria
CXZO01000020.1
III
2


411
GCA_001297965.1
562
562

Escherichia coli

STEC 915
Proteobacteria
LFUH01000101.1
III
2


412
GCA_001297975.1
562
562

Escherichia coli

STEC 343
Proteobacteria
LDOZ01000007.1
III
2


413
GCA_001297985.1
562
562

Escherichia coli

STEC 623
Proteobacteria
LFUB01000011.1
III
2


414
GCA_001297995.1
562
562

Escherichia coli

STEC 605
Proteobacteria
LFUA01000020.1
III
2


415
GCA_001309715.1
562
562

Escherichia coli

PARC447
Proteobacteria
LECJ01000192.1
III
2


416
GCA_001309815.1
562
562

Escherichia coli

03-6430
Proteobacteria
LEAB01000117.1
III
2


417
GCA_001309835.1
562
562

Escherichia coli

PARC449
Proteobacteria
LEAC01000125.1
III
2


418
GCA_001309885.1
562
562

Escherichia coli

CO6CE900
Proteobacteria
LEAE01000148.1
III
2


419
GCA_001309895.1
562
562

Escherichia coli

CO6CE1353
Proteobacteria
LEAF01000141.1
III
2


420
GCA_001309905.1
562
562

Escherichia coli

CO6CE1943
Proteobacteria
LEAG01000046.1
III
2


421
GCA_001309925.1
562
562

Escherichia coli

CO6CE2940
Proteobacteria
LEAH01000084.1
III
2


422
GCA_001309965.1
562
562

Escherichia coli

CO283
Proteobacteria
LEAI01000013.1
III
2


423
GCA_001309985.1
562
562

Escherichia coli

1935
Proteobacteria
LEAD01000163.1
III
2


424
GCA_001309995.1
562
562

Escherichia coli

E0122
Proteobacteria
LEAJ01000145.1
III
2


425
GCA_001310005.1
562
562

Escherichia coli

LCDC7236
Proteobacteria
LEAK01000079.1
III
2


426
GCA_001484355.1
562
562

Escherichia coli

AY71
Proteobacteria
LLYJ01000063.1
III
2


427
GCA_001484485.1
562
562

Escherichia coli

AZ74
Proteobacteria
LLYM01000074.1
III
2


428
GCA_001518365.1
562
562

Escherichia coli

GN02740
Proteobacteria
LQZU01000211.1
III
2


429
GCA_001518955.1
562
562

Escherichia coli

SEC470
Proteobacteria
CP013962.1
III
2


430
GCA_001519395.1
562
562

Escherichia coli

GN02270
Proteobacteria
LQST01000002.1
III
2


431
GCA_001519635.1
562
562

Escherichia coli

GN02354
Proteobacteria
LQTF01000057.1
III
2


432
GCA_001519685.1
562
562

Escherichia coli

GN02094
Proteobacteria
LQSC01000049.1
III
2


433
GCA_001519775.1
562
562

Escherichia coli

GN02140
Proteobacteria
LQSF01000099.1
III
2


434
GCA_001519815.1
562
562

Escherichia coli

GN02298
Proteobacteria
LQSX01000125.1
III
2


435
GCA_001519835.1
562
562

Escherichia coli

GN02290
Proteobacteria
LQSW01000149.1
III
2


436
GCA_001519975.1
562
562

Escherichia coli

GN02415
Proteobacteria
LQTQ01000061.1
III
2


437
GCA_001520115.1
562
562

Escherichia coli

GN02343
Proteobacteria
LQTC01000029.1
III
2


438
GCA_001520255.1
562
562

Escherichia coli

GN03578
Proteobacteria
LQVZ01000203.1
III
2


439
GCA_001520375.1
562
562

Escherichia coli

GN02460
Proteobacteria
LQTZ01000058.1
III
2


440
GCA_001520435.1
562
562

Escherichia coli

GN02430
Proteobacteria
LQTU01000172.1
III
2


441
GCA_001520495.1
562
562

Escherichia coli

GN02426
Proteobacteria
LQTS01000163.1
III
2


442
GCA_001520575.1
562
562

Escherichia coli

GN02674
Proteobacteria
LQVA01000248.1
III
2


443
GCA_001520835.1
562
562

Escherichia coli

GN02707
Proteobacteria
LQVE01000001.1
III
2


444
GCA_001520935.1
562
562

Escherichia coli

GN03218
Proteobacteria
LQVQ01000300.1
III
2


445
GCA_001520995.1
562
562

Escherichia coli

GN02953
Proteobacteria
LQVM01000164.1
III
2


446
GCA_001521225.1
562
562

Escherichia coli

GN02350
Proteobacteria
LQTE01000128.1
III
2


447
GCA_001521635.1
562
562

Escherichia coli

GN04153
Proteobacteria
LQWI01000295.1
III
2


448
GCA_001521695.1
562
562

Escherichia coli

GN03624
Proteobacteria
LQWB01000001.1
III
2


449
GCA_001558995.1
562
562

Escherichia coli

JEONG-1266
Proteobacteria
CP014314.1
III
2


450
GCA_001562855.1
562
562

Escherichia coli

JPH493
Proteobacteria
KQ961400.1
III
2


451
GCA_001571675.1
562
562

Escherichia coli

UC5
Proteobacteria
LRXT01000038.1
III
2


452
GCA_001575305.1
562
562

Escherichia coli

G19
Proteobacteria
LONY01000024.1
III
2


453
GCA_001575755.1
562
562

Escherichia coli

G111
Proteobacteria
LONJ01000019.1
III
2


454
GCA_001575775.1
562
562

Escherichia coli

G114
Proteobacteria
LONK01000063.1
III
2


455
GCA_001575885.1
562
562

Escherichia coli

G169
Proteobacteria
LONQ01000006.1
III
2


456
GCA_001576035.1
562
562

Escherichia coli

G27
Proteobacteria
LOOY01000022.1
III
2


457
GCA_001576105.1
562
562

Escherichia coli

G314
Proteobacteria
LOPH01000016.1
III
2


458
GCA_001576135.1
562
562

Escherichia coli

G313
Proteobacteria
LOPG01000001.1
III
2


459
GCA_001576325.1
562
562

Escherichia coli

G28
Proteobacteria
LOOZ010000011.1
III
2


460
GCA_001576375.1
562
562

Escherichia coli

G26
Proteobacteria
LOOX01000037.1
III
2


461
GCA_001576385.1
562
562

Escherichia coli

G35
Proteobacteria
LOPL01000002.1
III
2


462
GCA_000303235.2
1005441
562

Escherichia coli 0.1304
0.1304
Proteobacteria
JH943332.1
III
2


463
GCA_000462305.2
1081888
562

Escherichia coli 08BKT055439
08BKT055439
Proteobacteria
AVRI01000134.1
III
2


464
GCA_000462325.2
1081895
562

Escherichia coli 08BKT77219
08BKT77219
Proteobacteria
AVRJ01000125.1
III
2


465
GCA_000462345.2
1081894
562

Escherichia coli 09BKT024447
09BKT024447
Proteobacteria
AVRK01000010.1
III
2


466
GCA_000461935.2
1081889
562

Escherichia coli 09BKT076207
09BKT076207
Proteobacteria
AVQR01000067.1
III
2


467
GCA_000340455.2
1081887
562

Escherichia coli 09BKT078844
09BKT078844
Proteobacteria
KB453231.1
III
2


468
GCA_000304855.2
1005469
562

Escherichia coli 10.0821
10.0821
Proteobacteria
AMTO01000004.1
III
2


469
GCA_000305415.2
1005466
562

Escherichia coli 10.0833
10.0833
Proteobacteria
JH969098.1
III
2


470
GCA_000305435.2
1005467
562

Escherichia coli 10.0869
10.0869
Proteobacteria
JH968727.1
III
2


471
GCA_000601155.1
1444132
562

Escherichia coli 1-110-08_S3_C1
1-110-08_S3_C1
Proteobacteria
JHDN01000003.1
III
2


472
GCA_000601175.1
1444160
562

Escherichia coli 1-110-08_S3_C2
1-110-08_S3_C2
Proteobacteria
JHDM01000091.1
III
2


473
GCA_000601335.1
1444190
562

Escherichia coli 1-110-08_S3_C3
1-110-08_S3_C3
Proteobacteria
JHDL01000001.1
III
2


474
GCA_000485635.1
1268976
562

Escherichia coli 113290
113290
Proteobacteria
KI521766.1
III
2


475
GCA_000627435.1
1444135
562

Escherichia coli 1-250-04_S3_C1
1-250-04_S3_C1
Proteobacteria
JJLU01000053.1
III
2


476
GCA_000713815.1
1444163
562

Escherichia coli 1-250-04_S3_C2
1-250-04_S3_C2
Proteobacteria
JOSR01000197.1
III
2


477
GCA_000687105.1
1444147
562

Escherichia coli 2-005-03_S3_C2
2-005-03_S3_C2
Proteobacteria
JMGT01000075.1
III
2


478
GCA_000700165.1
1444093
562

Escherichia coli 2-011-08_S1_C3
2-011-08_S1_C3
Proteobacteria
JNNA01000159.1
III
2


479
GCA_000700605.1
1444119
562

Escherichia coli 2-052-05_S3_C1
2-052-05_S3_C1
Proteobacteria
JNNF01000074.1
III
2


480
GCA_000713655.1
1444149
562

Escherichia coli 2-052-05_S3_C2
2-052-05_S3_C2
Proteobacteria
JOSJ01000098.1
III
2


481
GCA_000703605.1
1444177
562

Escherichia coli 2-052-05_S3_C3
2-052-05_S3_C3
Proteobacteria
JNOZ01000070.1
III
2


482
GCA_000703725.1
1444150
562

Escherichia coli 2-156-04_S3_C2
2-156-04_S3_C2
Proteobacteria
JNPK01000053.1
III
2


483
GCA_000713695.1
1444123
562

Escherichia coli 2-222-05_S3_C1
2-222-05_S3_C1
Proteobacteria
JOSM01000267.1
III
2


484
GCA_000713735.1
1444153
562

Escherichia coli 2-222-05_S3_C2
2-222-05_S3_C2
Proteobacteria
JOSN01000002.1
III
2


485
GCA_000704145.1
1444181
562

Escherichia coli 2-222-05_S3_C3
2-222-05_S3_C3
Proteobacteria
JNQN01000045.1
III
2


486
GCA_000711475.1
1444042
562

Escherichia coli 2-316-03_S1_C1
2-316-03_S1_C1
Proteobacteria
JOMW01000194.1
III
2


487
GCA_000711415.1
1444071
562

Escherichia coli 2-316-03_S1_C2
2-316-03_S1_C2
Proteobacteria
JOMX01000159.1
III
2


488
GCA_000355155.2
1116119
562

Escherichia coli 2719100
2719100
Proteobacteria
AQFG01000015.1
III
2


489
GCA_000354775.2
1116010
562

Escherichia coli 2747800
2747800
Proteobacteria
AQEA01000085.1
III
2


490
GCA_000354875.1
1116011
562

Escherichia coli 2749250
2749250
Proteobacteria
AQDZ01000107.1
III
2


491
GCA_000355615.2
1116014
562

Escherichia coli 2770900
2770900
Proteobacteria
AQDW01000088.1
III
2


492
GCA_000354995.2
1116021
562

Escherichia coli 2860050
2860050
Proteobacteria
AQDL01000093.1
III
2


493
GCA_000356445.2
1116022
562

Escherichia coli 2860650
2860650
Proteobacteria
APXG01000173.1
III
2


494
GCA_000356505.2
1116027
562

Escherichia coli 2866350
2866350
Proteobacteria
APXJ01000134.1
III
2


495
GCA_000462245.2
1207038
562

Escherichia coli 2886-75
2886-75
Proteobacteria
AVRR01000001.1
III
2


496
GCA_000304815.2
1005450
562

Escherichia coli 3.4870
3.4870
Proteobacteria
JH970627.1
III
2


497
GCA_000335195.2
1051347
562

Escherichia coli 3.4880
3.4880
Proteobacteria
AOET01000122.1
III
2


498
GCA_000700285.1
1444059
562

Escherichia coli 3-475-03_S1_C1
3-475-03_S1_C1
Proteobacteria
JNMJ01000048.1
III
2


499
GCA_000713905.1
1444087
562

Escherichia coli 3-475-03_S1_C2
3-475-03_S1_C2
Proteobacteria
JOQC01000025.1
III
2


500
GCA_000714055.1
1444171
562

Escherichia coli 4-203-08_S3_C2
4-203-08_S3_C2
Proteobacteria
JOQK01000042.1
III
2


501
GCA_000713985.1
1444196
562

Escherichia coli 4-203-08_S3_C3
4-203-08_S3_C3
Proteobacteria
JOQH01000040.1
III
2


502
GCA_000304875.2
1005452
562

Escherichia coli 5.2239
5.2239
Proteobacteria
JH970990.1
III
2


503
GCA_000304055.2
1005561
562

Escherichia coli 5412
5412
Proteobacteria
JH954949.1
III
2


504
GCA_000264135.1
752787
562

Escherichia coli 576-1
576-1
Proteobacteria
AJWS01000293.1
III
2


505
GCA_000303995.2
1005558
562

Escherichia coli 5905
5905
Proteobacteria
JH958373.1
III
2


506
GCA_000714385.1
1444226
562

Escherichia coli 6-175-07_S4_C1
6-175-07_S4_C1
Proteobacteria
JORB01000108.1
III
2


507
GCA_000714415.1
1444255
562

Escherichia coli 6-175-07_S4_C2
6-175-07_S4_C2
Proteobacteria
JORC01000054.1
III
2


508
GCA_000713175.1
1444281
562

Escherichia coli 6-175-07_S4_C3
6-175-07_S4_C3
Proteobacteria
JORK01000060.1
III
2


509
GCA_000713335.1
1444062
562

Escherichia coli 6-319-05_S1_C1
6-319-05_S1_C1
Proteobacteria
JORT01000068.1
III
2


510
GCA_000713025.1
1444090
562

Escherichia coli 6-319-05_S1_C2
6-319-05_S1_C2
Proteobacteria
JORD01000183.1
III
2


511
GCA_000713015.1
1444115
562

Escherichia coli 6-319-05_S1_C3
6-319-05_S1_C3
Proteobacteria
JORE01000064.1
III
2


512
GCA_000713255.1
1444227
562

Escherichia coli 6-537-08_S4_C1
6-537-08_S4_C1
Proteobacteria
JORS01000112.1
III
2


513
GCA_000713605.1
1444257
562

Escherichia coli 6-537-08_S4_C2
6-537-08_S4_C2
Proteobacteria
JOSG01000027.1
III
2


514
GCA_000335115.1
1051348
562

Escherichia coli 7.1982
7.1982
Proteobacteria
AOEP01000011.1
III
2


515
GCA_000304835.2
1005463
562

Escherichia coli 8.0416
8.0416
Proteobacteria
AMTN01000133.1
III
2


516
GCA_000305375.2
1005461
562

Escherichia coli 8.0586
8.0586
Proteobacteria
JH969648.1
III
2


517
GCA_000305395.2
1005460
562

Escherichia coli 8.2524
8.2524
Proteobacteria
JH969044.1
III
2


518
GCA_000305455.2
1005397
562

Escherichia coli 88.0221
88.0221
Proteobacteria
JH968005.1
III
2


519
GCA_000316345.2
1005398
562

Escherichia coli 88.1042
88.1042
Proteobacteria
KB006081.1
III
2


520
GCA_000316365.2
1005399
562

Escherichia coli 89.0511
89.0511
Proteobacteria
KB007266.1
III
2


521
GCA_000316385.2
1005400
562

Escherichia coli 90.0091
90.0091
Proteobacteria
KB007294.1
III
2


522
GCA_000316425.2
1005402
562

Escherichia coli 90.2281
90.2281
Proteobacteria
KB005715.1
III
2


523
GCA_000488355.1
1268982
562

Escherichia coli 907672
907672
Proteobacteria
KI531258.1
III
2


524
GCA_000485695.1
1268986
562

Escherichia coli 907713
907713
Proteobacteria
KI522246.1
III
2


525
GCA_000488435.1
1268987
562

Escherichia coli 907715
907715
Proteobacteria
KI531882.1
III
2


526
GCA_000488515.1
1268992
562

Escherichia coli 908521
908521
Proteobacteria
KI532686.1
III
2


527
GCA_000488535.1
1268993
562

Escherichia coli 908522
908522
Proteobacteria
KI532821.1
III
2


528
GCA_000488575.1
1268995
562

Escherichia coli 908525
908525
Proteobacteria
KI533062.1
III
2


529
GCA_000488655.1
1268999
562

Escherichia coli 908585
908585
Proteobacteria
KI533791.1
III
2


530
GCA_000488675.1
1269000
562

Escherichia coli 908616
908616
Proteobacteria
KI533940.1
III
2


531
GCA_000316445.2
1005403
562

Escherichia coli 93.0055
93.0055
Proteobacteria
KB004131.1
III
2


532
GCA_000316465.1
1005404
562

Escherichia coli 93.0056
93.0056
Proteobacteria
KB004997.1
III
2


533
GCA_000267945.2
1005481
562

Escherichia coli 93-001
93-001
Proteobacteria
JH710997.1
III
2


534
GCA_000316485.1
1005405
562

Escherichia coli 94.0618
94.0618
Proteobacteria
KB005707.1
III
2


535
GCA_000335375.2
1051346
562

Escherichia coli 95.0083
95.0083
Proteobacteria
AOEU01000192.1
III
2


536
GCA_000316865.2
1005407
562

Escherichia coli 95.1288
95.1288
Proteobacteria
KB001712.1
III
2


537
GCA_000316765.2
1005415
562

Escherichia coli 96.0107
96.0107
Proteobacteria
KB003449.1
III
2


538
GCA_000318425.2
1005414
562

Escherichia coli 96.0109
96.0109
Proteobacteria
KB009454.1
III
2


539
GCA_000316825.2
1005411
562

Escherichia coli 96.0427
96.0427
Proteobacteria
KB002687.1
III
2


540
GCA_000316905.2
1005410
562

Escherichia coli 96.0428
96.0428
Proteobacteria
KB000504.1
III
2


541
GCA_000316805.2
1005413
562

Escherichia coli 96.0932
96.0932
Proteobacteria
KB003092.1
III
2


542
GCA_000316745.2
1005416
562

Escherichia coli 97.0003
97.0003
Proteobacteria
JH999738.1
III
2


543
GCA_000316505.2
1005420
562

Escherichia coli 97.0007
97.0007
Proteobacteria
ANMC01000275.1
III
2


544
GCA_000318445.2
1005419
562

Escherichia coli 97.0010
97.0010
Proteobacteria
KB008878.1
III
2


545
GCA_000316725.2
1005418
562

Escherichia coli 97.1742
97.1742
Proteobacteria
KB004341.1
III
2


546
GCA_000335215.2
1005423
562

Escherichia coli 99.0670
99.0670
Proteobacteria
AOEV01000013.1
III
2


547
GCA_000316545.2
1005422
562

Escherichia coli 99.0678
99.0678
Proteobacteria
ANME01000013.1
III
2


548
GCA_000316565.2
1005424
562

Escherichia coli 99.0713
99.0713
Proteobacteria
ANMF01000001.1
III
2


549
GCA_000335255.2
1005432
562

Escherichia coli 99.0839
99.0839
Proteobacteria
AOEB01000180.1
III
2


550
GCA_000335275.2
1005431
562

Escherichia coli 99.0848
99.0848
Proteobacteria
AOEC01000227.1
III
2


551
GCA_000335295.2
1005440
562

Escherichia coli 99.1753
99.1753
Proteobacteria
AOED01000248.1
III
2


552
GCA_000335155.2
1005435
562

Escherichia coli 99.1762
99.1762
Proteobacteria
AOER01000006.1
III
2


553
GCA_000335315.2
1005438
562

Escherichia coli 99.1775
99.1775
Proteobacteria
AOEE01000251.1
III
2


554
GCA_000335135.1
1005439
562

Escherichia coli 99.1781
99.1781
Proteobacteria
AOEQ01000012.1
III
2


555
GCA_000335015.2
1005437
562

Escherichia coli 99.1793
99.1793
Proteobacteria
AOEF01000014.1
III
2


556
GCA_000473725.2
1389955
562

Escherichia coli ATCC 35150
ATCC 35150
Proteobacteria
AWXM02000035.1
III
2


557
GCA_000335055.2
1051353
562

Escherichia coli ATCC 700728
ATCC 700728
Proteobacteria
AOEH01000126.1
III
2


558
GCA_000019385.1
481805
562

Escherichia coli ATCC 8739
ATCC 8739
Proteobacteria
CP000946.1
III
2


559
GCA_000496345.2
1404261
562

Escherichia coli ATCC BAA-2192
ATCC BAA-2192
Proteobacteria
AYGW02000190.1
III
2


560
GCA_000461955.2
1151213
562

Escherichia coli B102
B102
Proteobacteria
AVQS01000008.1
III
2


561
GCA_000462485.2
1151234
562

Escherichia coli B103
B103
Proteobacteria
AVRS01000001.1
III
2


562
GCA_000462505.2
1151243
562

Escherichia coli B104
B104
Proteobacteria
AVRT01000005.1
III
2


563
GCA_000462525.2
1151247
562

Escherichia coli B105
B105
Proteobacteria
AVRU01000005.1
III
2


564
GCA_000462545.2
1151248
562

Escherichia coli B106
B106
Proteobacteria
AVRV01000001.1
III
2


565
GCA_000461995.2
1151214
562

Escherichia coli B107
B107
Proteobacteria
AVQT01000005.1
III
2


566
GCA_000462565.2
550673
562

Escherichia coli B108
B108
Proteobacteria
AVRW01000007.1
III
2


567
GCA_000462585.2
1151244
562

Escherichia coli B109
B109
Proteobacteria
AVRX01000001.1
III
2


568
GCA_000462605.2
1151249
562

Escherichia coli B112
B112
Proteobacteria
AVRY01000010.1
III
2


569
GCA_000462625.2
1151250
562

Escherichia coli B113
B113
Proteobacteria
AVRZ01000133.1
III
2


570
GCA_000462645.2
1151251
562

Escherichia coli B114
B114
Proteobacteria
AVSA01000001.1
III
2


571
GCA_000462185.2
1151237
562

Escherichia coli B15
B15
Proteobacteria
AVSB01000112.1
III
2


572
GCA_000462665.2
1151238
562

Escherichia coli B17
B17
Proteobacteria
AVSC01000121.1
III
2


573
GCA_000462025.2
1151225
562

Escherichia coli B26-1
B26-1
Proteobacteria
AVQU01000001.1
III
2


574
GCA_000461915.2
1151226
562

Escherichia coli B26-2
B26-2
Proteobacteria
AVQV01000001.1
III
2


575
GCA_000462045.2
1151217
562

Escherichia coli B28-1
B28-1
Proteobacteria
AVQW01000010.1
III
2


576
GCA_000477495.2
1151218
562

Escherichia coli B28-2
B28-2
Proteobacteria
AVQX01000012.1
III
2


577
GCA_000461975.2
1151219
562

Escherichia coli B29-1
B29-1
Proteobacteria
AVQY01000001.1
III
2


578
GCA_000462105.2
1151220
562

Escherichia coli B29-2
B29-2
Proteobacteria
AVQZ01000006.1
III
2


579
GCA_000462125.2
1151221
562

Escherichia coli B36-1
B36-1
Proteobacteria
AVRA01000107.1
III
2


580
GCA_000462065.2
1151222
562

Escherichia coli B36-2
B36-2
Proteobacteria
AVRB01000001.1
III
2


581
GCA_000462685.2
1151227
562

Escherichia coli B40-1
B40-1
Proteobacteria
AVSD01000010.1
III
2


582
GCA_000462705.2
1151228
562

Escherichia coli B40-2
B40-2
Proteobacteria
AVSE01000003.1
III
2


583
GCA_000462725.2
1151246
562

Escherichia coli B49-2
B49-2
Proteobacteria
AVSF01000006.1
III
2


584
GCA_000462745.2
1151224
562

Escherichia coli B5-2
B5-2
Proteobacteria
AVSG01000001.1
III
2


585
GCA_000462085.2
1151215
562

Escherichia coli B7-1
B7-1
Proteobacteria
AVRC01000049.1
III
2


586
GCA_000462405.2
1151216
562

Escherichia coli B7-2
B7-2
Proteobacteria
AVRD01000050.1
III
2


587
GCA_000462765.2
1151239
562

Escherichia coli B83
B83
Proteobacteria
AVSH01000001.1
III
2


588
GCA_000462785.2
1151240
562

Escherichia coli B84
B84
Proteobacteria
AVSI01000012.1
III
2


589
GCA_000462805.2
1151241
562

Escherichia coli B85
B85
Proteobacteria
AVSJ01000007.1
III
2


590
GCA_000462825.2
1151242
562

Escherichia coli B86
B86
Proteobacteria
AVSK01000136.1
III
2


591
GCA_000462845.2
1151235
562

Escherichia coli B89
B89
Proteobacteria
AVSL01000001.1
III
2


592
GCA_000462865.2
1151236
562

Escherichia coli B90
B90
Proteobacteria
AVSM01000129.1
III
2


593
GCA_000462425.2
1151231
562

Escherichia coli B93
B93
Proteobacteria
AVRE01000046.1
III
2


594
GCA_000462445.2
1151232
562

Escherichia coli B94
B94
Proteobacteria
AVRF01000052.1
III
2


595
GCA_000462465.2
1151233
562

Escherichia coli B95
B95
Proteobacteria
AVRG01000053.1
III
2


596
GCA_000522245.1
1328440
562

Escherichia coli BIDMC 15
BIDMC 15
Proteobacteria
KI929736.1
III
2


597
GCA_000522225.1
1328441
562

Escherichia coli BIDMC 17A
BIDMC 17A
Proteobacteria
KI929720.1
III
2


598
GCA_000522205.1
1328442
562

Escherichia coli BIDMC 17B
BIDMC 17B
Proteobacteria
KI929706.1
III
2


599
GCA_000522185.1
1328443
562

Escherichia coli BIDMC 19A
BIDMC 19A
Proteobacteria
KI929698.1
III
2


600
GCA_000522165.1
1328444
562

Escherichia coli BIDMC 19B
BIDMC 19B
Proteobacteria
KI929691.1
III
2


601
GCA_000474825.1
1328445
562

Escherichia coli BIDMC 19C
BIDMC 19C
Proteobacteria
AXLI01000001.1
III
2


602
GCA_000522305.1
1328436
562

Escherichia coli BIDMC 2B
BIDMC 2B
Proteobacteria
KI929775.1
III
2


603
GCA_000522285.1
1328437
562

Escherichia coli BIDMC 3
BIDMC 3
Proteobacteria
KI929768.1
III
2


604
GCA_000492235.1
1328450
562

Escherichia coli BIDMC 39
BIDMC 39
Proteobacteria
KI535383.1
III
2


605
GCA_000522105.1
1400156
562

Escherichia coli BIDMC 43a
BIDMC 43a
Proteobacteria
KI929669.1
III
2


606
GCA_000522085.1
1400157
562

Escherichia coli BIDMC 43b
BIDMC 43b
Proteobacteria
KI929660.1
III
2


607
GCA_000522405.1
1328438
562

Escherichia coli BIDMC 6
BIDMC 6
Proteobacteria
KI929808.1
III
2


608
GCA_000633675.1
1445862
562

Escherichia coli BIDMC 82
BIDMC 82
Proteobacteria
KK214161.1
III
2


609
GCA_000522265.1
1328439
562

Escherichia coli BIDMC 9
BIDMC 9
Proteobacteria
KI929754.1
III
2


610
GCA_000304015.2
1005559
562

Escherichia coli CB7326
CB7326
Proteobacteria
JH956766.1
III
2


611
GCA_000731355.1
1400022
562

Escherichia coli D6-113.11
D6-113.11
Proteobacteria
HG977177.1
III
2


612
GCA_000249495.2
868155
562

Escherichia coli DEC5A
DEC5A
Proteobacteria
AIFQ01000037.1
III
2


613
GCA_000267045.1
1005536
562

Escherichia coli EC1734
EC1734
Proteobacteria
AKMO01000001.1
III
2


614
GCA_000303615.2
1005537
562

Escherichia coli EC1735
EC1735
Proteobacteria
JH958312.1
III
2


615
GCA_000303595.2
1005538
562

Escherichia coli EC1736
EC1736
Proteobacteria
JH965238.1
III
2


616
GCA_000303575.2
1005539
562

Escherichia coli EC1737
EC1737
Proteobacteria
JH963529.1
III
2


617
GCA_000267025.1
1005535
562

Escherichia coli EC1738
EC1738
Proteobacteria
AKMN01000003.1
III
2


618
GCA_000267225.2
1005540
562

Escherichia coli EC1845
EC1845
Proteobacteria
JH693448.1
III
2


619
GCA_000303555.2
1005541
562

Escherichia coli EC1846
EC1846
Proteobacteria
JH956315.1
III
2


620
GCA_000303535.2
1005542
562

Escherichia coli EC1847
EC1847
Proteobacteria
JH963080.1
III
2


621
GCA_000303515.2
1005543
562

Escherichia coli EC1848
EC1848
Proteobacteria
JH955442.1
III
2


622
GCA_000303495.2
1005544
562

Escherichia coli EC1849
EC1849
Proteobacteria
JH953696.1
III
2


623
GCA_000303475.2
1005545
562

Escherichia coli EC1850
EC1850
Proteobacteria
JH952886.1
III
2


624
GCA_000303455.2
1005546
562

Escherichia coli EC1856
EC1856
Proteobacteria
JH952880.1
III
2


625
GCA_000303435.2
1005547
562

Escherichia coli EC1862
EC1862
Proteobacteria
JH952466.1
III
2


626
GCA_000267205.2
1005548
562

Escherichia coli EC1863
EC1863
Proteobacteria
JH692972.1
III
2


627
GCA_000303415.2
1005549
562

Escherichia coli EC1864
EC1864
Proteobacteria
JH945870.1
III
2


628
GCA_000303375.2
1005551
562

Escherichia coli EC1866
EC1866
Proteobacteria
JH944315.1
III
2


629
GCA_000303355.2
1005552
562

Escherichia coli EC1868
EC1868
Proteobacteria
JH944350.1
III
2


630
GCA_000303335.2
1005553
562

Escherichia coli EC1869
EC1869
Proteobacteria
JH946714.1
III
2


631
GCA_000303315.2
1005554
562

Escherichia coli EC1870
EC1870
Proteobacteria
JH945214.1
III
2


632
GCA_000267345.2
1005529
562

Escherichia coli EC4013
EC4013
Proteobacteria
JH698305.1
III
2


633
GCA_000267445.2
1005524
562

Escherichia coli EC4196
EC4196
Proteobacteria
JH699193.1
III
2


634
GCA_000267465.2
1005523
562

Escherichia coli EC4203
EC4203
Proteobacteria
JH699677.1
III
2


635
GCA_000267325.1
1005530
562

Escherichia coli EC4402
EC4402
Proteobacteria
JH697728.1
III
2


636
GCA_000267385.2
1005527
562

Escherichia coli EC4421
EC4421
Proteobacteria
JH696600.1
III
2


637
GCA_000267365.2
1005528
562

Escherichia coli EC4422
EC4422
Proteobacteria
JH695870.1
III
2


638
GCA_000267285.2
1005532
562

Escherichia coli EC4436
EC4436
Proteobacteria
JH694746.1
III
2


639
GCA_000267265.2
1005533
562

Escherichia coli EC4437
EC4437
Proteobacteria
JH694340.1
III
2


640
GCA_000267305.2
1005531
562

Escherichia coli EC4439
EC4439
Proteobacteria
JH697080.1
III
2


641
GCA_000267245.2
1005534
562

Escherichia coli EC4448
EC4448
Proteobacteria
JH693935.1
III
2


642
GCA_000304035.2
1005560
562

Escherichia coli EC96038
EC96038
Proteobacteria
JH955436.1
III
2


643
GCA_000498235.1
758832
562

Escherichia coli ECC-Z
ECC-Z
Proteobacteria
AHHN01000002.1
III
2


644
GCA_000355195.2
1115998
562

Escherichia coli Envira 10/1
Envira 10/1
Proteobacteria
AQFD01000020.1
III
2


645
GCA_000355215.2
1115997
562

Escherichia coli Envira 8/11
Envira 8/11
Proteobacteria
AQFC01000021.1
III
2


646
GCA_000303755.2
1005470
562

Escherichia coli FDA504
FDA504
Proteobacteria
JH961871.1
III
2


647
GCA_000267005.2
1005471
562

Escherichia coli FDA505
FDA505
Proteobacteria
JH692596.1
III
2


648
GCA_000303715.2
1005474
562

Escherichia coli FDA506
FDA506
Proteobacteria
JH964536.1
III
2


649
GCA_000303735.2
1005472
562

Escherichia coli FDA507
FDA507
Proteobacteria
JH963945.1
III
2


650
GCA_000267485.2
1005473
562

Escherichia coli FDA517
FDA517
Proteobacteria
JH701995.1
III
2


651
GCA_000267525.2
1005476
562

Escherichia coli FRIK1985
FRIK1985
Proteobacteria
JH701533.1
III
2


652
GCA_000303795.2
1005480
562

Escherichia coli FRIK1997
FRIK1997
Proteobacteria
JH961362.1
III
2


653
GCA_000303275.2
1005482
562

Escherichia coli FRIK523
FRIK523
Proteobacteria
JH943936.1
III
2


654
GCA_000163215.1
656379
562

Escherichia coli FVEC1302
FVEC1302
Proteobacteria
GG774899.1
III
2


655
GCA_000163235.1
656380
562

Escherichia coli FVEC1412
FVEC1412
Proteobacteria
GG749206.1
III
2


656
GCA_000456165.1
1280964
562

Escherichia coli HVH 10 (4-6832164)
HVH 10 (4-6832164)
Proteobacteria
KE698889.1
III
2


657
GCA_000457475.1
1281042
562

Escherichia coli HVH 106 (4-6881831)
HVH 106 (4-6881831)
Proteobacteria
KE699746.1
III
2


658
GCA_000457535.1
1281046
562

Escherichia coli HVH 110 (4-6978754)
HVH 110 (4-6978754)
Proteobacteria
KE699792.1
III
2


659
GCA_000457595.1
1281049
562

Escherichia coli HVH 113 (4-7535473)
HVH 113 (4-7535473)
Proteobacteria
KE699840.1
III
2


660
GCA_000457735.1
1281056
562

Escherichia coli HVH 119 (4-6879578)
HVH 119 (4-6879578)
Proteobacteria
KE699940.1
III
2


661
GCA_000457795.1
1281059
562

Escherichia coli HVH 122 (4-6851606)
HVH 122 (4-6851606)
Proteobacteria
KE699976.1
III
2


662
GCA_000457895.1
1281064
562

Escherichia coli HVH 130 (4-7036876)
HVH 130 (4-7036876)
Proteobacteria
KE700051.1
III
2


663
GCA_000457955.1
1281067
562

Escherichia coli HVH 134 (4-6073441)
HVH 134 (4-6073441)
Proteobacteria
KE700096.1
III
2


664
GCA_000457975.1
1281068
562

Escherichia coli HVH 135 (4-4449320)
HVH 135 (4-4449320)
Proteobacteria
KE700100.1
III
2


665
GCA_000494995.1
1281069
562

Escherichia coli HVH 136 (4-5970458)
HVH 136 (4-5970458)
Proteobacteria
KI538714.1
III
2


666
GCA_000458055.1
1281073
562

Escherichia coli HVH 140 (4-5894387)
HVH 140 (4-5894387)
Proteobacteria
KE700176.1
III
2


667
GCA_000458155.1
1281078
562

Escherichia coli HVH 145 (4-5672112)
HVH 145 (4-5672112)
Proteobacteria
KE700231.1
III
2


668
GCA_000458235.1
1281083
562

Escherichia coli HVH 150 (4-3258106)
HVH 150 (4-3258106)
Proteobacteria
KE700264.1
III
2


669
GCA_000458255.1
1281084
562

Escherichia coli HVH 151 (4-5755573)
HVH 151 (4-5755573)
Proteobacteria
KE700275.1
III
2


670
GCA_000458315.1
1281088
562

Escherichia coli HVH 155 (4-4509048)
HVH 155 (4-4509048)
Proteobacteria
KE700348.1
III
2


671
GCA_000458475.1
1281096
562

Escherichia coli HVH 163 (4-4697553)
HVH 163 (4-4697553)
Proteobacteria
KE700462.1
III
2


672
GCA_000458515.1
1281098
562

Escherichia coli HVH 167 (4-6073565)
HVH 167 (4-6073565)
Proteobacteria
KE700479.1
III
2


673
GCA_000458625.1
1281103
562

Escherichia coli HVH 173 (3-9175482)
HVH 173 (3-9175482)
Proteobacteria
KE700542.1
III
2


674
GCA_000458705.1
1281109
562

Escherichia coli HVH 182 (4-0985554)
HVH 182 (4-0985554)
Proteobacteria
KE700608.1
III
2


675
GCA_000458725.1
1281110
562

Escherichia coli HVH 183 (4-3205932)
HVH 183 (4-3205932)
Proteobacteria
KE700619.1
III
2


676
GCA_000458915.1
1281120
562

Escherichia coli HVH 193 (4-3331423)
HVH 193 (4-3331423)
Proteobacteria
KE700785.1
III
2


677
GCA_000458995.1
1281124
562

Escherichia coli HVH 197 (4-4466217)
HVH 197 (4-4466217)
Proteobacteria
KE700814.1
III
2


678
GCA_000459175.1
1281133
562

Escherichia coli HVH 206 (4-3128229)
HVH 206 (4-3128229)
Proteobacteria
KE700892.1
III
2


679
GCA_000459215.1
1281135
562

Escherichia coli HVH 208 (4-3112292)
HVH 208 (4-3112292)
Proteobacteria
KE700918.1
III
2


680
GCA_000459335.1
1281142
562

Escherichia coli HVH 215 (4-3008371)
HVH 215 (4-3008371)
Proteobacteria
KE700987.1
III
2


681
GCA_000456325.1
1280973
562

Escherichia coli HVH 22 (4-2258986)
HVH 22 (4-2258986)
Proteobacteria
KE699031.1
III
2


682
GCA_000459475.1
1281149
562

Escherichia coli HVH 223 (4-2976528)
HVH 223 (4-2976528)
Proteobacteria
KE701095.1
III
2


683
GCA_000456445.1
1280980
562

Escherichia coli HVH 29 (4-3418073)
HVH 29 (4-3418073)
Proteobacteria
KE699106.1
III
2


684
GCA_000456685.1
1280993
562

Escherichia coli HVH 43 (4-2173468)
HVH 43 (4-2173468)
Proteobacteria
KE699249.1
III
2


685
GCA_000456705.1
1280994
562

Escherichia coli HVH 44 (4-2298570)
HVH 44 (4-2298570)
Proteobacteria
KE699258.1
III
2


686
GCA_000456725.1
1280995
562

Escherichia coli HVH 45 (4-3129918)
HVH 45 (4-3129918)
Proteobacteria
KE699267.1
III
2


687
GCA_000456925.1
1281007
562

Escherichia coli HVH 63 (4-2542528)
HVH 63 (4-2542528)
Proteobacteria
KE699373.1
III
2


688
GCA_000456985.1
1281010
562

Escherichia coli HVH 69 (4-2837072)
HVH 69 (4-2837072)
Proteobacteria
KE699403.1
III
2


689
GCA_000457205.1
1281022
562

Escherichia coli HVH 85 (4-0792144)
HVH 85 (4-0792144)
Proteobacteria
KE699590.1
III
2


690
GCA_000459655.1
1281158
562

Escherichia coli KOEGE 33 (68a)
KOEGE 33 (68a)
Proteobacteria
KE701249.1
III
2


691
GCA_000459795.1
1281165
562

Escherichia coli KOEGE 62 (175a)
KOEGE 62 (175a)
Proteobacteria
KE701351.1
III
2


692
GCA_000459815.1
1281166
562

Escherichia coli KOEGE 68 (182a)
KOEGE 68 (182a)
Proteobacteria
KE701357.1
III
2


693
GCA_000459875.1
1281169
562

Escherichia coli KOEGE 73 (195a)
KOEGE 73 (195a)
Proteobacteria
KE701395.1
III
2


694
GCA_000407665.1
1169315
562

Escherichia coli KTE1
KTE1
Proteobacteria
KE136571.1
III
2


695
GCA_000408585.1
1182701
562

Escherichia coli KTE102
KTE102
Proteobacteria
KE137162.1
III
2


696
GCA_000351885.1
1182708
562

Escherichia coli KTE116
KTE116
Proteobacteria
KB732889.1
III
2


697
GCA_000326945.1
1169380
562

Escherichia coli KTE122
KTE122
Proteobacteria
KB731963.1
III
2


698
GCA_000326965.1
1169382
562

Escherichia coli KTE125
KTE125
Proteobacteria
KB732191.1
III
2


699
GCA_000408705.1
1182714
562

Escherichia coli KTE127
KTE127
Proteobacteria
KE137233.1
III
2


700
GCA_000326245.1
1169383
562

Escherichia coli KTE128
KTE128
Proteobacteria
ANXW01000117.1
III
2


701
GCA_000408725.1
1182715
562

Escherichia coli KTE130
KTE130
Proteobacteria
KE137242.1
III
2


702
GCA_000408745.1
1182716
562

Escherichia coli KTE132
KTE132
Proteobacteria
KE137261.1
III
2


703
GCA_000408765.1
1182717
562

Escherichia coli KTE134
KTE134
Proteobacteria
KE137276.1
III
2


704
GCA_000352725.1
1182728
562

Escherichia coli KTE154
KTE154
Proteobacteria
KB733130.1
III
2


705
GCA_000352745.1
1182731
562

Escherichia coli KTE158
KTE158
Proteobacteria
KB733136.1
III
2


706
GCA_000351985.1
1182733
562

Escherichia coli KTE161
KTE161
Proteobacteria
KB732934.1
III
2


707
GCA_000326765.1
1169397
562

Escherichia coli KTE166
KTE166
Proteobacteria
ANYK01000003.1
III
2


708
GCA_000408825.1
1182737
562

Escherichia coli KTE170
KTE170
Proteobacteria
KE137303.1
III
2


709
GCA_000350925.1
1181727
562

Escherichia coli KTE181
KTE181
Proteobacteria
KB732408.1
III
2


710
GCA_000350625.1
1169324
562

Escherichia coli KTE2
KTE2
Proteobacteria
KB732209.1
III
2


711
GCA_000408185.1
1181746
562

Escherichia coli KTE200
KTE200
Proteobacteria
KE136942.1
III
2


712
GCA_000352965.1
1181748
562

Escherichia coli KTE202
KTE202
Proteobacteria
KB733186.1
III
2


713
GCA_000351065.1
1181750
562

Escherichia coli KTE204
KTE204
Proteobacteria
KB732469.1
III
2


714
GCA_000351125.1
1181754
562

Escherichia coli KTE208
KTE208
Proteobacteria
KB732511.1
III
2


715
GCA_000408245.1
1181768
562

Escherichia coli KTE222
KTE222
Proteobacteria
KE136972.1
III
2


716
GCA_000408265.1
1181771
562

Escherichia coli KTE225
KTE225
Proteobacteria
KE136980.1
III
2


717
GCA_000351365.1
1181779
562

Escherichia coli KTE235
KTE235
Proteobacteria
KB732610.1
III
2


718
GCA_000350825.1
1169345
562

Escherichia coli KTE26
KTE26
Proteobacteria
KB732334.1
III
2


719
GCA_000350885.1
1169361
562

Escherichia coli KTE44
KTE44
Proteobacteria
KB732364.1
III
2


720
GCA_000352325.1
1182657
562

Escherichia coli KTE50
KTE50
Proteobacteria
KB733431.1
III
2


721
GCA_000351465.1
1182658
562

Escherichia coli KTE51
KTE51
Proteobacteria
KB732658.1
III
2


722
GCA_000351525.1
1182663
562

Escherichia coli KTE56
KTE56
Proteobacteria
KB732702.1
III
2


723
GCA_000408385.1
1182675
562

Escherichia coli KTE68
KTE68
Proteobacteria
KE137040.1
III
2


724
GCA_000351765.1
1182688
562

Escherichia coli KTE81
KTE81
Proteobacteria
KB732854.1
III
2


725
GCA_000326505.1
1169363
562

Escherichia coli KTE82
KTE82
Proteobacteria
ANYT01000130.1
III
2


726
GCA_000351785.1
1182689
562

Escherichia coli KTE83
KTE83
Proteobacteria
KB733405.1
III
2


727
GCA_000176575.2
656419
562

Escherichia coli M718
M718
Proteobacteria
GL884102.1
III
2


728
GCA_000261145.1
656421
562

Escherichia coli M919
M919
Proteobacteria
JH659569.1
III
2


729
GCA_000692775.1
1438688
562

Escherichia coli MGH 58
MGH 58
Proteobacteria
KK736506.1
III
2


730
GCA_000164275.1
749540
562

Escherichia coli MS 146-1
MS 146-1
Proteobacteria
GG772126.1
III
2


731
GCA_000164335.1
749547
562

Escherichia coli MS 187-1
MS 187-1
Proteobacteria
GG772497.1
III
2


732
GCA_000164555.1
749548
562

Escherichia coli MS 196-1
MS 196-1
Proteobacteria
GG773987.1
III
2


733
GCA_000164195.1
749549
562

Escherichia coli MS 198-1
MS 198-1
Proteobacteria
GG771459.1
III
2


734
GCA_000303835.2
1005484
562

Escherichia coli NE037
NE037
Proteobacteria
JH960043.1
III
2


735
GCA_000303295.2
1005486
562

Escherichia coli NE098
NE098
Proteobacteria
JH946265.1
III
2


736
GCA_000350045.2
1090929
562

Escherichia coli O127:H27 str. C43/90
C43/90
Proteobacteria
AHAW01000071.1
III
2


737
GCA_000695155.1
1078035
562

Escherichia coli O145:H28 str. 4865/96
4865/96
Proteobacteria
JHEY01000012.1
III
2


738
GCA_000671295.1
1248823
562

Escherichia coli O145:H28 str. RM12581
RM12581
Proteobacteria
CP007136.1
III
2


739
GCA_000520035.1
1248902
562

Escherichia coli O145:H28 str. RM13514
RM13514
Proteobacteria
CP006027.1
III
2


740
GCA_000617345.1
1446585
562

Escherichia coli O145:NM str. 06-3484
06-3484
Proteobacteria
JHNN01000002.1
III
2


741
GCA_000616665.2
1446586
562

Escherichia coli O145:NM str. 08-4270
08-4270
Proteobacteria
JHKV01000030.1
III
2


742
GCA_000615085.1
1446587
562

Escherichia coli O145:NM str. 2010C-3507
2010C-3507
Proteobacteria
JHFW01000006.1
III
2


743
GCA_000619185.1
1446588
562

Escherichia coli O145:NM str. 2010C-3508
2010C-3508
Proteobacteria
JHFV01000110.1
III
2


744
GCA_000615175.1
1446590
562

Escherichia coli O145:NM str. 2010C-3510
2010C-3510
Proteobacteria
JHFT01000001.1
III
2


745
GCA_000615225.2
1446591
562

Escherichia coli O145:NM str. 2010C-3511
2010C-3511
Proteobacteria
JHFS01000035.1
III
2


746
GCA_000615265.1
1446592
562

Escherichia coli O145:NM str. 2010C-3516
2010C-3516
Proteobacteria
JHFR01000094.1
III
2


747
GCA_000615305.1
1446593
562

Escherichia coli O145:NM str. 2010C-3517
2010C-3517
Proteobacteria
JHFQ01000117.1
III
2


748
GCA_000615345.1
1446594
562

Escherichia coli O145:NM str. 2010C-3518
2010C-3518
Proteobacteria
JHFP01000105.1
III
2


749
GCA_000615385.1
1446595
562

Escherichia coli O145:NM str. 2010C-3521
2010C-3521
Proteobacteria
JHF001000022.1
III
2


750
GCA_000615415.2
1446596
562

Escherichia coli O145:NM str. 2010C-3526
2010C-3526
Proteobacteria
JHFN01000018.1
III
2


751
GCA_000617765.2
1446597
562

Escherichia coli O145:NM str. 2010C-4557C2
2010C-4557C2
Proteobacteria
JHNA01000067.1
III
2


752
GCA_000632555.1
1446606
562

Escherichia coli O157: str. 2010EL-2044
2010EL-2044
Proteobacteria
JHME01000103.1
III
2


753
GCA_000632655.1
1446607
562

Escherichia coli O157: str. 2010EL-2045
2010EL-2045
Proteobacteria
JHMD01000001.1
III
2


754
GCA_000187305.2
926027
562

Escherichia coli O157:H- str. 493-89
493-89
Proteobacteria
AETY01000104.1
III
2


755
GCA_000187325.2
926028
562

Escherichia coli O157:H- str. H 2687
H 2687
Proteobacteria
AETZ01000110.1
III
2


756
GCA_000978815.1
83334
562

Escherichia coli O157:H7
7.1_Anguil
Proteobacteria
LAZD01000130.1
III
2


757
GCA_000978845.1
83334
562

Escherichia coli O157:H7
Rafaela_II
Proteobacteria
LAYW01000314.1
III
2


758
GCA_001006425.1
83334
562

Escherichia coli O157:H7
HB74
Proteobacteria
LCWU01000234.1
III
2


759
GCA_001307215.1
83334
562

Escherichia coli O157:H7
WS4202
Proteobacteria
CP012802.1
III
2


760
GCA_001440045.1
83334
562

Escherichia coli O157:H7
G10
Proteobacteria
LMXL01000097.1
III
2


761
GCA_000617445.2
1446609
562

Escherichia coli O157:H7 str. 06-3745
06-3745
Proteobacteria
JHNI01000020.1
III
2


762
GCA_000617705.2
1446610
562

Escherichia coli O157:H7 str. 06-4039
06-4039
Proteobacteria
JHNG01000005.1
III
2


763
GCA_000617665.2
1446611
562

Escherichia coli O157:H7 str. 07-3091
07-3091
Proteobacteria
JHNF01000007.1
III
2


764
GCA_000617725.2
1446612
562

Escherichia coli O157:H7 str. 07-3391
07-3391
Proteobacteria
JHNE01000001.1
III
2


765
GCA_000616585.2
1446613
562

Escherichia coli O157:H7 str. 08-3037
08-3037
Proteobacteria
JHKZ01000011.1
III
2


766
GCA_000616605.2
1446614
562

Escherichia coli O157:H7 str. 08-3527
08-3527
Proteobacteria
JHKY01000032.1
III
2


767
GCA_000616645.2
1446615
562

Escherichia coli O157:H7 str. 08-4169
08-4169
Proteobacteria
JHKW01000004.1
III
2


768
GCA_000619665.1
1446616
562

Escherichia coli O157:H7 str. 08-4529
08-4529
Proteobacteria
JHHI01000009.1
III
2


769
GCA_000619145.1
1446618
562

Escherichia coli O157:H7 str. 2009EL1449
2009EL1449
Proteobacteria
JHGF01000005.1
III
2


770
GCA_000614965.1
1446619
562

Escherichia coli O157:H7 str. 2009EL1705
2009EL1705
Proteobacteria
JHGE01000007.1
III
2


771
GCA_000619165.1
1446620
562

Escherichia coli O157:H7 str. 2009EL1913
2009EL1913
Proteobacteria
JHGD01000001.1
III
2


772
GCA_000615015.1
1446621
562

Escherichia coli O157:H7 str. 2009EL2109
2009EL2109
Proteobacteria
JHGC01000001.1
III
2


773
GCA_000616365.1
1446623
562

Escherichia coli O157:H7 str. 2011EL-1107
2011EL-1107
Proteobacteria
JHLK01000001.1
III
2


774
GCA_000616405.2
1446624
562

Escherichia coli O157:H7 str. 2011EL-2090
2011EL-2090
Proteobacteria
JHLI01000033.1
III
2


775
GCA_000616425.2
1446625
562

Escherichia coli O157:H7 str. 2011EL-2091
2011EL-2091
Proteobacteria
JHLH01000026.1
III
2


776
GCA_000616445.2
1446626
562

Escherichia coli O157:H7 str. 2011EL-2092
2011EL-2092
Proteobacteria
JHLG01000030.1
III
2


777
GCA_000616465.2
1446627
562

Escherichia coli O157:H7 str. 2011EL-2093
2011EL-2093
Proteobacteria
JHLF01000012.1
III
2


778
GCA_000616485.2
1446628
562

Escherichia coli O157:H7 str. 2011EL-2094
2011EL-2094
Proteobacteria
JHLE01000001.1
III
2


779
GCA_000616505.2
1446629
562

Escherichia coli O157:H7 str. 2011EL-2096
2011EL-2096
Proteobacteria
JHLD01000033.1
III
2


780
GCA_000616525.2
1446630
562

Escherichia coli O157:H7 str. 2011EL-2097
2011EL-2097
Proteobacteria
JHLC01000005.1
III
2


781
GCA_000616545.2
1446631
562

Escherichia coli O157:H7 str. 2011EL-2098
2011EL-2098
Proteobacteria
JHLB01000003.1
III
2


782
GCA_000616705.2
1446632
562

Escherichia coli O157:H7 str. 2011EL-2099
2011EL-2099
Proteobacteria
JHKT01000015.1
III
2


783
GCA_000615695.1
1446633
562

Escherichia coli O157:H7 str. 2011EL-2101
2011EL-2101
Proteobacteria
JHKS01000001.1
III
2


784
GCA_000615745.2
1446634
562

Escherichia coli O157:H7 str. 2011EL-2103
2011EL-2103
Proteobacteria
JHKR01000031.1
III
2


785
GCA_000615785.2
1446635
562

Escherichia coli O157:H7 str. 2011EL-2104
2011EL-2104
Proteobacteria
JHKQ01000016.1
III
2


786
GCA_000615815.2
1446636
562

Escherichia coli O157:H7 str. 2011EL-2105
2011EL-2105
Proteobacteria
JHKP01000014.1
III
2


787
GCA_000615865.2
1446637
562

Escherichia coli O157:H7 str. 2011EL-2106
2011EL-2106
Proteobacteria
JHKO01000009.1
III
2


788
GCA_000615925.2
1446638
562

Escherichia coli O157:H7 str. 2011EL-2107
2011EL-2107
Proteobacteria
JHKN01000006.1
III
2


789
GCA_000615965.2
1446639
562

Escherichia coli O157:H7 str. 2011EL-2108
2011EL-2108
Proteobacteria
JHKM01000031.1
III
2


790
GCA_000616005.2
1446640
562

Escherichia coli O157:H7 str. 2011EL-2109
2011EL-2109
Proteobacteria
JHKL01000015.1
III
2


791
GCA_000616035.2
1446641
562

Escherichia coli O157:H7 str. 2011EL-2111
2011EL-2111
Proteobacteria
JHKK01000003.1
III
2


792
GCA_000616075.2
1446642
562

Escherichia coli O157:H7 str. 2011EL-2112
2011EL-2112
Proteobacteria
JHKJ01000005.1
III
2


793
GCA_000614645.2
1446643
562

Escherichia coli O157:H7 str. 2011EL-2113
2011EL-2113
Proteobacteria
JHKI01000015.1
III
2


794
GCA_000614255.1
1446644
562

Escherichia coli O157:H7 str. 2011EL-2114
2011EL-2114
Proteobacteria
JHKH01000002.1
III
2


795
GCA_000614305.2
1446645
562

Escherichia coli O157:H7 str. 2011EL-2286
2011EL-2286
Proteobacteria
JHKG01000013.1
III
2


796
GCA_000614405.2
1446646
562

Escherichia coli O157:H7 str. 2011EL-2287
2011EL-2287
Proteobacteria
JHKF01000001.1
III
2


797
GCA_000614085.2
1446647
562

Escherichia coli O157:H7 str. 2011EL-2288
2011EL-2288
Proteobacteria
JHKE01000007.1
III
2


798
GCA_000614685.2
1446648
562

Escherichia coli O157:H7 str. 2011EL-2289
2011EL-2289
Proteobacteria
JHKD01000001.1
III
2


799
GCA_000618945.2
1446649
562

Escherichia coli O157:H7 str. 2011EL-2290
2011EL-2290
Proteobacteria
JHKC01000008.1
III
2


800
GCA_000614345.2
1446650
562

Escherichia coli O157:H7 str. 2011EL-2312
2011EL-2312
Proteobacteria
JHKB01000003.1
III
2


801
GCA_000618985.2
1446651
562

Escherichia coli O157:H7 str. 2011EL-2313
2011EL-2313
Proteobacteria
JHKA01000028.1
III
2


802
GCA_000181775.1
444449
562

Escherichia coli O157:H7 str. EC4042
EC4042
Proteobacteria
ABHM02000001.1
III
2


803
GCA_000181755.1
444448
562

Escherichia coli O157:H7 str. EC4045
EC4045
Proteobacteria
ABHL02000001.1
III
2


804
GCA_000171955.1
444453
562

Escherichia coli O157:H7 str. EC4076
EC4076
Proteobacteria
ABHQ01000017.1
III
2


805
GCA_000171935.1
444452
562

Escherichia coli O157:H7 str. EC4113
EC4113
Proteobacteria
ABHP01000015.1
III
2


806
GCA_000021125.1
444450
562

Escherichia coli O157:H7 str. EC4115
EC4115
Proteobacteria
CP001164.1
III
2


807
GCA_000171915.1
444451
562

Escherichia coli O157:H7 str. EC4196
EC4196
Proteobacteria
ABHO01000006.1
III
2


808
GCA_000181735.1
444447
562

Escherichia coli O157:H7 str. EC4206
EC4206
Proteobacteria
ABHK02000001.1
III
2


809
GCA_000171975.1
478004
562

Escherichia coli O157:H7 str. EC4401
EC4401
Proteobacteria
ABHR01000005.1
III
2


810
GCA_000171995.1
478005
562

Escherichia coli O157:H7 str. EC4486
EC4486
Proteobacteria
ABHS01000002.1
III
2


811
GCA_000172015.1
478006
562

Escherichia coli O157:H7 str. EC4501
EC4501
Proteobacteria
ABHT01000004.1
III
2


812
GCA_000172055.1
478007
562

Escherichia coli O157:H7 str. EC508
EC508
Proteobacteria
ABHW01000003.1
III
2


813
GCA_000006665.1
155864
562

Escherichia coli O157:H7 str. EDL933
EDL933
Proteobacteria
AE005174.2
III
2


814
GCA_000732965.1
155864
562

Escherichia coli O157:H7 str. EDL933
EDL933
Proteobacteria
CP008957.1
III
2


815
GCA_000618105.2
1446652
562

Escherichia coli O157:H7 str. F6142
F6142
Proteobacteria
JHJT01000009.1
III
2


816
GCA_000618045.1
1446653
562

Escherichia coli O157:H7 str. F6749
F6749
Proteobacteria
JHJQ01000001.1
III
2


817
GCA_000618305.2
1446654
562

Escherichia coli O157:H7 str. F6750
F6750
Proteobacteria
JHJP01000010.1
III
2


818
GCA_000618265.2
1446655
562

Escherichia coli O157:H7 str. F6751
F6751
Proteobacteria
JHJO01000004.1
III
2


819
GCA_000614805.2
1446656
562

Escherichia coli O157:H7 str. F7350
F7350
Proteobacteria
JHJN01000036.1
III
2


820
GCA_000618225.2
1446657
562

Escherichia coli O157:H7 str. F7377
F7377
Proteobacteria
JHJM01000002.1
III
2


821
GCA_000618065.2
1446658
562

Escherichia coli O157:H7 str. F7384
F7384
Proteobacteria
JHJL01000002.1
III
2


822
GCA_000618145.2
1446659
562

Escherichia coli O157:H7 str. F7410
F7410
Proteobacteria
JHJK01000004.1
III
2


823
GCA_000187285.4
926026
562

Escherichia coli O157:H7 str. G5101
G5101
Proteobacteria
AETX01000114.1
III
2


824
GCA_000618185.1
1446660
562

Escherichia coli O157:H7 str. G5303
G5303
Proteobacteria
JHJI01000027.1
III
2


825
GCA_000618245.1
1446661
562

Escherichia coli O157:H7 str. H2495
H2495
Proteobacteria
JHJH01000020.1
III
2


826
GCA_000618285.2
1446662
562

Escherichia coli O157:H7 str. H2498
H2498
Proteobacteria
JHJG01000003.1
III
2


827
GCA_000618025.1
1446663
562

Escherichia coli O157:H7 str. K1420
K1420
Proteobacteria
JHJF01000008.1
III
2


828
GCA_000618425.1
1446664
562

Escherichia coli O157:H7 str. K1792
K1792
Proteobacteria
JHJD01000136.1
III
2


829
GCA_000618365.1
1446665
562

Escherichia coli O157:H7 str. K1793
K1793
Proteobacteria
JHJC01000041.1
III
2


830
GCA_000618325.1
1446667
562

Escherichia coli O157:H7 str. K1796
K1796
Proteobacteria
JHJA01000003.1
III
2


831
GCA_000618345.1
1446668
562

Escherichia coli O157:H7 str. K1845
K1845
Proteobacteria
JHIZ01000038.1
III
2


832
GCA_000618445.1
1446669
562

Escherichia coli O157:H7 str. K1921
K1921
Proteobacteria
JHIY01000012.1
III
2


833
GCA_000618465.1
1446670
562

Escherichia coli O157:H7 str. K1927
K1927
Proteobacteria
JHIX01000108.1
III
2


834
GCA_000618485.1
1446671
562

Escherichia coli O157:H7 str. K2188
K2188
Proteobacteria
JHIW01000103.1
III
2


835
GCA_000618665.1
1446674
562

Escherichia coli O157:H7 str. K2324
K2324
Proteobacteria
JHIT01000105.1
III
2


836
GCA_000618525.1
1446675
562

Escherichia coli O157:H7 str. K2581
K2581
Proteobacteria
JHIS01000002.1
III
2


837
GCA_000618605.1
1446679
562

Escherichia coli O157:H7 str. K4396
K4396
Proteobacteria
JHI001000002.1
III
2


838
GCA_000617965.1
1446680
562

Escherichia coli O157:H7 str. K4405
K4405
Proteobacteria
JHIN01000100.1
III
2


839
GCA_000618625.1
1446681
562

Escherichia coli O157:H7 str. K4406
K4406
Proteobacteria
JHIM01000001.1
III
2


840
GCA_000618685.1
1446682
562

Escherichia coli O157:H7 str. K4527
K4527
Proteobacteria
JHIL01000001.1
III
2


841
GCA_000618745.1
1446683
562

Escherichia coli O157:H7 str. K5418
K5418
Proteobacteria
JHII01000001.1
III
2


842
GCA_000618765.1
1446684
562

Escherichia coli O157:H7 str. K5448
K5448
Proteobacteria
JHIH01000007.1
III
2


843
GCA_000618785.1
1446685
562

Escherichia coli O157:H7 str. K5449
K5449
Proteobacteria
JHIG01000002.1
III
2


844
GCA_000618805.1
1446686
562

Escherichia coli O157:H7 str. K5453
K5453
Proteobacteria
JHIF01000066.1
III
2


845
GCA_000618885.1
1446687
562

Escherichia coli O157:H7 str. K5460
K5460
Proteobacteria
JHIE01000002.1
III
2


846
GCA_000618825.1
1446688
562

Escherichia coli O157:H7 str. K5467
K5467
Proteobacteria
JHID01000001.1
III
2


847
GCA_000618845.1
1446689
562

Escherichia coli O157:H7 str. K5602
K5602
Proteobacteria
JHIC01000015.1
III
2


848
GCA_000618865.1
1446690
562

Escherichia coli O157:H7 str. K5607
K5607
Proteobacteria
JHIB01000088.1
III
2


849
GCA_000619445.1
1446691
562

Escherichia coli O157:H7 str. K5609
K5609
Proteobacteria
JHIA01000021.1
III
2


850
GCA_000616745.1
1446692
562

Escherichia coli O157:H7 str. K5806
K5806
Proteobacteria
JHHZ01000001.1
III
2


851
GCA_000619365.1
1446693
562

Escherichia coli O157:H7 str. K5852
K5852
Proteobacteria
JHHY01000003.1
III
2


852
GCA_000619385.1
1446694
562

Escherichia coli O157:H7 str. K6590
K6590
Proteobacteria
JHHX01000004.1
III
2


853
GCA_000619405.1
1446695
562

Escherichia coli O157:H7 str. K6676
K6676
Proteobacteria
JHHW01000001.1
III
2


854
GCA_000619425.1
1446696
562

Escherichia coli O157:H7 str. K6687
K6687
Proteobacteria
JHHV01000121.1
III
2


855
GCA_000618925.2
1446697
562

Escherichia coli O157:H7 str. k7140
K7140
Proteobacteria
JHHK01000016.1
III
2


856
GCA_000008865.1
386585
562

Escherichia coli O157:H7 str. Sakai
Sakai substr. RIMD
Proteobacteria
BA000007.2
III
2







0509952


857
GCA_000730345.1
1328859
562

Escherichia coli O157:H7 str. SS17
SS17
Proteobacteria
CP008805.1
III
2


858
GCA_000803705.1
1330457
562

Escherichia coli O157:H7 str. SS52
SS52
Proteobacteria
CP010304.1
III
2


859
GCA_000022225.1
544404
562

Escherichia coli O157:H7 str. TW14359
TW14359
Proteobacteria
CP001368.1
III
2


860
GCA_000155125.1
502346
562

Escherichia coli O157:H7 str. TW14588
TW14588
Proteobacteria
CM000662.1
III
2


861
GCA_000617385.1
1446745
562

Escherichia coli O55:H7 str. 06-3555
06-3555
Proteobacteria
JHNL01000009.1
III
2


862
GCA_000187345.2
926029
562

Escherichia coli O55:H7 str. 3256-97
3256-97 TW 07815
Proteobacteria
AEUA01000088.1
III
2


863
GCA_000025165.1
701177
562

Escherichia coli O55:H7 str. CB9615
CB9615
Proteobacteria
CP001846.1
III
2


864
GCA_000357145.2
1116131
562

Escherichia coli P02997067.6
P02997067.6
Proteobacteria
APYJ01000201.1
III
2


865
GCA_000356665.2
1116047
562

Escherichia coli P0299917.1
P0299917.1
Proteobacteria
AQER01000001.1
III
2


866
GCA_000356605.2
1116089
562

Escherichia coli p0305293.1
p0305293.1
Proteobacteria
AQEK01000045.1
III
2


867
GCA_000358555.1
1116098
562

Escherichia coli p0305293.10
p0305293.10
Proteobacteria
AQBT01000187.1
III
2


868
GCA_000358575.2
1116099
562

Escherichia coli p0305293.11
p0305293.11
Proteobacteria
AQBU01000292.1
III
2


869
GCA_000358595.2
1116100
562

Escherichia coli p0305293.12
p0305293.12
Proteobacteria
AQBV01000163.1
III
2


870
GCA_000356865.2
1116101
562

Escherichia coli p0305293.13
p0305293.13
Proteobacteria
APZI01000451.1
III
2


871
GCA_000357485.2
1125646
562

Escherichia coli p0305293.14
p0305293.14
Proteobacteria
APZZ01000159.1
III
2


872
GCA_000358615.2
1116102
562

Escherichia coli p0305293.15
p0305293.15
Proteobacteria
AQBW01000104.1
III
2


873
GCA_000358635.2
1116090
562

Escherichia coli p0305293.2
p0305293.2
Proteobacteria
AQBX01000150.1
III
2


874
GCA_000358655.2
1116091
562

Escherichia coli p0305293.3
p0305293.3
Proteobacteria
AQBY01000159.1
III
2


875
GCA_000358675.2
1116092
562

Escherichia coli p0305293.4
p0305293.4
Proteobacteria
AQBZ01000242.1
III
2


876
GCA_000359055.2
1116093
562

Escherichia coli p0305293.5
p0305293.5
Proteobacteria
AQCA01000251.1
III
2


877
GCA_000358695.2
1116096
562

Escherichia coli p0305293.8
p0305293.8
Proteobacteria
AQCD01000162.1
III
2


878
GCA_000358715.2
1116097
562

Escherichia coli p0305293.9
p0305293.9
Proteobacteria
AQCE01000149.1
III
2


879
GCA_000498255.1
1097579
562

Escherichia coli P4-96
P4-96
Proteobacteria
AHH001000034.1
III
2


880
GCA_000498275.1
1117111
562

Escherichia coli P4-NR
P4-NR
Proteobacteria
AHHP01000046.1
III
2


881
GCA_000267865.2
1005494
562

Escherichia coli PA10
PA10
Proteobacteria
JH709066.1
III
2


882
GCA_000335415.2
1051349
562

Escherichia coli PA11
PA11
Proteobacteria
AOEI01000002.1
III
2


883
GCA_000335435.2
1051350
562

Escherichia coli PA13
PA13
Proteobacteria
AOEK01000001.1
III
2


884
GCA_000267845.2
1005495
562

Escherichia coli PA14
PA14
Proteobacteria
JH708600.1
III
2


885
GCA_000267825.2
1005496
562

Escherichia coli PA15
PA15
Proteobacteria
JH707559.1
III
2


886
GCA_000335335.2
1051351
562

Escherichia coli PA19
PA19
Proteobacteria
AOEJ01000133.1
III
2


887
GCA_000335355.2
1005487
562

Escherichia coli PA2
PA2
Proteobacteria
AOEL01000002.1
III
2


888
GCA_000267085.1
1005497
562

Escherichia coli PA22
PA22
Proteobacteria
AKLI01000001.1
III
2


889
GCA_000303895.2
1005498
562

Escherichia coli PA23
PA23
Proteobacteria
JH959990.1
III
2


890
GCA_000267805.2
1005499
562

Escherichia coli PA24
PA24
Proteobacteria
JH707528.1
III
2


891
GCA_000267785.2
1005500
562

Escherichia coli PA25
PA25
Proteobacteria
JH706538.1
III
2


892
GCA_000267765.2
1005501
562

Escherichia coli PA28
PA28
Proteobacteria
JH705685.1
III
2


893
GCA_000267925.2
1005488
562

Escherichia coli PA3
PA3
Proteobacteria
JH711390.1
III
2


894
GCA_000267745.2
1005502
562

Escherichia coli PA31
PA31
Proteobacteria
JH707077.1
III
2


895
GCA_000267725.2
1005503
562

Escherichia coli PA32
PA32
Proteobacteria
JH705678.1
III
2


896
GCA_000267705.2
1005504
562

Escherichia coli PA33
PA33
Proteobacteria
JH705112.1
III
2


897
GCA_000303695.2
1005505
562

Escherichia coli PA34
PA34
Proteobacteria
JH963946.1
III
2


898
GCA_000335175.2
1051352
562

Escherichia coli PA35
PA35
Proteobacteria
AOES01000151.1
III
2


899
GCA_000303675.2
1005506
562

Escherichia coli PA38
PA38
Proteobacteria
JH966118.1
III
2


900
GCA_000267685.2
1005507
562

Escherichia coli PA39
PA39
Proteobacteria
JH704564.1
III
2


901
GCA_000303875.2
1005489
562

Escherichia coli PA4
PA4
Proteobacteria
JH960549.1
III
2


902
GCA_000267645.2
1005510
562

Escherichia coli PA42
PA42
Proteobacteria
JH702836.1
III
2


903
GCA_000303935.2
1005511
562

Escherichia coli PA45
PA45
Proteobacteria
JH958691.1
III
2


904
GCA_000335075.2
1005512
562

Escherichia coli PA47
PA47
Proteobacteria
AOEM01000157.1
III
2


905
GCA_000335095.2
1005513
562

Escherichia coli PA48
PA48
Proteobacteria
AOEN01000122.1
III
2


906
GCA_000303915.2
1005514
562

Escherichia coli PA49
PA49
Proteobacteria
JH959133.1
III
2


907
GCA_000267905.2
1005490
562

Escherichia coli PA5
PA5
Proteobacteria
JH709975.1
III
2


908
GCA_000302735.1
1005491
562

Escherichia coli PA7
PA7
Proteobacteria
AMTQ01000008.1
III
2


909
GCA_000335455.2
1005492
562

Escherichia coli PA8
PA8
Proteobacteria
AOEO01000008.1
III
2


910
GCA_000267885.2
1005493
562

Escherichia coli PA9
PA9
Proteobacteria
JH709102.1
III
2


911
GCA_000019645.1
439855
562

Escherichia coli SMS-3-5
SMS-3-5
Proteobacteria
CP000970.1
III
2


912
GCA_000462145.2
1081891
562

Escherichia coli T1282_01
T1282_01
Proteobacteria
AVRM01000132.1
III
2


913
GCA_000462265.2
1081896
562

Escherichia coli T1840_97
T1840_97
Proteobacteria
AVRN01000121.1
III
2


914
GCA_000462385.2
1081892
562

Escherichia coli T234_00
T234_00
Proteobacteria
AVRO01000124.1
III
2


915
GCA_000462165.2
1081893
562

Escherichia coli T924_01
T924_01
Proteobacteria
AVRP01000002.1
III
2


916
GCA_000176615.2
656437
562

Escherichia coli TA143
TA143
Proteobacteria
GL884236.1
III
2


917
GCA_000303955.2
1005555
562

Escherichia coli TT12B
TT12B
Proteobacteria
JH957216.1
III
2


918
GCA_000267125.1
1005515
562

Escherichia coli TW06591
TW06591
Proteobacteria
AKLT01000044.1
III
2


919
GCA_000267625.2
1005516
562

Escherichia coli TW07945
TW07945
Proteobacteria
JH702467.1
III
2


920
GCA_000267605.2
1005519
562

Escherichia coli TW09098
TW09098
Proteobacteria
JH702452.1
III
2


921
GCA_000267065.1
1005520
562

Escherichia coli TW09109
TW09109
Proteobacteria
AKLY01000005.1
III
2


922
GCA_000267145.1
1005517
562

Escherichia coli TW10246
TW10246
Proteobacteria
AKLV01000003.1
III
2


923
GCA_000267165.1
1005518
562

Escherichia coli TW11039
TW11039
Proteobacteria
AKLW01000006.1
III
2


924
GCA_000267405.2
1005526
562

Escherichia coli TW14301
TW14301
Proteobacteria
JH695863.1
III
2


925
GCA_000267425.2
1005525
562

Escherichia coli TW14313
TW14313
Proteobacteria
JH695401.1
III
2


926
GCA_000462885.2
1207037
562

Escherichia coli Tx1686
Tx1686
Proteobacteria
AVSN01000001.1
III
2


927
GCA_000462905.2
1207036
562

Escherichia coli Tx3800
Tx3800
Proteobacteria
AVS001000014.1
III
2


928
GCA_000692835.1
1438693
562

Escherichia coli UCI 57
UCI 57
Proteobacteria
KK736542.1
III
2


929
GCA_000692855.1
1438694
562

Escherichia coli UCI 58
UCI 58
Proteobacteria
KK736552.1
III
2


930
GCA_000460315.1
1281191
562

Escherichia coli UMEA 3144-1
UMEA 3144-1
Proteobacteria
KE701670.1
III
2


931
GCA_000460355.1
1281194
562

Escherichia coli UMEA 3151-1
UMEA 3151-1
Proteobacteria
KE701689.1
III
2


932
GCA_000460755.1
1281214
562

Escherichia coli UMEA 3201-1
UMEA 3201-1
Proteobacteria
KE701998.1
III
2


933
GCA_000461015.1
1281227
562

Escherichia coli UMEA 3240-1
UMEA 3240-1
Proteobacteria
KE702179.1
III
2


934
GCA_000461115.1
1281233
562

Escherichia coli UMEA 3271-1
UMEA 3271-1
Proteobacteria
KE702260.1
III
2


935
GCA_000461255.1
1281242
562

Escherichia coli UMEA 3329-1
UMEA 3329-1
Proteobacteria
KE702361.1
III
2


936
GCA_000461315.1
1281247
562

Escherichia coli UMEA 3355-1
UMEA 3355-1
Proteobacteria
KE702386.1
III
2


937
GCA_000461675.1
1281269
562

Escherichia coli UMEA 3718-1
UMEA 3718-1
Proteobacteria
KE702585.1
III
2


938
GCA_000461855.1
1281278
562

Escherichia coli UMEA 4076-1
UMEA 4076-1
Proteobacteria
KE702725.1
III
2


939
GCA_000026325.1
585056
562

Escherichia coli UMN026
UMN026
Proteobacteria
CU928163.2
III
2


940
GCA_000262125.1
741093
562

Escherichia coli Xuzhou21
Xuzhou21
Proteobacteria
CP001925.1
III
2


941
GCA_000968905.2
564
564

Escherichia fergusonii

GTA-EF02
Proteobacteria
JZWQ02000016.1
III
2


942
GCA_000026225.1
585054
564

Escherichia fergusonii ATCC 35469

Proteobacteria
CU928158.2
III
2


943
GCA_000190495.1
550694
564

Escherichia fergusonii B253
B253
Proteobacteria
GL870856.1
III
2


944
GCA_000408845.1
1279005
1279005

Escherichia sp. KTE172
KTE172
Proteobacteria
KE137316.1
III
2


945
GCA_000961035.1
35554
35554

Geobacter sulfurreducens

AM-1
Proteobacteria
CP010430.1
III
2


946
GCA_000181475.1
344747
122

Gimesia maris DSM 8797
DSM 8797
Planctomycetes
ABCE01000001.1
III
2


947
GCA_000333895.2
1056512
1056512

Grimontia indica

AK16
Proteobacteria
ANFM02000056.1
III
2


948
GCA_000961635.1
1629712
1629712

Hoeflea sp. BRH_c9

Proteobacteria
LADQ01000154.1
III
2


949
GCA_000152885.1
314276
190892

Idiomarina baltica OS145
OS145
Proteobacteria
CH672405.1
III
2


950
GCA_001577655.1
1794809
1794809

Idiomarina sp. T82-3

Proteobacteria
LSBQ01000017.1
III
2


951
GCA_000723165.1
1349767
55508

Janthinobacterium agaricidamnosum NBRC 102515 = DSM 9628
DSM 9628
Proteobacteria
HG322949.1
III
2


952
GCA_001038305.1
571
571

Klebsiella oxytoca

GY84G39
Proteobacteria
LDZM01000006.1
III
2


953
GCA_001078255.1
883124
571

Klebsiella oxytoca 10-5249
10-5249
Proteobacteria
KQ235791.1
III
2


954
GCA_000607265.1
1409787
571

Klebsiella oxytoca G54
G54
Proteobacteria
KK097710.1
III
2


955
GCA_000764635.1
573
573

Klebsiella pneumoniae

BAMC 07-18
Proteobacteria
JRQE01000009.1
III
2


956
GCA_000786375.1
573
573

Klebsiella pneumoniae

223/14
Proteobacteria
JRTV01000011.1
III
2


957
GCA_000788005.1
573
573

Klebsiella pneumoniae

101712
Proteobacteria
JSZJ01000008.1
III
2


958
GCA_000807515.2
573
573

Klebsiella pneumoniae

6234
Proteobacteria
JWRK01000001.1
III
2


959
GCA_001031325.1
573
573

Klebsiella pneumoniae

CHS112
Proteobacteria
KQ088280.1
III
2


960
GCA_001031795.1
573
573

Klebsiella pneumoniae

CHS140
Proteobacteria
KQ088469.1
III
2


961
GCA_001033505.1
573
573

Klebsiella pneumoniae

MGH84
Proteobacteria
KQ089360.1
III
2


962
GCA_001033525.1
573
573

Klebsiella pneumoniae

MGH89
Proteobacteria
KQ089366.1
III
2


963
GCA_001033725.1
573
573

Klebsiella pneumoniae

MGH101
Proteobacteria
KQ089465.1
III
2


964
GCA_001033925.1
573
573

Klebsiella pneumoniae

MGH124
Proteobacteria
KQ089571.1
III
2


965
GCA_001185865.1
573
573

Klebsiella pneumoniae

CHS175
Proteobacteria
KQ236856.1
III
2


966
GCA_001307175.1
573
573

Klebsiella pneumoniae

KP617
Proteobacteria
CP012753.1
III
2


967
GCA_001441285.1
573
573

Klebsiella pneumoniae

B86
Proteobacteria
UCD01000021.1
III
2


968
GCA_001456055.1
573
573

Klebsiella pneumoniae

KpN01
Proteobacteria
CP012987.1
III
2


969
GCA_001456095.1
573
573

Klebsiella pneumoniae

KpN06
Proteobacteria
CP012992.1
III
2


970
GCA_001462825.1
573
573

Klebsiella pneumoniae

K68-18
Proteobacteria
LNHE01000086.1
III
2


971
GCA_001462845.1
573
573

Klebsiella pneumoniae

K68-73
Proteobacteria
LNHF01000070.1
III
2


972
GCA_001463085.1
573
573

Klebsiella pneumoniae

50580255
Proteobacteria
LNHK01000055.1
III
2


973
GCA_001463165.1
573
573

Klebsiella pneumoniae

U25
Proteobacteria
CP012043.1
III
2


974
GCA_001463475.1
573
573

Klebsiella pneumoniae

50884375
Proteobacteria
LNIS01000067.1
III
2


975
GCA_001483055.1
573
573

Klebsiella pneumoniae

K1
Proteobacteria
LOEJ01000055.1
III
2


976
GCA_001483725.1
573
573

Klebsiella pneumoniae

K45-67
Proteobacteria
LLWB01000171.1
III
2


977
GCA_001574505.1
573
573

Klebsiella pneumoniae

U41
Proteobacteria
LSTN01000011.1
III
2


978
GCA_001597015.1
573
573

Klebsiella pneumoniae

KP-33P
Proteobacteria
JXJG01000034.1
III
2


979
GCA_000474635.1
1381121
573

Klebsiella pneumoniae 303K
303K
Proteobacteria
AVAN01000039.1
III
2


980
GCA_000567405.1
1328405
573

Klebsiella pneumoniae BIDMC 11
BIDMC 11
Proteobacteria
KK036859.1
III
2


981
GCA_000492295.1
1328425
573

Klebsiella pneumoniae BIDMC 36
BIDMC 36
Proteobacteria
KI535412.1
III
2


982
GCA_000694235.1
1438772
573

Klebsiella pneumoniae CHS 66
CHS 66
Proteobacteria
KK737378.1
III
2


983
GCA_000530055.1
1432547
573

Klebsiella pneumoniae IS22
IS22
Proteobacteria
CBWF010000048.1
III
2


984
GCA_000316265.2
1236101
573

Klebsiella pneumoniae JHCK1
JHCK1
Proteobacteria
ANGH02000162.1
III
2


985
GCA_000406505.1
1284834
573

Klebsiella pneumoniae KP-11
KP-11
Proteobacteria
APWE01000228.1
III
2


986
GCA_000406385.1
1284833
573

Klebsiella pneumoniae KP-7
KP-7
Proteobacteria
AQQD01000021.1
III
2


987
GCA_000493135.1
1328363
573

Klebsiella pneumoniae MGH 18
MGH 18
Proteobacteria
KI535680.1
III
2


988
GCA_000567745.1
1328371
573

Klebsiella pneumoniae MGH 35
MGH 35
Proteobacteria
KK036965.1
III
2


989
GCA_000492775.1
1328378
573

Klebsiella pneumoniae MGH 46
MGH 46
Proteobacteria
KI535587.1
III
2


990
GCA_000694715.1
1438797
573

Klebsiella pneumoniae MGH 74
MGH 74
Proteobacteria
KK737643.1
III
2


991
GCA_000785005.1
72407
573

Klebsiella pneumoniae subsp. pneumoniae
KPNIH31
Proteobacteria
CP009876.1
III
2


992
GCA_000733255.1
1406314
573

Klebsiella pneumoniae subsp. pneumoniae PittNDM01
PittNDM01
Proteobacteria
CP006798.1
III
2


993
GCA_000300675.1
1203545
573

Klebsiella pneumoniae subsp. pneumoniae WGLW2
WGLW2
Proteobacteria
JH930419.1
III
2


994
GCA_000492595.1
1328391
573

Klebsiella pneumoniae UCICRE 4
UCICRE 4
Proteobacteria
KI535510.1
III
2


995
GCA_000417465.1
1284818
573

Klebsiella pneumoniae UHKPC179
UHKPC179
Proteobacteria
ARSM01000005.1
III
2


996
GCA_000409125.1
1284817
573

Klebsiella pneumoniae UHKPC57
UHKPC57
Proteobacteria
ARPR01000126.1
III
2


997
GCA_000280495.1
1177180
283686

Kosakonia radicincitans DSM 16656
DSM 16656
Proteobacteria
JH725436.1
III
2


998
GCA_000691205.1
1455607
283686

Kosakonia radicincitans UMEnt01/12
UMEnt01/12
Proteobacteria
JDYJ01000004.1
III
2


999
GCA_000048665.1
297245
446

Legionella pneumophila str. Lens
Lens
Proteobacteria
CR628337.1
III
2


1000
GCA_001468025.1
1122169
45075

Legionella shakespearei DSM 23087
ATCC 49655
Proteobacteria
LNYW01000016.1
III
2


1001
GCA_000521805.1
1122207
263818

Marinomonas ushuaiensis DSM 15871
DSM 15871
Proteobacteria
JAMB01000003.1
III
2


1002
GCA_000502395.1
1287232
1287232

Mesorhizobium sp. LNHC220B00
LNHC220B00
Proteobacteria
AYWS01000016.1
III
2


1003
GCA_000502435.1
1287243
1287243

Mesorhizobium sp. LNHC232B00
LNHC232B00
Proteobacteria
AYWP01000014.1
III
2


1004
GCA_000502975.1
1287268
1287268

Mesorhizobium sp. LNJC384A00
LNJC384A00
Proteobacteria
AYWK01000002.1
III
2


1005
GCA_001425625.1
1736422
1736422

Mesorhizobium sp. Root102
Root102
Proteobacteria
LMCP01000044.1
III
2


1006
GCA_000364445.1
908290
39956

Methylobacterium mesophilicum SR1.6/6
SR1.6/6
Proteobacteria
ANPA01000017.1
III
2


1007
GCA_000364445.1
908290
39956

Methylobacterium mesophilicum SR1.6/6
SR1.6/6
Proteobacteria
ANPA01000017.1
III
2


1008
GCA_001423385.1
1736262
1736262

Methylobacterium sp. Leaf121
Leaf121
Proteobacteria
LMNP01000003.1
III
2


1009
GCA_001422165.1
1736242
1736242

Methylobacterium sp. Leaf86
Leaf86
Proteobacteria
LMMG01000005.1
III
2


1010
GCA_001422265.1
1736246
1736246

Methylobacterium sp. Leaf90
Leaf90
Proteobacteria
LMMN01000010.1
III
2


1011
GCA_000186165.1
435832
488

Neisseria mucosa C102
C102
Proteobacteria
GL635793.1
III
2


1012
GCA_000235975.2
1088721
205844

Novosphingobium pentaromativorans US6-1
US6-1
Proteobacteria
AGFM01000037.1
III
2


1013
GCA_000767465.1
1088721
205844

Novosphingobium pentaromativorans US6-1
US6-1
Proteobacteria
CP009291.1
III
2


1014
GCA_000253255.1
702113
702113

Novosphingobium sp. PP1Y
PP1Y
Proteobacteria
FR856862.1
III
2


1015
GCA_001476715.1
59814
59814

Pantoea dispersa

NS215
Proteobacteria
LDRY01000017.1
III
2


1016
GCA_001477165.1
59814
59814

Pantoea dispersa

RSA31
Proteobacteria
LDSC01000016.1
III
2


1017
GCA_000179655.1
517433
517433

Pantoea sp. aB
aB
Proteobacteria
AEDL01000002.1
III
2


1018
GCA_000754715.1
78398
554

Pectobacterium carotovorum subsp. odoriferum
NCPPB3841
Proteobacteria
JQOF01000009.1
III
2


1019
GCA_000024645.1
561231
55208

Pectobacterium wasabiae WPP163
WPP163
Proteobacteria
CP001790.1
III
2


1020
GCA_000153725.1
314265
344736

Pelagibaca bermudensis HTCC2601
HTCC2601
Proteobacteria
DS022276.1
III
2


1021
GCA_000153425.1
314280
74109

Photobacterium profundum 3TCK
3TCK
Proteobacteria
CH724134.1
III
2


1022
GCA_000957245.1
61647
61647

Pluralibacter gergoviae

40874
Proteobacteria
JZYL01000003.1
III
2


1023
GCA_001038225.1
61647
61647

Pluralibacter gergoviae

JS81F13
Proteobacteria
LDZF01000024.1
III
2


1024
GCA_001038285.1
61647
61647

Pluralibacter gergoviae

SS84A28
Proteobacteria
LDZJ01000006.1
III
2


1025
GCA_001546565.2
28125
28125

Prevotella bivia

GED7760C
Bacteroidetes
KQ971199.1
III
2


1026
GCA_000224595.1
563031
563031

Prevotella sp. C561
C561
Bacteroidetes
JH114144.1
III
2


1027
GCA_001463025.1
584
584

Proteus mirabilis

50664164
Proteobacteria
LNHT01000079.1
III
2


1028
GCA_001469205.1
1761893
1761893

Pseudoalteromonas sp. H103
H103
Proteobacteria
LOFG01000015.1
III
2


1029
GCA_000756575.1
287
287

Pseudomonas aeruginosa

ATCC 33988
Proteobacteria
JPQQ01000086.1
III
2


1030
GCA_000786565.1
287
287

Pseudomonas aeruginosa

PS3
Proteobacteria
JRGP01000061.1
III
2


1031
GCA_001420245.1
287
287

Pseudomonas aeruginosa

ATCC 33351
Proteobacteria
LJNX01000028.1
III
2


1032
GCA_001444915.1
287
287

Pseudomonas aeruginosa

ATCC 33364
Proteobacteria
LJZK01000128.1
III
2


1033
GCA_001449395.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07066
Proteobacteria
LLLQ01000001.1
III
2


1034
GCA_001449485.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07166
Proteobacteria
LLLV01000015.1
III
2


1035
GCA_001450095.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07245
Proteobacteria
LLNQ01000041.1
III
2


1036
GCA_001450195.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07374
Proteobacteria
LLNY01000068.1
III
2


1037
GCA_001450665.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07224
Proteobacteria
LLMV01000078.1
III
2


1038
GCA_001450705.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07230
Proteobacteria
LLNB01000014.1
III
2


1039
GCA_001450785.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07242
Proteobacteria
LLNN01000029.1
III
2


1040
GCA_001450795.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07246
Proteobacteria
LLNR01000113.1
III
2


1041
GCA_001450825.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07371
Proteobacteria
LLNV01000083.1
III
2


1042
GCA_001450875.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07382
Proteobacteria
LLOG01000021.1
III
2


1043
GCA_001451255.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07388
Proteobacteria
LLOM01000115.1
III
2


1044
GCA_001451265.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07404
Proteobacteria
LLOR01000110.1
III
2


1045
GCA_001451335.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07409
Proteobacteria
LLOW01000068.1
III
2


1046
GCA_001451445.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07422
Proteobacteria
LLPJ01000077.1
III
2


1047
GCA_001451455.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07424
Proteobacteria
LLPL01000049.1
III
2


1048
GCA_001451505.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07426
Proteobacteria
LLPN01000082.1
III
2


1049
GCA_001451865.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07502
Proteobacteria
LLQI01000034.1
III
2


1050
GCA_001451975.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07621
Proteobacteria
LLQS01000023.1
III
2


1051
GCA_001452235.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07642
Proteobacteria
LLRN01000045.1
III
2


1052
GCA_001452325.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07647
Proteobacteria
LLRS01000097.1
III
2


1053
GCA_001452495.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07689
Proteobacteria
LLSJ01000050.1
III
2


1054
GCA_001452565.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07693
Proteobacteria
LLSN01000128.1
III
2


1055
GCA_001453025.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07267
Proteobacteria
LLTY01000116.1
III
2


1056
GCA_001453065.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07272
Proteobacteria
LLUA01000034.1
III
2


1057
GCA_001453235.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07503
Proteobacteria
LLQJ01000004.1
III
2


1058
GCA_001453385.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07629
Proteobacteria
LLRA01000034.1
III
2


1059
GCA_001453415.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07632
Proteobacteria
LLRD01000060.1
III
2


1060
GCA_001453435.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07638
Proteobacteria
LLRJ01000019.1
III
2


1061
GCA_001453545.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07678
Proteobacteria
LLRY01000012.1
III
2


1062
GCA_001453585.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07682
Proteobacteria
LLSC01000012.1
III
2


1063
GCA_001453645.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07686
Proteobacteria
LLSG01000023.1
III
2


1064
GCA_001453665.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07691
Proteobacteria
LLSL01000020.1
III
2


1065
GCA_001453735.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07701
Proteobacteria
LLSV01000117.1
III
2


1066
GCA_001453775.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07710
Proteobacteria
LLTE01000056.1
III
2


1067
GCA_001453905.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07273
Proteobacteria
LLUB01000034.1
III
2


1068
GCA_001454085.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07284
Proteobacteria
LLUK01000105.1
III
2


1069
GCA_001454145.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07291
Proteobacteria
LLUO01000065.1
III
2


1070
GCA_001454325.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07310
Proteobacteria
LLUZ01000067.1
III
2


1071
GCA_001454415.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07317
Proteobacteria
LLVF01000026.1
III
2


1072
GCA_001454725.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07305
Proteobacteria
LLUW01000034.1
III
2


1073
GCA_001454745.1
287
287

Pseudomonas aeruginosa

WH-SGI-V-07311
Proteobacteria
LLVA01000045.1
III
2


1074
GCA_001516245.1
287
287

Pseudomonas aeruginosa

F23197
Proteobacteria
CP008856.1
III
2


1075
GCA_001516325.1
287
287

Pseudomonas aeruginosa

H27930
Proteobacteria
CP008860.1
III
2


1076
GCA_001554535.1
287
287

Pseudomonas aeruginosa

AU12175
Proteobacteria
LRYP01000010.1
III
2


1077
GCA_001554545.1
287
287

Pseudomonas aeruginosa

AU13212
Proteobacteria
LRYQ01000033.1
III
2


1078
GCA_001554585.1
287
287

Pseudomonas aeruginosa

AU15431
Proteobacteria
LRYV01000009.1
III
2


1079
GCA_001554615.1
287
287

Pseudomonas aeruginosa

AU13213
Proteobacteria
LRYS01000006.1
III
2


1080
GCA_001554625.1
287
287

Pseudomonas aeruginosa

AU16960
Proteobacteria
LRYT01000005.1
III
2


1081
GCA_001555135.1
287
287

Pseudomonas aeruginosa

AU7032
Proteobacteria
LRYU01000008.1
III
2


1082
GCA_001555145.1
287
287

Pseudomonas aeruginosa

AU6923
Proteobacteria
LRYO01000006.1
III
2


1083
GCA_001555415.1
287
287

Pseudomonas aeruginosa

AU14820
Proteobacteria
LSAG01000007.1
III
2


1084
GCA_001555425.1
287
287

Pseudomonas aeruginosa

AU23529
Proteobacteria
LSAI01000005.1
III
2


1085
GCA_001555455.1
287
287

Pseudomonas aeruginosa

AU17965
Proteobacteria
LSAH01000005.1
III
2


1086
GCA_001601595.1
287
287

Pseudomonas aeruginosa

105738
Proteobacteria
LOHK01000062.1
III
2


1087
GCA_000647595.1
1339263
287

Pseudomonas aeruginosa 148
148
Proteobacteria
ATAJ01000107.1
III
2


1088
GCA_000481105.1
1402543
287

Pseudomonas aeruginosa BL02
BL02
Proteobacteria
KI518950.1
III
2


1089
GCA_000481085.1
1402544
287

Pseudomonas aeruginosa BL03
BL03
Proteobacteria
KI518942.1
III
2


1090
GCA_000480965.1
1402550
287

Pseudomonas aeruginosa BL09
BL09
Proteobacteria
KI518886.1
III
2


1091
GCA_000480905.1
1402553
287

Pseudomonas aeruginosa BL12
BL12
Proteobacteria
KI518869.1
III
2


1092
GCA_000480885.1
1402554
287

Pseudomonas aeruginosa BL13
BL13
Proteobacteria
KI518852.1
III
2


1093
GCA_000480745.1
1402561
287

Pseudomonas aeruginosa BL20
BL20
Proteobacteria
KI518796.1
III
2


1094
GCA_000481485.1
1402511
287

Pseudomonas aeruginosa BWHPSA011
BWHPSA011
Proteobacteria
KI519089.1
III
2


1095
GCA_000481245.1
1402523
287

Pseudomonas aeruginosa BWHPSA023
BWHPSA023
Proteobacteria
KI519011.1
III
2


1096
GCA_000481145.1
1402528
287

Pseudomonas aeruginosa BWHPSA028
BWHPSA028
Proteobacteria
KI518967.1
III
2


1097
GCA_000520415.1
1402531
287

Pseudomonas aeruginosa BWHPSA039
BWHPSA039
Proteobacteria
KI914530.1
III
2


1098
GCA_000480515.1
1402572
287

Pseudomonas aeruginosa C20
C20
Proteobacteria
KI518719.1
III
2


1099
GCA_000480495.1
1402573
287

Pseudomonas aeruginosa C23
C23
Proteobacteria
KI518716.1
III
2


1100
GCA_000705175.1
1441459
287

Pseudomonas aeruginosa C2773C
C2773C
Proteobacteria
JGZW01000193.1
III
2


1101
GCA_000481945.1
1402488
287

Pseudomonas aeruginosa CF127
CF127
Proteobacteria
KI519290.1
III
2


1102
GCA_000291745.1
1078464
287

Pseudomonas aeruginosa NCMG1179
NCGM1179
Proteobacteria
DF126593.1
III
2


1103
GCA_000342145.1
1285581
287

Pseudomonas aeruginosa PA21_ST175
PA21_ST175
Proteobacteria
AOIH01000011.1
III
2


1104
GCA_000611995.2
1437873
287

Pseudomonas aeruginosa PA99
PA99
Proteobacteria
KK111942.1
III
2


1105
GCA_000408865.1
1009714
287

Pseudomonas aeruginosa PAK
PAK
Proteobacteria
KE137323.1
III
2


1106
GCA_000520195.1
1402581
287

Pseudomonas aeruginosa PS42
PS42
Proteobacteria
KI914450.1
III
2


1107
GCA_000481725.1
1402499
287

Pseudomonas aeruginosa S35004
S35004
Proteobacteria
KI519208.1
III
2


1108
GCA_000568215.1
1443105
287

Pseudomonas aeruginosa SG17M
SG17M
Proteobacteria
JALF01000002.1
III
2


1109
GCA_000467105.1
1215092
43263

Pseudomonas alcaligenes NBRC 14159
NBRC 14159
Proteobacteria
BATI01000047.1
III
2


1110
GCA_000467105.1
1215092
43263

Pseudomonas alcaligenes NBRC 14159
NBRC 14159
Proteobacteria
BATI01000005.1
III
2


1111
GCA_000632535.1
653930
653930

Pseudomonas bauzanensis

W13Z2
Proteobacteria
JFHS01000003.1
III
2


1112
GCA_001586155.1
53408
53408

Pseudomonas citronellolis

P3B5
Proteobacteria
CP014158.1
III
2


1113
GCA_001400695.1
129135
53409

Pseudomonas coronafaciens pv. atropurpurea
ICMP4457
Proteobacteria
LJPS01000041.1
III
2


1114
GCA_001411475.1
1563157
1563157

Pseudomonas endophytica

BSTT44
Proteobacteria
LLWH01000162.1
III
2


1115
GCA_000242115.2
1117958
359110

Pseudomonas extremaustralis 14-3 substr. 14-3b
14-3 substr. 14-3b
Proteobacteria
AHIP01000001.1
III
2


1116
GCA_000876155.1
294
294

Pseudomonas fluorescens

2-79
Proteobacteria
JXCQ01000014.1
III
2


1117
GCA_000952735.1
294
294

Pseudomonas fluorescens

NT0133
Proteobacteria
JYHW01000034.1
III
2


1118
GCA_001542725.1
294
294

Pseudomonas fluorescens

Ps_40
Proteobacteria
LCYC01000002.1
III
2


1119
GCA_000166515.1
746360
294

Pseudomonas fluorescens WH6
WH6
Proteobacteria
CM001025.1
III
2


1120
GCA_001043005.1
122355
122355

Pseudomonas psychrophila

DSM 17535
Proteobacteria
JYKZ01000009.1
III
2


1121
GCA_000367825.1
1227924
303

Pseudomonas putida TRO1
TRO1
Proteobacteria
APBQ01000056.1
III
2


1122
GCA_000478505.2
1203578
1203578

Pseudomonas sp. HPB0071
HPB0071
Proteobacteria
KI517369.1
III
2


1123
GCA_000307775.2
1218352
316

Pseudomonas stutzeri KOS6
KOS6
Proteobacteria
KK020676.1
III
2


1124
GCA_000341615.1
1212548
316

Pseudomonas stutzeri NF13
NF13
Proteobacteria
AOBS01000069.1
III
2


1125
GCA_001293855.1
59511
251701

Pseudomonas syringae pv. maculicola
90_32
Proteobacteria
LGLH01000088.1
III
2


1126
GCA_000735435.1
1005996
575

Raoultella planticola ATCC 33531
ATCC 33531
Proteobacteria
JMPP01000005.1
III
2


1127
GCA_000020265.1
491916
29449

Rhizobium etli CIAT 652
CIAT 652
Proteobacteria
CP001074.1
III
2


1128
GCA_000268285.2
1128399
396

Rhizobium phaseoli Ch24-10
Ch24-10
Proteobacteria
AHJU02000014.1
III
2


1129
GCA_001425605.1
1736380
1736380

Rhizobium sp. Leaf453
Leaf453
Proteobacteria
LMRG01000007.1
III
2


1130
GCA_000967425.1
1125847
1125847

Rhizobium sp. NT-26
NT-26
Proteobacteria
FO082820.1
III
2


1131
GCA_001427345.1
1736473
1736473

Rhizobium sp. Root149
Root149
Proteobacteria
LMGD01000001.1
III
2


1132
GCA_000931365.1
1604021
1604021

Rhizobium sp. UR51a
UR51a
Proteobacteria
JYFU01000014.1
III
2


1133
GCA_001402715.1
1061
1061

Rhodobacter capsulatus

B41
Proteobacteria
LLVU01000015.1
III
2


1134
GCA_001402725.1
1061
1061

Rhodobacter capsulatus

A52
Proteobacteria
LLVV01000015.1
III
2


1135
GCA_000521785.1
1449350
93683

Roseivivax halodurans JCM 10272
JCM 10272
Proteobacteria
JALZ01000004.1
III
2


1136
GCA_000961715.1
1629709
1629709

Roseovarius sp. BRH_c41

Proteobacteria
LADY01000060.1
III
2


1137
GCA_000442315.1
1123069
295419

Rubellimicrobium thermophilum DSM 16684
DSM 16684
Proteobacteria
KE557322.1
III
2


1138
GCA_001570325.1
28901
28901

Salmonella enterica

NGUA40
Proteobacteria
BCPM01000156.1
III
2


1139
GCA_001570345.1
28901
28901

Salmonella enterica

NGUA41
Proteobacteria
BCPN01000199.1
III
2


1140
GCA_000806705.1
59201
28901

Salmonella enterica subsp. enterica
CFSAN024770
Proteobacteria
JWQJ01000002.1
III
2


1141
GCA_000806725.1
59201
28901

Salmonella enterica subsp. enterica
CFSAN024771
Proteobacteria
JWQI01000002.1
III
2


1142
GCA_000487735.1
1194156
28901

Salmonella enterica subsp. enterica serovar Havana str.
CFSAN001082
Proteobacteria
APAH01000409.1
III
2






CFSAN001082


1143
GCA_001187365.1
595
28901

Salmonella enterica subsp. enterica serovar Infantis
Sal280
Proteobacteria
LFGW01000205.1
III
2


1144
GCA_000818075.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A
CMCC 50973
Proteobacteria
CP009049.1
III
2


1145
GCA_000818115.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A
CMCC 50503
Proteobacteria
CP009559.1
III
2


1146
GCA_000983135.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCTC01000001.1
III
2


1147
GCA_000983155.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCTP01000001.1
III
2


1148
GCA_000983175.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCLD01000002.1
III
2


1149
GCA_000983195.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCTT01000001.1
III
2


1150
GCA_000983215.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCVA01000001.1
III
2


1151
GCA_000983235.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCUS01000001.1
III
2


1152
GCA_000983255.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCNZ01000001.1
III
2


1153
GCA_000983275.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCVV01000001.1
III
2


1154
GCA_000983295.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCLR01000001.1
III
2


1155
GCA_000983315.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CGIE01000004.1
III
2


1156
GCA_000983335.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCNY01000001.1
III
2


1157
GCA_000983355.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCUY01000004.1
III
2


1158
GCA_000983375.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCLN01000001.1
III
2


1159
GCA_000983395.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCTO01000001.1
III
2


1160
GCA_000983415.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCUE01000001.1
III
2


1161
GCA_000983435.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCSP01000001.1
III
2


1162
GCA_000983485.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCLS01000001.1
III
2


1163
GCA_000983505.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCSN01000001.1
III
2


1164
GCA_000983535.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCVL01000001.1
III
2


1165
GCA_000983565.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCUC01000004.1
III
2


1166
GCA_000983595.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCNT01000003.1
III
2


1167
GCA_000983625.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCUP01000001.1
III
2


1168
GCA_000983645.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCLA01000004.1
III
2


1169
GCA_000983685.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCLI01000001.1
III
2


1170
GCA_000983705.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCKR01000004.1
III
2


1171
GCA_000983735.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCTA01000001.1
III
2


1172
GCA_000983755.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCLQ01000001.1
III
2


1173
GCA_000983775.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCSR01000004.1
III
2


1174
GCA_000983795.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCKX01000001.1
III
2


1175
GCA_000983835.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCLZ01000001.1
III
2


1176
GCA_000983855.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCUI01000001.1
III
2


1177
GCA_000983875.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCTL01000001.1
III
2


1178
GCA_000983895.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCUH01000001.1
III
2


1179
GCA_000983915.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCUJ01000001.1
III
2


1180
GCA_000983935.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCUV01000001.1
III
2


1181
GCA_000983955.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCUM01000001.1
III
2


1182
GCA_000983975.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCLM01000001.1
III
2


1183
GCA_000983995.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCMD01000001.1
III
2


1184
GCA_000984025.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCTI01000001.1
III
2


1185
GCA_000984045.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCVG01000001.1
III
2


1186
GCA_000984075.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCSV01000001.1
III
2


1187
GCA_000984095.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCLX01000001.1
III
2


1188
GCA_000984115.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCUD01000001.1
III
2


1189
GCA_000984135.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCUX01000001.1
III
2


1190
GCA_000984175.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCTZ01000003.1
III
2


1191
GCA_000984195.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCML01000001.1
III
2


1192
GCA_000984215.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCTN01000001.1
III
2


1193
GCA_000984235.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCUB01000001.1
III
2


1194
GCA_000984255.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCUR01000001.1
III
2


1195
GCA_000984275.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCVD01000005.1
III
2


1196
GCA_000984295.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCKT01000001.1
III
2


1197
GCA_000984315.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCUO01000002.1
III
2


1198
GCA_000984335.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCME01000001.1
III
2


1199
GCA_000984355.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCVJ01000005.1
III
2


1200
GCA_000984375.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCSY01000004.1
III
2


1201
GCA_000984395.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCUU01000001.1
III
2


1202
GCA_000984415.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCMA01000001.1
III
2


1203
GCA_000984435.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCSU01000001.1
III
2


1204
GCA_000984455.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCKS01000001.1
III
2


1205
GCA_000984475.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCVF01000001.1
III
2


1206
GCA_000984495.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCST01000001.1
III
2


1207
GCA_000984515.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCKU01000001.1
III
2


1208
GCA_000984535.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCUL01000001.1
III
2


1209
GCA_000984555.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCKY01000002.1
III
2


1210
GCA_000984575.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCUG01000001.1
III
2


1211
GCA_000984595.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCLG01000001.1
III
2


1212
GCA_000984615.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCLO01000005.1
III
2


1213
GCA_000984635.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCTM01000001.1
III
2


1214
GCA_000984655.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCKZ01000001.1
III
2


1215
GCA_000984675.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCTJ01000001.1
III
2


1216
GCA_000984695.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCSW01000001.1
III
2


1217
GCA_000984715.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCVH01000001.1
III
2


1218
GCA_000984735.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCKW01000001.1
III
2


1219
GCA_000984755.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCTE01000001.1
III
2


1220
GCA_000984795.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCLJ01000001.1
III
2


1221
GCA_000984815.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCSX01000002.1
III
2


1222
GCA_000984835.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCTW01000001.1
III
2


1223
GCA_000984855.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCLU01000001.1
III
2


1224
GCA_000984875.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCTK01000001.1
III
2


1225
GCA_000984895.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCNU01000001.1
III
2


1226
GCA_000984915.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCNV01000001.1
III
2


1227
GCA_000984935.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCLW01000001.1
III
2


1228
GCA_000984955.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCLY01000001.1
III
2


1229
GCA_000984975.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCLL01000004.1
III
2


1230
GCA_000984995.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCSM01000001.1
III
2


1231
GCA_000985015.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCUF01000001.1
III
2


1232
GCA_000985035.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCLT01000001.1
III
2


1233
GCA_000985055.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCMC01000001.1
III
2


1234
GCA_000985075.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCUZ01000001.1
III
2


1235
GCA_000985095.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCLF01000001.1
III
2


1236
GCA_000985115.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCTU01000001.1
III
2


1237
GCA_000985135.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCUN01000001.1
III
2


1238
GCA_000985155.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCLE01000001.1
III
2


1239
GCA_000985175.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCTR01000001.1
III
2


1240
GCA_000985195.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCUW01000001.1
III
2


1241
GCA_000985215.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCLP01000001.1
III
2


1242
GCA_000985235.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCLK01000001.1
III
2


1243
GCA_000985255.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCSS01000001.1
III
2


1244
GCA_000985275.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCSO01000001.1
III
2


1245
GCA_000985295.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCUT01000001.1
III
2


1246
GCA_000985315.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCTQ01000001.1
III
2


1247
GCA_000985335.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCVC01000001.1
III
2


1248
GCA_000985355.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCVE01000001.1
III
2


1249
GCA_000985375.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCTG01000001.1
III
2


1250
GCA_000985395.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCSL01000001.1
III
2


1251
GCA_000985415.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCVB01000003.1
III
2


1252
GCA_000985435.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCUA01000001.1
III
2


1253
GCA_000985455.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCNX01000001.1
III
2


1254
GCA_000985475.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCSZ01000004.1
III
2


1255
GCA_000985495.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCTD01000002.1
III
2


1256
GCA_000985515.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCVI01000001.1
III
2


1257
GCA_000985535.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCUK01000001.1
III
2


1258
GCA_000985555.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCTX01000003.1
III
2


1259
GCA_000985575.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCTF01000001.1
III
2


1260
GCA_000985595.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCUQ01000001.1
III
2


1261
GCA_000985615.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCMF01000001.1
III
2


1262
GCA_000985655.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCTY01000001.1
III
2


1263
GCA_000985675.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCKV01000001.1
III
2


1264
GCA_000985695.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCTV01000001.1
III
2


1265
GCA_000985715.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCVK01000001.1
III
2


1266
GCA_000985735.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCMB01000001.1
III
2


1267
GCA_000985755.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCLH01000001.1
III
2


1268
GCA_000985775.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCSQ01000001.1
III
2


1269
GCA_000985795.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCTH01000001.1
III
2


1270
GCA_000985815.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCSK01000001.1
III
2


1271
GCA_000985835.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCNW01000001.1
III
2


1272
GCA_000985855.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A

Proteobacteria
CCTB01000001.1
III
2


1273
GCA_001045395.1
54388
28901

Salmonella enterica subsp. enterica serovar Paratyphi A
CMCC50093
Proteobacteria
CP011967.1
III
2


1274
GCA_000026565.1
554290
28901

Salmonella enterica subsp. enterica serovar Paratyphi A str.
AKU12601
Proteobacteria
FM200053.1
III
2






AKU_12601


1275
GCA_000486725.1
941189
28901

Salmonella enterica subsp. enterica serovar Paratyphi A str.
ATCC 11511
Proteobacteria
AOYH01000034.1
III
2






ATCC 11511


1276
GCA_000011885.1
295319
28901

Salmonella enterica subsp. enterica serovar Paratyphi A str.
ATCC 9150
Proteobacteria
CP000026.1
III
2






ATCC 9150


1277
GCA_000411815.1
1072568
28901

Salmonella enterica subsp. enterica serovar Paratyphi A str.
GXS2268
Proteobacteria
AFYX01000025.1
III
2






GXS2268


1278
GCA_000411795.1
1072569
28901

Salmonella enterica subsp. enterica serovar Paratyphi A str.
GZ9A00052
Proteobacteria
AFYW01000030.1
III
2






GZ9A00052


1279
GCA_000411835.1
1072570
28901

Salmonella enterica subsp. enterica serovar Paratyphi A str. JX05-
JX05-19
Proteobacteria
AFYY01000027.1
III
2






19


1280
GCA_001448825.1
1243588
28901

Salmonella enterica subsp. enterica serovar Paratyphi A str.
SA19950809
Proteobacteria
LHTE01000005.1
III
2






SA19950809


1281
GCA_000335835.1
687914
28901

Salmonella enterica subsp. enterica serovar Rissen str. 150
150
Proteobacteria
AHUI01000053.1
III
2


1282
GCA_000231685.2
913082
28901

Salmonella enterica subsp. enterica serovar Senftenberg str. A4-
A4-543
Proteobacteria
AFCU01002067.1
III
2






543


1283
GCA_000486525.1
930772
28901

Salmonella enterica subsp. enterica serovar Senftenberg str.
ATCC 43845
Proteobacteria
AOXX01000100.1
III
2






ATCC 43845


1284
GCA_001409135.1
57743
28901

Salmonella enterica subsp. enterica serovar Weltevreden
2511STDY5462388
Proteobacteria
LN890518.1
III
2


1285
GCA_001409155.1
57743
28901

Salmonella enterica subsp. enterica serovar Weltevreden
2511STDY5712384
Proteobacteria
LN890522.1
III
2


1286
GCA_001409175.1
57743
28901

Salmonella enterica subsp. enterica serovar Weltevreden
2511STDY5712385
Proteobacteria
LN890524.1
III
2


1287
GCA_001409195.1
57743
28901

Salmonella enterica subsp. enterica serovar Weltevreden
2511STDY5462413
Proteobacteria
LN890520.1
III
2


1288
GCA_000230505.1
936157
28901

Salmonella enterica subsp. enterica serovar Weltevreden str.
2007-60-3289-1
Proteobacteria
FR775224.1
III
2






2007-60-3289-1


1289
GCA_000171495.1
465518
28901

Salmonella enterica subsp. enterica serovar Weltevreden str.
HI_N05-537
Proteobacteria
ABFF01000010.1
III
2






HI_N05-537


1290
GCA_001241965.1
1160769
28901

Salmonella enterica subsp. enterica serovar Worthingtor
CVM N45406
Proteobacteria
LHGK01000019.1
III
2


1291
GCA_001242245.1
1160769
28901

Salmonella enterica subsp. enterica serovar Worthingtor
CVM N45931
Proteobacteria
LHGV01000001.1
III
2


1292
GCA_001243275.1
1160769
28901

Salmonella enterica subsp. enterica serovar Worthingtor
CVM N46835
Proteobacteria
LHIL01000018.1
III
2


1293
GCA_001247285.1
1160769
28901

Salmonella enterica subsp. enterica serovar Worthingtor
CVM N51304
Proteobacteria
LHOK01000001.1
III
2


1294
GCA_001479505.1
1160769
28901

Salmonella enterica subsp. enterica serovar Worthingtor
CVM N32773
Proteobacteria
JYWH01000045.1
III
2


1295
GCA_001480165.1
1160769
28901

Salmonella enterica subsp. enterica serovar Worthingtor
CVM N40374
Proteobacteria
JYYI01000001.1
III
2


1296
GCA_000486265.1
1173940
28901

Salmonella enterica subsp. enterica serovar Worthington str.
ATCC 9607
Proteobacteria
AOXK01000084.1
III
2






ATCC 9607


1297
GCA_001034405.1
615
615

Serratia marcescens

UCI88
Proteobacteria
KQ089789.1
III
2


1298
GCA_001537045.1
615
615

Serratia marcescens

2880STDY5682914
Proteobacteria
FCMH01000002.1
III
2


1299
GCA_001537345.1
615
615

Serratia marcescens

2880STDY5682872
Proteobacteria
FCHZ01000003.1
III
2


1300
GCA_000633715.1
1445864
615

Serratia marcescens BIDMC 80
BIDMC 80
Proteobacteria
KK214321.1
III
2


1301
GCA_000163595.1
667129
618

Serratia odorifera DSM 4582
DSM 4582
Proteobacteria
GG753567.1
III
2


1302
GCA_000743355.1
1524467
1524467

Serratia sp. Ag1
Ag1
Proteobacteria
JQEI01000016.1
III
2


1303
GCA_000743365.1
1532556
1532556

Serratia sp. Ag2
Ag2
Proteobacteria
JQEJ01000056.1
III
2


1304
GCA_000203935.1
94122
94122

Shewanella sp. ANA-3
ANA-3
Proteobacteria
CP000469.1
III
2


1305
GCA_000262305.1
630626
563

Shimwellia blattae DSM 4481 = NBRC 105725
DSM 4481
Proteobacteria
CP001560.1
III
2


1306
GCA_000327265.1
630626
563

Shimwellia blattae DSM 4481 = NBRC 105725
NBRC 105725
Proteobacteria
BAHA01000013.1
III
2


1307
GCA_000018545.1
394
380

Sinorhizobium fredii NGR234
NGR234
Proteobacteria
CP001389.1
III
2


1308
GCA_000067165.1
448385
56

Sorangium cellulosum So ce56
So ce 56
Proteobacteria
AM746676.1
III
2


1309
GCA_000421925.1
1346790
420233

Sphingobium chinhatense IP26
IP26
Proteobacteria
AUDA01000025.1
III
2


1310
GCA_001005725.1
56193
56193

Sphingobium chungbukense

DJ77
Proteobacteria
LBIC01000001.1
III
2


1311
GCA_000382885.1
1301087
332056

Sphingobium japonicum BiD32
BiD32
Proteobacteria
CAVK010000098.1
III
2


1312
GCA_000633575.2
1450518
440518

Sphingobium lucknowense F2
F2
Proteobacteria
JANF02000056.1
III
2


1313
GCA_001421635.1
1735692
1735692

Sphingomonas sp. Leaf25
Leaf25
Proteobacteria
LMKU01000030.1
III
2


1314
GCA_001399755.1
381306
381306

Thiohalorhabdus denitrificans

HL 19
Proteobacteria
LJCP01000010.1
III
2


1315
GCA_001425205.1
1736530
1736530

Variovorax sp. Root411
Root411
Proteobacteria
LMDW01000005.1
III
2


1316
GCA_001010935.1
663
663

Vibrio alginolyticus

V2
Proteobacteria
LCSG01000013.1
III
2


1317
GCA_000154025.1
410291
680

Vibrio campbellii HY01
HY01
Proteobacteria
DS179487.1
III
2


1318
GCA_000785575.1
701175
701175

Vibrio caribbeanicus

T14
Proteobacteria
JRWR01000004.1
III
2


1319
GCA_000736945.1
666
666

Vibrio cholerae

571-88
Proteobacteria
JIDO01000026.1
III
2


1320
GCA_000737005.1
666
666

Vibrio cholerae

234-93
Proteobacteria
JMBO01000023.1
III
2


1321
GCA_000279285.1
991946
666

Vibrio cholerae HE-45
HE-45
Proteobacteria
ALED01000027.1
III
2


1322
GCA_000348345.2
1095649
666

Vibrio cholerae O1 str. EM-1676A
EM-1676A
Proteobacteria
KB662755.1
III
2


1323
GCA_000152465.2
345075
666

Vibrio cholerae V51
V51
Proteobacteria
KQ257379.1
III
2


1324
GCA_000467185.1
1219080
252583

Vibrio ezurae NBRC 102218
NBRC 102218
Proteobacteria
BATM01000020.1
III
2


1325
GCA_001262735.1
669
669

Vibrio harveyi

VH2
Proteobacteria
LGYS01000041.1
III
2


1326
GCA_000786865.1
670
670

Vibrio parahaemolyticus

09.5357
Proteobacteria
JTGT01000603.1
III
2


1327
GCA_001270155.1
670
670

Vibrio parahaemolyticus

S439-9
Proteobacteria
LFZA01000109.1
III
2


1328
GCA_000808535.1
379097
379097

Vibrio sinaloensis

AD048
Proteobacteria
JWLV01000045.1
III
2


1329
GCA_001597935.1
1763885
1763885

Vibrio sp. 2538-88
2538-88
Proteobacteria
LOBR01000072.1
III
2


1330
GCA_000305755.2
992012
992012

Vibrio sp. HENC-03
HENC-03
Proteobacteria
JH976122.1
III
2


1331
GCA_001048635.1
1507980
1507980

Vibrio sp. J2-31
J2-31
Proteobacteria
CCKO01000056.1
III
2


1332
GCA_000091465.1
575788
212663

Vibrio tasmaniensis LGP32
LGP32
Proteobacteria
FM954972.2
III
2


1333
GCA_001541335.1
1194427
1194427

Vibrio toranzoniae

Vb 10.8
Proteobacteria
LMXU01000013.1
III
2


1334
GCA_001274855.1
170661
170661

Vibrio xuii

DSM 17185
Proteobacteria
LHPK01000025.1
III
2


1335
GCA_001131685.1
634
634

Yersinia bercovieri

127/84
Proteobacteria
CQBU01000002.1
III
2


1336
GCA_001219605.1
630
630

Yersinia enterocolitica

YE04/02
Proteobacteria
CTKX01000003.1
III
2


1337
GCA_001220145.1
630
630

Yersinia enterocolitica

YE38/03
Proteobacteria
CTKL01000007.1
III
2


1338
GCA_001319585.1
29484
29484

Yersinia frederiksenii

38/83
Proteobacteria
CGCC01000006.1
III
2


1339
GCA_001142305.1
419257
419257

Yersinia massiliensis

24070
Proteobacteria
CQBH01000001.1
III
2


1340
GCA_001319885.1
633
633

Yersinia pseudotuberculosis

OK6088
Proteobacteria
CGGM01000007.1
III
2


1341
GCA_000737165.1
29486
29486

Yersinia ruckeri

37551
Proteobacteria
JPF001000008.1
III
2


1342
GCA_000964565.1
29486
29486

Yersinia ruckeri

Big Creek 74
Proteobacteria
CP011078.1
III
2


1343
GCA_000239335.1
1002368
158877

Yokenella regensburgei ATCC 43003
ATCC 43003
Proteobacteria
JH417862.1
III
2










(Part B)


























M



Q



U









DruA



DruB



DruC



J
K
L
protein
N
O
P
protein
R
S
T
protein
V
W
X



DruA
PRT SEQ
DNA SEQ
length
DruB
PRT SEQ
DNA SEQ
length
DruC
PRT SEQ
DNA SEQ
length
DruD
PRT SEQ
DNA SEQ


1
protein_accession
ID NO:
ID NO:
(aa)
protein_accession
ID NO:
ID NO:
(aa)
protein_accession
ID NO:
ID NO:
(aa)
protein_accession
ID NO:
ID NO:





2




CEP95570.1
23934
27163
531
CEP95571.1
23935
27164
669
CEP95572.1
23936
27165


3
KUO96130.1
23938
27167
411
KUO96131.1
23939
27168
468
KUO96132.1
23940
27169
604
KUO96133.1
23941
27170


4




GAC90451.1
23943
27172
504
GAC90452.1
23944
27173
659
GAC90453.1
23945
27174


5
KQT61309.1
23947
27176
678








KQT61312.1
23948
27177


6
KQT62611.1
23950
27179
678








KQT62614.1
23951
27180


7




KMN72587.1
23953
27182
502
KMN72586.1
23954
27183
662
KMN72585.1
23955
27184


8




EJQ91443.1
23957
27186
502
EJQ91444.1
23958
27187
662
EJQ91445.1
23959
27188


9




CRK83009.1
23961
27190
481
CRK83010.1
23962
27191
640
CRK83011.1
23963
27192


10




KEF29420.1
23965
27194
519




KEF29418.1
23966
27195


11




ETO96271.1
23968
27197
513




ETO96375.1
23969
27198


12
ALK08980.1
23971
27200
418








ALK08978.1
23972
27201


13
CUU41641.1
23974
27203
418








CUU41639.1
23975
27204


14
KGC93367.1
23977
27206
400
KGC93228.1
23978
27207
505
KGC93290.1
23979
27208
854
KGC93264.1
23980
27209


15
KGV74617.1
23982
27211
405








KGV74230.1
23983
27212


16
EDO89776.1
23985
27214
400
EDO89775.1
23986
27215
523
EDO89774.1
23987
27216
858


17
AJX60919.1
23989
27218
400
AJX61068.1
23990
27219
457
AJX59269.1
23991
27220
858
AJX59244.1
23992
27221


18
AIP62558.1
23994
27223
400
AJT48645.1
23995
27224
211


19
KVO65551.1
23997
27226
400
KVO65550.1
23998
27227
211
KVO65549.1
23999
27228
841


20
KVO87083.1
24001
27230
400
KVO87084.1
24002
27231
211


21
CDI04329.1
24004
27233
401








CDI04327.1
24005
27234


22




KPA09471.1
24007
27236
522
KPA09470.1
24008
27237
594
KPA09469.1
24009
27238


23








KHD06506.1
24011
27240
632
KHD06507.1
24012
27241


24
KJH65670.1
24014
27243
409
KJH65671.1
24015
27244
555
KJH65672.1
24016
27245
623
KJH65673.1
24017
27246


25




CDM70052.1
24019
27248
531
CDM70054.1
24020
27249
299
CDM70055.1
24021
27250


26








KEI16341.1
24023
27252
674
KEI16342.1
24024
27253


27




EGB92907.1
24026
27255
478
EGB92908.1
24027
27256
483
EGB92909.1
24028
27257


28




ACL18694.1
24030
27259
479




ACL18696.1
24031
27260


29




ACV64027.1
24033
27262
480




ACV64029.1
24034
27263


30




AMC93642.1
24036
27265
481




AMC93640.1
24037
27266


31
KHG78165.1
24039
27268
404
KHG78164.1
24040
27269
548
KHG78163.1
24041
27270
627
KHG78162.1
24042
27271


32
KHI73843.1
24044
27273
404
KHI73842.1
24045
27274
548
KHI73841.1
24046
27275
627
KHI73840.1
24047
27276


33








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58








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97








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106
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108
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109
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110
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111
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112
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652








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118
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981


982


983


984


985


986


987


988


989


990


991


992


993


994


995


996


997


998


999


1000


1001


1002


1003


1004


1005


1006


1007


1008


1009


1010


1011


1012


1013


1014


1015


1016


1017


1018


1019


1020


1021


1022


1023


1024


1025


1026


1027


1028


1029


1030


1031


1032


1033


1034


1035


1036


1037


1038


1039


1040


1041


1042


1043


1044


1045


1046


1047


1048


1049


1050


1051


1052


1053


1054


1055


1056


1057


1058


1059


1060


1061


1062


1063


1064


1065


1066


1067


1068


1069


1070


1071


1072


1073


1074


1075


1076


1077


1078


1079


1080


1081


1082


1083


1084


1085


1086


1087


1088


1089


1090


1091


1092


1093


1094


1095


1096


1097


1098


1099


1100


1101


1102


1103


1104


1105


1106


1107


1108


1109


1110


1111


1112


1113


1114


1115


1116


1117


1118


1119


1120


1121


1122


1123


1124


1125


1126


1127


1128


1129


1130


1131


1132


1133


1134


1135


1136


1137


1138


1139


1140


1141


1142


1143


1144


1145


1146


1147


1148


1149


1150


1151


1152


1153


1154


1155


1156


1157


1158


1159


1160


1161


1162


1163


1164


1165


1166


1167


1168


1169


1170


1171


1172


1173


1174


1175


1176


1177


1178


1179


1180


1181


1182


1183


1184


1185


1186


1187


1188


1189


1190


1191


1192


1193


1194


1195


1196


1197


1198


1199


1200


1201


1202


1203


1204


1205


1206


1207


1208


1209


1210


1211


1212


1213


1214


1215


1216


1217


1218


1219


1220


1221


1222


1223


1224


1225


1226


1227


1228


1229


1230


1231


1232


1233


1234


1235


1236


1237


1238


1239


1240


1241


1242


1243


1244


1245


1246


1247


1248


1249


1250


1251


1252


1253


1254


1255


1256


1257


1258


1259


1260


1261


1262


1263


1264


1265


1266


1267


1268


1269


1270


1271


1272


1273


1274


1275


1276


1277


1278


1279


1280


1281


1282


1283


1284


1285


1286


1287


1288


1289


1290


1291


1292


1293


1294


1295


1296


1297


1298


1299


1300


1301


1302


1303


1304


1305


1306


1307


1308


1309


1310


1311


1312


1313


1314


1315


1316


1317


1318


1319


1320


1321


1322


1323


1324


1325


1326


1327


1328


1329


1330


1331


1332


1333


1334


1335


1336


1337


1338


1339


1340


1341


1342


1343











(Part C)
























Y



AC



AG



AK





DruD



DruE



DruM



DruF



protein
Z
AA
AB
protein
AD
AE
AF
protein
AH
AI
AJ
protein
AL
AM



length
DruE
PRT SEQ
DNA SEQ
length
DruM
PRT SEQ
DNA SEQ
length
DruF
PRT SEQ
DNA SEQ
length
DruG
PRT SEQ


1
(aa)
protein_accession
ID NO:
ID NO:
(aa)
protein_accession
ID NO:
ID NO:
(aa)
protein_accession
ID NO:
ID NO:
(aa)
protein_accession
ID NO:





2

CEP95573.1
23937
27166
1753


3
363
KUO96134.1
23942
27171
1851


4
312
GAC90454.1
23946
27175
1784


5
358
KQT61311.1
23949
27178
1847


6
358
KQT62613.1
23952
27181
1847


7
316
KMN72584.1
23956
27185
1775


8
316
EJQ91446.1
23960
27189
1777


9
292
CRK83012.1
23964
27193
1752


10
333
KEF29417.1
23967
27196
1743


11
330
ETO96255.1
23970
27199
1747


12
360
ALK08977.1
23973
27202
1854


13
360
CUU41638.1
23976
27205
1854


14
260
KGC93324.1
23981
27210
1752


15
359
KGV75903.1
23984
27213
1856


16

EDO89777.1
23988
27217
1787


17
260
AJX60137.1
23993
27222
1752


18

AIP62511.1
23996
27225
1752


19

KVO65552.1
24000
27229
1752


20

KVO87082.1
24003
27232
1753


21
359
CDI04326.1
24006
27235
1842


22
351
KPA09466.1
24010
27239
1795


23
359
KHD06508.1
24013
27242
1796


24
350
KJH65674.1
24018
27247
1843


25
340
CDM70056.1
24022
27251
1761


26
352
KEI16343.1
24025
27254
1767


27
342
EGB92910.1
24029
27258
1738


28
339
ACL18697.1
24032
27261
1740


29
338
ACV64030.1
24035
27264
1741


30
341
AMC93639.1
24038
27267
1739


31
347
KHG78161.1
24043
27272
1836


32
347
KHI73839.1
24048
27277
1836


33
347
KHI66628.1
24051
27280
1836


34
347
KHI48868.1
24056
27285
1836


35
347
KHI24186.1
24060
27289
1836


36
347
KMV42880.1
24065
27294
1836


37
347
KQJ50743.1
24070
27299
1836


38
347
ALN47014.1
24075
27304
1836


39
347
KSY14480.1
24080
27309
1836


40
347
KXR68575.1
24085
27314
1836


41
347
KIO85003.1
24090
27319
1836


42
347
EQS48047.1
24095
27324
1836


43
347
EQO85270.1
24100
27329
1836


44
347
EQO74909.1
24105
27334
1836


45
347
EYT06142.1
24110
27339
1836


46
347
EQV41650.1
24115
27344
1836


47
347
ELC24072.1
24120
27349
1836


48
347
ELH39088.1
24125
27354
1836


49
347
EOV00815.1
24130
27359
1836


50
347
EOU57730.1
24135
27364
1836


51
347
ELE47062.1
24140
27369
1836


52
347
ELE76870.1
24145
27374
1836


53
347
EU64787.1
24150
27379
1836


54
347
EOV85621.1
24155
27384
1836


55
347
ELE86434.1
24160
27389
1836


56
347
EWY52042.1
24165
27394
1836


57
260
EFK51867.1
24170
27399
1836


58
260
EGU96603.1
24173
27402
1836


59
347
EMZ39753.1
24178
27407
1836


60
347
EGI33544.1
24182
27411
1836


61
347
EQX30248.1
24187
27416
1836


62
347
EQZ12281.1
24192
27421
1836


63
347
ERA40833.1
24197
27426
1836


64
338
CDA97614.1
24201
27430
1732


65
317
KFX30968.1
24205
27434
1786


66
317
KYD25146.1
24209
27438
1786


67
317
KLR73617.1
24212
27441
1786


68
317
ADU94759.1
24216
27445
1787


69
317
ACX76986.1
24220
27449
1787


70
317
KFL17493.1
24224
27453
1786


71
317
KFX35841.1
24228
27457
1786


72
365
EDQ34543.1
24231
27460
1848


73
360
KRB96439.1
24234
27463
1851


74
370
AGK57209.1
24237
27466
1846


75
342
KMV96846.1
24242
27471
1303


76
354
ESN04441.1
24246
27475
1846


77
351
ABX40975.1
24249
27478
1759


78
338
EOS72128.1
24253
27482
1728


79

EDM25763.1
24256
27485
1813


80
356
ESY17005.1
24259
27488
1853


81
346
KUK70365.1
24263
27492
1774


82
343
EHQ36505.1
24267
27496
1763


83
347
KKG83060.1
24271
27500
1775


84
362
EQM86810.1
24274
27503
1857


85
363
AU18570.1
24277
27506
1858


86
363
GAD34406.1
24280
27509
1858


87
360
ADJ29891.1
24283
27512
1849


88
308
KMP10707.1
24286
27515
1844


89
354
EGY00301.1
24289
27518
1849


90
349
EPY09172.1
24293
27522
1746


91
352
ACX63340.1
24297
27526
1759


92
347
KHN90282.1
24302
27531
1836


93
354
KGA32596.1
24305
27534
1848


94
339
AJQ25680.1
24309
27538
1735


95
352
CUH95395.1
24313
27542
1734


96

KSF97362.1
24317
27546
1840


97
346
KSL25394.1
24320
27549
1841


98

KSO15705.1
24324
27553
1840


99
353
BAR67381.2
24329
27558
1844


100
289
KAJ21864.1
24333
27562
1802


101

AGI81183.1
24336
27565
1844


102
343
ERY34408.1
24341
27570
1840


103
353
EZP23713.1
24346
27575
1844


104
345
ERV69459.1
24351
27580
1840


105

EQM83906.1
24355
27584
1840


106
344
AJP52376.1
24360
27589
1848


107
344
EST14434.1
24365
27594
1845


108
343
ENY74502.1
24370
27599
1840


109
353
KWR75282.1
24373
27602
1844


110
344
KFE46440.1
24378
27607
1851


111
371
AMP72545.1
24383
27612
1853


112
361
KQQ11278.1
24386
27615
1860


113
356
KQS82594.1
24389
27618
1849


114
356
KQS78957.1
24392
27621
1849


115
345
AKE89963.1
24395
27624
2149


116
347
EME23885.1
24398
27627
1805


117
364
CDZ88162.1
24402
27631
2149


118
355
ETI62662.1
24405
27634
1847


119
363
EFL24975.1
24408
27637
1860


120
332
AGA58892.1
24411
27640
1735


121
343
EEY51342.1
24416
27645
1831


122
304
AIL69853.1
24421
27650
1831


123
347
CNL41877.1
24426
27655
1835


124

CUI54792.1
24427
27656
1891
CUI54813.1
24428
27657
382
CUI54751.1
24429
27658
659
CUI54773.1
24430


125

KUL31266.1
24431
27660
1778
KUL31262.1
24432
27661
427
KUL31267.1
24433
27662
1018


126

AGL13716.1
24434
27663
1783
AGL13720.1
24435
27664
354
AGL13717.1
24436
27665
1021


127

EGP54151.1
24437
27666
1957
EGP54154.1
24438
27667
614
EGP54153.1
24439
27668
822
EGP54152.1
24440


128

ABW19397.1
24441
27670
1903
ABW19395.1
24442
27671
329
ABW19399.1
24443
27672
683


129

ALO16789.1
24444
27673
2026
ALO16791.1
24445
27674
390
ALO16788.1
24446
27675
948


130

EIG62888.1
24447
27676
1953
EIG62885.1
24448
27677
409
EIG62886.1
24449
27678
852
EIG62887.1
24450


131

ADL01345.1
24451
27680
1954
ADL01343.1
24452
27681
377
ADL01347.1
24453
27682
718
ADL01346.1
24454


132

EEE02134.1
24455
27684
1968




EEE02132.1
24456
27685
927
EEE02133.1
24457


133

KWF28731.1
24458
27687
1948
KWF28730.1
24459
27688
391
KWF28733.1
24460
27689
892
KWF28732.1
24461


134

KQR76945.1
24462
27691
1956
KQR76951.1
24463
27692
382
KQR76943.1
24464
27693
844
KQR76944.1
24465


135

KVO29147.1
24466
27695
1947
KVO29144.1
24467
27696
385




KVO29146.1
24468


136

KVP15001.1
24469
27698
1947
KVP14998.1
24470
27699
385




KVP15000.1
24471


137

KVU67372.1
24472
27701
1948
KVU67373.1
24473
27702
391
KVU67370.1
24474
27703
892
KVU67371.1
24475


138

KWH22082.1
24476
27705
1948
KWH22081.1
24477
27706
391
KWH22084.1
24478
27707
892
KWH22083.1
24479


139

KWO52778.1
24480
27709
1947
KWO52775.1
24481
27710
385




KWO52777.1
24482


140

KQY41878.1
24483
27712
1833
KQY41875.1
24484
27713
436
KQY41880.1
24485
27714
692


141

ABP36100.1
24486
27715
1887
ABP36104.1
24487
27716
467
ABP36098.1
24488
27717
581


142

KXH85115.1
24489
27718
2009
KXH85112.1
24490
27719
377
KXH85116.1
24491
27720
948


143

ALD78636.1
24492
27721
1982
ALD78633.1
24493
27722
361
ALD78634.1
24494
27723
921
ALD78635.1
24495


144

EEH92508.2
24496
27725
1947
EEH92511.1
24497
27726
411
EEH92510.1
24498
27727
854
EEH92509.2
24499


145

GAL44508.1
24500
27729
1946
GAL44505.1
24501
27730
395
GAL44506.1
24502
27731
852
GAL44507.1
24503


146

KUO74508.1
24504
27733
1914
KUO74511.1
24505
27734
378
KUO74506.1
24506
27735
675


147

AMP07507.1
24507
27736
1971
AMP07506.1
24508
27737
379
AMP07509.1
24509
27738
860
AMP07508.1
24510


148

AIF40724.1
24511
27740
1809
AIF40718.1
24512
27741
331
AIF40722.1
24513
27742
683


149

ACT06326.1
24514
27743
1948
ACT06329.1
24515
27744
411
ACT06328.1
24516
27745
853
ACT06327.1
24517


150

KLF19647.1
24518
27747
1982
KLF19650.1
24519
27748
361
KLF19649.1
24520
27749
921
KLF19648.1
24521


151

KUQ16675.1
24522
27751
1982
KUQ16672.1
24523
27752
361
KUQ16673.1
24524
27753
921
KUQ16674.1
24525


152

KUR17280.1
24526
27755
1982
KUR17283.1
24527
27756
361
KUR17282.1
24528
27757
921
KUR17281.1
24529


153

KLG20346.1
24530
27759
1980
KLG20343.1
24531
27760
361




KLG20345.1
24532


154

KJL89848.1
24533
27762
1998
KJL89845.1
24534
27763
361
KJL89846.1
24535
27764
925
KJL89847.1
24536


155

KJL84453.1
24537
27766
1998
KJL84456.1
24538
27767
361
KJL84455.1
24539
27768
925
KJL84454.1
24540


156

KJL75892.1
24541
27770
1998
KJL75889.1
24542
27771
361
KJL75890.1
24543
27772
925
KJL75891.1
24544


157

KJX56014.1
24545
27774
1998
KJX56011.1
24546
27775
361
KJX56012.1
24547
27776
925
KJX56013.1
24548


158

KJX41325.1
24549
27778
1998
KJX41322.1
24550
27779
361
KJX41323.1
24551
27780
925
KJX41324.1
24552


159

KJX62526.1
24553
27782
1998
KJX62523.1
24554
27783
361
KJX62524.1
24555
27784
925
KJX62525.1
24556


160

KJX64332.1
24557
27786
1998
KJX64329.1
24558
27787
361
KJX64330.1
24559
27788
925
KJX64331.1
24560


161

KJW84168.1
24561
27790
1998
KJW84165.1
24562
27791
361
KJW84166.1
24563
27792
925
KJW84167.1
24564


162

KJX04040.1
24565
27794
1998
KJX04037.1
24566
27795
361
KJX04038.1
24567
27796
925
KJX04039.1
24568


163

KJW83867.1
24569
27798
1998
KJW83864.1
24570
27799
361
KJW83865.1
24571
27800
925
KJW83866.1
24572


164

KJX49731.1
24573
27802
1998
KJX49728.1
24574
27803
361
KJX49729.1
24575
27804
925
KJX49730.1
24576


165

KKA32833.1
24577
27806
1998
KKA32830.1
24578
27807
361
KKA32831.1
24579
27808
925
KKA32832.1
24580


166

AFM58287.1
24581
27810
1945
AFM58284.1
24582
27811
411
AFM58285.1
24583
27812
850
AFM58286.1
24584


167

KTJ18639.1
24585
27814
1998
KTJ18636.1
24586
27815
361
KTJ18637.1
24587
27816
925
KTJ18638.1
24588


168

KTH34056.1
24589
27818
1998
KTH34053.1
24590
27819
361
KTH34054.1
24591
27820
925
KTH34055.1
24592


169

EWG70005.1
24593
27822
1982
EWG70008.1
24594
27823
361
EWG70007.1
24595
27824
921
EWG70006.1
24596


170

BAH40614.1
24597
27826
2009
BAH40611.1
24598
27827
407
BAH40612.1
24599
27828
983
BAH40613.1
24600


171

GAB92720.1
24601
27830
1755
GAB92713.1
24602
27831
422
GAB92719.1
24603
27832
1025


172

KOP23146.1
24604
27833
1766
KOP23135.1
24605
27834
388
KOP23134.1
24606
27835
689


173

EWE15861.1
24607
27836
1946
EWE15858.1
24608
27837
381
EWE15859.1
24609
27838
854
EWE15860.1
24610


174

CDI15591.1
24611
27840
1998
CDI15594.1
24612
27841
361
CDI15593.1
24613
27842
925
CDI15592.1
24614


175

EAW41505.1
24615
27844
2067
EAW41501.1
24616
27845
463
EAW41506.1
24617
27846
1000


176

KQQ96139.1
24618
27847
1983
KQQ96136.1
24619
27848
363
KQQ96141.1
24620
27849
940
KQQ96140.1
24621


177

AKB67566.1
24622
27851
2047
AKB67569.1
24623
27852
489
AKB67568.1
24624
27853
697


178

AIQ93138.1
24625
27854
1960
AIQ93137.1
24626
27855
340
AIQ93140.1
24627
27856
925
AIQ93139.1
24628


179

AMB47692.1
24629
27858
1963
AMB47695.1
24630
27859
315
AMB47694.1
24631
27860
851
AMB47693.1
24632


180

KIP90348.1
24633
27862
1813
KIP90388.1
24634
27863
331
KIP90346.1
24635
27864
683


181

EWM65738.1
24636
27865
1812
EWM65736.1
24637
27866
392
EWM65739.1
24638
27867
1027


182

CCH89535.1
24639
27868
1805
CCH89539.1
24640
27869
355
CCH89533.1
24641
27870
668


183

EMP50968.1
24642
27871
1945
EMP50971.1
24643
27872
411
EMP50970.1
24644
27873
852
EMP50969.1
24645


184

GAS97121.1
24646
27875
1827
GAS97126.1
24647
27876
329
GAS97123.1
24648
27877
703


185

ALI28820.1
24649
27878
1753
ALI28823.1
24650
27879
431
ALI28821.1
24651
27880
1085


186

AKS35859.1
24652
27881
1753
AKS36815.1
24653
27882
431
AKS35860.1
24654
27883
1031


187

GAT08462.1
24655
27884
1822
GAT08465.1
24656
27885
326
GAT08464.1
24657
27886
702


188

ACV78352.1
24658
27887
1780
ACV78350.1
24659
27888
467
ACV78351.1
24660
27889
1002


189

KJV46415.1
24661
27890
1946
KJV46418.1
24662
27891
411
KJV46417.1
24663
27892
852
KJV46416.1
24664


190

KRW97754.1
24665
27894
1953
KRW97756.1
24666
27895
603




KRW97755.1
24667


191

KHT34503.1
24668
27897
1986
KHT34506.1
24669
27898
361
KHT34505.1
24670
27899
927
KHT34504.1
24671


192

AFR03569.1
24672
27901
1980
AFR03572.1
24673
27902
361
AFR03571.1
24674
27903
921
AFR03570.1
24675


193

AKJ41264.1
24676
27905
1983
AKJ41261.1
24677
27906
361
AKJ41262.1
24678
27907
932
AKJ41263.1
24679


194

BAP50995.1
24680
27909
1946




BAP50997.1
24681
27910
850
BAP50996.1
24682


195

BAP23387.1
24683
27912
1946




BAP23389.1
24684
27913
850
BAP23388.1
24685


196

KSE43346.1
24686
27915
1946




KSE43345.1
24687
27916
850
KSE43344.1
24688


197

KSE74811.1
24689
27918
1946




KSE74753.1
24690
27919
850
KSE74754.1
24691


198

KSH20463.1
24692
27921
1946
KSH20466.1
24693
27922
394
KSH20465.1
24694
27923
850
KSH20464.1
24695


199

KSD81170.1
24696
27925
1946
KSD81167.1
24697
27926
394
KSD81166.1
24698
27927
850
KSD81165.1
24699


200

KSD90962.1
24700
27929
1946




KSD90904.1
24701
27930
850
KSD90905.1
24702


201

KSH64632.1
24703
27932
1946
KSH64629.1
24704
27933
394
KSH64628.1
24705
27934
850
KSH64627.1
24706


202

KSH80104.1
24707
27936
1946
KSH80101.1
24708
27937
394
KSH80100.1
24709
27938
850
KSH80099.1
24710


203

KSJ28920.1
24711
27940
1946
KSJ28917.1
24712
27941
394
KSJ28916.1
24713
27942
850
KSJ28915.1
24714


204

KSK06443.1
24715
27944
1946
KSK06442.1
24716
27945
394
KSK06441.1
24717
27946
850
KSK06440.1
24718


205

KSJ60779.1
24719
27948
1946
KSJ60711.1
24720
27949
394
KSJ60712.1
24721
27950
850
KSJ60713.1
24722


206

KSK54149.1
24723
27952
1946
KSK54146.1
24724
27953
394
KSK54145.1
24725
27954
850
KSK54144.1
24726


207

KSK39571.1
24727
27956
1946
KSK39566.1
24728
27957
394
KSK39565.1
24729
27958
850
KSK39564.1
24730


208

KSL10852.1
24731
27960
1946
KSL10784.1
24732
27961
394
KSL10785.1
24733
27962
850
KSL10786.1
24734


209

KSL65229.1
24735
27964
1946
KSL65226.1
24736
27965
394
KSL65225.1
24737
27966
850
KSL65224.1
24738


210

KSL37891.1
24739
27968
1946
KSL37823.1
24740
27969
394
KSL37824.1
24741
27970
850
KSL37825.1
24742


211

KSM35820.1
24743
27972
1946
KSM35817.1
24744
27973
394
KSM35816.1
24745
27974
850
KSM35815.1
24746


212

KSM77524.1
24747
27976
1956




KSM77522.1
24748
27977
846
KSM77523.1
24749


213

KSO31601.1
24750
27979
1946
KSO31533.1
24751
27980
394
KSO31534.1
24752
27981
850
KSO31535.1
24753


214

KSO28498.1
24754
27983
1946
KSO28430.1
24755
27984
394
KSO28431.1
24756
27985
850
KSO28432.1
24757


215

KSL52322.1
24758
27987
1946
KSL52254.1
24759
27988
394
KSL52255.1
24760
27989
850
KSL52256.1
24761


216

KSL73599.1
24762
27991
1946
KSL73596.1
24763
27992
394
KSL73595.1
24764
27993
850
KSL73594.1
24765


217

KSL62790.1
24766
27995
1956




KSL62788.1
24767
27996
846
KSL62789.1
24768


218

KSM90742.1
24769
27998
1946
KSM90740.1
24770
27999
394
KSM90739.1
24771
28000
850
KSM90738.1
24772


219

KSN64557.1
24773
28002
1946
KSN64554.1
24774
28003
394
KSN64553.1
24775
28004
850
KSN64552.1
24776


220

KSO10606.1
24777
28006
1946
KSO10538.1
24778
28007
394
KSO10539.1
24779
28008
850
KSO10540.1
24780


221

KSR13053.1
24781
28010
1946
KSR12985.1
24782
28011
394
KSR12986.1
24783
28012
850
KSR12987.1
24784


222

KSR82354.1
24785
28014
1946
KSR82286.1
24786
28015
394
KSR82287.1
24787
28016
850
KSR82288.1
24788


223

KSQ84593.1
24789
28018
1946
KSQ84590.1
24790
28019
394
KSQ84589.1
24791
28020
850
KSQ84588.1
24792


224

EFQ41826.1
24793
28022
1946




EFQ41828.1
24794
28023
850
EFQ41827.1
24795


225

ERX42740.1
24796
28025
1946
ERX42743.1
24797
28026
379
ERX42742.1
24798
28027
850
ERX42741.1
24799


226

ERV57398.1
24800
28029
1946
ERV57401.1
24801
28030
379
ERV57400.1
24802
28031
850
ERV57399.1
24803


227

ERV46141.1
24804
28033
1946
ERV46144.1
24805
28034
379
ERV46143.1
24806
28035
850
ERV46142.1
24807


228

ERV15095.1
24808
28037
1946
ERV15098.1
24809
28038
379
ERV15097.1
24810
28039
850
ERV15096.1
24811


229

EZN68207.1
24812
28041
1946
EZN68210.1
24813
28042
379
EZN68209.1
24814
28043
850
EZN68208.1
24815


230

EZP10099.1
24816
28045
1956
EZP10096.1
24817
28046
384
EZP10097.1
24818
28047
876
EZP10098.1
24819


231

ERW79837.1
24820
28049
1946
ERW79840.1
24821
28050
379
ERW79839.1
24822
28051
850
ERW79838.1
24823


232

ERU64537.1
24824
28053
1942
ERU64534.1
24825
28054
398
ERU64535.1
24826
28055
839
ERU64536.1
24827


233

ERZ11046.1
24828
28057
1946
ERZ11049.1
24829
28058
379
ERZ11048.1
24830
28059
850
ERZ11047.1
24831


234

CDH77378.1
24832
28061
1946




CDH77380.1
24833
28062
511
CDH77379.1
24834


235

BAK90082.1
24835
28064
1946




BAK90080.1
24836
28065
850
BAK90081.1
24837


236

ERX37642.1
24838
28067
1946
ERX37645.1
24839
28068
379
ERX37644.1
24840
28069
850
ERX37643.1
24841


237

CDM51955.1
24842
28071
1946
CDM51958.1
24843
28072
379
CDM51957.1
24844
28073
850
CDM51956.1
24845


238

AAY92286.1
24846
28075
1948
AAY96277.1
24847
28076
394
AAY92284.1
24848
28077
851
AAY92285.1
24849


239

ELP96357.1
24850
28079
1945
ELP96354.1
24851
28080
399
ELP96355.1
24852
28081
838
ELP96356.1
24853


240

ELQ02809.1
24854
28083
1945
ELQ02806.1
24855
28084
399
ELQ02807.1
24856
28085
838
ELQ02808.1
24857


241

KGK94204.1
24858
28087
1957
KGK94314.1
24859
28088
406
KGK94207.1
24860
28089
847
KGK94205.1
24861


242

KUR43160.1
24862
28091
1957
KUR43163.1
24863
28092
384
KUR43162.1
24864
28093
847
KUR43161.1
24865


243

KUR49796.1
24866
28095
1957
KUR49793.1
24867
28096
384
KUR49794.1
24868
28097
847
KUR49795.1
24869


244

EEB59176.1
24870
28099
1957
EEB59179.1
24871
28100
406
EEB59178.1
24872
28101
847
EEB59177.1
24873


245

ERL54332.1
24874
28103
1930




ERL54330.1
24875
28104
845
ERL54331.1
24876


246

KPH05039.1
24877
28106
1961
KPH05036.1
24878
28107
353
KPH05037.1
24879
28108
854
KPH05038.1
24880


247

KQS76378.1
24881
28110
1626




KQS76380.1
24882
28111
853
KQS76379.1
24883


248

KUJ85953.1
24884
28113
1804
KUJ86243.1
24885
28114
472
KUJ85952.1
24886
28115
1026


249

KTM77905.1
24887
28116
1980
KTM77908.1
24888
28117
361
KTM77907.1
24889
28118
921
KTM77906.1
24890


250

GAR19711.1
24891
28120
1945
GAR19708.1
24892
28121
395
GAR19709.1
24893
28122
852
GAR19710.1
24894


251

GAR29094.1
24895
28124
1945
GAR29097.1
24896
28125
395
GAR29096.1
24897
28126
852
GAR29095.1
24898


252

GAR48964.1
24899
28128
1945
GAR48967.1
24900
28129
395
GAR48966.1
24901
28130
852
GAR48965.1
24902


253

GAR51851.1
24903
28132
1980
GAR51848.1
24904
28133
361
GAR51849.1
24905
28134
921
GAR51850.1
24906


254

GAR68135.1
24907
28136
1945
GAR68138.1
24908
28137
395
GAR68137.1
24909
28138
852
GAR68136.1
24910


255

GAR79837.1
24911
28140
1945
GAR79834.1
24912
28141
395
GAR79835.1
24913
28142
852
GAR79836.1
24914


256

GAS04635.1
24915
28144
1945
GAS04638.1
24916
28145
395
GAS04637.1
24917
28146
852
GAS04636.1
24918


257

GAS14633.1
24919
28148
1945
GAS14636.1
24920
28149
395
GAS14635.1
24921
28150
852
GAS14634.1
24922


258

GAS22419.1
24923
28152
1945
GAS22416.1
24924
28153
395
GAS22417.1
24925
28154
852
GAS22418.1
24926


259

GAS34224.1
24927
28156
1945
GAS34221.1
24928
28157
395
GAS34222.1
24929
28158
852
GAS34223.1
24930


260

GAS44702.1
24931
28160
1945
GAS44699.1
24932
28161
395
GAS44700.1
24933
28162
852
GAS44701.1
24934


261

KSB75754.1
24935
28164
1945
KSB75751.1
24936
28165
411
KSB75752.1
24937
28166
849
KSB75753.1
24938


262

AIP97316.1
24939
28168
1945
AIP94652.1
24940
28169
411
AIP97314.1
24941
28170
849
AIP97315.1
24942


263

KFS83334.1
24943
28172
1980
KFS83337.1
24944
28173
361
KFS83336.1
24945
28174
921
KFS83335.1
24946


264

KFS82350.1
24947
28176
1980




KFS82348.1
24948
28177
617
KFS82349.1
24949


265

KFS54100.1
24950
28179
1980
KFS54103.1
24951
28180
361
KFS54102.1
24952
28181
921
KFS54101.1
24953


266

ETA85463.1
24954
28183
1946
ETA85466.1
24955
28184
411
ETA85465.1
24956
28185
852
ETA85464.1
24957


267

AGQ75543.1
24958
28187
1946
AGQ73595.1
24959
28188
395
AGQ75541.1
24960
28189
852
AGQ75542.1
24961


268

ESV53477.1
24962
28191
1946
ESV53381.1
24963
28192
395
ESV53475.1
24964
28193
852
ESV53476.1
24965


269

ESJ68059.1
24966
28195
1980
ESJ68062.1
24967
28196
361
ESJ68061.1
24968
28197
921
ESJ68060.1
24969


270

ESE97307.1
24970
28199
1980
ESE97310.1
24971
28200
361
ESE97309.1
24972
28201
921
ESE97308.1
24973


271

EDZ02526.1
24974
28203
1980
EDZ04146.1
24975
28204
361




EDZ04762.1
24976


272

ETO88599.1
24977
28206
1980
ETO88602.1
24978
28207
361
ETO88601.1
24979
28208
921
ETO88600.1
24980


273

CUS01271.1
24981
28210
1982
CUS01249.1
24982
28211
361
CUS01256.1
24983
28212
921
CUS01267.1
24984


274

CUR99590.1
24985
28214
1982
CUR99579.1
24986
28215
361
CUR99583.1
24987
28216
921
CUR99587.1
24988


275

CUR99591.1
24989
28218
1982
CUR99580.1
24990
28219
361
CUR99582.1
24991
28220
921
CUR99586.1
24992


276

CUR99699.1
24993
28222
1982
CUR99684.1
24994
28223
361
CUR99689.1
24995
28224
921
CUR99695.1
24996


277

CBY98492.1
24997
28226
1982
CBY98489.1
24998
28227
361
CBY98490.1
24999
28228
921
CBY98491.1
25000


278

EDZ28883.1
25001
28230
1982
EDZ28906.1
25002
28231
361
EDZ28845.1
25003
28232
921
EDZ28831.1
25004


279

KHQ80350.1
25005
28234
1946
KHQ80347.1
25006
28235
411
KHQ80348.1
25007
28236
852
KHQ80349.1
25008


280

ESE86334.1
25009
28238
1946
ESE86332.1
25010
28239
411




ESE86333.1
25011


281

ETX40265.1
25012
28241
1947
ETX40262.1
25013
28242
411
ETX40263.1
25014
28243
852
ETX40264.1
25015


282

EZQ62320.1
25016
28245
1947
EZQ62323.1
25017
28246
411
EZQ62322.1
25018
28247
852
EZQ62321.1
25019


283

CAC47725.1
25020
28249
1832
CAC47727.1
25021
28250
440
CAC47726.1
25022
28251
997


284

AGG75744.1
25023
28252
1832
AGG75746.1
25024
28253
440
AGG75745.1
25025
28254
997


285

KSV87560.1
25026
28255
1961
KSV87563.1
25027
28256
383
KSV87562.1
25028
28257
854
KSV87561.1
25029


286

EJJ06042.1
25030
28259
1849
EJJ06043.1
25031
28260
405
EJJ06040.1
25032
28261
705


287

KND14004.1
25033
28262
1857
KND14010.1
25034
28263
405
KND14006.1
25035
28264
712


288

EGU44860.1
25036
28265
2093
EGU44862.1
25037
28266
528
EGU44859.1
25038
28267
1014


289

CNL16915.1
25039
28268
1981
CNL16836.1
25040
28269
362
CNL16872.1
25041
28270
928
CNL16894.1
25042


290

CNJ89349.1
25043
28272
1981
CNJ89455.1
25044
28273
362
CNJ89414.1
25045
28274
928
CNJ89387.1
25046


291

CNK54575.1
25047
28276
1982
CNK54663.1
25048
28277
376
CNK54635.1
25049
28278
927
CNK54608.1
25050


292

CNK94601.1
25051
28280
1981
CNK94669.1
25052
28281
362
CNK94646.1
25053
28282
928
CNK94618.1
25054


293

CNI43727.1
25055
28284
1982
CNI43814.1
25056
28285
376
CNI43794.1
25057
28286
927
CNI43767.1
25058


294

AJJ11891.1
25059
28288
1986
AJJ11355.1
25060
28289
362
AJJ10816.1
25061
28290
928
AJJ11516.1
25062


295

EEQ02997.1
25063
28292
1986
EEQ03000.1
25064
28293
362
EEQ02999.1
25065
28294
928
EEQ02998.1
25066


296

KXV70696.1
25067
28296
2166


297

AKQ30571.1
25069
28298
2105


298

KOP86148.1
25071
28300
2105


299

KRS04352.1
25073
28302
2105


300

KRS02342.1
25075
28304
2105


301

KRS03107.1
25077
28306
2105


302

KRR94714.1
25079
28308
2105


303

KRS09258.1
25081
28310
2105


304

EXE63524.1
25083
28312
2107


305

EXC47766.1
25085
28314
2099


306

ELW92979.1
25087
28316
2107


307

ENW35933.1
25089
28318
2105


308

ENW44602.1
25091
28320
2105


309

ENW49012.1
25093
28322
2098


310

EKP68370.1
25095
28324
2098


311

EKL42013.1
25097
28326
2105


312

ENV15228.1
25099
28328
2099


313

ENX21439.1
25101
28330
2105


314

ENV06099.1
25103
28332
2099


315

EDS03747.1
25105
28334
2047


316

AMN11450.1
25107
28336
2100


317

AFT94989.1
25109
28338
2100


318

EGF91079.1
25111
28340
2037


319

ESQ74519.1
25113
28342
2035


320

CAL94925.1
25115
28344
2109


321

AJE23874.1
25117
28346
1705


322

CUA18545.1
25119
28348
2048


323

CBW22536.1
25121
28350
2048


324

EYA28061.1
25123
28352
2046


325

EYA33839.1
25125
28354
2048


326

EXY44320.1
25127
28356
2048


327

EYB10318.1
25129
28358
2048


328

EXZ67979.1
25131
28360
2048


329

EXY49048.1
25133
28362
2048


330

EXY53777.1
25135
28364
2048


331

EDS16320.1
25137
28366
2047


332

KXT38969.1
25139
28368
2047


333

EGW44032.1
25141
28370
2053


334

EEA03717.1
25143
28372
2083


335

KVM07646.1
25145
28374
2080


336

KVM11423.1
25147
28376
2080


337

KVM41744.1
25149
28378
2080


338

KVU39940.1
25151
28380
2084


339

KVX50941.1
25153
28382
2080


340

CDH43330.1
25155
28384
2062


341

KPA18787.1
25157
28386
2057


342

AIY12566.1
25159
28388
1978


343

EYF08672.1
25161
28390
1820


344

KQM35753.1
25163
28392
1956


345

ALD78156.1
25165
28394
2108


346

KPR54498.1
25167
28396
2106


347

KLV49873.1
25169
28398
2162


348

KLV71165.1
25171
28400
2106


349

BAO81224.1
25173
28402
2099


350

ALB51925.1
25175
28404
2106


351

AGE87745.1
25177
28406
1380


352

KJR98717.1
25179
28408
2076


353

KLE94551.1
25181
28410
2106


354

KLF52638.1
25183
28412
2106


355

KLW28645.1
25185
28414
2106


356

KLW04619.1
25187
28416
2106


357

KLQ05990.1
25189
28418
2108


358

KJI56236.1
25191
28420
2108


359

KLP80553.1
25193
28422
2106


360

KLW09755.1
25195
28424
2106


361

KLW05113.1
25197
28426
2106


362

KUQ64543.1
25199
28428
2080


363

KUQ79081.1
25201
28430
2080


364

KPS33776.1
25203
28432
2106


365

ESL79957.1
25205
28434
2106


366

KLW78405.1
25207
28436
2106


367

KFC20758.1
25209
28438
1950


368

AKQ40859.1
25211
28440
1989


369

EDL49427.1
25213
28442
1988


370

KDM84272.1
25215
28444
2104


371

CDU40545.1
25217
28446
2114


372

KHJ28072.1
25219
28448
2114


373

KHI41602.1
25221
28450
2104


374

KHH60282.1
25223
28452
2114


375

KHH50418.1
25225
28454
2114


376

KHI22226.1
25227
28456
2104


377

KHH70907.1
25229
28458
2114


378

KIG29571.1
25231
28460
2104


379

AJE58952.1
25233
28462
2114


380

KIY28272.1
25235
28464
2104


381

KIZ09778.1
25237
28466
2104


382

KJJ46593.1
25239
28468
2104


383

KJW55354.1
25241
28470
2104


384

KJW51696.1
25243
28472
2104


385

KLG52811.1
25245
28474
2104


386

KLX28162.1
25247
28476
2114


387

KNF16836.1
25249
28478
2104


388

KNF20995.1
25251
28480
2104


389

KNF39640.1
25253
28482
2104


390

KNG40958.1
25255
28484
2104


391

KNZ99111.1
25257
28486
2114


392

KOZ12765.1
25259
28488
2104


393

KOZ62647.1
25261
28490
2104


394

KOZ92031.1
25263
28492
2104


395

KOZ11137.1
25265
28494
2104


396

KOZ14566.1
25267
28496
2104


397

KOZ32809.1
25269
28498
2104


398

KOZ23191.1
25271
28500
2104


399

KOZ33147.1
25273
28502
2104


400

KOZ37736.1
25275
28504
2104


401

KOZ50072.1
25277
28506
2104


402

KOZ47195.1
25279
28508
2104


403

KOZ49645.1
25281
28510
2104


404

KOZ66201.1
25283
28512
2104


405

KOZ69676.1
25285
28514
2104


406

KOZ74923.1
25287
28516
2104


407

KOZ84735.1
25289
28518
2104


408

KOZ80210.1
25291
28520
2104


409

KOZ97677.1
25293
28522
2104


410

CTS44204.1
25295
28524
2116


411

KPH47383.1
25297
28526
2104


412

KPH45899.1
25299
28528
2104


413

KPH35130.1
25301
28530
2104


414

KPH38257.1
25303
28532
2104


415

KPO74170.1
25305
28534
2104


416

KPP03700.1
25307
28536
2104


417

KPP08799.1
25309
28538
2104


418

KPP18124.1
25311
28540
2104


419

KPP23767.1
25313
28542
2104


420

KPP34281.1
25315
28544
2104


421

KPP38851.1
25317
28546
2104


422

KPP49039.1
25319
28548
2104


423

KPP10067.1
25321
28550
2104


424

KPP41789.1
25323
28552
2104


425

KPP53630.1
25325
28554
2104


426

KUH02052.1
25327
28556
2104


427

KUH15976.1
25329
28558
2114


428

KUR31930.1
25331
28560
2114


429

ALZ66920.1
25333
28562
2114


430

KUT20744.1
25335
28564
2114


431

KUT66046.1
25337
28566
2114


432

KUS25060.1
25339
28568
2114


433

KUS40192.1
25341
28570
2104


434

KUT25847.1
25343
28572
2104


435

KUT18408.1
25345
28574
2104


436

KUU15347.1
25347
28576
2114


437

KUT50287.1
25349
28578
2104


438

KUX11783.1
25351
28580
2114


439

KUU59436.1
25353
28582
2114


440

KUU32865.1
25355
28584
2104


441

KUU24011.1
25357
28586
2104


442

KUV87992.1
25359
28588
2104


443

KUW19154.1
25361
28590
2104


444

KUW69105.1
25363
28592
2104


445

KUW47130.1
25365
28594
2104


446

KUT58081.1
25367
28596
2114


447

KUX52751.1
25369
28598
2114


448

KUX36550.1
25371
28600
2114


449

AMG80375.1
25373
28602
2104


450

KXG88717.1
25375
28604
2090


451

KXK90271.1
25377
28606
2104


452

KXP75339.1
25379
28608
2104


453

KXP56977.1
25381
28610
2114


454

KXP32136.1
25383
28612
2114


455

KXP24174.1
25385
28614
2114


456

KXR08922.1
25387
28616
2114


457

KXR32560.1
25389
28618
2114


458

KXR26310.1
25391
28620
2114


459

KXR92242.1
25393
28622
2114


460

KXR64178.1
25395
28624
2114


461

KXR53387.1
25397
28626
2114


462

EKJ54998.1
25399
28628
2104


463

ERC53519.1
25401
28630
2104


464

ERE00883.1
25403
28632
2104


465

ERE21799.1
25405
28634
2104


466

ERB68143.1
25407
28636
2104


467

ELV15311.1
25409
28638
2104


468

EKK91185.1
25411
28640
2104


469

EKK67942.1
25413
28642
2104


470

EKK62293.1
25415
28644
2104


471

EYE30769.1
25417
28646
2104


472

EYE15511.1
25419
28648
2104


473

EYE15598.1
25421
28650
2104


474

ESA76409.1
25423
28652
2090


475

EZJ86908.1
25425
28654
2104


476

KEO21429.1
25427
28656
2104


477

KDA70980.1
25429
28658
2104


478

KDS94627.1
25431
28660
2114


479

KDT14053.1
25433
28662
2114


480

KEN70536.1
25435
28664
2114


481

KDV77036.1
25437
28666
2114


482

KDW27005.1
25439
28668
2114


483

KEN84157.1
25441
28670
2114


484

KEO02789.1
25443
28672
2114


485

KDX84120.1
25445
28674
2114


486

KEJ20443.1
25447
28676
2071


487

KEJ21099.1
25449
28678
2104


488

EMX91855.1
25451
28680
2657


489

EMW69586.1
25453
28682
2114


490

EMW64104.1
25455
28684
2114


491

EMW45432.1
25457
28686
2114


492

EMV86399.1
25459
28688
2114


493

ENA88227.1
25461
28690
2114


494

ENB03534.1
25463
28692
2090


495

ERD09266.1
25465
28694
2104


496

EKK37396.1
25467
28696
2104


497

ELW28319.1
25469
28698
2104


498

KDT83303.1
25471
28700
2104


499

KEK80770.1
25473
28702
2104


500

KEL07348.1
25475
28704
2104


501

KEK94607.1
25477
28706
2104


502

EKK37001.1
25479
28708
2104


503

EKI06062.1
25481
28710
2104


504

EIL64995.1
25483
28712
2114


505

EKI02734.1
25485
28714
2104


506

KEL97939.1
25487
28716
2104


507

KEM08515.1
25489
28718
2104


508

KEM49607.1
25491
28720
2104


509

KEN01218.1
25493
28722
2114


510

KEM09157.1
25495
28724
2114


511

KEM25601.1
25497
28726
2114


512

KEM85724.1
25499
28728
2104


513

KEN65096.1
25501
28730
2104


514

ELW21807.1
25503
28732
2104


515

EKK71769.1
25505
28734
2104


516

EKK61091.1
25507
28736
2104


517

EKK52335.1
25509
28738
2104


518

EKK87669.1
25511
28740
2104


519

EKV85101.1
25513
28742
2104


520

EKV70655.1
25515
28744
2104


521

EKW05774.1
25517
28746
2104


522

EKW03229.1
25519
28748
2104


523

ESD10541.1
25521
28750
2104


524

ESA83483.1
25523
28752
2090


525

ESD19201.1
25525
28754
2090


526

ESD45641.1
25527
28756
2090


527

ESD61126.1
25529
28758
2090


528

ESD71191.1
25531
28760
2104


529

ESD92014.1
25533
28762
2090


530

ESD92684.1
25535
28764
2090


531

EKW04204.1
25537
28766
2104


532

EKW19026.1
25539
28768
2104


533

EIN33839.1
25541
28770
2104


534

EKW08489.1
25543
28772
2104


535

ELW29953.1
25545
28774
2104


536

EKW22423.1
25547
28776
2104


537

EKW74828.1
25549
28778
2104


538

EKY34593.1
25551
28780
2104


539

EKW38126.1
25553
28782
2104


540

EKW51346.1
25555
28784
2104


541

EKW70677.1
25557
28786
2104


542

EKW68015.1
25559
28788
2104


543

EKW71373.1
25561
28790
2104


544

EKY34710.1
25563
28792
2104


545

EKW75844.1
25565
28794
2104


546

ELW46373.1
25567
28796
2104


547

EKW96658.1
25569
28798
2104


548

EKW96262.1
25571
28800
2104


549

ELV31252.1
25573
28802
2104


550

ELV35525.1
25575
28804
2104


551

ELV44385.1
25577
28806
2104


552

ELW27709.1
25579
28808
2104


553

ELV47170.1
25581
28810
2104


554

ELW24264.1
25583
28812
2104


555

ELV62894.1
25585
28814
2104


556

ETJ70882.1
25587
28816
2104


557

ELV63261.1
25589
28818
2104


558

ACA79488.1
25591
28820
2104


559

ETJ79055.1
25593
28822
2104


560

ERB88976.1
25595
28824
2104


561

ERD08450.1
25597
28826
2104


562

ERD05022.1
25599
28828
2104


563

ERD20749.1
25601
28830
2104


564

ERD22952.1
25603
28832
2104


565

ERB79218.1
25605
28834
2104


566

ERD23993.1
25607
28836
2104


567

ERD35139.1
25609
28838
2104


568

ERD37186.1
25611
28840
2104


569

ERD26785.1
25613
28842
2104


570

ERD52932.1
25615
28844
2104


571

ERD40233.1
25617
28846
2104


572

ERD45130.1
25619
28848
2104


573

ERB91933.1
25621
28850
2104


574

ERC00105.1
25623
28852
2104


575

ERC08313.1
25625
28854
2104


576

ERC07683.1
25627
28856
2104


577

ERC15356.1
25629
28858
2104


578

ERC23447.1
25631
28860
2104


579

ERC10661.1
25633
28862
2104


580

ERC32307.1
25635
28864
2104


581

ERD72600.1
25637
28866
2104


582

ERD68378.1
25639
28868
2104


583

ERD73346.1
25641
28870
2104


584

ERD83190.1
25643
28872
2104


585

ERC25312.1
25645
28874
2104


586

ERC30062.1
25647
28876
2104


587

ERD87992.1
25649
28878
2104


588

ERD91778.1
25651
28880
2104


589

ERD98685.1
25653
28882
2104


590

ERD88430.1
25655
28884
2104


591

ERE36113.1
25657
28886
2104


592

ERE23642.1
25659
28888
2104


593

ERC33936.1
25661
28890
2104


594

ERC40343.1
25663
28892
2104


595

ERC48260.1
25665
28894
2104


596

ETY20411.1
25667
28896
2114


597

ETY13489.1
25669
28898
2114


598

ETY13648.1
25671
28900
2114


599

ETY08682.1
25673
28902
2114


600

ETX96687.1
25675
28904
2114


601

ERO99484.1
25677
28906
2114


602

ETY35402.1
25679
28908
2114


603

ETY29966.1
25681
28910
2114


604

ESL20614.1
25683
28912
2104


605

ETX82126.1
25685
28914
2114


606

ETX76976.1
25687
28916
2114


607

ETY61260.1
25689
28918
2114


608

EZQ66604.1
25691
28920
2114


609

ETY23955.1
25693
28922
2114


610

EKH96740.1
25695
28924
2104


611

CDU33063.1
25697
28926
2114


612

EHV18501.1
25699
28928
2104


613

EIP71495.1
25701
28930
2104


614

EKI46661.1
25703
28932
2104


615

EKI57136.1
25705
28934
2104


616

EKI59126.1
25707
28936
2104


617

EIP63563.1
25709
28938
2104


618

EIP72315.1
25711
28940
2104


619

EKI64841.1
25713
28942
2104


620

EKI72765.1
25715
28944
2104


621

EKI91872.1
25717
28946
2104


622

EKI82677.1
25719
28948
2104


623

EKJ05431.1
25721
28950
2104


624

EKI92955.1
25723
28952
2104


625

EKJ00854.1
25725
28954
2104


626

EIP72928.1
25727
28956
2104


627

EKJ19827.1
25729
28958
2104


628

EKJ20864.1
25731
28960
2104


629

EKJ36038.1
25733
28962
2104


630

EKJ47665.1
25735
28964
2104


631

EKJ36501.1
25737
28966
2104


632

EIP38855.1
25739
28968
2104


633

EIO92486.1
25741
28970
2104


634

EIO87517.1
25743
28972
2104


635

EIP27283.1
25745
28974
2104


636

EIP10343.1
25747
28976
2104


637

EIP33944.1
25749
28978
2104


638

EIP40257.1
25751
28980
2104


639

EIP48993.1
25753
28982
2104


640

EIP35357.1
25755
28984
2104


641

EIP50032.1
25757
28986
2104


642

EKI03043.1
25759
28988
2104


643

EST65289.1
25761
28990
2114


644

EMX76370.1
25763
28992
1715


645

EMX78116.1
25765
28994
1715


646

EKH36317.1
25767
28996
2104


647

EIN15911.1
25769
28998
2104


648

EKH25288.1
25771
29000
2104


649

EKH13354.1
25773
29002
2104


650

EIN16634.1
25775
29004
2104


651

EIN33026.1
25777
29006
2104


652

EKH48832.1
25779
29008
2104


653

EKJ48076.1
25781
29010
2104


654

EFI22364.1
25783
29012
2114


655

EFF02931.1
25785
29014
2114


656

EQN36980.1
25787
29016
2114


657

EQQ54038.1
25789
29018
2114


658

EQQ62151.1
25791
29020
1302


659

EQQ82445.1
25793
29022
2114


660

EQR15650.1
25795
29024
2114


661

EQR29834.1
25797
29026
2114


662

EQR56342.1
25799
29028
2114


663

EQR70531.1
25801
29030
2114


664

EQR73388.1
25803
29032
2114


665

ESP12228.1
25805
29034
2104


666

EQR98265.1
25807
29036
2114


667

EQS19620.1
25809
29038
2114


668

EQS44554.1
25811
29040
2114


669

EQS43788.1
25813
29042
2114


670

ERA63201.1
25815
29044
2114


671

EQS73534.1
25817
29046
2114


672

EQS83533.1
25819
29048
2114


673

EQT06519.1
25821
29050
2114


674

EQT31741.1
25823
29052
2104


675

EQT33091.1
25825
29054
2114


676

EQT84560.1
25827
29056
2104


677

EQU07296.1
25829
29058
2114


678

EQU46108.1
25831
29060
2114


679

EQU56271.1
25833
29062
2114


680

EQU82066.1
25835
29064
2114


681

EQN74806.1
25837
29066
2114


682

EQV15999.1
25839
29068
2114


683

EQO01912.1
25841
29070
2114


684

EQO57394.1
25843
29072
2104


685

EQO66405.1
25845
29074
2104


686

EQO74550.1
25847
29076
2114


687

EQP20054.1
25849
29078
2114


688

EQP30926.1
25851
29080
2114


689

EQP87867.1
25853
29082
2114


690

EQV39985.1
25855
29084
2114


691

EQV77954.1
25857
29086
2114


692

EQV75318.1
25859
29088
2114


693

EQV93985.1
25861
29090
2114


694

EOX00083.1
25863
29092
2114


695

EOW11795.1
25865
29094
2114


696

ELF04268.1
25867
29096
2114


697

ELI36532.1
25869
29098
2114


698

ELI49202.1
25871
29100
2104


699

EOW43092.1
25873
29102
2114


700

ELI49522.1
25875
29104
2114


701

EOW53696.1
25877
29106
2114


702

EOW53661.1
25879
29108
2114


703

EOW60866.1
25881
29110
2114


704

ELG97963.1
25883
29112
2114


705

ELH03274.1
25885
29114
2114


706

ELF28434.1
25887
29116
2104


707

EU30967.1
25889
29118
2114


708

EOW72675.1
25891
29120
2114


709

ELC68673.1
25893
29122
2114


710

ELC04770.1
25895
29124
2114


711

EOV27243.1
25897
29126
2114


712

ELH63192.1
25899
29128
2104


713

ELD00702.1
25901
29130
2114


714

ELD16727.1
25903
29132
2114


715

EOV39942.1
25905
29134
2114


716

EOX13560.1
25907
29136
2114


717

ELD74209.1
25909
29138
2114


718

ELC51202.1
25911
29140
2114


719

ELC65367.1
25913
29142
2114


720

ELG08157.1
25915
29144
2104


721

ELE06192.1
25917
29146
1584


722

ELE13901.1
25919
29148
2114


723

EOV54810.1
25921
29150
2114


724

ELE75378.1
25923
29152
2114


725

ELJ61315.1
25925
29154
2114


726

ELE76412.1
25927
29156
2114


727

EGI23327.1
25929
29158
2114


728

EIF87148.1
25931
29160
2104


729

KDG67767.1
25933
29162
2114


730

EFK89793.1
25935
29164
2090


731

EFK27050.1
25937
29166
2104


732

EFI89547.1
25939
29168
2114


733

EFJ73000.1
25941
29170
2090


734

EKH61308.1
25943
29172
2104


735

EKJ53063.1
25945
29174
2104


736

EMS03602.1
25947
29176
2104


737

KDM81021.1
25949
29178
2104


738

AHY73976.1
25951
29180
2104


739

AHG12157.1
25953
29182
2104


740

EYZ76662.1
25955
29184
2104


741

EYW98552.1
25957
29186
2104


742

EYV59037.1
25959
29188
2104


743

EZE90567.1
25961
29190
2104


744

EYV46017.1
25963
29192
2104


745

EYV44258.1
25965
29194
2104


746

EYV24875.1
25967
29196
2104


747

EYV22943.1
25969
29198
2104


748

EYV18168.1
25971
29200
2104


749

EYV20078.1
25973
29202
2104


750

EYV16484.1
25975
29204
2104


751

EYZ14529.1
25977
29206
2104


752

EZQ47394.1
25979
29208
2104


753

EZQ50282.1
25981
29210
2104


754

EFX13464.1
25983
29212
2104


755

EFX18241.1
25985
29214
2104


756

KKF77973.1
25987
29216
2104


757

KKF80397.1
25989
29218
2104


758

KKY44751.1
25991
29220
2104


759

ALH93595.1
25993
29222
2104


760

KRQ04755.1
25995
29224
2104


761

EYZ52258.1
25997
29226
2104


762

EYZ38307.1
25999
29228
2104


763

EYZ37416.1
26001
29230
2104


764

EYZ36217.1
26003
29232
2104


765

EYX13628.1
26005
29234
2104


766

EYX12327.1
26007
29236
2104


767

EYX02204.1
26009
29238
2104


768

EZD85330.1
26011
29240
2104


769

EZE88806.1
26013
29242
2104


770

EYV70456.1
26015
29244
2104


771

EZE89449.1
26017
29246
2104


772

EYV67648.1
26019
29248
2104


773

EYX70060.1
26021
29250
2104


774

EYX57443.1
26023
29252
2104


775

EYX54548.1
26025
29254
2104


776

EYX48134.1
26027
29256
2104


777

EYX44881.1
26029
29258
2104


778

EYX43993.1
26031
29260
2104


779

EYX33004.1
26033
29262
2104


780

EYX30696.1
26035
29264
2104


781

EYX27761.1
26037
29266
2104


782

EYW85332.1
26039
29268
2104


783

EYW83365.1
26041
29270
2104


784

EYW75521.1
26043
29272
2104


785

EYW71151.1
26045
29274
2104


786

EYW67179.1
26047
29276
2104


787

EYW64048.1
26049
29278
2104


788

EYW57176.1
26051
29280
2104


789

EYW49142.1
26053
29282
2104


790

EYW49455.1
26055
29284
2104


791

EYW43048.1
26057
29286
2104


792

EYW39162.1
26059
29288
2104


793

EYW34611.1
26061
29290
2104


794

EYW25812.1
26063
29292
2104


795

EYW27182.1
26065
29294
2104


796

EYW24511.1
26067
29296
2104


797

EYW09905.1
26069
29298
2104


798

EYW13502.1
26071
29300
2104


799

EZF08560.1
26073
29302
2104


800

EYW07433.1
26075
29304
2104


801

EZF05481.1
26077
29306
2104


802

EDZ87478.1
26079
29308
2104


803

EDZ81928.1
26081
29310
2104


804

EDU68725.1
26083
29312
2104


805

EDU54295.1
26085
29314
2104


806

ACI39430.1
26087
29316
2104


807

EDU34122.1
26089
29318
2104


808

EDZ76631.1
26091
29320
2104


809

EDU76303.1
26093
29322
2104


810

EDU82569.1
26095
29324
2104


811

EDU87409.1
26097
29326
2104


812

EDU98012.1
26099
29328
2104


813

AAG59484.1
26101
29330
2104


814

AIG71774.1
26103
29332
2104


815

EZA89751.1
26105
29334
2104


816

EZB05974.1
26107
29336
2104


817

EZB04403.1
26109
29338
2104


818

EZB11565.1
26111
29340
2104


819

EYV89285.1
26113
29342
2104


820

EZB20620.1
26115
29344
2104


821

EZB18143.1
26117
29346
2104


822

EZB30349.1
26119
29348
2104


823

EFX08675.1
26121
29350
2104


824

EZB32015.1
26123
29352
2104


825

EZB41524.1
26125
29354
2104


826

EZB46985.1
26127
29356
2104


827

EZB48638.1
26129
29358
2104


828

EZB48354.1
26131
29360
2104


829

EZB52648.1
26133
29362
2104


830

EZB74690.1
26135
29364
2104


831

EZB73674.1
26137
29366
2104


832

EZB87911.1
26139
29368
2104


833

EZB80135.1
26141
29370
2104


834

EZB81695.1
26143
29372
2104


835

EZB95442.1
26145
29374
2104


836

EZC17285.1
26147
29376
2104


837

EZC37645.1
26149
29378
2104


838

EZC28524.1
26151
29380
2104


839

EZC43983.1
26153
29382
2104


840

EZC48748.1
26155
29384
2104


841

EZC62955.1
26157
29386
2104


842

EZC70422.1
26159
29388
2104


843

EZC77662.1
26161
29390
2104


844

EZC64795.1
26163
29392
2104


845

EZC83414.1
26165
29394
2104


846

EZC90333.1
26167
29396
2104


847

EZC92771.1
26169
29398
2104


848

EZC86953.1
26171
29400
2104


849

EZD00267.1
26173
29402
2104


850

EYV84723.1
26175
29404
2104


851

EZD08968.1
26177
29406
2104


852

EZD17519.1
26179
29408
2104


853

EZD15757.1
26181
29410
2104


854

EZD19488.1
26183
29412
2104


855

EZD75269.1
26185
29414
2104


856

BAB38683.1
26187
29416
2104


857

AIF96934.1
26189
29418
2104


858

AJA29436.1
26191
29420
2104


859

ACT75064.1
26193
29422
2104


860

EEC30693.1
26195
29424
2104


861

EYZ63880.1
26197
29426
2104


862

EFX22734.1
26199
29428
2104


863

ADD59519.1
26201
29430
2104


864

ENC26729.1
26203
29432
2114


865

ENA10896.1
26205
29434
2114


866

EMZ79273.1
26207
29436
2114


867

ENG24753.1
26209
29438
2114


868

ENG35039.1
26211
29440
2114


869

ENG38631.1
26213
29442
2090


870

END33529.1
26215
29444
2090


871

ENE04446.1
26217
29446
2114


872

ENG47569.1
26219
29448
2090


873

ENG50954.1
26221
29450
2114


874

ENG56305.1
26223
29452
2114


875

ENG57264.1
26225
29454
2090


876

ENH40674.1
26227
29456
2090


877

ENG66730.1
26229
29458
2114


878

ENG74277.1
26231
29460
2114


879

EST67460.1
26233
29462
2104


880

EST67374.1
26235
29464
2104


881

EIN65416.1
26237
29466
2104


882

ELV75969.1
26239
29468
2104


883

ELV90964.1
26241
29470
2104


884

EIN69805.1
26243
29472
2104


885

EIN85485.1
26245
29474
2104


886

ELV76555.1
26247
29476
2104


887

ELV98807.1
26249
29478
2104


888

EIN94452.1
26251
29480
2104


889

EKH63851.1
26253
29482
2104


890

EIN88182.1
26255
29484
2104


891

EIN89808.1
26257
29486
2104


892

EIO09765.1
26259
29488
2104


893

EIN49114.1
26261
29490
2104


894

EIO07035.1
26263
29492
2104


895

EIO07406.1
26265
29494
2104


896

EIO11195.1
26267
29496
2104


897

EKH20919.1
26269
29498
2104


898

ELW23234.1
26271
29500
2104


899

EKI33366.1
26273
29502
2104


900

EIO24463.1
26275
29504
2104


901

EKH71757.1
26277
29506
2104


902

EIO49135.1
26279
29508
2104


903

EKH87903.1
26281
29510
2104


904

ELV91644.1
26283
29512
2104


905

ELV93152.1
26285
29514
2104


906

EKH83479.1
26287
29516
2104


907

EIN52368.1
26289
29518
2104


908

EKH07683.1
26291
29520
2104


909

ELW12426.1
26293
29522
2104


910

EIN68648.1
26295
29524
2104


911

ACB19214.1
26297
29526
2104


912

ERE14330.1
26299
29528
2104


913

ERC65825.1
26301
29530
2104


914

ERC74189.1
26303
29532
2104


915

ERC92370.1
26305
29534
2104


916

EGI28995.1
26307
29536
2104


917

EKH95568.1
26309
29538
2104


918

EIO46248.1
26311
29540
2104


919

EIO79506.1
26313
29542
2104


920

EIO65789.1
26315
29544
2106


921

EIO79103.1
26317
29546
2104


922

EIO63560.1
26319
29548
2104


923

EIO69660.1
26321
29550
2104


924

EIP05657.1
26323
29552
2104


925

EIP03388.1
26325
29554
2104


926

ERE42063.1
26327
29556
2104


927

ERE45411.1
26329
29558
2104


928

KDG81462.1
26331
29560
2114


929

KDG84325.1
26333
29562
2114


930

ERB08806.1
26335
29564
2104


931

ERB13350.1
26337
29566
2104


932

EQX93205.1
26339
29568
2114


933

EQY50266.1
26341
29570
2114


934

ERB23701.1
26343
29572
2114


935

EQY93867.1
26345
29574
2114


936

EQZ08532.1
26347
29576
2114


937

EQZ94053.1
26349
29578
2114


938

ERA40555.1
26351
29580
2114


939

CAR16064.1
26353
29582
2114


940

AFJ31995.1
26355
29584
2104


941

KWW01508.1
26357
29586
2113


942

CAQ90578.1
26359
29588
2113


943

EGC09238.1
26361
29590
2114


944

EOW71262.1
26363
29592
2114


945

AJY69764.1
26365
29594
2084


946

EDL62312.1
26367
29596
2084


947

EOD77322.1
26369
29598
2144


948

KJS14046.1
26371
29600
2046


949

EAQ32828.1
26373
29602
2099


950

KXS34467.1
26375
29604
2099


951

CDG80809.1
26377
29606
2106


952

KMK41965.1
26379
29608
2106


953

KMV95474.1
26381
29610
2108


954

EYT05883.1
26383
29612
2108


955

KGK50933.1
26385
29614
2106


956

KHE28071.1
26387
29616
2106


957

KHF57366.1
26389
29618
2106


958

KHQ22239.1
26391
29620
2106


959

KLZ78427.1
26393
29622
2106


960

KMB09547.1
26395
29624
2106


961

KMG65749.1
26397
29626
2108


962

KMG69376.1
26399
29628
2106


963

KMH23798.1
26401
29630
2106


964

KMH84528.1
26403
29632
2106


965

KMX40524.1
26405
29634
2106


966

ALH86088.1
26407
29636
2106


967

KRR31027.1
26409
29638
2108


968

ALQ84490.1
26411
29640
2106


969

ALQ89985.1
26413
29642
2106


970

KSX16169.1
26415
29644
2106


971

KSX18601.1
26417
29646
2106


972

KSX52402.1
26419
29648
2106


973

ALP76744.1
26421
29650
2106


974

KSZ32505.1
26423
29652
2106


975

KUF65064.1
26425
29654
2106


976

KUG47427.1
26427
29656
2106


977

KXO23872.1
26429
29658
2106


978

KYM26278.1
26431
29660
2106


979

ERN57701.1
26433
29662
2082


980

EWE85118.1
26435
29664
2106


981

ESL33173.1
26437
29666
2106


982

KDK59886.1
26439
29668
2106


983

CDK69438.1
26441
29670
2114


984

EMH91682.1
26443
29672
2106


985

EOZ63311.1
26445
29674
2082


986

EOY66995.1
26447
29676
2106


987

ESN46753.1
26449
29678
2108


988

EWF66266.1
26451
29680
2106


989

ESM58757.1
26453
29682
2106


990

KDL89512.1
26455
29684
2108


991

AIX83032.1
26457
29686
2106


992

AIG86151.1
26459
29688
2082


993

EKB81085.1
26461
29690
2106


994

ESM10101.1
26463
29692
2106


995

EPO98451.1
26465
29694
2106


996

EPA89958.1
26467
29696
2106


997

EJI89219.1
26469
29698
2103


998

KDE37040.1
26471
29700
2103


999

CAH16734.1
26473
29702
2106


1000

KTD65146.1
26475
29704
2108


1001

ETX11506.1
26477
29706
2097


1002

ESY80708.1
26479
29708
2007


1003

ESY66205.1
26481
29710
2034


1004

ESY44731.1
26483
29712
2037


1005

KQU80074.1
26485
29714
2042


1006

EMS40059.1
26487
29716
2080


1007

EMS40205.1
26489
29718
2080


1008

KQQ15550.1
26491
29720
2079


1009

KQO59081.1
26493
29722
2002


1010

KQO90918.1
26495
29724
2035


1011

EFV81023.1
26497
29726
1694


1012

EHJ60591.1
26499
29728
1959


1013

AIT79632.1
26501
29730
1987


1014

CCA92392.1
26503
29732
1985


1015

KTS15500.1
26505
29734
2108


1016

KTS86096.1
26507
29736
2108


1017

EFM21232.1
26509
29738
2109


1018

KGA41246.1
26511
29740
2104


1019

ACX87465.1
26513
29742
2104


1020

EAU47586.1
26515
29744
2003


1021

EAS45763.1
26517
29746
2065


1022

KJM66695.1
26519
29748
2105


1023

KMK11833.1
26521
29750
2105


1024

KMK24779.1
26523
29752
2105


1025

KXU56724.1
26525
29754
2024


1026

EGW47202.1
26527
29756
2027


1027

KSX98964.1
26529
29758
2094


1028

KTF11893.1
26531
29760
2100


1029

KGB84628.1
26533
29762
2102


1030

KHE32029.1
26535
29764
2071


1031

KQJ75582.1
26537
29766
2111


1032

KRV15964.1
26539
29768
2071


1033

KSD09758.1
26541
29770
2111


1034

KSD19533.1
26543
29772
2071


1035

KSG03215.1
26545
29774
2071


1036

KSG67481.1
26547
29776
2111


1037

KSE90523.1
26549
29778
2065


1038

KSF67271.1
26551
29780
2111


1039

KSG19233.1
26553
29782
2071


1040

KSG75230.1
26555
29784
2071


1041

KSG85551.1
26557
29786
2071


1042

KSH39435.1
26559
29788
2071


1043

KSH60318.1
26561
29790
2071


1044

KSI21888.1
26563
29792
2071


1045

KSI51647.1
26565
29794
2111


1046

KSI82065.1
26567
29796
2111


1047

KSI99534.1
26569
29798
2071


1048

KSJ34446.1
26571
29800
2111


1049

KSK63577.1
26573
29802
2111


1050

KSL53780.1
26575
29804
2071


1051

KSM73159.1
26577
29806
2111


1052

KSM79529.1
26579
29808
2071


1053

KSN72433.1
26581
29810
2071


1054

KSO70043.1
26583
29812
2065


1055

KSQ54928.1
26585
29814
2071


1056

KSQ13665.1
26587
29816
2071


1057

KSK33061.1
26589
29818
2071


1058

KSL80809.1
26591
29820
2071


1059

KSL64950.1
26593
29822
2071


1060

KSM29110.1
26595
29824
2111


1061

KSN07702.1
26597
29826
2111


1062

KSN22462.1
26599
29828
2111


1063

KSN45602.1
26601
29830
2071


1064

KSO16559.1
26603
29832
2111


1065

KSO84740.1
26605
29834
2071


1066

KSO99160.1
26607
29836
2111


1067

KSQ29773.1
26609
29838
2071


1068

KSR12008.1
26611
29840
2071


1069

KSR96663.1
26613
29842
2063


1070

KSS25407.1
26615
29844
2066


1071

KSS39723.1
26617
29846
2102


1072

KSR72291.1
26619
29848
2071


1073

KSS45916.1
26621
29850
2111


1074

ALY37667.1
26623
29852
2111


1075

ALY62761.1
26625
29854
2111


1076

KXC98055.1
26627
29856
2071


1077

KXC86270.1
26629
29858
2071


1078

KXD25935.1
26631
29860
2071


1079

KXD08976.1
26633
29862
2071


1080

KXD14400.1
26635
29864
2071


1081

KXD23256.1
26637
29866
2071


1082

KXC87701.1
26639
29868
2071


1083

KXF38181.1
26641
29870
2071


1084

KXF47395.1
26643
29872
2071


1085

KXF43344.1
26645
29874
2071


1086

KYO95528.1
26647
29876
2111


1087

KAJ18077.1
26649
29878
2071


1088

ERY57593.1
26651
29880
2071


1089

ERY65607.1
26653
29882
2071


1090

ERV59835.1
26655
29884
2071


1091

ERY33374.1
26657
29886
2071


1092

ERY37451.1
26659
29888
2071


1093

ERY30829.1
26661
29890
2071


1094

ERW68206.1
26663
29892
2071


1095

ERW13882.1
26665
29894
2071


1096

ERV79732.1
26667
29896
2071


1097

ETV52349.1
26669
29898
1470


1098

ERU88468.1
26671
29900
2071


1099

ERU86603.1
26673
29902
2071


1100

KEA15335.1
26675
29904
2071


1101

ERZ32986.1
26677
29906
2071


1102

GAA19670.1
26679
29908
2071


1103

EME92221.1
26681
29910
2111


1104

EYU00121.1
26683
29912
2111


1105

EOT13873.1
26685
29914
2066


1106

ETU84934.1
26687
29916
2068


1107

ERX16723.1
26689
29918
2071


1108

EWH25347.1
26691
29920
2071


1109

GAD64771.1
26693
29922
2066


1110

GAD61323.1
26695
29924
2066


1111

EZQ18206.1
26697
29926
2105


1112

AMO73922.1
26699
29928
2112


1113

KPW38759.1
26701
29930
2073


1114

KQB53691.1
26703
29932
2111


1115

EZI30291.1
26705
29934
2087


1116

KIR22316.1
26707
29936
2085


1117

KJH86793.1
26709
29938
2065


1118

KWV84209.1
26711
29940
2065


1119

EFQ63350.1
26713
29942
2099


1120

KMM97951.1
26715
29944
2111


1121

ENY78086.1
26717
29946
2084


1122

ENA27917.1
26719
29948
1970


1123

EWC41755.1
26721
29950
1771


1124

EMD98966.1
26723
29952
2068


1125

KPB88882.1
26725
29954
1448


1126

KFD13679.1
26727
29956
2106


1127

ACE91184.1
26729
29958
2041


1128

KKZ86596.1
26731
29960
2036


1129

KQU04981.1
26733
29962
2042


1130

CCF21881.1
26735
29964
1778


1131

KQZ63426.1
26737
29966
2007


1132

KIV64827.1
26739
29968
2033


1133

KQB14222.1
26741
29970
2012


1134

KQB14197.1
26743
29972
2012


1135

ETX15683.1
26745
29974
2020


1136

KJS41398.1
26747
29976
1995


1137

EPX84387.1
26749
29978
1417


1138

GAS73920.1
26751
29980
2106


1139

GAS79508.1
26753
29982
2106


1140

KHP17885.1
26755
29984
2106


1141

KHP06994.1
26757
29986
2106


1142

ESJ40086.1
26759
29988
2106


1143

KNB22031.1
26761
29990
2106


1144

AJD94187.1
26763
29992
2106


1145

AJD98581.1
26765
29994
2106


1146

CEA95105.1
26767
29996
2106


1147

CEB50843.1
26769
29998
2106


1148

CDU93374.1
26771
30000
2106


1149

CEB74773.1
26773
30002
2106


1150

CED02079.1
26775
30004
2106


1151

CEC70256.1
26777
30006
2106


1152

CDZ07208.1
26779
30008
2106


1153

CED89041.1
26781
30010
2106


1154

CDV50414.1
26783
30012
2106


1155

CFW88482.1
26785
30014
2106


1156

CDZ03619.1
26787
30016
2106


1157

CEC95426.1
26789
30018
2106


1158

CDV33411.1
26791
30020
2106


1159

CEB60520.1
26793
30022
2106


1160

CEC11581.1
26795
30024
2106


1161

CEA33004.1
26797
30026
2106


1162

CDV54740.1
26799
30028
2106


1163

CEA34479.1
26801
30030
2106


1164

CED50260.1
26803
30032
2106


1165

CEC06544.1
26805
30034
2106


1166

CDY81479.1
26807
30036
2106


1167

CEC66459.1
26809
30038
2106


1168

CDU75276.1
26811
30040
2106


1169

CDV02402.1
26813
30042
2106


1170

CDU44889.1
26815
30044
2106


1171

CEA82129.1
26817
30046
2106


1172

CDV48179.1
26819
30048
2106


1173

CEA48949.1
26821
30050
2106


1174

CDU62790.1
26823
30052
2106


1175

CDV82103.1
26825
30054
2106


1176

CEC15870.1
26827
30056
2106


1177

CEB34159.1
26829
30058
2106


1178

CEC22809.1
26831
30060
2106


1179

CEC29439.1
26833
30062
2106


1180

CEC81190.1
26835
30064
2106


1181

CEC27073.1
26837
30066
2106


1182

CDV36502.1
26839
30068
2106


1183

CDV99879.1
26841
30070
2106


1184

CEB21249.1
26843
30072
2106


1185

CED29538.1
26845
30074
2106


1186

CEA65653.1
26847
30076
2106


1187

CDV77393.1
26849
30078
2106


1188

CEB99322.1
26851
30080
2106


1189

CEC87091.1
26853
30082
2106


1190

CEC03349.1
26855
30084
2106


1191

CDW68451.1
26857
30086
2106


1192

CEB36538.1
26859
30088
2106


1193

CEB92475.1
26861
30090
2106


1194

CEC70642.1
26863
30092
2106


1195

CED19417.1
26865
30094
2106


1196

CDU57393.1
26867
30096
2106


1197

CEC55614.1
26869
30098
2106


1198

CDW10769.1
26871
30100
2106


1199

CED40434.1
26873
30102
2106


1200

CEA77527.1
26875
30104
2106


1201

CEC78576.1
26877
30106
2106


1202

CDV87318.1
26879
30108
2106


1203

CEA60260.1
26881
30110
2106


1204

CDU45976.1
26883
30112
2106


1205

CED26176.1
26885
30114
2106


1206

CEA55542.1
26887
30116
2106


1207

CDU57356.1
26889
30118
2106


1208

CEC22620.1
26891
30120
2106


1209

CDU81239.1
26893
30122
2106


1210

CEC22198.1
26895
30124
2106


1211

CDV00136.1
26897
30126
2106


1212

CDV32907.1
26899
30128
2106


1213

CEB32341.1
26901
30130
2106


1214

CDU66154.1
26903
30132
2106


1215

CEB23430.1
26905
30134
2106


1216

CEA69988.1
26907
30136
2106


1217

CED34529.1
26909
30138
2106


1218

CDU60154.1
26911
30140
2106


1219

CEB02150.1
26913
30142
2106


1220

CDV16494.1
26915
30144
2106


1221

CEA70647.1
26917
30146
2106


1222

CEB86467.1
26919
30148
2106


1223

CDV63738.1
26921
30150
2106


1224

CEB22316.1
26923
30152
2106


1225

CDY85018.1
26925
30154
2106


1226

CDY91991.1
26927
30156
2106


1227

CDV63669.1
26929
30158
2106


1228

CDV76959.1
26931
30160
2106


1229

CDV25167.1
26933
30162
2106


1230

CEA29072.1
26935
30164
2106


1231

CEC16650.1
26937
30166
2106


1232

CDV58579.1
26939
30168
2106


1233

CDV98717.1
26941
30170
2106


1234

CED02849.1
26943
30172
2106


1235

CDU96709.1
26945
30174
2106


1236

CEB76238.1
26947
30176
2106


1237

CEC37117.1
26949
30178
2106


1238

CDU99401.1
26951
30180
2106


1239

CEB54811.1
26953
30182
2106


1240

CEC86156.1
26955
30184
2106


1241

CDV41199.1
26957
30186
2106


1242

CDV19346.1
26959
30188
2106


1243

CEA51459.1
26961
30190
2106


1244

CEA31321.1
26963
30192
2106


1245

CEC70728.1
26965
30194
2106


1246

CEB55402.1
26967
30196
2106


1247

CED14441.1
26969
30198
2106


1248

CED18823.1
26971
30200
2106


1249

CEB11068.1
26973
30202
2106


1250

CEA27404.1
26975
30204
2106


1251

CED08652.1
26977
30206
2106


1252

CEB93594.1
26979
30208
2106


1253

CDY97806.1
26981
30210
2106


1254

CEA81537.1
26983
30212
2106


1255

CEA95804.1
26985
30214
2106


1256

CED39167.1
26987
30216
2106


1257

CEC46303.1
26989
30218
2106


1258

CEB93174.1
26991
30220
2106


1259

CEB06233.1
26993
30222
2106


1260

CEC59899.1
26995
30224
2106


1261

CDW11869.1
26997
30226
2106


1262

CEB87176.1
26999
30228
2106


1263

CDU53202.1
27001
30230
2106


1264

CEB57382.1
27003
30232
2106


1265

CED48957.1
27005
30234
2106


1266

CDW00036.1
27007
30236
2106


1267

CDV01782.1
27009
30238
2106


1268

CEA40515.1
27011
30240
2106


1269

CEB13671.1
27013
30242
2106


1270

CEA18907.1
27015
30244
2106


1271

CDY92810.1
27017
30246
2106


1272

CEA88151.1
27019
30248
2106


1273

AKO82197.1
27021
30250
2106


1274

CAR62300.1
27023
30252
2106


1275

ESF93194.1
27025
30254
2106


1276

AAV80042.1
27027
30256
2106


1277

EPE40530.1
27029
30258
2106


1278

EPE40312.1
27031
30260
2106


1279

EPE40094.1
27033
30262
2106


1280

KSB43365.1
27035
30264
2106


1281

ELX27348.1
27037
30266
2106


1282

EHC78169.1
27039
30268
2106


1283

ESF47592.1
27041
30270
2106


1284

CUS01661.1
27043
30272
2106


1285

CUS00363.1
27045
30274
2106


1286

CUS00365.1
27047
30276
2106


1287

CUS00364.1
27049
30278
2106


1288

CBY96201.1
27051
30280
2106


1289

EDZ29121.1
27053
30282
2106


1290

KNM15295.1
27055
30284
2106


1291

KNM69140.1
27057
30286
2106


1292

KNO58854.1
27059
30288
2106


1293

KNW78917.1
27061
30290
2106


1294

KTZ77423.1
27063
30292
2106


1295

KUC23741.1
27065
30294
2106


1296

ESF03066.1
27067
30296
2106


1297

KMJ09049.1
27069
30298
2106


1298

CVG51413.1
27071
30300
1441


1299

CVB32145.1
27073
30302
1441


1300

EZQ69787.1
27075
30304
2106


1301

EFE97640.1
27077
30306
2084


1302

KFK98826.1
27079
30308
2114


1303

KFK92331.1
27081
30310
2114


1304

ABK48269.1
27083
30312
2120


1305

AFJ48530.1
27085
30314
2106


1306

GAB81433.1
27087
30316
2106


1307

ACP25985.1
27089
30318
2042


1308

CAN98362.1
27091
30320
2099


1309

EPR18398.1
27093
30322
1312


1310

KKW93259.1
27095
30324
1989


1311

CCW17775.1
27097
30326
1558


1312

KER36316.1
27099
30328
1987


1313

KQM97530.1
27101
30330
1999


1314

KPV39946.1
27103
30332
2084


1315

KQW61501.1
27105
30334
2113


1316

KLE23444.1
27107
30336
2066


1317

EDL70258.1
27109
30338
1452


1318

KHD25449.1
27111
30340
2145


1319

KFE26121.1
27113
30342
2068


1320

KFD94244.1
27115
30344
2068


1321

EJH60535.1
27117
30346
2104


1322

EMQ54782.1
27119
30348
2068


1323

KNA52262.1
27121
30350
2068


1324

GAD79748.1
27123
30352
2141


1325

KNY42355.1
27125
30354
2065


1326

KHF16000.1
27127
30356
2066


1327

KOF25301.1
27129
30358
2068


1328

KHT39219.1
27131
30360
2104


1329

KYN85117.1
27133
30362
2068


1330

EKM24799.1
27135
30364
2143


1331

CDU08194.1
27137
30366
2107


1332

CAV18548.1
27139
30368
2085


1333

KWU01490.1
27141
30370
2066


1334

KOO13422.1
27143
30372
2065


1335

CNI05795.1
27145
30374
2106


1336

CQJ58418.1
27147
30376
2106


1337

CQJ21067.1
27149
30378
2109


1338

CFR01911.1
27151
30380
2106


1339

CNH31705.1
27153
30382
2106


1340

CFV22963.1
27155
30384
2106


1341

KFE39720.1
27157
30386
2106


1342

AKA39096.1
27159
30388
2106


1343

EHM51572.1
27161
30390
2082










(Part D)


















AO



AS







DruG



DruH



AN
protein
AP
AQ
AR
protein
AT
AU



DNA SEQ
length
DruH
PRT SEQ
DNA SEQ
length
Genomic Start
Genomic End
AV


1
ID NO:
(aa)
protein_accession
ID NO:
ID NO:
(aa)
Point
Point
Comments





2






285161
295071


3






23658
35022


4






122429
132246


5






5336
16034


6






5300
15998


7






4236
14105


8






859665
869540


9






346656
356168


10






43741
53633


11






227293
237188


12






1304116
1314874


13






704089
714847


14






1053641
1062444


15






2593529
2604285


16






102484
110617


17






718104
726907


18






621905
629933


19






58930
69532


20






130247
138278


21






3789
14436


22






7008
18501


23






650
9027


24






5201
16574


25






245534
255452


26






2444
10852


27






252885
262420


28






692119
701372


29






3488434
3497693


30






1381151
1390413


31






26796
38135


32






86252
97591


33






1
7760


34






226285
237624


35






825
12164


36






45166
56505


37






6539
17878


38






2707610
2718949


39






111135
122474


40






26765
38104


41






1618476
1629815


42






389081
400420


43






189561
200900


44






33964
45303


45






316476
327815


46






198709
210048


47






203020
214359


48






3735099
3746438


49






170794
182133


50






170697
182036


51






395842
407181


52






314697
326036


53






2239
13578


54






1513766
1525105


55






318207
329546


56






23620
34959


57






90793
102132


58






1
8155


59






30224
41563


60






31431
41533


61






393726
405065


62






1485066
1496405


63






318709
330048


64






7772
17322


65






57001
66608


66






84320
94149


67






1
9036


68






2431766
2441378


69






298110
307722


70






1
9075


71






68076
77685


72






678847
689572


73






267564
278272


74






993973
1004769


75






1471479
1481221


76






1814944
1833410


77






756187
764469


78






273674
283215


79






33201
43136


80






82360
93087


81






207
10677


82






2573999
2584115


83






17690
27795


84






88811
98680


85






233470
243330


86






1894236
1904088


87






18610
29425


88






225
10961


89






5302
15990


90






48622
58258


91






1226195
1236109


92






340028
351370


93






2729
13414


94






426089
435318


95






245308
254531


96






6222
17587


97






10445
17368


98






1131
12496


99






2602750
2614148


100






27199
38358


101






2402449
2413847


102






383162
394525


103






1671024
1682422


104






137353
148718


105






36724
47675


106






3018853
3030235


107






149958
161333


108






17322
28685


109






150639
162037


110






34865
46258


111






19937
31423


112






2177440
2186149


113






118192
128839


114






443806
454453


115






2764522
2775796


116






8919
17199


117






83723
99028


118






10459
21092


119






5588864
5599650


120






2918005
2927268


121






8795
20113


122






808851
820169


123






232897
244248


124
27659
699




112735
123898


125






79463
92802


126






220561
233009


127
27669
639




246334
258609


128






1958381
1969570


129






3844801
3855950


130
27679
696




7678787
7690517


131
27683
689




2014187
2025976


132
27686
700




550646
561413


133
27690
707




5526
17650


134
27694
716




112272
128556


135
27697
541




308758
321298


136
27700
541




305254
317794


137
27704
655




46911
59042


138
27708
655




104315
116446


139
27711
541




5069
17609


140






27101
39571


141






80817
95890


142






1127089
1138713


143
27724
926




4083820
4096459


144
27728
696




701693
713454


145
27732
698




337549
349277


146






2777
14206


147
27739
695




5370773
5382607


148






1480736
1493419


149
27746
695




1679797
1691556


150
27750
926




220348
232987


151
27754
926




6453
19092


152
27758
926




46058
58697


153
27761
926




46480
59113


154
27765
937




96516
109246


155
27769
937




1092
13822


156
27773
937




96516
109246


157
27777
937




96516
109246


158
27781
937




96516
109246


159
27785
937




96516
109246


160
27789
937




96516
109246


161
27793
937




96516
109246


162
27797
937




96516
109246


163
27801
937




96516
109246


164
27805
937




96516
109246


165
27809
937




96516
109246


166
27813
690




581118
592872


167
27817
937




115861
128591


168
27821
937




96538
109268


169
27825
926




1528
14167


170
27829
754




4194850
4207568


171






3329
19651


172






39907
50236


173
27839
696




2598976
2610644


174
27843
937




5340349
5353079


175






236820
251252


176
27850
872




66102
80532


177






1203521
1214561


178
27857
684




5406366
5418388


179
27861
715




4827708
4839442


180






49526
60017


181






3247787
3258736


182






4110265
4122706


183
27874
695




163466
175215


184






8136
20398


185






5149282
5160143


186






6943666
6954529


187






115793
125399


188






2162370
2172185


189
27893
696




43659
55415


190
27896
530




441
12638


191
27900
940




1385409
1398159


192
27904
931




2442587
2455235


193
27908
938




864468
877224


194
27911
711




3263838
3274393


195
27914
711




4548827
4559382


196
27917
711




63393
73948


197
27920
711




743
11298


198
27924
711




72805
84541


199
27928
711




72805
84541


200
27931
711




741
11296


201
27935
711




72805
84541


202
27939
711




72805
84541


203
27943
711




70442
82178


204
27947
711




37743
49479


205
27951
711




982
12718


206
27955
711




72805
84541


207
27959
711




205420
217156


208
27963
711




915
12651


209
27967
711




72805
84541


210
27971
711




977
12713


211
27975
711




72805
84541


212
27978
697




5833
16378


213
27982
711




915
12651


214
27986
711




988
12724


215
27990
711




915
12651


216
27994
711




72805
84541


217
27997
697




5631
16176


218
28001
711




72805
84541


219
28005
711




72805
84541


220
28009
711




915
12651


221
28013
711




915
12651


222
28017
711




732
12468


223
28021
711




72805
84541


224
28024
711




2632018
2642573


225
28028
711




2471032
2482723


226
28032
711




795908
807599


227
28036
711




2515204
2526895


228
28040
711




3347675
3359366


229
28044
711




73643
85334


230
28048
697




353197
365180


231
28052
711




3317256
3328947


232
28056
710




2412440
2424132


233
28060
711




328927
340618


234
28063
713




90286
99824


235
28066
711




3447532
3458087


236
28070
711




2935764
2947455


237
28074
711




27284
38975


238
28078
712




3467956
3479700


239
28082
711




128157
139861


240
28086
711




39127
50831


241
28090
611




18407
30437


242
28094
697




18502
30466


243
28098
697




119061
131025


244
28102
697




18386
30416


245
28105
627




1131
11369


246
28109
688




51400
63317


247
28112
688




25409
35277


248






619907
631929


249
28119
926




86254
98887


250
28123
698




84624
96349


251
28127
698




260934
272659


252
28131
698




260934
272659


253
28135
926




138803
151436


254
28139
698




254096
265821


255
28143
698




84624
96349


256
28147
698




260934
272659


257
28151
698




260934
272659


258
28155
698




84624
96349


259
28159
698




84624
96349


260
28163
698




84624
96349


261
28167
698




105497
117255


262
28171
698




941313
953071


263
28175
926




36048
48681


264
28178
926




1
10627


265
28182
926




4052
16685


266
28186
698




75007
86783


267
28190
698




3128238
3139966


268
28194
698




117975
129703


269
28198
926




30971
43604


270
28202
926




55282
67915


271
28205
926




1886892
1899525


272
28209
926




2821816
2834449


273
28213
679




4744370
4757010


274
28217
926




4554614
4567253


275
28221
926




4646084
4658723


276
28225
679




4811280
4823920


277
28229
926




149904
162543


278
28233
618




11206
23846


279
28237
695




4232584
4244337


280
28240
695




3948
15701


281
28244
693




3412342
3424101


282
28248
696




92338
104097


283






3419212
3429296


284






3422352
3432436


285
28258
639




16523
28443


286






3523471
3533850


287






1624260
1637507


288






12158
24902


289
28271
938




39835
52569


290
28275
938




225795
238529


291
28279
929




32560
45315


292
28283
938




1842
14576


293
28287
929




288594
301349


294
28291
938




4116123
4128871


295
28295
901




101530
114278


296


KXV70697.1
25068
28297
557
3917
12134


297


AKQ30570.1
25070
28299
1096
1915082
1924692


298


KOP86149.1
25072
28301
1096
5407
15017


299


KRS04353.1
25074
28303
1096
11453
21063


300


KRS02341.1
25076
28305
1096
71328
80938


301


KRS03108.1
25078
28307
1096
11453
21063


302


KRR94713.1
25080
28309
1096
29556
39166


303


KRS09272.1
25082
28311
1096
71328
80938


304


EXE63525.1
25084
28313
1096
695254
704870


305


EXC47767.1
25086
28315
1122
5489
15158


306


ELW93014.1
25088
28317
1096
15113
24729


307


ENW35932.1
25090
28319
404
469715
477249


308


ENW44601.1
25092
28321
1097
573781
583394


309


ENW49013.1
25094
28323
1122
463130
472796


310


EKP68253.1
25096
28325
1122
270846
280512


311


EKL42058.1
25098
28327
1096
30124
39734


312


ENV15229.1
25100
28329
1120
3309500
3319165


313


ENX21438.1
25102
28331
1097
509761
519374


314


ENV06098.1
25104
28333
1122
771437
781106


315


EDS03748.1
25106
28335
1065
88763
98100


316


AMN11449.1
25108
28337
1132
1725136
1734833


317


AFT94988.1
25110
28339
1132
1765863
1775560


318


EGF91080.1
25112
28341
1147
331550
341110


319


ESQ74518.1
25114
28343
1147
32073
41627


320


CAL94924.1
25116
28345
1192
2527848
2537752


321


AJE23875.1
25118
28347
1110
197536
206001


322


CUA18546.1
25120
28349
1065
2356943
2366283


323


CBW22537.1
25122
28351
1065
2371910
2381250


324


EYA28062.1
25124
28353
1065
293528
302868


325


EYA33840.1
25126
28355
1037
163999
173255


326


EXY44319.1
25128
28357
1052
187
9488


327


EYB10317.1
25130
28359
1065
1271019
1280359


328


EXZ67957.1
25132
28361
1037
20085
29341


329


EXY49047.1
25134
28363
1065
152
9492


330


EXY53776.1
25136
28365
1065
152
9492


331


EDS16319.1
25138
28367
1065
257362
266699


332


KXT38968.1
25140
28369
1065
23341
32678


333


EGW44031.1
25142
28371
1115
780950
790461


334


EEA03716.1
25144
28373
1107
62115
71698


335


KVM07645.1
25146
28375
1046
33574
42969


336


KVM11422.1
25148
28377
1046
33574
42969


337


KVM41743.1
25150
28379
1046
33574
42969


338


KVU39939.1
25152
28381
247
370491
377497


339


KVX50940.1
25154
28383
1046
44196
53591


340


CDH43329.1
25156
28385
655
4045
12202


341


KPA18786.1
25158
28387
1131
595
10180


342


AIY12567.1
25160
28389
1006
1117511
1126448


343


EYF08671.1
25162
28391
1135
53327
62186


344


KQM35754.1
25164
28393
995
5095
13992


345


ALD78155.1
25166
28395
212
3535505
3542469


346


KPR54497.1
25168
28397
1099
99
9732


347


KLV49874.1
25170
28399
1204
585396
595495


348


KLV71166.1
25172
28401
1099
3121291
3130924


349


BAO81223.1
25174
28403
1185
1467812
1477691


350


ALB51924.1
25176
28405
581
3364334
3372410


351


AGE87744.1
25178
28407
581
3364989
3373065


352


KJR98716.1
25180
28409
1125
158922
168526


353


KLE94550.1
25182
28411
1099
34358
43990


354


KLF52639.1
25184
28413
1095
284140
293760


355


KLW28644.1
25186
28415
1099
100681
110313


356


KLW04618.1
25188
28417
1099
307954
317586


357


KLQ05989.1
25190
28419
978
81311
90573


358


KJI56237.1
25192
28421
978
146027
155289


359


KLP80554.1
25194
28423
736
56455
64988


360


KLW09756.1
25196
28425
1098
216709
226328


361


KLW05114.1
25198
28427
1098
663448
673067


362


KUQ64465.1
25200
28429
1098
1
9538


363


KUQ79075.1
25202
28431
736
1
8452


364


KPS33775.1
25204
28433
1098
80541
90160


365


ESL79956.1
25206
28435
981
2192087
2201355


366


KLW78404.1
25208
28437
736
3877717
3886250


367


KFC20757.1
25210
28439
1007
9124
18004


368


AKQ40860.1
25212
28441
1098
94495
103750


369


EDL49428.1
25214
28443
1099
20106
29358


370


KDM84273.1
25216
28445
978
6814
16064


371


CDU40544.1
25218
28447
1096
393610
403257


372


KHJ28073.1
25220
28449
1096
77599
87246


373


KHI41603.1
25222
28451
978
158488
167738


374


KHH60356.1
25224
28453
1096
25725
35372


375


KHH50449.1
25226
28455
1096
78872
88519


376


KHI22271.1
25228
28457
978
6097
15347


377


KHH70906.1
25230
28459
1096
36388
46035


378


KIG29579.1
25232
28461
978
23204
32454


379


AJE58951.1
25234
28463
1112
4932802
4942497


380


KIY28286.1
25236
28465
978
14480
23730


381


KIZ10080.1
25238
28467
978
13870
23120


382


KJJ46597.1
25240
28469
978
70937
80187


383


KJW55358.1
25242
28471
978
141103
150353


384


KJW51708.1
25244
28473
978
107073
116323


385


KLG52822.1
25246
28475
978
104422
113672


386


KLX28161.1
25248
28477
1096
4718573
4728220


387


KNF16924.1
25250
28479
978
6097
15347


388


KNF21006.1
25252
28481
978
104562
113812


389


KNF39647.1
25254
28483
978
6770
16020


390


KNG41000.1
25256
28485
978
150782
160032


391


KNZ99176.1
25258
28487
1096
44216
53863


392


KOZ12890.1
25260
28489
978
82598
91848


393


KOZ62952.1
25262
28491
978
13754
23004


394


KOZ92097.1
25264
28493
978
37881
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395


KOZ11136.1
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396


KOZ14878.1
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252679
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KOZ33113.1
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79917
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398


KOZ23285.1
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351820
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KOZ38041.1
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13755
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401


KOZ50107.1
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351727
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402


KOZ47197.1
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13752
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403


KOZ49679.1
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351882
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404


KOZ66206.1
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71615
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405


KOZ69711.1
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351658
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406


KOZ74971.1
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21854
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407


KOZ84785.1
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408


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70889
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409


KOZ97703.1
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140404
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410


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411


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2323
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413


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429


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432


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433


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436


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442


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448


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451


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454


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455


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456


KXR08921.1
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458


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459


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460


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461


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463


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465


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466


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80083
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467


ELV15310.1
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468


EKK91184.1
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10348
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469


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471


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472


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473


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474


ESA76410.1
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475


EZJ86914.1
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476


KEO21428.1
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477


KDA70971.1
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478


KDS94687.1
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479


KDT14123.1
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29694
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480


KEN70535.1
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481


KDV77073.1
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29694
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482


KDW26987.1
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483


KEN84156.1
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824
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484


KEO02788.1
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667
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485


KDX84121.1
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30771
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486


KEJ20442.1
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12363
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487


KEJ21098.1
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12378
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488


EMX91852.1
25452
28681
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75564
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489


EMW69585.1
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28683
580
227
8326


490


EMW64103.1
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28685
580
250
8349


491


EMW45431.1
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28687
580
353
8452


492


EMV86374.1
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228
811
7854


493


ENA88226.1
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8462


494


ENB03533.1
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1250
8293


495


ERD09265.1
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14046
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496


EKK37395.1
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13796
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497


ELW28318.1
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28699
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13976
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498


KDT83307.1
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16955
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499


KEK80771.1
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51355
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500


KEL07352.1
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15020
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501


KEK94608.1
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17085
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502


EKK36705.1
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13809
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503


EKI06061.1
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70939
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504


EIL64996.1
25484
28713
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48987
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505


EKI02733.1
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71504
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506


KEL97938.1
25488
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5160
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507


KEM08516.1
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28719
1119
17042
26715


508


KEM49611.1
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28721
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17146
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509


KEN01217.1
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28723
648
970
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510


KEM09156.1
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28725
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1056
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511


KEM25600.1
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28727
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1069
9372


512


KEM85725.1
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16764
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513


KEN65097.1
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4411
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514


ELW21806.1
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28733
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23163
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515


EKK71768.1
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72931
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516


EKK61090.1
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13790
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517


EKK52334.1
25510
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13792
23042


518


EKK87668.1
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81736
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519


EKV85100.1
25514
28743
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13804
23054


520


EKV70654.1
25516
28745
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13802
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521


EKW05773.1
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28747
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79877
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522


EKW03271.1
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28749
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13798
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523


ESD10540.1
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4185
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524


ESA83484.1
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48996
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525


ESD19200.1
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399
1
7559


526


ESD45642.1
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48833
58528


527


ESD61125.1
25530
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18577
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528


ESD71192.1
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20331
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529


ESD92013.1
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60634
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530


ESD92685.1
25536
28765
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1234
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531


EKW04268.1
25538
28767
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13806
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532


EKW19025.1
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13808
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533


EIN33838.1
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13788
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534


EKW08488.1
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13808
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535


ELW29952.1
25546
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2439
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536


EKW22422.1
25548
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7070


537


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13790
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538


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13806
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539


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25554
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13800
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540


EKW51347.1
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13792
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541


EKW70676.1
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79810
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542


EKW68014.1
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14005
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543


EKW71372.1
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10852
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544


EKY34709.1
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416
10083


545


EKW75843.1
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13959
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546


ELW46372.1
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13998
23248


547


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548


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13993
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549


ELV31250.1
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30317
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550


ELV35524.1
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30154
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551


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842
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552


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13946
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553


ELV47168.1
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13933
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554


ELW24263.1
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4040
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555


ELV62897.1
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19714
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556


ETJ70883.1
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37993
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557


ELV63260.1
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4590
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558


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4256022
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559


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15819
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560


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13919
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561


ERD08337.1
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14296
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562


ERD05021.1
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14116
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563


ERD20748.1
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14235
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564


ERD22951.1
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14065
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565


ERB79217.1
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81295
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566


ERD23992.1
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13981
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567


ERD35316.1
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14139
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568


ERD37185.1
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14019
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569


ERD26786.1
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19748
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570


ERD52931.1
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14048
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571


ERD40232.1
25618
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14087
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572


ERD45129.1
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14048
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573


ERB91861.1
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81300
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574


ERC00104.1
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81417
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575


ERC08312.1
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14059
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576


ERC07682.1
25628
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13951
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577


ERC15339.1
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13964
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578


ERC23446.1
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1
7395


579


ERC10660.1
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13969
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580


ERC32306.1
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13936
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581


ERD72599.1
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14036
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582


ERD68377.1
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13984
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583


ERD73456.1
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14079
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584


ERD83189.1
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13972
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585


ERC25311.1
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253340
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586


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253529
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587


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14029
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588


ERD91777.1
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14154
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589


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14071
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590


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14016
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591


ERE36112.1
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14071
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592


ERE23641.1
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4432
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593


ERC33935.1
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256038
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594


ERC40342.1
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252555
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595


ERC48259.1
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317955
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596


ETY20410.1
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597


ETY13488.1
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598


ETY13649.1
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599


ETY08683.1
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600


ETX96686.1
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601


ERO99483.1
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602


ETY35401.1
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603


ETY29967.1
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604


ESL20615.1
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2595377
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605


ETX82125.1
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606


ETX76975.1
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607


ETY61261.1
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608


EZQ66603.1
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609


ETY23956.1
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610


EKH96739.1
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13540
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611


CDU33064.1
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612


EHV18500.1
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613


EIP71502.1
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14462
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614


EKI46647.1
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13801
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615


EKI57123.1
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616


EKI59125.1
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13801
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617


EIP63440.1
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618


EIP72314.1
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30328
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619


EKI64840.1
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30338
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620


EKI72764.1
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30328
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621


EKI91871.1
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79661
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622


EKI82676.1
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30380
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623


EKJ05365.1
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30254
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624


EKI92954.1
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116536
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625


EKJ00853.1
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27618
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626


EIP72927.1
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13800
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627


EKJ19826.1
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13802
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628


EKJ20863.1
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13806
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629


EKJ36028.1
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13806
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630


EKJ47664.1
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13808
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631


EKJ36500.1
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13802
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632


EIP38854.1
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633


EIO92502.1
25742
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30370
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634


EIO87495.1
25744
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30410
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635


EIP27285.1
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858
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636


EIP10340.1
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13800
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637


EIP33943.1
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13798
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638


EIP40273.1
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13804
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639


EIP48989.1
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13794
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640


EIP35348.1
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30343
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641


EIP50031.1
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30347
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642


EKI03042.1
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13596
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643


EST65290.1
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644


EMX76367.1
25764
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49211
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645


EMX78113.1
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53674
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646


EKH36316.1
25768
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13812
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647


EIN15910.1
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13808
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648


EKH25287.1
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332440
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649


EKH13353.1
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13810
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650


EIN16633.1
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384
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651


EIN33028.1
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392
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652


EKH48831.1
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13808
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653


EKJ48108.1
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13813
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654


EFI22363.1
25784
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655


EFF02930.1
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656


EQN36979.1
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657


EQQ54037.1
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658


EQQ62152.1
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659


EQQ82444.1
25794
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390614
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660


EQR15649.1
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661


EQR29833.1
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710


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716


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719


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720


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721


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730


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731


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732


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733


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736


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737


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746


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748


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749


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750


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756


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757


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758


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759


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760


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761


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762


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763


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764


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765


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766


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767


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768


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80155
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769


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770


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771


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251411
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772


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302523
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773


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250164
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774


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775


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776


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777


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778


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780


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781


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782


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783


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784


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793


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351733
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795


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796


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80111
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797


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351749
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798


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80139
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799


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351749
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800


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801


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351681
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3701544
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804


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82700
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808


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2713466
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810


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811


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812


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80068
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815


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816


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817


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818


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819


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820


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821


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825


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826


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827


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14769
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828


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488
1
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829


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20977
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830


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14053
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831


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832


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833


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834


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835


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836


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838


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839


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840


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841


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842


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14637
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843


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844


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846


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847


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848


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850


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851


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852


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853


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854


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855


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856


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858


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859


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860


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861


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12253
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862


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280
1
7159


863


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864


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865


ENA10895.1
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866


EMZ79274.1
26208
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79591
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867


ENG24752.1
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868


ENG35038.1
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8407


869


ENG38630.1
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8398


870


END33528.1
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225
8324


871


ENE04445.1
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299
8398


872


ENG47568.1
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8377


873


ENG50953.1
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274
8373


874


ENG56304.1
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580
275
8374


875


ENG57263.1
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248
8347


876


ENH40673.1
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580
249
8348


877


ENG66729.1
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580
341
8440


878


ENG74276.1
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133
8436


879


EST67461.1
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52346
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880


EST67375.1
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26084
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881


EIN65415.1
26238
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15190
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882


ELV75968.1
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13903
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883


ELV90963.1
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4036
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884


EIN69804.1
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13804
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885


EIN85520.1
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886


ELV76554.1
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22913
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887


ELV98806.1
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13633
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888


EIN94345.1
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982
80889
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889


EKH63850.1
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13810
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890


EIN88191.1
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30257
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891


EIN89776.1
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116447
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892


EIO09773.1
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13804
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893


EIN49113.1
26262
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30335
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894


EIO07042.1
26264
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13806
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895


EIO07418.1
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896


EIO11194.1
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13808
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897


EKH20918.1
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13807
23057


898


ELW23233.1
26272
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4450
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899


EKI33365.1
26274
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1119
328
10001


900


EIO24462.1
26276
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233
60
7075


901


EKH71762.1
26278
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13807
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902


EIO49153.1
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13808
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903


EKH87902.1
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13810
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904


ELV91643.1
26284
29513
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30222
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905


ELV93151.1
26286
29515
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6984
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906


EKH83462.1
26288
29517
978
13812
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907


EIN52367.1
26290
29519
978
13804
23054


908


EKH07682.1
26292
29521
978
369039
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909


ELW12425.1
26294
29523
978
13985
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910


EIN68647.1
26296
29525
978
13804
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911


ACB20170.1
26298
29527
1119
4912969
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912


ERE14329.1
26300
29529
978
82268
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913


ERC65824.1
26302
29531
978
80921
90171


914


ERC74188.1
26304
29533
287
14108
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915


ERC92369.1
26306
29535
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4611
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916


EGI28994.1
26308
29537
1119
296390
306063


917


EKH95567.1
26310
29539
978
13812
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918


EIO46356.1
26312
29541
978
245564
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919


EIO79510.1
26314
29543
978
7053
16303


920


EIO65811.1
26316
29545
978
13799
23055


921


EIO79102.1
26318
29547
982
81173
90435


922


EIO63487.1
26320
29549
978
254421
263671


923


EIO69659.1
26322
29551
978
14347
23597


924


EIP05663.1
26324
29553
978
11135
20385


925


EIP03387.1
26326
29555
375
1
7442


926


ERE42062.1
26328
29557
978
80488
89738


927


ERE45410.1
26330
29559
978
80936
90186


928


KDG81461.1
26332
29561
1096
4589703
4599350


929


KDG84324.1
26334
29563
1096
577940
587587


930


ERB08805.1
26336
29565
1119
3410757
3420430


931


ERB13351.1
26338
29567
1119
312752
322425


932


EQX93206.1
26340
29569
1096
1299123
1308770


933


EQY50265.1
26342
29571
333
972500
979858


934


ERB23700.1
26344
29573
580
575397
583496


935


EQY93866.1
26346
29575
580
381918
390017


936


EQZ08531.1
26348
29577
1096
4369199
4378846


937


EQZ94052.1
26350
29579
1096
413548
423195


938


ERA40554.1
26352
29581
1096
440488
450135


939


CAR16063.1
26354
29583
1112
5111725
5121420


940


AFJ31994.1
26356
29585
1117
5251667
5261334


941


KWW01507.1
26358
29587
1096
161157
170801


942


CAQ90579.1
26360
29589
1112
3162768
3172460


943


EGC09237.1
26362
29591
1096
152611
162258


944


EOW71261.1
26364
29593
894
3729077
3738118


945


AJY69763.1
26366
29595
1141
2031423
2041104


946


EDL62311.1
26368
29597
1176
180740
190521


947


EOD77323.1
26370
29599
1172
615
10570


948


KJS14045.1
26372
29601
1149
1372
10961


949


EAQ32829.1
26374
29603
1113
307409
317059


950


KXS34468.1
26376
29605
1113
44606
54256


951


CDG80808.1
26378
29607
1090
170928
180527


952


KMK41964.1
26380
29609
1095
35196
44816


953


KMV95473.1
26382
29611
1117
1146551
1156230


954


EYT05882.1
26384
29613
1117
319260
328939


955


KGK50932.1
26386
29615
1095
410829
420449


956


KHE28070.1
26388
29617
1099
5171646
5181278


957


KHF57367.1
26390
29619
1095
316218
325838


958


KHQ22240.1
26392
29621
1095
2386538
2396158


959


KLZ78428.1
26394
29623
1095
5093831
5103451


960


KMB09548.1
26396
29625
1095
318671
328291


961


KMG65748.1
26398
29627
1117
5116317
5125996


962


KMG69377.1
26400
29629
1095
565524
575144


963


KMH23799.1
26402
29631
1095
5137914
5147534


964


KMH84529.1
26404
29633
1095
1291264
1300884


965


KMX40525.1
26406
29635
1095
315214
324834


966


ALH86087.1
26408
29637
1095
3020287
3029907


967


KRR31028.1
26410
29639
978
49625
58887


968


ALQ84489.1
26412
29641
1095
2158397
2168017


969


ALQ89984.1
26414
29643
1095
2150002
2159622


970


KSX16170.1
26416
29645
1095
8524
18144


971


KSX18602.1
26418
29647
1095
8564
18184


972


KSX52403.1
26420
29649
1095
137974
147594


973


ALP76745.1
26422
29651
1095
840774
850394


974


KSZ32506.1
26424
29653
1095
26187
35807


975


KUF65063.1
26426
29655
1008
109
9468


976


KUG47426.1
26428
29657
1095
20414
30034


977


KXO23871.1
26430
29659
1095
14263
23883


978


KYM26277.1
26432
29661
1095
41531
51151


979


ERN57702.1
26434
29663
983
10160
19444


980


EWE85119.1
26436
29665
1095
328445
338065


981


ESL33174.1
26438
29667
1095
5034330
5043950


982


KDK59887.1
26440
29669
1095
315804
325424


983


CDK69437.1
26442
29671
1096
45317
54964


984


EMH91691.1
26444
29673
1095
9198
18818


985


EOZ63296.1
26446
29675
1095
5980
15600


986


EOY67007.1
26448
29677
1095
5980
15600


987


ESN46752.1
26450
29679
1117
360085
369764


988


EWF66267.1
26452
29681
1095
4867354
4876974


989


ESM58758.1
26454
29683
286
1837389
1844582


990


KDL89511.1
26456
29685
1117
324473
334152


991


AIX83031.1
26458
29687
1095
1046321
1055941


992


AIG86150.1
26460
29689
983
2966500
2975784


993


EKB81086.1
26462
29691
1095
363340
372960


994


ESM10102.1
26464
29693
1095
362779
372399


995


EPO98435.1
26466
29695
1095
8713
18333


996


EPA89974.1
26468
29697
1095
25993
35613


997


EJI89218.1
26470
29699
997
541259
550532


998


KDE37041.1
26472
29701
1095
322666
332267


999


CAH16733.1
26474
29703
1130
2836365
2846089


1000


KTD65147.1
26476
29705
1129
286299
296026


1001


ETX11656.1
26478
29707
1143
71478
81199


1002


ESY80721.1
26480
29709
1033
45837
54964


1003


ESY66318.1
26482
29711
1047
196269
205519


1004


ESY44730.1
26484
29713
1088
453521
462897


1005


KQU80075.1
26486
29715
1774
218186
229640


1006


EMS40058.1
26488
29717
1141
3688
13384


1007


EMS40204.1
26490
29719
1141
172603
182299


1008


KQQ15549.1
26492
29721
1141
42064
51757


1009


KQO59080.1
26494
29723
1161
65935
75509


1010


KQO90880.1
26496
29725
1161
25635
35221


1011


EFV81024.1
26498
29727
1115
1071595
1080026


1012


EHJ60590.1
26500
29729
1099
90561
99810


1013


AIT79633.1
26502
29731
1099
1555853
1565102


1014


CCA92391.1
26504
29733
1099
1584078
1593321


1015


KTS15499.1
26506
29735
978
42898
52160


1016


KTS86095.1
26508
29737
978
116960
126222


1017


EFM21231.1
26510
29739
1117
215561
225243


1018


KGA41247.1
26512
29741
1098
133311
142924


1019


ACX87466.1
26514
29743
1097
1819036
1828646


1020


EAU47587.1
26516
29745
964
2465108
2474018


1021


EAS45762.1
26518
29747
1124
716356
725945


1022


KJM66694.1
26520
29749
1104
103727
113355


1023


KMK11834.1
26522
29751
1104
56209
65837


1024


KMK24778.1
26524
29753
1104
35136
44764


1025


KXU56725.1
26526
29755
1044
4561
13774


1026


EGW47199.1
26528
29757
292
245464
254742


1027


KSX98965.1
26530
29759
1012
140775
150099


1028


KTF11892.1
26532
29761
1090
229654
239236


1029


KGB84629.1
26534
29763
1099
215
9832


1030


KHE32030.1
26536
29765
1019
23646
32926


1031


KQJ75583.1
26538
29767
1111
16183
25846


1032


KRV15978.1
26540
29769
1036
3295
12626


1033


KSD09759.1
26542
29771
1109
5385
15042


1034


KSD19547.1
26544
29773
1036
60524
69855


1035


KSG03395.1
26546
29775
1036
438855
448186


1036


KSG67482.1
26548
29777
1111
15322
24985


1037


KSE90722.1
26550
29779
1036
21419
30732


1038


KSF67272.1
26552
29781
1111
15322
24985


1039


KSG19247.1
26554
29783
1036
1688
11019


1040


KSG75426.1
26556
29785
1036
22047
31378


1041


KSG85748.1
26558
29787
1036
21450
30781


1042


KSH39447.1
26560
29789
1036
194095
203426


1043


KSH60514.1
26562
29791
1036
22047
31378


1044


KSI22085.1
26564
29793
1036
22046
31377


1045


KSI51646.1
26566
29795
1109
518066
527723


1046


KSI82064.1
26568
29797
1111
199155
208818


1047


KSI99556.1
26570
29799
1036
449321
458652


1048


KSJ34445.1
26572
29801
1111
21403
31066


1049


KSK63576.1
26574
29803
1109
573017
582674


1050


KSL54235.1
26576
29805
1036
24722
34053


1051


KSM73158.1
26578
29807
1111
23541
33204


1052


KSM79531.1
26580
29809
1036
22039
31370


1053


KSN72845.1
26582
29811
1036
24722
34053


1054


KSO70094.1
26584
29813
1036
8292
17605


1055


KSQ54942.1
26586
29815
1036
31335
40666


1056


KSQ13844.1
26588
29817
1036
443745
453076


1057


KSK33231.1
26590
29819
1036
61118
70449


1058


KSL81229.1
26592
29821
1036
194095
203426


1059


KSL64952.1
26594
29823
1036
22039
31370


1060


KSM29109.1
26596
29825
1111
42134
51797


1061


KSN07703.1
26598
29827
1111
378604
388267


1062


KSN22463.1
26600
29829
1111
16138
25801


1063


KSN45780.1
26602
29831
1036
438815
448146


1064


KSO16560.1
26604
29833
1111
15322
24985


1065


KSO84936.1
26606
29835
1036
605
9936


1066


KSO99159.1
26608
29837
1111
23415
33078


1067


KSQ29951.1
26610
29839
1036
438855
448186


1068


KSR12022.1
26612
29841
1036
3385
12716


1069


KSR96744.1
26614
29843
1036
518449
527756


1070


KSS25556.1
26616
29845
1028
203854
213146


1071


KSS39722.1
26618
29847
1099
12270
21887


1072


KSR72710.1
26620
29849
1036
194095
203426


1073


KSS45915.1
26622
29851
1109
472018
481675


1074


ALY37666.1
26624
29853
1111
4647649
4657312


1075


ALY62762.1
26626
29855
1111
5985465
5995128


1076


KXC98082.1
26628
29857
1036
73491
82822


1077


KXC86337.1
26630
29859
1036
478140
487471


1078


KXD25984.1
26632
29861
1036
24577
33908


1079


KXD09025.1
26634
29863
1036
84962
94293


1080


KXD14448.1
26636
29865
1036
47987
57318


1081


KXD23305.1
26638
29867
1036
24766
34097


1082


KXC87753.1
26640
29869
1036
84679
94010


1083


KXF38232.1
26642
29871
1036
73251
82582


1084


KXF47447.1
26644
29873
1036
84960
94291


1085


KXF43394.1
26646
29875
1036
84964
94295


1086


KYO95527.1
26648
29877
1111
13894
23557


1087


KAJ18078.1
26650
29879
970
68033
77166


1088


ERY57592.1
26652
29881
1115
1472487
1482055


1089


ERY65606.1
26654
29883
1115
3001215
3010783


1090


ERV59834.1
26656
29885
1115
3014713
3024281


1091


ERY33375.1
26658
29887
1115
276729
286297


1092


ERY37452.1
26660
29889
1115
303965
313533


1093


ERY30830.1
26662
29891
1115
323839
333407


1094


ERW68207.1
26664
29893
1115
321053
330621


1095


ERW13881.1
26666
29895
1115
438293
447861


1096


ERV79733.1
26668
29897
1115
316993
326561


1097


ETV52348.1
26670
29899
1115
387845
395610


1098


ERU88469.1
26672
29901
1115
308446
318014


1099


ERU86604.1
26674
29903
1115
308446
318014


1100


KEA15334.1
26676
29905
1140
772974
782617


1101


ERZ32987.1
26678
29907
1115
332366
341934


1102


GAA19669.1
26680
29909
970
5052470
5061603


1103


EME92222.1
26682
29911
1111
15085
24748


1104


EYU00120.1
26684
29913
1111
198162
207825


1105


EOT13872.1
26686
29915
1028
4956028
4965320


1106


ETU84933.1
26688
29917
1115
527654
537213


1107


ERX16724.1
26690
29919
1115
629489
639057


1108


EWH25348.1
26692
29921
1140
1491323
1500966


1109


GAD64770.1
26694
29923
1115
16216
25769


1110


GAD61322.1
26696
29925
1116
202461
212017


1111


EZQ18205.1
26698
29927
1099
419637
429263


1112


AMO73921.1
26700
29929
1111
445996
455662


1113


KPW38787.1
26702
29931
1158
36556
46279


1114


KQB53692.1
26704
29933
1111
1406
11069


1115


EZI30290.1
26706
29935
1099
22889
32461


1116


KIR22317.1
26708
29937
1099
33962
43528


1117


KJH86852.1
26710
29939
1029
114387
123676


1118


KWV84208.1
26712
29941
1029
9497
18786


1119


EFQ63351.1
26714
29943
634
3228353
3236566


1120


KMM97952.1
26716
29945
1111
145121
154784


1121


ENY78085.1
26718
29947
1043
45721
55116


1122


ENA27916.1
26720
29949
1116
122129
131384


1123


EWC41654.1
26722
29951
1140
1199767
1208507


1124


EMD98965.1
26724
29953
1027
61976
71271


1125


KPB88881.1
26726
29955
794
33409
40166


1126


KFD13680.1
26728
29957
1099
44083
53715


1127


ACE91185.1
26730
29959
1074
2221342
2230688


1128


KKZ86595.1
26732
29961
1140
262183
271712


1129


KQU05107.1
26734
29963
1079
513
9877


1130


CCF21880.1
26736
29965
911
4095719
4104474


1131


KQZ63425.1
26738
29967
1079
733975
743234


1132


KIV64826.1
26740
29969
1133
375717
385216


1133


KQB14223.1
26742
29971
1033
23685
32821


1134


KQB14198.1
26744
29973
1033
23685
32821


1135


ETX15682.1
26746
29975
1055
1000
10241


1136


KJS41397.1
26748
29977
1042
38507
47619


1137


EPX84388.1
26750
29979
547
176357
182232


1138


GAS73921.1
26752
29981
1099
341435
351068


1139


GAS79507.1
26754
29983
1099
214261
223894


1140


KHP17886.1
26756
29985
1099
348692
358324


1141


KHP06993.1
26758
29987
1099
389798
399430


1142


ESJ40085.1
26760
29989
1099
28
9660


1143


KNB22032.1
26762
29991
1099
41580
51212


1144


AJD94188.1
26764
29993
1099
505155
514787


1145


AJD98580.1
26766
29995
1099
968609
978241


1146


CEA95106.1
26768
29997
1099
1741830
1751462


1147


CEB50849.1
26770
29999
1099
1749103
1758735


1148


CDU93373.1
26772
30001
1099
743440
753072


1149


CEB74778.1
26774
30003
1099
3835521
3845153


1150


CED02081.1
26776
30005
1099
1754122
1763754


1151


CEC70259.1
26778
30007
1099
1753225
1762857


1152


CDZ07209.1
26780
30009
1099
1754686
1764318


1153


CED89042.1
26782
30011
1099
3619879
3629511


1154


CDV50415.1
26784
30013
1099
1753988
1763620


1155


CFW88484.1
26786
30015
1099
309528
319160


1156


CDZ03620.1
26788
30017
1099
2401412
2411044


1157


CEC95430.1
26790
30019
1099
343828
353460


1158


CDV33413.1
26792
30021
1099
1855125
1864757


1159


CEB60512.1
26794
30023
1099
3889568
3899200


1160


CEC11573.1
26796
30025
1099
2654142
2663774


1161


CEA33006.1
26798
30027
1099
607822
617454


1162


CDV54742.1
26800
30029
1099
1754224
1763856


1163


CEA34475.1
26802
30031
1099
2091180
2100812


1164


CED50261.1
26804
30033
1099
676459
686091


1165


CEC06550.1
26806
30035
1099
309528
319160


1166


CDY81480.1
26808
30037
1099
310058
319690


1167


CEC66464.1
26810
30039
1099
3761780
3771412


1168


CDU75282.1
26812
30041
1099
309308
318940


1169


CDV02408.1
26814
30043
1099
642213
651845


1170


CDU44895.1
26816
30045
1099
343655
353287


1171


CEA82133.1
26818
30047
1099
1789537
1799169


1172


CDV48178.1
26820
30049
1099
3855153
3864785


1173


CEA48951.1
26822
30051
1099
344237
353869


1174


CDU62795.1
26824
30053
1099
1785128
1794760


1175


CDV82107.1
26826
30055
1099
2344699
2354331


1176


CEC15878.1
26828
30057
1099
607549
617181


1177


CEB34163.1
26830
30059
1099
1754745
1764377


1178


CEC22818.1
26832
30061
1099
1753415
1763047


1179


CEC29447.1
26834
30063
1099
1962606
1972238


1180


CEC81193.1
26836
30065
1099
1752823
1762455


1181


CEC27085.1
26838
30067
1099
643261
652893


1182


CDV36505.1
26840
30069
1099
3830845
3840477


1183


CDV99881.1
26842
30071
1099
1788948
1798580


1184


CEB21254.1
26844
30073
1099
1785448
1795080


1185


CED29540.1
26846
30075
1099
2414784
2424416


1186


CEA65654.1
26848
30077
1099
2411587
2421219


1187


CDV77398.1
26850
30079
1099
1754018
1763650


1188


CEB99329.1
26852
30081
1099
666458
676090


1189


CEC87093.1
26854
30083
1099
102895
112527


1190


CEC03343.1
26856
30085
1099
2038905
2048537


1191


CDW68452.1
26858
30087
1099
1754895
1764527


1192


CEB36542.1
26860
30089
1099
1505242
1514874


1193


CEB92481.1
26862
30091
1099
1754998
1764630


1194


CEC70640.1
26864
30093
1099
2655621
2665253


1195


CED19421.1
26866
30095
1099
309298
318930


1196


CDU57399.1
26868
30097
1099
1744361
1753993


1197


CEC55612.1
26870
30099
1099
3432850
3442482


1198


CDW10772.1
26872
30101
1099
1775102
1784734


1199


CED40437.1
26874
30103
1099
309601
319233


1200


CEA77531.1
26876
30105
1099
344224
353856


1201


CEC78581.1
26878
30107
1099
1754570
1764202


1202


CDV87320.1
26880
30109
1099
1754358
1763990


1203


CEA60264.1
26882
30111
1099
2553269
2562901


1204


CDU45979.1
26884
30113
1099
1753121
1762753


1205


CED26178.1
26886
30115
1099
1854653
1864285


1206


CEA55546.1
26888
30117
1099
1754980
1764612


1207


CDU57361.1
26890
30119
1099
1753795
1763427


1208


CEC22628.1
26892
30121
1099
309060
318692


1209


CDU81244.1
26894
30123
1099
2357174
2366806


1210


CEC22208.1
26896
30125
1099
1746204
1755836


1211


CDV00141.1
26898
30127
1099
1753396
1763028


1212


CDV32910.1
26900
30129
1099
309248
318880


1213


CEB32348.1
26902
30131
1099
1787540
1797172


1214


CDU66161.1
26904
30133
1099
134848
144480


1215


CEB23433.1
26906
30135
1099
1754743
1764375


1216


CEA69989.1
26908
30137
1099
1788795
1798427


1217


CED34531.1
26910
30139
1099
1762471
1772103


1218


CDU60158.1
26912
30141
1099
1772870
1782502


1219


CEB02153.1
26914
30143
1099
1505400
1515032


1220


CDV16495.1
26916
30145
1099
1753390
1763022


1221


CEA70649.1
26918
30147
1099
309354
318986


1222


CEB86473.1
26920
30149
1099
3281543
3291175


1223


CDV63744.1
26922
30151
1099
1753068
1762700


1224


CEB22320.1
26924
30153
1099
1298956
1308588


1225


CDY85019.1
26926
30155
1099
633632
643264


1226


CDY91993.1
26928
30157
1099
2414151
2423783


1227


CDV63674.1
26930
30159
1099
601562
611194


1228


CDV76963.1
26932
30161
1099
1298539
1308171


1229


CDV25168.1
26934
30163
1099
77424
87056


1230


CEA29073.1
26936
30165
1099
3746810
3756442


1231


CEC16657.1
26938
30167
1099
1743338
1752970


1232


CDV58583.1
26940
30169
1099
1753914
1763546


1233


CDV98720.1
26942
30171
1099
601239
610871


1234


CED02856.1
26944
30173
1099
2381174
2390806


1235


CDU96713.1
26946
30175
1099
642929
652561


1236


CEB76242.1
26948
30177
1099
3766799
3776431


1237


CEC37126.1
26950
30179
1099
597747
607379


1238


CDU99405.1
26952
30181
1099
1754390
1764022


1239


CEB54820.1
26954
30183
1099
1847245
1856877


1240


CEC86157.1
26956
30185
1099
165417
175049


1241


CDV41201.1
26958
30187
1099
608177
617809


1242


CDV19348.1
26960
30189
1099
608193
617825


1243


CEA51462.1
26962
30191
1099
1785262
1794894


1244


CEA31323.1
26964
30193
1099
669961
679593


1245


CEC70731.1
26966
30195
1099
1753358
1762990


1246


CEB55411.1
26968
30197
1099
1749599
1759231


1247


CED14443.1
26970
30199
1099
1754022
1763654


1248


CED18826.1
26972
30201
1099
607130
616762


1249


CEB11072.1
26974
30203
1099
1753867
1763499


1250


CEA27402.1
26976
30205
1099
3814476
3824108


1251


CED08653.1
26978
30207
1099
668385
678017


1252


CEB93599.1
26980
30209
1099
2227341
2236973


1253


CDY97807.1
26982
30211
1099
706460
716092


1254


CEA81540.1
26984
30213
1099
309301
318933


1255


CEA95806.1
26986
30215
1099
309463
319095


1256


CED39170.1
26988
30217
1099
2443048
2452680


1257


CEC46310.1
26990
30219
1099
3244245
3253877


1258


CEB93178.1
26992
30221
1099
517816
527448


1259


CEB06236.1
26994
30223
1099
2332565
2342197


1260


CEC59901.1
26996
30225
1099
1788361
1797993


1261


CDW11872.1
26998
30227
1099
1789272
1798904


1262


CEB87182.1
27000
30229
1099
1777428
1787060


1263


CDU53208.1
27002
30231
1099
503202
512834


1264


CEB57391.1
27004
30233
1099
676605
686237


1265


CED48958.1
27006
30235
1099
3782745
3792377


1266


CDW00039.1
27008
30237
1099
1754437
1764069


1267


CDV01787.1
27010
30239
1099
1788427
1798059


1268


CEA40519.1
27012
30241
1099
1783442
1793074


1269


CEB13673.1
27014
30243
1099
1753084
1762716


1270


CEA18908.1
27016
30245
1099
1854428
1864060


1271


CDY92812.1
27018
30247
1099
1752529
1762161


1272


CEA88154.1
27020
30249
1099
1506435
1516067


1273


AKO82198.1
27022
30251
1099
4482333
4491965


1274


CAR62301.1
27024
30253
1099
4477563
4487195


1275


ESF93195.1
27026
30255
1099
11502
21134


1276


AAV80043.1
27028
30257
1099
4482333
4491965


1277


EPE40531.1
27030
30259
1099
85913
95545


1278


EPE40313.1
27032
30261
1099
85780
95412


1279


EPE40095.1
27034
30263
1099
85905
95537


1280


KSB43364.1
27036
30265
1099
156994
166626


1281


ELX27349.1
27038
30267
1099
65113
74745


1282


EHC78170.1
27040
30269
77
221
6787


1283


ESF47593.1
27042
30271
1099
172275
181907


1284


CUS01662.1
27044
30273
1099
4951384
4961016


1285


CUS00367.1
27046
30275
944
4759655
4768822


1286


CUS00368.1
27048
30277
944
4851124
4860291


1287


CUS00366.1
27050
30279
1099
5018293
5027925


1288


CBY96200.1
27052
30281
944
85
9252


1289


EDZ29008.1
27054
30283
285
63002
70192


1290


KNM15296.1
27056
30285
1099
282369
292001


1291


KNM69141.1
27058
30287
1099
343834
353466


1292


KNO58855.1
27060
30289
1099
206734
216366


1293


KNW78916.1
27062
30291
1099
1907
11539


1294


KTZ77424.1
27064
30293
1099
96532
106164


1295


KUC23740.1
27066
30295
1099
171297
180929


1296


ESF03067.1
27068
30297
1099
120111
129743


1297


KMJ09050.1
27070
30299
1099
529831
539463


1298


CVG51486.1
27072
30301
1099
238999
248631


1299


CVB32240.1
27074
30303
1099
239061
248693


1300


EZQ69786.1
27076
30305
1099
90156
99788


1301


EFE97639.1
27078
30307
482
743953
751819


1302


KFK98827.1
27080
30309
1095
286734
296378


1303


KFK92330.1
27082
30311
1095
1654
11298


1304


ABK48268.1
27084
30313
1180
2437310
2447236


1305


AFJ48529.1
27086
30315
263
3585169
3592293


1306


GAB81434.1
27088
30317
269
178785
185928


1307


ACP25984.1
27090
30319
1083
2298324
2307700


1308


CAN98361.1
27092
30321
1152
11387949
11397690


1309


EPR18397.1
27094
30323
1038
2646
9729


1310


KKW93258.1
27096
30325
1099
135724
144994


1311


CCW17774.1
27098
30327
1098
7698
15633


1312


KER36315.1
27100
30329
1064
2812
11959


1313


KQM97529.1
27102
30331
1002
1512
10520


1314


KPV39945.1
27104
30333
499
46068
53818


1315


KQW61500.1
27106
30335
1187
77355
87231


1316


KLE23445.1
27108
30337
1121
177407
186987


1317


EDL70290.1
27110
30339
1125
191775
201360


1318


KHD25448.1
27112
30341
1169
189282
199238


1319


KFE26106.1
27114
30343
1118
33695
43271


1320


KFD94236.1
27116
30345
1118
12302
21878


1321


EJH60536.1
27118
30347
1102
68538
78157


1322


EMQ54781.1
27120
30349
1118
244112
253688


1323


KNA52261.1
27122
30351
1118
12538
22114


1324


GAD79747.1
27124
30353
1169
25836
35781


1325


KNY42356.1
27126
30355
1125
111138
120729


1326


KHF16001.1
27128
30357
1121
3364
12944


1327


KOF25302.1
27130
30359
1121
11973
21559


1328


KHT39220.1
27132
30361
1102
105669
115288


1329


KYN85118.1
27134
30363
1118
68509
78085


1330


EKM24798.1
27136
30365
1169
448059
458009


1331


CDU08195.1
27138
30367
1102
291331
300963


1332


CAV18547.1
27140
30369
1124
1498484
1508125


1333


KWU01491.1
27142
30371
1119
60437
70011


1334


KOO13423.1
27144
30373
1125
88330
97921


1335


CNI05770.1
27146
30375
1100
395449
405084


1336


CQJ58416.1
27148
30377
1100
455230
464865


1337


CQJ21073.1
27150
30379
1117
22700
32382


1338


CFR01913.1
27152
30381
1100
235368
245003


1339


CNH31670.1
27154
30383
1100
474426
484061


1340


CFV22965.1
27156
30385
1100
113536
123171


1341


KFE39719.1
27158
30387
1100
4143
13778


1342


AKA39097.1
27160
30389
1100
2710693
2720328


1343


EHM51571.1
27162
30391
944
252227
261394









Example 7
Genomic Identification and Analysis of an Anti-Plasmid System

Objective:


Some of the putative defense systems experimentally tested did not show any anti-phage activity despite being strongly associated with known defense genes. It was reasoned that some of these systems may defend against other forms of foreign nucleic acid. The objective in this case was to analyze a candidate defense system, which we hereby denote Wadjet (god protector of ancient Egypt) for further experimentation.


Methods:


To test this hypothesis, the Wadjet system was selected for further experimentation. The selected candidate system is a 4-gene system, jetA, jetB, jetC, and jetC, that is common in microbial genomes and is very frequently found next to defense genes (FIG. 7A). Three different types of the Wadjet system were cloned from three separate Bacillus species into B. subtilis BEST7003 (FIG. 7B).


Results:


While none of these systems provided protection against any of the 10 Bacillus phages in the array tested (data not shown), all three consistently and significantly reduced transformation efficiency of the episomal plasmid pHCMC05 (FIG. 7C). These results suggest that this may be a defense system specifically targeting foreign plasmids.


Three different domain compositions were identified, each encoding a different set of pfams, but all with common sequence signatures marking them as three types of Wadjet (FIG. 7B). While the pfam domains of Wadjet genes are mostly defined as “domains of unknown function”, structural modeling using Phyre2 showed structural homology between JetA, JetB and JetC and genes belonging to the housekeeping condensin system MukF, MukE and MukB, respectively. Bacterial condensins are chromosome-organizing complexes that are responsible for DNA condensation and accurate segregation during replication, and mutations in the housekeeping condensins lead to severe defects in chromosome segregation and viability. Several versions of housekeeping codensins appear in bacterial genomes: SMC, MukBEF and MksBEF; the Wadjet system was previously noted as a distant homolog of the MksBEF system described in P. aeruginosa.


While the domain organization of the jetABC genes may lead to the hypothesis that Wadjet is an alternative condensin system involved in bacterial chromosome maintenance, the data herein presented imply that its role is defensive. This system is highly enriched within defense islands, undergoes extensive horizontal gene transfer, and is only sporadically found within strains of the same species, all of which is inconsistent with a core, essential role in chromosome maintenance. The Wadjet system may have adapted from a MukBEF condensin ancestor to become a defense system. Possibly, the system identifies foreign plasmids and uses its condensin properties to interfere with proper plasmid segregation into daughter cells. Notably, plasmid transformation in B. subtilis takes place via the natural competence of this organism, during which the plasmid DNA is transformed to the cell through dedicated transporters as single-stranded DNA (ssDNA). It is possible that the Wadjet system protects against rampant natural transformation or, alternatively, may specifically target ssDNA phages. However, as no ssDNA phage was reported for B. subtilis, it could not be tested whether ssDNA phages are specifically blocked by the Wadjet systems we cloned in B. subtilis BEST7003.


The Wadjet system is broadly spread in bacterial and archaeal genomes (found in ˜6% of the genomes that were studied), where it presents high sequence diversity (Table 11; FIG. 3H). Deletion of each of the four genes in Type I Wadjet from B. cereus Q1 abolished its activity and restored plasmid transformation, indicating that each of the genes is essential for anti-plasmid defense (FIG. 7C). Moreover, point mutations E59K/K60E in JetB, predicted to disrupt the MukE-MukF-like protein-protein interactions, resulted in loss of protective activity against plasmids (data not shown), and so has the E1025Q mutation in the Walker-B motif of JetC that is predicted to abolish ATPase activity. The JetD gene, which has no homology to genes in the Muk system has a putative topoisomerase VI domain based on structural predictions; a point mutation JetD:E226A, predicted to diminish binding of the topoisomerase VI domain to DNA, also abolished the protective activity of the system.


Table 11: The Wadjet Defense System and Components Thereof


This table is presented in landscape orientation. Due to the number of columns, the table has been split into parts. Part A includes the first set of columns and therefore should be place to the left of subsequent parts (Part B and where relevant Part C). To avoid any doubt, the rows of the table in each part line up once the tables are placed together.










Lengthy table referenced here




US20200109395A1-20200409-T00001


Please refer to the end of the specification for access instructions.






Example 8
Genomic Identification and Analysis of Additional Defense System

Objective:


To identify additional Defense Systems


Methods:


As above for Examples 1-7, wherein anchor protein families used in the searches were as follows:


for the Hachiman Family: pfam08878;


for the Gabija Family: pfam13175, pfam13304;


for the Kiwa Family: pfam16162;


for the Lamassu Family: pfam14130;


for the Shedu Family: pfam14082;


for the Septu Family: COG3950; and


for the Wadjet Family: COG4913, COG4924, pfam11796, pfam09664, pfam13555.


Results:


each of these systems was validated by introducing the system constructs into an appropriate bacterial host. The Hachiman, Shedu, Gabija, Septu, and Lamassu candidate Defense Systems were each individually engineered into B. subtilis BEST7003, which does not contain the respective defense systems identified. The correct insertion of the system into the B. subtilis BEST7003 genome was verified by whole genome sequencing. The defense system containing B. subtilis BEST7003 strains were challenged with multiple phages spanning the three families Myoviridae, Siphoviridae, and Podoviridae. The cloned systems were found to confer defense against myophages (FIG. 3B), with different fold protection to all or a subset of the phage provided as shown.


The Kiwa candidate Defense System was engineered into a host E. coli (E. coli MG1655; correct insertion checked by whole genome sequencing), wherein it was shown to provide protection against viruses in the Siphoviridae family (FIG. 3C).


The Hachiman, Shedu, Gabija, Septu, and Lamassu candidate Defense Systems were broadly distributed in bacteria and archaea (Tables 12-17; FIG. 3H).










Lengthy table referenced here




US20200109395A1-20200409-T00002


Please refer to the end of the specification for access instructions.














Lengthy table referenced here




US20200109395A1-20200409-T00003


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Lengthy table referenced here




US20200109395A1-20200409-T00004


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Lengthy table referenced here




US20200109395A1-20200409-T00005


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Lengthy table referenced here




US20200109395A1-20200409-T00006


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Lengthy table referenced here




US20200109395A1-20200409-T00007


Please refer to the end of the specification for access instructions.






Summary Examples 1-8

Examples 1-8 significantly expand the known arsenal of defense systems used by prokaryotes for protection against phages. This knowledge leads to broader understanding of the global defense capabilities of bacteria, and indeed with our results the content of defense islands now becomes much clearer (FIGS. 4A, 4D, 5A, 6A, 7A). However, the results do not yet expose the complete set of prokaryotic defense systems. Out of the 28 candidate systems tested, 10 were verified as anti-phage defense systems and an additional one showed protection against plasmids. The remaining 17, although not verified by the experiments, do not necessarily represent false predictions, as exemplified by the fact that only 50% of our positive control systems showed defense in the assays. Lack of activity could possibly stem from incompatibility of some tested systems with the recipient organism (E. coli or B. subtilis), or due to pseudogenization of some systems in their genome of origin. Some systems can be highly specific against a certain type of phages or foreign genetic element not represented in the phage set, while others may work in a specific condition not tested in the study. Clade-specific potential systems such as those found only in archaea or cyanobacteria (Table 3) were not tested in this study and can represent a more specialized defense arsenal unique only to a subset of organisms. Finally, some true systems may have been missed by falsely tagging them as belonging to the “mobilome” (Table 2), as mobile genetic elements have intimate evolutionary relationship with defense systems.


While certain features have been illustrated and described herein, many modifications, substitutions, changes, and equivalents will now occur to those of ordinary skill in the art. It is, therefore, to be understood that the appended claims are intended to cover all such modifications and changes as fall within the true spirit of the disclosure presented herein.










LENGTHY TABLES




The patent application contains a lengthy table section. A copy of the table is available in electronic form from the USPTO web site (). An electronic copy of the table will also be available from the USPTO upon request and payment of the fee set forth in 37 CFR 1.19(b)(3).





Claims
  • 1. A method of protecting bacteria from foreign nucleic acid invasion, said method comprising a step of introducing into the bacteria at least one defense system (a) to (o), said at least one defense system comprising: (a) a Defense System IV comprising at least two different polypeptide components selected from a HamA polypeptide comprising a pfam08878 domain or a DUF1837 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 12 rows 2-1782 columns H and I; anda HamB polypeptide comprising COG1204 domain or a pfam00270 domain or a pfam00271 domain or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 12 rows 2-1782 columns L and M; or(b) a Defense System Ia comprising at least two different polypeptide components selected from a ZorA polypeptide comprising a pfam01618 domain, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 8 rows 2-1830 columns J and K;a ZorB polypeptide comprising a pfam13677 domain or a pfam00691 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 8 rows 2-1830 columns N and O;a ZorC polypeptide comprising a pfam15611 domain, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 8 rows 2-1174 columns R and S; anda ZorD polypeptide comprising a pfam00176 domain or a pfam00271 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 8 rows 2-1174 columns V and W;or(c) a Defense System Ib comprising a ZorE polypeptide comprising a pfam01844 domain or a COG3183 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 8 rows 1175-1830 columns Z and AA; and at least one other polypeptide component selected from a ZorA polypeptide comprising a pfam01618 domain, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 8 rows 2-1830 columns J and K; anda ZorB polypeptide comprising a pfam13677 domain or a pfam00691 domain or a combination thereof, or comprising an amino acid sequence having at leak 80% identity to a sequence selected from the group referenced in Table 8 rows 2-1830 columns N and O; or(d) a Defense System II comprising at least two different polypeptide components selected from a ThsA polypeptide comprising a pfam13289 domain or a pfam14519 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 9 rows 2-2100 columns I and J; anda ThsB polypeptide comprising a pfam13676 domain or a pfam08937 domain or a pfam08357 domain or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 9 rows 2-2100 columns M and N, Q and R, U and V, Y and Z, and AC and AD; or(e) a Defense System IIIa comprising at least two different polypeptide components selected from a DruA polypeptide comprising a DUF4338 domain or a pfam14236 domain or a combination thereof; or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-123 columns J and K, or a combination thereof;a DruB polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-123 columns N and O;a DruC polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-123 columns R and S;a DruD polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-123 columns V and W; anda DruE polypeptide comprising a pfam00270 domain or a pfam00271 domain or a pfam09369 domain or a DUF1998 domain or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-1343 columns Z and AA; or(f) a Defense System IIIb comprising at least two different polypeptide components selected from a DruM polypeptide comprising a pfam00145 domain or a COG0270 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 124-295 columns AD and AE;a DruF polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 124-295 columns AH and AI;a DruG polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 124-295 columns AL and AM; anda DruE polypeptide comprising a pfam00270 domain or a pfam00271 domain or a pfam09369 domain or a DUF1998 domain or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-1343 column Z and AA; or(g) a Defense System IIIc comprising at least two different polypeptide components selected from a DruH polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 296-1343 columns AP and AQ; anda DruE polypeptide comprising a pfam00270 domain or a pfam00271 domain or a pfam09369 domain or a DUF1998 domain or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-1343 columns Z and AA; or(h) a Defense System V comprising a SduA polypeptide comprising a pfam14082 domain or a pfam01939 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 13 rows 2-1247 columns H and I; or(i) a Defense System VI comprising at least two different polypeptide components selected from a GajA polypeptide comprising a pfam13175 domain or a COG3593 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 14 rows 2-4599 columns H and I; anda GajB polypeptide comprising a pfam04257 domain or a pfam00580 domain or a pfam13361 domain or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 14 rows 2-4599 columns L and M; or(j) a Defense System VII comprising at least two different polypeptide components selected from a PtuA polypeptide comprising a pfam13304 domain or a pfam02463 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 15 rows 2-12507 columns H and I; anda PtuB polypeptide comprising pfam13395 domain or a pfam 01844 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 15 rows 2-2507 columns L and M; or(k) a Defense System VIII comprising at least two different polypeptide components selected from a LmuA polypeptide comprising a pfam14130 domain or a DUF4297 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 16 rows 2-698 columns H and I; anda LmuB polypeptide comprising a pfam02463 domain, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 16 rows 2-698 columns L and M; or(l) a Defense System IX comprising at least two different polypeptide components selected from a KwaA polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 17 rows 2-935 columns H and I; anda KwaB polypeptide comprising a pfam16162 domain or a DUF4868 domain or a combination thereof; or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 17 rows 2-935 columns L and M; or(m) a Defense System Xa comprising at least two different polypeptide components selected from a JetA polypeptide comprising a pfam11855 domain or a DUF3375 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2-2322 columns J and K;a JetB polypeptide comprising a pfam13835 domain or a DUF4194 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2-2322 columns N and O;a JetC polypeptide comprising a pfam13555 domain or a pfam13558 domain or a COG4913 domain or any combination thereof; or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2-2322 columns R and S; anda JetD polypeptide comprising a pfam11795 domain or a DUF3322 domain or a pfam09983 domain or a DUF2220 domain or a COG4924 domain or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2-2322 columns V and W; or(n) a Defense System Xb comprising at least two different polypeptide components selected from a JetAii polypeptide comprising a pfam09660 domain or a DUF2397 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2323-2844 columns J and K;a JetBii polypeptide comprising a pfam09661 domain or a DUF2398 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2323-2844 columns N and O;a JetCii polypeptide comprising a pfam13558 domain, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2323-2844 columns R and S; anda JetDii polypeptide comprising a pfam11796 domain or a DUF3323 domain or a pfam09664 domain or a DUF2399 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2323-2844 columns V and W; or(o) a Defense System Xc comprising at least two different polypeptide components selected from a JetAiii polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2845-3174 columns and K;a JetBiii polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2845-3174 columns N and O;a JetCiii polypeptide comprising a COG1196 domain or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2845-3174 columns R and S; anda JetDiii polypeptide comprising a pfam09983 domain or a pfam09664 domain or a DUF2220 or a DUF2399 domain or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2845-3174 columns V and W; or(p) any combination of Defense Systems Ia-Xc (a)-(o);
  • 2. The method of claim 1, wherein said protecting bacteria from foreign nucleic acid invasion comprises protecting from phage infection, protection from plasmid transformation, or protecting from entry of conjugative elements, or any combination thereof.
  • 3. The method of claim 2, wherein said phage comprises a single stranded DNA (ssDNA) phage, a double stranded DNA (dsDNA) phage, a single stranded RNA (ssRNA) phage, a double stranded RNA (dsRNA) phage, a lytic phage, or a lysogenic phage, or a combination thereof.
  • 4. The method of claim 1, wherein said at least one defense system comprises (a) a Defense System IV comprising the HamA polypeptide and the HamB polypeptide; or(b) a Defense System Ia comprising the ZorA polypeptide, the ZorB polypeptide, the ZorC polypeptide, and the ZorD polypeptide; or(c) a Defense System Ib comprising the ZorA polypeptide, the ZorB polypeptide, and the ZorE polypeptide; or(d) a Defense System II comprising the ThsA polypeptide, and the ThsB polypeptide; or(e) a Defense System IIIa comprising the DruA polypeptide, the DruB polypeptide, the DruC polypeptide, the DruD polypeptide, and the DruE polypeptide; or(f) a Defense System IIIb comprising the DruM polypeptide, the DruF polypeptide, the DruG polypeptide, and the DruE polypeptide; or(g) a Defense System IIIc comprising the DruH polypeptide and the DruE polypeptide; or(h) a Defense System V comprising the SduA polypeptide; or(i) a Defense System VI comprising the GajA polypeptide and the GajB polypeptide; or(j) a Defense System VII comprising the PtuA polypeptide and the PtuB polypeptide; or(k) a Defense System VIII comprising the LmuA polypeptide and the LmuB polypeptide; or(l) a Defense System IX comprising the KwaA polypeptide and the KwaB polypeptide; or(m) a Defense System Xa comprising the JetA polypeptide, the JetB polypeptide, the JetC polypeptide, and the JetD polypeptide; or(n) a Defense System Xb comprising the JetAii polypeptide, the JetBii polypeptide, the JetCii polypeptide, and the JetDii polypeptide; or(o) a Defense System Xc comprising the JetAiii polypeptide, the JetBiii polypeptide, the JetCiii polypeptide, and the JetDiii polypeptide; or(p) any combination of Defense Systems Ia-Xc (a)-(o).
  • 5. The method of claim 1, wherein (a) said Defense System IV is encoded by a nucleic acid sequence selected from the group referenced in Table 12, rows 2-1782, columns G, P, and Q or the nucleic acid sequence set forth in SEQ ID NO: 4; ora nucleic acid sequence encoding the at least two different polypeptide sequences recited in claim 1; ora nucleic acid sequence encoding the HamA polypeptide and HamB polypeptide recited in claim 4;(b) said Defense System Ia is encoded by a nucleic acid sequence selected from the group referenced in Table 8 rows 2-1174 columns G, AD, and AE or the nucleic acid sequence set forth in SEQ ID NO: 14; ora nucleic acid sequence encoding the at least two different polypeptide sequences recited in claim 1; ora nucleic acid sequence encoding the ZorA polypeptide, the ZorB polypeptide, the ZorC polypeptide, and ZorD polypeptide recited in claim 4;(c) said Defense System Ib is encoded by a nucleic acid sequence selected from the group referenced in Table 8 rows 1175-1830 columns G, AD, and AE or set forth in SEQ ID NO: 15; ora nucleic acid sequence encoding the at least two different polypeptide sequences recited in claim 1; ora nucleic acid sequence encoding the ZorA polypeptide, the ZorB polypeptide, and ZorE polypeptide recited in claim 4;(d) said Defense System II is encoded by a nucleic acid sequence selected from the group referenced in Table 9 rows 2-2100 columns G, AG, and AH or set forth in the nucleic acid sequence set forth in SEQ ID NO: 10 or SEQ ID NO: 11; ora nucleic acid sequence encoding the at least two different polypeptide sequences recited in claim 1; ora nucleic acid sequence encoding the ThsA polypeptide and the ThsB polypeptide recited in claim 4;(e) said Defense System IIIa is encoded by a nucleic acid sequence selected from the group referenced in Table 10 rows 2-123 columns G, AT, and AU or set forth in SEQ ID NO: 16; ora nucleic acid sequence encoding the at least two different polypeptide sequences recited in claim 1; ora nucleic acid sequence encoding the DruA polypeptide, the DruB polypeptide, the DruC, the DruD, and the DruE polypeptide recited in claim 4;(f) said Defense System IIIb is encoded by a nucleic acid sequence selected from the group referenced in Table 10 rows 124-295 columns G, AT, AU; ora nucleic acid sequence encoding the at least two different polypeptide sequences recited in claim 1; ora nucleic acid sequence encoding the DruM polypeptide, the DruF polypeptide, the DruG polypeptide, and the DruE polypeptide recited in claim 4;(g) said Defense System IIIc is encoded by a nucleic acid sequence selected from the group referenced in Table 10 rows 296-1343 columns G, AT, and AU; ora nucleic acid sequence encoding the at least two different polypeptide sequences recited in claim 1; ora nucleic acid sequence encoding the DruH polypeptide and the DruE polypeptide recited in claim 4;(h) said Defense System V is encoded by a nucleic acid sequence selected from the group referenced in Table 13, rows 2-1247, columns H and J; ora nucleic acid sequence encoding the SduA polypeptide of claim 1 and claim 4;(i) said Defense System VI is encoded by a nucleic acid sequence selected from the group referenced in Table 14, rows 2-4599, columns G, P, and Q or the sequences set forth in SEQ ID NO: 5 and SEQ ID NO: 6; ora nucleic acid sequence encoding the at least two different polypeptide sequences recited in claim 1; ora nucleic acid sequence encoding the GajA polypeptide and the GajB polypeptide recited in claim 4;(j) said Defense System VII is encoded by a nucleic acid sequence selected from the group referenced in Table 15, rows 2-2507, columns G, P, and Q or the sequences set forth in SEQ ID NO: 12 and SEQ ID NO: 13; ora nucleic acid sequence encoding the at least two different polypeptide sequences recited in claim 1; ora nucleic acid sequence encoding the Ptu polypeptide and the PtuB polypeptide recited in claim 4;(k) said Defense System VIII is encoded by a nucleic acid sequence selected from the group referenced in Table 16, rows 2-698, columns G, P, and Q or the sequences set forth in SEQ ID NO: 7 and SEQ ID NO: 8; ora nucleic acid sequence encoding the at least two different polypeptide sequences recited in claim 1; ora nucleic acid sequence encoding the LmuA polypeptide and LmuB polypeptide recited in claim 4;(l) said Defense System IX is encoded by a nucleic acid sequence selected from the group referenced in Table 17, rows 2-935, columns G, P, and Q or the sequence set forth in SEQ ID NO: 3; ora nucleic acid sequence encoding the at least two different polypeptide sequences recited in claim 1; ora nucleic acid sequence encoding the KwaA polypeptide and the KwaB polypeptide recited in claim 4;(m) said Defense System Xa is encoded by a nucleic acid sequence selected from the group referenced in Table 11, rows 2-2322, columns G, Z, and AA or the sequence set forth in SEQ ID NO: 17; ora nucleic acid sequence encoding the at least two different polypeptide sequences recited in claim 1; ora nucleic acid sequence encoding the JetA polypeptide, the JetB polypeptide, the JetC polypeptide, and the JetD polypeptide recited in claim 4;(n) said Defense System Xb is encoded by a nucleic acid sequence having at least 80% homology to a sequence selected from the group referenced in Table 11, rows 2323-2844, columns G, Z, and AA or the sequence set forth in SEQ ID NO: 18; ora nucleic acid sequence encoding the at least two different polypeptide sequences recited in claim 1; ora nucleic acid sequence encoding the JetAii polypeptide, the JetBii polypeptide, the JetCii polypeptide, and the JetDii polypeptide recited in claim 4;(o) said Defense System Xc is encoded by a nucleic acid sequence selected from the group referenced in Table 11, rows 2845-3174, columns G, Z, and AA or the sequence set forth in SEQ ID NO: 19; ora nucleic acid sequence encoding the at least two different polypeptide sequences recited in claim 1; ora nucleic acid sequence encoding the JetAiii polypeptide, the JetBiii polypeptide, the JetCiii polypeptide, and the JetDiii polypeptide recited in claim 4.
  • 6. The method of claim 1, wherein (a) for said Defense system IV, said HamA polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 12, rows 2-1782, columns H and J, or said HamB polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 12, rows 2-1782, columns L and N, ora combination thereof;(b) for said Defense system Ia, said ZorA polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 8 rows 2-1830 columns J and L, said ZorB polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 8 rows 2-1830 columns N and P,said ZorC polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 8 rows 2-1174 columns R and T, orsaid ZorD polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 8 rows 2-1174 columns V and X, ora combination thereof;(c) for said Defense system Ib, said ZorA polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 8 rows 2-1830 columns J and L, said ZorB polypeptide is encoded by a nucleic acid sequence selected from the group Table 8 rows 2-1830 columns N and P,said ZorE polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 8 rows 1175-1830 columns Z and AB, or a combination thereof;(d) for said Defense system II, said ThsA polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 9 rows 2-2100 columns I and K, said ThsB polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 9 rows 2-2100 columns M and O, Q and S, U and W, Y and AA, and AC and AE, ora combination thereof;(e) for said Defense system IIIa, said DruA polypeptide is encoded by a nucleic acid sequences selected from the group referenced in Table 10 rows 2-123 columns J and L, or said DruB polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 10 rows 2-123 columns N and P, orsaid DruC polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 10 rows 2-123 columns R and T, orsaid DruD polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 10 rows 2-123 columns V and X, orsaid DruE polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 10 rows 2-1343 columns Z and AB, ora combination thereof;(f) for said Defense system IIIb, said DruM polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 10 rows 124-295 columns AD and AF, or said DruF polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 10 rows 124-295 columns AH and AJ, orsaid DruG polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 10 rows 124-295 columns AL and AN, orsaid DruE polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 10 rows 2-1343 columns Z and AB, ora combination thereof;(g) for said Defense system IIIc, said DruH polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 10 rows 296-1343 columns AP and AR, or said DruE polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 10 rows 2-1343 columns Z and ZB, ora combination thereof;(h) for said Defense system V, said SduA polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 13; rows 2-1247, columns H and J;(i) for said Defense system VI, said GajA polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 14, rows 2-4599, columns H and J, or said GajB polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 14, rows 2-4599, columns L and N, ora combination thereof;(j) for said Defense system VII, said PtuA polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 15, rows 2-2507, columns H and J, or said PtuB polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 15, rows 2-2507, columns L and N, ora combination thereof;(k) for said Defense system VIII, said LmuA polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 16, rows 2-698, columns H and J, or said LmuB polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 16, rows 2-698, columns L and N, ora combination thereof;(l) for said Defense system IX, said KwaA polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 17, rows 2-935, columns H and J, or said KwaB polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 17, rows 2-935, columns L and N, ora combination thereof;(m) for said Defense system Xa, said JetA polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 11, rows 2-2322, columns J and L, or said JetB polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 11, rows 2-2322, columns N and P, orsaid JetC polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 11, rows 2-2322, columns R and T, orsaid JetD polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 11, rows 2-2322, columns V and X, ora combination thereof;(n) for said Defense system Xb, said JetAii polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 11, rows 2323-2844, columns J and L, or said JetBii polypeptide is encoded by a nucleic acid sequence selected group referenced in Table 11, rows 2323-2844, columns N and P, orsaid JetCii polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 11, rows 2323-2844, columns R and T, orsaid JetDii polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 11, rows 2323-2844, columns V and X, ora combination thereof;(o) for said Defense system Xc, said JetAiii polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 11, rows 2845-3174, columns J and L, or said JetBiii polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 11, rows 2845-3174, columns N and P, orsaid JetCiii polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 11, rows 2845-3174, columns R and T, orsaid JetDiii polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 11, rows 2845-3174, columns V and X, ora combination thereof.
  • 7. An at least one defense system (a)-(o), said at least one defense system comprising (a) a Defense System IV comprising at least two different polypeptide components selected from a HamA polypeptide comprising a pfam08878 domain or a DUF1837 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 12 rows 2-1782 columns H and I; anda HamB polypeptide comprising COG-1204 domain or a pfam00270 domain or a pfam00271 domain or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 12 rows 2-1782 columns L and M; or(b) a Defense System Ia comprising at least two different polypeptide components selected from a ZorA polypeptide comprising a pfam01618 domain, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 8 rows 2-1830 columns J and K;a ZorB polypeptide comprising a pfam13677 domain or a pfam00691 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 8 rows 2-1830 columns N and O;a ZorC polypeptide comprising a pfam15611 domain, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 8 rows 2-1174 columns R and S; anda ZorD polypeptide comprising a pfam00176 domain or a pfam00271 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 8 rows 2-1174 columns V and W;or(c) a Defense System Ib comprising a ZorE polypeptide comprising a pfam01844 domain or a COG3183 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 8 rows 1175-1830 columns Z and AA; and at least one other polypeptide component selected from a ZorA polypeptide comprising a pfam01618 domain, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 8 rows 2-1830 columns J and K; anda ZorB polypeptide comprising a pfam13677 domain or a pfam00691 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 8 rows 2-1830 columns N and O; or(d) a Defense System II comprising at least two different polypeptide components selected from a ThsA polypeptide comprising a pfam13289 domain or a pfam14519 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 9 rows 2-2100 columns I and J; anda ThsB polypeptide comprising a pfam13676 domain or a pfam08937 domain or a pfam08357 domain or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 9 rows 2-2100 columns M and N, Q and R, U and V, Y and Z, and AC and AD; or(e) a Defense System IIIa comprising at least two different polypeptide components selected from a DruA polypeptide comprising a DUF4338 domain or a pfam14236 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-123 columns J and K, or a combination thereof;a DruB polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-123 columns N and O;a DruC polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-123 columns R and S;a DruD polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-123 columns V and W; anda DruE polypeptide comprising a pfam00270 domain or a pfam00271 domain or a pfam09369 domain or a DUF1998 domain or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-1343 columns Z and AA; or(f) a Defense System IIIb comprising at least two different polypeptide components selected from a DruM polypeptide comprising a pfam00145 domain or a COG0270 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 124-295 columns AD and AE;a DruF polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 124-295 columns AH and AI;a DruG polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 124-295 columns AL and AM; anda DruE polypeptide comprising a pfam00270 domain or a pfam00271 domain or a pfam09369 domain or a DUF1998 domain, or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-1343 columns Z and AA; or(g) a Defense System IIIc comprising at least two different polypeptide components selected from a DruH polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 296-1343 columns AP and AQ; anda DruE polypeptide comprising a pfam00270 domain or a pfam00271 domain or a pfam09369 domain or a DUF1998 domain or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-1343 columns Z and AA; or(h) a Defense System V comprising a SduA polypeptide comprising a pfam14082 domain or a pfam01939 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 13 rows 2-1247 columns H and I; or(i) a Defense System VI comprising at least two different polypeptide components selected from a GajA polypeptide comprising a pfam13175 domain or a COG3593 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 14 rows 2-4599 columns H and I; anda GajB polypeptide comprising a pfam04257 domain or a pfam00580 domain or a pfam13361 domain or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 14 rows 2-4599 columns L and M; or(j) a Defense System VII comprising at least two different polypeptide components selected from a PtuA polypeptide comprising a pfam13304 domain or a pfam02463 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 15 rows 2-12507 columns H and I; anda PtuB polypeptide comprising pfam13395 domain or a pfam 01844 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 15 rows 2-2507 columns L and M; or(k) a Defense System VIII comprising at least two different polypeptide components selected from a LmuA polypeptide comprising a pfam14130 domain or a DUF4297 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 16 rows 2-698 columns H and I; anda LmuB polypeptide comprising a pfam02463 domain, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 16 rows 2-698 columns L and M; or(l) a Defense System IX comprising at least two different polypeptide components selected from a KwaA polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 17 rows 2-935 columns H and I; anda KwaB polypeptide comprising a pfam16162 domain or a DUF4868 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 17 rows 2-935 columns L and M; or(m) a Defense System Xa comprising at least two different polypeptide components selected from a JetA polypeptide comprising a pfam11855 domain or a DUF3375 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2-2322 columns J and K;a JetB polypeptide comprising a pfam13835 domain or a DUF4194 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2-2322 columns N and O;a JetC polypeptide comprising a pfam13555 domain or a pfam13558 domain or a COG4913 domain or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2-2322 columns R and S; anda JetD polypeptide comprising a pfam11795 domain or a DUF3322 domain or a pfam09983 domain or a DUF2220 domain or a COG4924 domain or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2-2322 columns V and W; or(n) a Defense System Xb comprising at least two different polypeptide components selected from a JetAii polypeptide comprising a pfam09660 domain or a DUF2397 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2323-2844 columns J and K;a JetBii polypeptide comprising a pfam09661 domain or a DUF2398 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2323-2844 columns N and O;a JetCii polypeptide comprising a pfam13558 domain comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2323-2844 columns R and S; anda JetDii polypeptide comprising a pfam11796 domain or a DUF3323 domain or a pfam09664 domain or a DUF2399 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2323-2844 columns V and W; or(o) a Defense System Xc comprising at least two different polypeptide components selected from a JetAiii polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2845-3174 columns J and K;a JetBiii polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2845-3174 columns N and O;a JetCiii polypeptide comprising a COG1196 domain or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2845-3174 columns R and S; anda JetDiii polypeptide comprising a pfam09983 domain or a pfam09664 domain or a DUF2220 or a DUF2399 domain or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2845-3174 columns V and W; or(p) any combination of the Defense Systems Ia-Xc (a)-(o);wherein said at least one defense system comprises a non-naturally occurring combination of components.
  • 8. The defense system of claim 7, wherein (a) said Defense System IV comprises the HamA polypeptide and the HamB polypeptide; or(b) said Defense System Ia comprises the ZorA polypeptide, the ZorB polypeptide, the ZorC polypeptide, and the ZorD polypeptide; or(c) said Defense System Ib comprises the ZorA polypeptide, the ZorB polypeptide, and the ZorE polypeptide; or(d) said Defense System II comprises the ThsA polypeptide, and the ThsB polypeptide; or(e) said Defense System IIIa comprises the DruA polypeptide, the DruB polypeptide, the DruC polypeptide, the DruD polypeptide, and the DruE polypeptide; or(f) said Defense System IIIb comprises the DruM polypeptide, the DruF polypeptide, the DruG polypeptide, and the DruE polypeptide; or(f) said Defense System IIIc comprises the DruH polypeptide and the DruE polypeptide; or(h) said Defense System V comprises the SduA polypeptide; or(i) said Defense System VI comprises the GajA polypeptide and the GajB polypeptide; or(j) said Defense System VII comprises the PtuA polypeptide and the PtuB polypeptide; or(k) said Defense System VIII comprises the LmuA polypeptide and the LmuB polypeptide; or(l) said Defense System IX comprises the KwaA polypeptide and the KwaB polypeptide; or(m) said Defense System Xa comprises the JetA polypeptide, the JetB polypeptide, the JetC polypeptide, and the JetD polypeptide; or(n) said Defense System Xb comprises the JetAii polypeptide, the JetBii polypeptide, the JetCii polypeptide, and the JetDii polypeptide; or(o) said Defense System Xc comprises the JetAiii polypeptide, the JetBiii polypeptide, the JetCiii polypeptide, and the JetDii polypeptide.
  • 9. The at least one defense system of claim 7, wherein said defense system provides a host cell with resistance to foreign nucleic acid invasion.
  • 10. The at least one defense system of claim 9, wherein said resistance to foreign nucleic acid invasion comprises resistance to at least one phage infection, or resistance to plasmid transformation, or resistance to entry of a conjugative element, or any combination thereof.
  • 11. A nucleic acid construct encoding an at least one defense system (a)-(o), said nucleic acid construct comprising (a) a nucleic acid construct encoding a Defense System IV comprising at least two different polypeptide components selected from a HamA polypeptide comprising a pfam08878 domain or a DUF1837 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 12 rows 2-1782 columns H and I; anda HamB polypeptide comprising COG1204 domain or a pfam00270 domain or a pfam00271 domain or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 12 rows 2-1782 columns L and M; or(b) a nucleic acid construct encoding a Defense System Ia comprising at least two different polypeptide components selected from a ZorA polypeptide comprising a pfam01618 domain, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 8 rows 2-1830 columns J and K;a ZorB polypeptide comprising a pfam 13677 domain or a pfam00691 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 8 rows 2-1830 columns N and O;a ZorC polypeptide comprising a pfam15611 domain, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 8 rows 2-1174 columns R and S; anda ZorD polypeptide comprising a pfam00176 domain or a pfam00271 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 8 rows 2-1174 columns V and W;or(c) a nucleic acid construct encoding a Defense System Ib comprising a ZorE polypeptide comprising a pfam01844 domain or a COG3183 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 8 rows 1175-1830 columns Z and AA; and at least one other polypeptide component selected from a ZorA polypeptide comprising a pfam01618 domain, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 8 rows 2-1830 columns J and K; anda ZorB polypeptide comprising a pfam13677 domain or a pfam00691 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 8 rows 2-1830 columns N and O; or(d) a nucleic acid construct encoding a Defense System II comprising at least two different polypeptide components selected from a ThsA polypeptide comprising a pfam13289 domain or a pfam14519 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 9 rows 2-2100 columns I and J; anda ThsB polypeptide comprising a pfam13676 domain or a pfam08937 domain or a pfam08357 domain or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 9 rows 2-2100 columns M and N, Q and R, U and V, Y and Z, and AC and AD; or(e) a nucleic acid construct encoding a Defense System IIIa comprising at least two different polypeptide components selected from a DruA polypeptide comprising a DUF4338 domain or a pfam14236 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-123 columns J and K, or a combination thereof;a DruB polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-123 columns N and O;a DruC polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-123 columns R and S;a DruD polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-123 columns V and W; anda DruE polypeptide comprising a pfam00270 domain or a pfam00271 domain or a pfam09369 domain or a DUF1998 domain or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-1343 columns Z and AA; or(f) a nucleic acid construct encoding a Defense System IIIb comprising at least two different polypeptide components selected from a DruM polypeptide comprising a pfam00145 domain or a COG0270 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 124-295 columns AD and AE;a DruF polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 124-295 columns AH and AI;a DruG polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 124-295 columns AL and AM; anda DruE polypeptide comprising a pfam00270 domain or a pfam00271 domain or a pfam09369 domain or a DUF1998 domain or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-1343 columns Z and AA; or(g) a nucleic acid construct encoding a Defense System IIIc comprising at least two different polypeptide components selected from a DruH polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 296-1343 columns AP and AQ; anda DruE polypeptide comprising a pfam00270 domain or a pfam00271 domain or a pfam09369 domain or a DUF1998 domain or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 10 rows 2-1343 columns Z and AA; or(h) a nucleic acid construct encoding a Defense System V comprising a SduA polypeptide comprising a pfam14082 domain or a pfam01939 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 13 rows 2-1247 columns H and I; or(i) a nucleic acid construct encoding a Defense System VI comprising at least two different polypeptide components selected from a GajA polypeptide comprising a pfam13175 domain or a COG3593 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 14 rows 2-4599 columns H and I; anda GajB polypeptide comprising a pfam04257 domain or a pfam00580 domain or a pfam13361 domain or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 14 rows 2-4599 columns L and M; or(j) a nucleic acid construct encoding a Defense System VII comprising at least two different polypeptide components selected from a PtuA polypeptide comprising a pfam13304 domain or a pfam02463 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 15 rows 2-12507 columns H and I; anda PtuB polypeptide comprising pfam13395 domain or a pfam 01844 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 15 rows 2-2507 columns L and M; or(k) a nucleic acid construct encoding a Defense System VIII comprising at least two different polypeptide components selected from a LmuA polypeptide comprising a pfam14130 domain or a DUF4297 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 16 rows 2-698 columns H and I; anda LmuB polypeptide comprising a pfam02463 domain, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 16 rows 2-698 columns L and M; or(l) a nucleic acid construct encoding a Defense System IX comprising at least different polypeptide components selected from a KwaA polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 17 rows 2-935 columns II and I; anda KwaB polypeptide comprising a pfam16162 domain or a DUF4868 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 17 rows 2-935 columns L and M; or(m) a nucleic acid construct encoding a Defense System Xa comprising at least two different polypeptide components selected from a JetA polypeptide comprising a pfam11855 domain or a DUF3375 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2-2322 columns J and K;a JetB polypeptide comprising a pfam13835 domain or a DUF4194 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2-2322 columns N and O;a JetC polypeptide comprising a pfam13555 domain or a pfam13558 domain or a COG4913 domain or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2-2322 columns R and S; anda JetD polypeptide comprising a pfam11795 domain or a DUF3322 domain or a pfam09983 domain or a DUF2220 domain or a COG4924 domain or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2-2322 columns V and W; or(n) a nucleic acid construct encoding a Defense System Xb comprising at least two different polypeptide components selected from a JetAii polypeptide comprising a pfam09660 domain or a DUF2397 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2323-2844 columns J and K;a JetBii polypeptide comprising a pfam09661 domain or a DUF2398 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2323-2844 columns N and O;a JetCii polypeptide comprising a pfam13558 domain comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2323-2844 columns R and S; anda JetDii polypeptide comprising a pfam11796 domain or a DUF3323 domain or a pfam09664 domain or a DUF2399 domain or a combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2323-2844 columns V and W; or(o) a nucleic acid construct encoding a Defense System Xc comprising at least two different polypeptide components selected from a JetAiii polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2845-3174 columns J and K;a JetBiii polypeptide comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2845-3174 columns N and O;a JetCiii polypeptide comprising a COG1196 domain or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2845-3174 columns R and S; anda JetDiii polypeptide comprising a pfam09983 domain or a pfam09664 domain or a DUF2220 or a DUF2399 domain or any combination thereof, or comprising an amino acid sequence having at least 80% identity to a sequence selected from the group referenced in Table 11 rows 2845-3174 columns V and W; or(p) any combination of nucleic acid constructs encoding a Defense Systems Ia-Xc (a)-(o);wherein each nucleic acid construct of each Defense System (a)-(o) further comprises a regulatory element operably linked to said construct comprising a cis-acting regulatory element for directing expression of said nucleic acid sequence, or a transmissible element for directing transfer of said nucleic acid sequence from one cell to another, or a recombination element for integrating said nucleic acid sequence into a genome of a cell transfected with said construct, or an element providing episomal maintenance of said construct within a cell transfected with said construct, or any combination thereof.
  • 12. The nucleic acid construct of claim 11, wherein said expressed defense system comprises (a) a Defense System IV comprising the HamA polypeptide, and the HamB polypeptide; or(b) a Defense System Ia comprising the ZorA polypeptide, the ZorB polypeptide, the ZorC polypeptide, and the ZorD polypeptide; or(c) a Defense System Ib comprising the ZorA polypeptide, the ZorB polypeptide, and the ZorE polypeptide; or(d) a Defense System II comprising the ThsA polypeptide, and the ThsB polypeptide; or(e) a Defense System IIIa comprising the DruA polypeptide, the DruB polypeptide, the DruC polypeptide, the DruD polypeptide, and the DruE polypeptide; or(f) a Defense System IIIb comprising the Drug polypeptide, the DruF polypeptide, the DruG polypeptide, and the DruE polypeptide; or(g) a Defense System IIIc comprising the DruH polypeptide and the DruE polypeptide; or(h) a Defense System V comprising the SduA polypeptide; or(i) a Defense System VI comprising the GajA polypeptide and the GajB polypeptide; or(j) a Defense System VII comprising the PtuA polypeptide and the PtuB polypeptide; or(k) a Defense System VIII comprising the LmuA polypeptide and the LmuB polypeptide; or(l) a Defense System IX comprising the KwaA polypeptide and the KwaB polypeptide; or(m) a Defense System Xa comprising the JetA polypeptide, the JetB polypeptide, the JetC polypeptide, and the JetD polypeptide; or(n) a Defense System Xb comprising the JetAii polypeptide, the JetBii polypeptide, the JetCii polypeptide, and the JetDii polypeptide; or(o) a Defense System Xc comprising the JetAiii polypeptide, the JetBiii polypeptide, the JetCiii polypeptide, and the JetDiii polypeptide.
  • 13. The nucleic acid construct of claim 11, wherein (a) said Defense System IV is encoded by a nucleic acid sequence selected from the group referenced in Table 12, rows 2-1782, columns G, P, and Q or the nucleic acid sequence set forth in SEQ ID NO: 4; ora nucleic acid sequence encoding the at least two different polypeptide sequences recited in claim 1; ora nucleic acid sequence encoding the HamA polypeptide and HamB polypeptide recited in claim 4;(b) said Defense System Ia is encoded by, a nucleic acid sequence selected from the group referenced in Table 8 rows 2-1174 columns G, AD, and AE or the nucleic acid sequence set forth in SEQ ID NO: 14; ora nucleic acid sequence encoding the at least two different polypeptide sequences recited in claim 1; ora nucleic acid sequence encoding the ZorA polypeptide, the ZorB polypeptide, the ZorC polypeptide, and ZorD polypeptide recited in claim 4;(c) said Defense System Ib is encoded by a nucleic acid sequence selected from the group referenced in Table 8 rows 1175-1830 columns G, AD, and AE or set forth in SEQ ID NO: 15; ora nucleic acid sequence encoding the at least two different polypeptide sequences recited in claim 1; or a nucleic acid sequence encoding the ZorA polypeptide, the ZorB polypeptide, and ZorE polypeptide recited in claim 4;(d) said Defense System II is encoded by a nucleic acid sequence selected from the group referenced in Table 9 rows 2-2100 columns G, AG, and AH or set forth in the nucleic acid sequence set forth in SEQ ID NO: 10 or SEQ ID NO: 11; ora nucleic acid sequence encoding the at least two different polypeptide sequences recited in claim 1; ora nucleic acid sequence encoding the ThsA polypeptide and the ThsB polypeptide recited in claim 4;(e) said Defense System IIIa is encoded by a nucleic acid sequence selected from the group referenced in Table 10 rows 2-123 columns G, AT, and AU or set forth in SEQ ID NO: 16; ora nucleic acid sequence encoding the at least two different polypeptide sequences recited in claim 1; ora nucleic acid sequence encoding the DruA polypeptide, the DruB polypeptide, the DruC, the DruD, and the DruE polypeptide recited in claim 4;(f) said Defense System IIIb is encoded by a nucleic acid sequence selected from the group referenced in Table 10 rows 124-295 columns G, AT, AU; ora nucleic acid sequence encoding the at least two different polypeptide sequences recited in claim 1; ora nucleic acid sequence encoding the DruM polypeptide, the DruF polypeptide, the DruG polypeptide, and the DruE polypeptide recited in claim 4;(g) said Defense System IIIc is encoded by a nucleic acid sequence selected from the group referenced in Table 10 rows 296-1343 columns G, AT, and AU; ora nucleic acid sequence encoding the at least two different polypeptide sequences recited in claim 1; ora nucleic acid sequence encoding the DruH polypeptide and the DruE polypeptide recited in claim 4;(h) said Defense System V is encoded by a nucleic acid sequence selected from the group referenced in Table 13; rows 2-1247, columns H and J; ora nucleic acid sequence encoding the SduA polypeptide of claim 1 and claim 4;(i) said Defense System VI is encoded by a nucleic acid sequence selected from the group referenced in Table 14, rows 2-4599, columns G, P, and Q or the sequences set forth in SEQ ID NO: 5 and SEQ ID NO: 6; ora nucleic acid sequence encoding the at least two different polypeptide sequences recited in claim 1; ora nucleic acid sequence encoding the GajA polypeptide and the GajB polypeptide recited in claim 4;(j) said Defense System VII is encoded by a nucleic acid sequence selected from the group referenced in Table 15, rows 2-2507, columns G, P, and Q or the sequences set forth in SEQ ID NO: 12 and SEQ ID NO: 13; ora nucleic acid sequence encoding the at least two different polypeptide sequences recited in claim 1; ora nucleic acid sequence encoding the Ptu polypeptide and the PtuB polypeptide recited in claim 4;(k) said Defense System VIII is encoded by a nucleic acid sequence selected from the group referenced in Table 16, rows 2-698, columns G, P, and Q or the sequences set forth in SEQ ID NO: 7 and SEQ ID NO: 8; ora nucleic acid sequence encoding the at least two different polypeptide sequences recited in claim 1; ora nucleic acid sequence encoding the LmuA polypeptide and LmuB polypeptide recited in claim 4;(l) said Defense System IX is encoded by a nucleic acid sequence selected from the group referenced in Table 17, rows 2-935, columns G, P, and Q or the sequence set forth in SEQ ID NO: 3; ora nucleic acid sequence encoding the at least two different polypeptide sequences recited in claim 1; ora nucleic acid sequence encoding the KwaA polypeptide and the KwaB polypeptide recited in claim 4;(m) said Defense System Xa is encoded by a nucleic acid sequence selected from the group referenced in Table 11, rows 2-2322, columns G, Z, and AA or the sequence set forth in SEQ ID NO: 17; ora nucleic acid sequence encoding the at least two different polypeptide sequences recited in claim 1; ora nucleic acid sequence encoding the JetA polypeptide, the JetB polypeptide, the JetC polypeptide, and the JetD polypeptide recited in claim 4;(n) said Defense System Xb is encoded by a nucleic acid sequence having at least 80% homology to a sequence selected from the group referenced in Table 11, rows 2323-2844, columns G, Z, and AA or the sequence set forth in SEQ ID NO: 18; ora nucleic acid sequence encoding the at least two different polypeptide sequences recited in claim 1; ora nucleic acid sequence encoding the JetAii polypeptide, the JetBii polypeptide, the JetCii polypeptide, and the JetDii polypeptide recited in claim 4;(o) said Defense System Xc is encoded by a nucleic acid sequence selected from the group referenced in Table 11, rows 2845-3174, columns G, Z, and AA or the sequence set forth in SEQ ID NO: 19; ora nucleic acid sequence encoding the at least two different polypeptide sequences recited in claim 1; ora nucleic acid sequence encoding the JetAiii polypeptide, the JetBiii polypeptide, the JetCiii polypeptide, and the JetDiii polypeptide recited in claim 4.
  • 14. The nucleic acid construct of claim 11, wherein (a) said HamA polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 12, rows 2-1782, columns H and J, or said HamB polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 12, rows 2-1782, columns L and N, or a combination thereof;(b) said ZorA polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 8 rows 2-1830 columns J and L, said ZorB polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 8 rows 2-1830 columns N and P,said ZorC polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 8 rows 2-1174 columns R and T, orsaid ZorD polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 8 rows 2-1174 columns V and X, ora combination thereof;(c) said ZorA polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 8 rows 2-1830 columns J and L, said ZorB polypeptide is encoded by a nucleic acid sequence selected from the group Table 8 rows 2-1830 columns N and P,said ZorE polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 8 rows 1175-1830 columns Z and AB, or a combination thereof;(d) said ThsA polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 9 rows 2-2100 columns I and K, said ThsB polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 9 rows 2-2100 columns M and O, Q and S, U and W, Y and AA, and AC and AE, ora combination thereof;(e) said DruA polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 10 rows 2-123 columns J and L, or said DruB polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 10 rows 2-123 columns N and P, orsaid DruC polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 10 rows 2-123 columns R and T, orsaid DruD polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 10 rows 2-123 columns V and X, orsaid DruE polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 10 rows 2-1343 columns Z and AB, or a combination thereof;(f) said DruM polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 10 rows 124-295 columns AD and AF, or said DruF polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 10 rows 124-295 columns AH and AJ, orsaid DruG polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 10 rows 124-295 columns AL and AN, orsaid DruE polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 10 rows 2-1343 columns Z and AB, ora combination thereof;(g) said DruH polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 10 rows 296-1343 columns AP and AR, or said DruE polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 10 rows 2-1343 columns Z and AB, ora combination thereof;(h) said SduA polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 13; rows 2-1247, columns H and J;(i) said GajA polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 14, rows 2-4599, columns H and J, or said GajB polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 14, rows 2-4599, columns L and N; ora combination thereof;(j) said PtuA polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 15, rows 2-2507, columns H and J, or said PtuB polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 15, rows 2-2507, columns L and N, ora combination thereof;(k) said LmuA polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 16, rows 2-698, columns H and J, or said LmuB polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 16, rows 2-698, columns L and N, ora combination thereof;(l) said KwaA polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 17, rows 2-935, columns H and J, or said KwaB polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 17, rows 2-935, columns L and N, ora combination thereof;(m) said JetA polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 11, rows 2-2322, columns J and L, or said JetB polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 11, rows 2-2322; columns N and P, orsaid JetC polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 11, rows 2-2322, columns R and T, orsaid JetD polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 11, rows 2-2322, columns V and X, ora combination thereof;(n) said JetAii polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 11, rows 2323-2844, columns J and L, or said JetBii polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 11, rows 2323-2844, columns N and P, orsaid JetCii polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 11, rows 2323-2844, columns R and T, orsaid JetDii polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 11, rows 2323-2844, columns V and X, ora combination thereof;(o) said JetAiii polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 11, rows 2845-3174, column J and L, or said JetBiii polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 11, rows 2845-3174, columns N and O, orsaid JetCiii polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 11, rows 2845-3174, columns R and T, orsaid JetDiii polypeptide is encoded by a nucleic acid sequence selected from the group referenced in Table 11, rows 2845-3174, columns V and X, ora combination thereof.
  • 15. The nucleic acid construct of claim 11, wherein expression of said defense system in a host cells provides the host cell with resistance to foreign nucleic acid invasion.
  • 16. The nucleic acid construct of claim 15, wherein said resistance to foreign nucleic acid invasion comprises resistance to at least one phage infection, or resistance to plasmid transformation, or resistance to entry of a conjugation element, or any combination thereof
  • 17. A transmissible genetic element or an expression vector comprising the nucleic acid construct of claim 1.
  • 18. An isolated cell expressing a nucleic acid construct of claim 1.
  • 19. The isolated cell of claim 18, wherein said cell comprises a gram-positive bacterium or a gram-negative bacterium.
  • 20. The isolated cell of claim 18, wherein said cell comprises resistance to foreign nucleic acid invasion.
  • 21. The isolated cell of claim 20, wherein resistance to foreign nucleic acid invasion comprises resistance to at least one phage infection, or reduced plasmid transformation efficiency, or resistance to entry of a conjugation element, or a combination thereof.
  • 22. A food, food additive, feed, nutritional supplement, probiotic supplement, personal care product, health care product, and or a veterinary product comprising the defense system of any one of claims 7-10, or the nucleic acid construct of any one of claims 11-16, or the transmissible genetic element of claim 17, or the isolated cell of any one of claims 18-21.
  • 23. The food, food additive, feed, nutritional supplement, probiotic supplement, personal care product, health care product, and or a veterinary product of claim 22, wherein said defense system comprises a combination of Defense Systems selected from Defense Systems Ia-Xc (a)-(o).
  • 24. A method of preparing a food, a food additive, a feed, a nutritional supplements, a probiotic supplement, a personal care product, a health care product or a veterinary product, the method comprising adding to the food, food additive, feed, nutritional supplement, probiotic supplement, personal care product, health care product, or veterinary product at least one defense system of any one of claims 7-10, or the nucleic acid construct of any one of claims 11-16, or the transmissible genetic element of claim 17, or the isolated cell of any one of claims 18-21.
  • 25. A method for identifying a defense system in a prokaryotic cell, comprising the steps of: (a) selecting, in-silico, a family of genes that are preferentially located in close proximity to a known defense-related gene family present in a plurality of prokaryotic genomes; and(b) analyzing, in-silico, the DNA upstream and downstream of said gene; and(c) identifying, in-silico, a cassette of genes within the upstream and downstream DNA analyzed in step (b) comprising said gene of step (a), wherein said cassette of genes has conserved synteny in said plurality of prokaryotic genomes.
  • 26. The method of claim 25, wherein the gene of step (a), located in close proximity to a known defense related gene family, is within 10 genes upstream and or 10 genes downstream of the known defense related gene family.
  • 27. A method gene editing; said method comprising contacting a nucleic acid sequence comprising a gene to be edited with at least one polypeptide component of a defense system, wherein said defense system component comprises a component selected from the defense system of claim 7; where said method results in the gene being edited.
PCT Information
Filing Document Filing Date Country Kind
PCT/IL2018/050559 5/23/2018 WO 00
Provisional Applications (3)
Number Date Country
62586911 Nov 2017 US
62512219 May 2017 US
62512216 May 2017 US