Patent Application
20230330167
This application claims priority benefit to United Kingdom Patent Application Nos. GB1719896.1 filed on Nov. 29, 2017 and GB1808063.0 filed on May 17, 2018, the contents of which are incorporated herein by reference in their entireties.
The content of the following submission on ASCII text file is incorporated herein by reference in its entirety: a computer readable form (CRF) of the Sequence Listing (file name: 786212000400SEQLIST.txt, date recorded: May 21, 2018, size: 71 KB).
The invention relates to the production of phage using DNAs (eg, plasmids and helper phage, or plasmids with chromosomally integrated helper phage genes), as well as the phage, helper phage, kits, compositions and methods involving these.
The use of helper phage to package phagemid DNA into phage virus particles is known. An example is the M13KO7 helper phage, a derivative of M13, used in E coli host cells. Other examples are R408 and CM13.
The invention relates to the production of phage and provides:—
In a First Configuration
A kit comprising
In a Second Configuration
A population of helper phage, wherein the helper phage are capable of packaging first phage, wherein the first phage are different from the helper phage and the helper phage are incapable of self-replication.
In a Third Configuration
A composition comprising a population of first phage, wherein the first phage require helper phage according to the First Configuration for replication; and wherein less than [20%] of total phage comprised by the composition are such helper phage.
In a Fourth Configuration
A method of producing first phage, wherein the first phage require helper phage to replicate, the method comprising
In a Fifth Configuration
A phage production system, for producing phage (eg, the first phage of any preceding claim) comprising a nucleotide sequence of interest (NSI-phage), the system comprising components (i) to (iii):—
A composition for use in antibacterial treatment of bacteria, the composition comprising an engineered mobile genetic element (MGE) that is capable of being mobilised in a first bacterial host cell of a first species or strain, the cell comprising a first phage genome, wherein in the cell the MGE is mobilised using proteins encoded by the phage and replication of first is inhibited, wherein the MGE encodes an antibacterial agent or encodes a component of such an agent.
A nucleic acid vector comprising the MGE integrated therein, wherein the vector is capable of transferring the MGE or a copy thereof into a host bacterial cell.
A non-self replicative transduction particle comprising said MGE or vector of the invention.
A composition comprising a plurality of transduction particles, wherein each particle comprises a MGE or vector according to the invention, wherein the transduction particles are capable of transferring the MGEs, or nucleic acid encoding the agent or component, or copies thereof into target bacterial cells, wherein
A composition comprising a plurality of non-self replicative transduction particles, wherein each particle comprises a MGE or plasmid according to the invention, wherein the transduction particles are capable of transferring the MGEs, or nucleic acid encoding the agent or component, or copies thereof into target bacterial cells, wherein the agent is a CRISPR/Cas system and the component comprises a nucleic acid encoding a crRNA or a guide RNA that is operable with a Cas in a target bacterial cell to guide the Cas to a target nucleic acid sequence of the cell to modify the sequence, whereby
A method of producing a plurality of transduction particles, the method comprising combining the composition of the invention with host bacterial cells of said first species, wherein the cells comprise the first phage, allowing a plurality of said MGEs to be introduced into host cells and culturing the host cells under conditions in which first phage-encoded proteins are expressed and MGE copies are packaged by first phage proteins to produce a plurality of transduction particles, and optionally separating the transduction particles from cells and obtaining a plurality of transduction particles separated from cells.
A bacterial host cell comprising a first phage and a MGE, vector or particle of the invention, wherein the agent is toxic to cells of the same species as the host cell, and wherein the host cell has been engineered so that the agent is not toxic to the host cell.
A bacterial host cell comprising a first phage, wherein the cell is comprised by a kit, the kit further comprising a composition of the invention, wherein the agent is toxic to cells of the same species as the host cell, and wherein the host cell has been engineered so that the agent is not toxic to the host cell.
A bacterial host cell comprising a first phage and a MGE, vector or particle of the invention, wherein the agent is not toxic to the host cell, but the agent is toxic to second cells of a species or strain that is different from the species or strain of the host cell, wherein the MGE is mobilizable in transduction particles producible by the host cell that are capable of transferring the MGE or a copy thereof into a said second cell, whereby the second cell is exposed to the antibacterial agent.
A bacterial host cell comprising a first phage, wherein the cell is comprised by a kit, the kit further comprising a composition of the invention, wherein the agent is not toxic to the host cell, but the agent is toxic to second cells of a species or strain that is different from the species or strain of the host cell, wherein the MGE is mobilizable in transduction particles producible by the host cell that are capable of transferring the MGE or a copy thereof into a said second cell, whereby the second cell is exposed to the antibacterial agent.
A bacterial host cell comprising a MGE, vector or particle of the invention and nucleic acid under the control of one or more inducible promoters, wherein the nucleic acid encodes all structural proteins necessary to produce a transduction particle that packages a copy of the MGE or plasmid, wherein the agent is not toxic to the host cell, but the agent is toxic to second cells of a species or strain that is different from the species or strain of the host cell, wherein the MGE is mobilizable in transduction particles producible by the host cell that are capable of transferring the MGE or a copy thereof into a said second cell, whereby the second cell is exposed to the antibacterial agent.
A plasmid comprising
A bacterial host cell comprising the genome of a helper phage that is incapable of self-replication, optionally wherein the genome is present as a prophage, and a plasmid according to the invention, wherein the helper phage is operable to package copies of the plasmid in transduction particles, wherein the particles are capable of infecting bacterial target cells to which the antibacterial agent is toxic.
A method of making a plurality of transduction particles, the method comprising culturing a plurality of host cells according to the invention, optionally inducing a lytic cycle of the helper phage, and incubating the cells under conditions wherein transducing particles comprising packaged copies of the plasmid are created, and optionally separating the particles from the cells to obtain a plurality of transduction particles.
A plurality of transduction particles obtainable by the method of the invention for use in medicine, eg, for treating or preventing an infection of a human or animal subject by target bacterial cells, wherein transducing particles are administered to the subject for infecting target cells and killing the cells using the antibacterial agent.
A method of making a plurality of transduction particles, the method comprising
A plurality of transduction particles obtainable by the method.
The invention relates to the production of phage using DNAs (eg, plasmids with helper phage), as well as the phage, helper phage, compositions and methods involving these. The invention finds utility, for example, for containing phage in environments ex vivo and in vivo, reducing the risk of acquisition of antibiotic resistance or other genes by phage, as well as controlling dosing of phage in an environment. The contamination of useful phage populations by helper phage may in examples also be restricted or eliminated, thereby controlling phage propagation and enhancing the proportion of desired phage in phage compositions, such as medicaments, herbicides and other agents where phage may usefully be used. Thus, the invention provides the following embodiments.
A kit comprising
For example the second DNA is devoid of a packaging signal for packaging second DNA. Additionally or alternatively, the second DNA is devoid of a nucleotide sequence required for replication of helper phage. Optionally, the nucleotide sequence encodes a sigma factor or comprises a sigma factor recognition site, a DNA polymerisation recognition site, or a promoter of a gene required for helper phage DNA replication when the second DNA is comprised by a helper prophage.
In an example, the second DNA is comprised by an M13 or M13-based helper phage. M13 encodes the following proteins required for phage packaging:—
In this example, the second DNA is devoid of one or more of the genes coding for these proteins, eg, is devoid of a gene encoding pIII, a gene encoding pV, a gene encoding pVII, a gene encoding pVIII, a gene encoding pIX, a gene encoding pI, a gene encoding pIV and/or a gene encoding XI.
In an embodiment, the phage particle of (i) is capable of infecting a target bacterium, the phage comprising a nucleotide sequence of interest (NSI) that is capable of expressing a protein or RNA in the target bacterium, or wherein the NSI comprises a regulatory element that is operable in the target bacterium. In an example, the NSI is capable of recombination with the target cell chromosome or an episome comprised by the target cell to modify the chromosome or episome. Optionally, this is carried out in a method wherein the chromosome or episome is cut (eg, at a predetermined site using a guided nuclease, such as a Cas, TALEN, zinc finger or meganuclease; or a restriction endonuclease) and simultaneously or sequentially the cell is infected by a phage particle that comprises the first DNA, wherein the DNA is introduced into the cell and the NSI or a sequence thereof is introduced into the chromosome or episome at or adjacent the cut site. In an example the first DNA comprises one or more components of a CRISPR/Cas system operable to perform the cutting (eg, comprising at least a nucleotide sequence encoding a guide RNA or crRNA for targeting the site to be cut) and further comprising the NSI.
In an embodiment, the presence in the target bacterium of the NSI or its encoded protein or RNA mediates target cell killing, or downregulation of growth or propagation of target cells, or mediates switching off of expression of one or more RNA or proteins encoded by the target cell genome, or downregulation thereof.
In an embodiment, the presence in the target bacterium of the NSI or its encoded protein or RNA mediates upregulation of growth or propagation of the target cell, or mediates switching on of expression of one or more RNA or proteins encoded by the target cell genome, or upregulation thereof.
In an embodiment, the NSI encodes a component of a CRISPR/Cas system that is toxic to the target bacterium.
In an embodiment, the DNA is a first DNA as defined in any preceding paragraph.
In an embodiment, the first DNA is comprised by a vector (eg, a plasmid or shuttle vector).
In an embodiment, the second DNA is comprised by a vector (eg, a plasmid or shuttle vector), helper phage (eg, a helper phagemid) or is integrated in the genome of a host bacterial cell.
An embodiment provides a bacterial cell comprising the first and second DNAs. Optionally, the cell is devoid of a functional CRISPR/Cas system before transfer therein of a first DNA, eg, a first DNA comprising a component of a CRISPR/Cas system that is toxic to the target bacterium. An embodiment provides an antibacterial composition comprising a plurality of cells, wherein each cell is optionally according to this paragraph, for administration to a human or animal subject for medical use.
A method of producing phage is provided, the method comprising expressing in a host bacterial cell the phage protein genes, wherein packaged phage are produced that comprise the first DNA, wherein the phage require the second DNA for replication thereof to produce further phage particles. Optionally, the method comprises isolating the phage particles.
A composition comprising a population of phage particles obtainable by the method is provided for administration to a human or animal subject for treating an infection of target bacterial cells, wherein the phage are capable of infecting and killing the target cells.
A method of treating an environment ex vivo, the method comprising exposing the environment to a population of phage particles obtainable by the method is provided, wherein the environment comprises target bacteria and the phage infect and kill the target bacteria. In an example the subject is further administered an agent simultaneously or sequentially with the phage administration. In an example, the agent is a herbicide, pesticide, insecticide, plant fertilizer or cleaning agent.
Optionally, the method is for containing the treatment in the environment.
Optionally, the method is for controlling the dosing of the phage treatment in the environment.
Optionally, the method is for reducing the risk of acquisition of foreign gene sequence(s) by the phage in the environment.
A method of treating an infection of target bacteria in a human or animal subject is provided, the method comprising exposing the bacteria to a population of phage particles obtainable by the production method, wherein the phage infect and kill the target bacteria.
Optionally, the method for treating is for containing the treatment in the subject.
Optionally, the method for treating is for containing the treatment in the environment in which the subject exists.
Optionally, the method for treating is for controlling the dosing of the phage treatment in the subject.
Optionally, the method for treating is for reducing the risk of acquisition of foreign gene sequence(s) by the phage in the subject.
Optionally, the method for treating is for reducing the risk of acquisition of foreign gene sequence(s) by the phage in the environment in which the subject exists.
Optionally, target bacteria herein are comprised by a microbiome of the subject, eg, a gut microbiome. Alternatively, the microbiome is a skin, scalp, hair, eye, ear, oral, throat, lung, blood, rectal, anal, vaginal, scrotal, penile, nasal or tongue microbiome.
In an example the subject is further administered a medicament simultaneously or sequentially with the phage administration. In an example, the medicament is an antibiotic, antibody, immune checkpoint inhibitor (eg, an anti-PD-1, anti-PD-L1 or anti-CTLA4 antibody), adoptive cell therapy (eg, CAR-T therapy) or a vaccine.
In an example, the invention employs helper phage for packaging the phage nucleic acid of interest. Thus, the invention provides the following illustrative Aspects:—
1. A population of helper phage, wherein the helper phage are capable of packaging first phage nucleic acid to produce first phage particles, wherein the first phage are different from the helper phage and the helper phage are incapable themselves of producing helper phage particles.
2. A composition comprising a population of first phage, wherein the first phage require helper phage according to Aspect 1 for replication of first phage particles; and optionally wherein less than 20, 15, 10, 5, 4, 3, 2, 1, 0.5, 0.4, 0.2 or 0.1% of total phage particles comprised by the composition are particles of such helper phage.
In an example, the population comprises at least 103, 104, 105 or 106 phage particles, as indicated a transduction assay, for example. To have a measure of the first phage concentration, for example, one can perform a standard transduction assay when the first phage genome contains an antibiotic marker. Thus, in this case the first phage are capable of infecting target bacteria and in a sample of 1 ml the population comprises at least 103, 104, 105 or 106 transducing particles, which can be determined by infecting susceptible bacteria at a multiplicity of infection <0.1 and determining the number of infected cells by plating on a selective agar plate corresponding to the antibiotic marker in vitro at 20 to 37 degrees centigrade, eg, at 20 or 37 degrees centrigrade.
Optionally at least 99.9, 99.8, 99.7, 99.6, 99.5, 99.4, 99.3, 99.2, 99.1, 90, 85, 80, 70, 60, 50 or 40% of total phage particles comprised by the composition are particles of first phage.
In an example, the first phage genome comprises an f1 origin of replication.
In an example, the helper phage are E coli phage. In an example, the first phage are E coli, C difficile, Streptococcus, Klebsiella, Pseudomonas, Acinetobacter, Enterobacteriaceae, Firmicutes or Bacteroidetes phage. In an example, the helper phage are engineered M13 phage.
In an example, the first phage genome comprises a phagemid, wherein the phagemid comprises a packaging signal for packaging first phage particles in the presence of the helper phage.
The first phage particles may contain a nucleotide sequence of interest (NSI), eg, as defined herein, such as a NSI that encodes a component of a CRISPR/Cas system operable in target bacteria that can be infected by the first phage particles. Once inside the target bacteria, the first phage DNA is incapable of being packaged to form first phage particles in the absence of the helper phage. This usefully contains the activity of the first phage genome and its encoded products (proteins and/or nucleic acid), as well as limits or controls dosing of the NSI and its encoded products in an environment comprising the target bacteria that have been exposed to the first phage. This is useful, for example to control the medical treatment of an environment comprised by a human or animal subject, plant or other environment (eg, soil or a foodstuff or food ingredient).
3. The helper phage or composition of any preceding Aspect, wherein the genome of each first phage is devoid of genes encoding first phage structural proteins.
4. The composition of Aspect 2 or 3, wherein the composition comprises helper phage DNA.
5. The composition of Aspect 4, wherein the DNA comprises helper DNA fragments.
6. The helper phage or composition of any one preceding Aspect, wherein the helper phage are in the form of prophage.
Thus, the prophage is integrated in the chromosome of a host cell.
Examples of phage structural proteins are phage coat proteins, collar proteins and phage tail fibre proteins.
7. The composition of any one of Aspects 2 or 3, wherein the composition comprises no helper phage DNA comprising a sequence of 20 contiguous nucleotides or more, eg, no helper phage DNA.
This can be determined, for example, using DNA probes (designed on the basis of the known helper phage genome sequence) with PCR, as is conventional. In an example, the composition may comprise residual helper prophage DNA, but essentially otherwise is devoid of helper DNA.
8. The composition of any one of Aspects 2 to 5 and 7, wherein the helper phage are capable of infecting host bacteria and the composition does not comprise host bacteria.
9. The composition of any one of Aspects 2 to 8, wherein the composition is a lysate of host bacterial cells, wherein the lysate comprises helper prophage DNA, eg, such DNA comprises 20 contiguous nucleotides or more of helper phage DNA.
10. The composition of any one of Aspects 2 to 8, wherein the composition is a lysate of host bacterial cells, wherein the lysate has been processed (eg, filtered) to remove all or some helper phage DNA; or the composition is a lysate of host bacterial cells that is devoid of cellular material.
11. The composition of any one of Aspects 2 to 10, wherein the composition does not comprise helper phage particles.
12. The composition of any one of Aspects 2 to 11, wherein at least 95% (eg, 100%) of phage particles comprised by the composition are first phage particles.
In another embodiment, the composition comprises second phage particles, wherein the second phage are different from the first phage and are not helper phage.
13. The composition of any one of Aspects 2 to 12, wherein the population comprises at least 103, 104, 105 or 106 phage particles, as indicated in a transduction assay.
14. The helper phage or composition of any preceding Aspect, wherein the first phage are capable of replicating in host bacteria in the presence of the helper phage (eg, helper prophage), wherein the first phage comprise antibacterial means for killing target bacteria of a first strain or species, wherein the target bacteria are of a different strain or species and the antibacterial means is not operable to kill the target bacteria.
15. A composition comprising a population of phage, the population comprising
In an example, the kit, DNA(s), first phage, helper phage or composition is comprised by a medical container, eg, a syringe, vial, IV bag, inhaler, eye dropper or nebulizer. In an example, the kit, DNA(s), first phage, helper phage or composition is comprised by a sterile container. In an example, the kit, DNA(s), first phage, helper phage or composition is comprised by a medically-compatible container. In an example, the kit, DNA(s), first first phage, helper phage or composition is comprised by a fermentation vessel, eg, a metal, glass or plastic vessel.
In an example, the kit, DNA(s), first phage, helper phage or composition is comprised by a medicament, e,g in combination with instructions or a packaging label with directions to administer the medicament by oral, IV, subcutaneous, intranasal, intraocular, vaginal, topical, rectal or inhaled administration to a human or animal subject. In an example, the kit, DNA(s), first phage, helper phage or composition is comprised by an oral medicament formulation. In an example, the kit, DNA(s), first phage, helper phage or composition is comprised by an intranasal or ocular medicament formulation. In an example, the kit, DNA(s), first phage, helper phage or composition is comprised by a personal hygiene composition (eg, shampoo, soap or deodorant) or cosmetic formulation. In an example, the kit, DNA(s), first phage, helper phage or composition is comprised by a detergent formulation. In an example, the kit, DNA(s), first phage, helper phage or composition is comprised by a cleaning formulation, eg, for cleaning a medical or industrial device or apparatus. In an example, the kit, DNA(s), first phage, helper phage or composition is comprised by foodstuff, foodstuff ingredient or foodstuff processing agent. In an example, the kit, DNA(s), first phage, helper phage or composition is comprised by beverage, beverage ingredient or beverage processing agent. In an example, the kit, DNA(s), first phage, helper phage or composition is comprised by a medical bandage, fabric, plaster or swab. In an example, the kit, DNA(s), first phage, helper phage or composition is comprised by a herbicide or pesticide. In an example, the kit, DNA(s), first phage, helper phage or composition is comprised by an insecticide.
In an example, the first phage is a is a Corticoviridae, Cystoviridae, Inoviridae, Leviviridae, Microviridae, Myoviridae, Podoviridae, Siphoviridae, or Tectiviridae virus. In an example, the helper phage is a is a Corticoviridae, Cystoviridae, Inoviridae, Leviviridae, Microviridae, Myoviridae, Podoviridae, Siphoviridae, or Tectiviridae virus. In an example, the helper phage is a filamentous M13, a Noviridae, a tailed phage (eg, a Myoviridae, Siphoviridae or Podoviridae), or a non-tailed phage (eg, a Tectiviridae).
In an example, both the first and helper phage are Corticoviridae. In an example, both the first and helper phage are Cystoviridae. In an example, both the first and helper phage are Inoviridae. In an example, both the first and helper phage are Leviviridae. In an example, both the first and helper phage are Microviridae. In an example, both the first and helper phage are Podoviridae. In an example, both the first and helper phage are Siphoviridae. In an example, both the first and helper phage are Tectiviridae.
In an example, the CRISPR/Cas component(s) are component(s) of a Type I CRISPR/Cas system. In an example, the CRISPR/Cas component(s) are component(s) of a Type II CRISPR/Cas system. In an example, the CRISPR/Cas component(s) are component(s) of a Type III CRISPR/Cas system. In an example, the CRISPR/Cas component(s) are component(s) of a Type IV CRISPR/Cas system. In an example, the CRISPR/Cas component(s) are component(s) of a Type V CRISPR/Cas system. In an example, the CRISPR/Cas component(s) comprise a Cas9-encoding nucleotide sequence (eg, S pyogenes Cas9, S aureus Cas9 or S thermophilus Cas9). In an example, the CRISPR/Cas component(s) comprise a Cas3-encoding nucleotide sequence (eg, E coli Cas3, C difficile Cas3 or Salmonella Cas3). In an example, the CRISPR/Cas component(s) comprise a Cpf-encoding nucleotide sequence. In an example, the CRISPR/Cas component(s) comprise a CasX-encoding nucleotide sequence. In an example, the CRISPR/Cas component(s) comprise a CasY-encoding nucleotide sequence.
In an example, the first DNA, first phage or vector encode a CRISPR/Cas component or protein of interest from a nucleotide sequence comprising a promoter that is operable in the target bacteria.
In an example, the host bacteria and/or target bacteria are E coli. In an example, the host bacteria and/or target bacteria are C difficile (eg, the vector is a shuttle vector operable in E coli and the host bacteria are C difficile). In an example, the host bacteria and/or target bacteria are Streptococcus, such as S thermophilus (eg, the vector is a shuttle vector operable in E coli and the host bacteria are Streptococcus). In an example, the host bacteria and/or target bacteria are Pseudomonas, such as P aeruginosa (eg, the vector is a shuttle vector operable in E coli and the host bacteria are P aeruginosa). In an example, the host bacteria and/or target bacteria are Klebsiella (eg, the vector is a shuttle vector operable in E coli and the host bacteria are Klebsiella). In an example, the host bacteria and/or target bacteria are Salmonella, eg, S typhimurium (eg, the vector is a shuttle vector operable in E coli and the host bacteria are Salmonella).
Optionally, host and/or target bacteria is a gram negative bacterium (eg, a spirilla or vibrio). Optionally, host and/or target bacteria is a gram positive bacterium. Optionally, host and/or target bacteria is a Mycoplasma, chlamydiae, spirochete or Mycobacterium. Optionally, host and/or target bacteria is a Streptococcus (eg, pyogenes or thermophilus). Optionally, host and/or target bacteria is a Staphylococcus (eg, aureus, eg, MRSA). Optionally, host and/or target bacteria is an E. coli (eg, O157: H7) host, eg, wherein the Cas is encoded by the vector or an endogenous host Cas nuclease activity is de-repressed. Optionally, host and/or target bacteria is a Pseudomonas (eg, aeruginosa). Optionally, host and/or target bacteria is a Vibrio (eg, cholerae (eg, 0139) or vulnificus). Optionally, host and/or target bacteria is a Neisseria (eg, gonorrhoeae or meningitidis). Optionally, host and/or target bacteria is a Bordetella (eg, pertussis). Optionally, host and/or target bacteria is a Haemophilus (eg, influenzae). Optionally, host and/or target bacteria is a Shigella (eg, dysenteriae). Optionally, host and/or target bacteria is a Brucella (eg, abortus). Optionally, host and/or target bacteria is a Francisella host. Optionally, host and/or target bacteria is a Xanthomonas host. Optionally, host and/or target bacteria is a Agrobacterium host. Optionally, host and/or target bacteria is a Erwinia host. Optionally, host and/or target bacteria is a Legionella (eg, pneumophila). Optionally, host and/or target bacteria is a Listeria (eg, monocytogenes). Optionally, host and/or target bacteria is a Campylobacter (eg, jejuni). Optionally, host and/or target bacteria is a Yersinia (eg, pestis). Optionally, host and/or target bacteria is a Borrelia (eg, burgdorferi). Optionally, host and/or target bacteria is a Helicobacter (eg, pylori). Optionally, host and/or target bacteria is a Clostridium (eg, difficile or botulinum). Optionally, host and/or target bacteria is a Ehrlichia (eg, chaffeensis). Optionally, host and/or target bacteria is a Salmonella (eg, typhi or enterica, eg, serotype typhimurium, eg, DT 104). Optionally, host and/or target bacteria is a Chlamydia (eg, pneumoniae). Optionally, host and/or target bacteria is a Parachlamydia host. Optionally, host and/or target bacteria is a Corynebacterium (eg, amycolatum). Optionally, host and/or target bacteria is a Klebsiella (eg, pneumoniae). Optionally, host and/or target bacteria is an Enterococcus (eg, faecalis or faecim, eg, linezolid-resistant). Optionally, host and/or target bacteria is an Acinetobacter (eg, baumannii, eg, multiple drug resistant).
Further examples of target cells and targeting of antibiotic resistance in such cells using the present invention are as follows:—
Genetic variation of bacteria and archaea can be achieved through mutations, rearrangements and horizontal gene transfers and recombinations. Increasing genome sequence data have demonstrated that, besides the core genes encoding house-keeping functions such as essential metabolic activities, information processing, and bacterial structural and regulatory components, a vast number of accessory genes encoding antimicrobial resistance, toxins, and enzymes that contribute to adaptation and survival under certain environmental conditions are acquired by horizontal gene transfer of mobile genetic elements (MGEs). Mobile genetic elements are a heterogeneous group of molecules that include plasmids, bacteriophages, genomic islands, chromosomal cassettes, pathogenicity islands, and integrative and conjugative elements. Genomic islands are relatively large segments of DNA ranging from 10 to 200 kb often integrated into tRNA gene clusters flanked by 16-20 bp direct repeats. They are recognized as discrete DNA segments acquired by horizontal gene transfer since they can differ from the rest of the chromosome in terms of GC content (% G+C) and codon usage.
Pathogenicity islands (PTIs) are a subset of horizontally transferred genetic elements known as genomic islands. There exists a particular family of highly mobile PTIs in Staphylococcus aureus that are induced to excise and replicate by certain resident prophages. These PTIs are packaged into small headed phage-like particles and are transferred at frequencies commensurate with the plaque-forming titer of the phage. This process is referred to as the SaPI excision replication-packaging (ERP) cycle, and the high-frequency SaPI transfer is referred to as SaPI-specific transfer (SPST) to distinguish it from classical generalized transduction (CGT). The SaPIs have a highly conserved genetic organization that parallels that of bacteriophages and clearly distinguishes them from all other horizontally acquired genomic islands. The SaPI1-encoded and SaPIbov2-encoded integrases are used for both excision and integration of the corresponding elements, and it is assumed that the same is true for the other SaPIs. Phage 80α can induce several different SaPIs, including SaPI1, SaPI2, and SaPIbov1, whereas φ11 can induce SaPIbov1 but neither of the other two SaPIs.
Reference is made to “Staphylococcal pathogenicity island DNA packaging system involving cos-site packaging and phage-encoded HNH endonucleases”, Quiles-Puchalt et al, PNAS Apr. 22, 2014. 111 (16) 6016-6021. Staphylococcal pathogenicity islands (SaPIs) are highly mobile and carry and disseminate superantigen and other virulence genes. It was reported that SaPIs hijack the packaging machinery of the phages they victimise, using two unrelated and complementary mechanisms. Phage packaging starts with the recognition in the phage DNA of a specific sequence, termed “pac” or “cos” depending on the phage type. The SaPI strategies involve carriage of the helper phage pac- or cos-like sequences in the SaPI genome, which ensures SaPI packaging in full-sized phage particles, depending on the helper phage machinery. These strategies interfere with phage reproduction, which ultimately is a critical advantage for the bacterial population by reducing the number of phage particles.
Staphylococcal pathogenicity islands (SaPIs) are the prototypical members of a widespread family of chromosomally located mobile genetic elements that contribute substantially to intra- and interspecies gene transfer, host adaptation, and virulence. The key feature of their mobility is the induction of SaPI excision and replication by certain helper phages and their efficient encapsidation into phage-like infectious particles. Most SaPIs use the headful packaging mechanism and encode small terminase subunit (TerS) homologs that recognize the SaPI-specific pac site and determine SaPI packaging specificity. Several of the known SaPIs do not encode a recognizable TerS homolog but are nevertheless packaged efficiently by helper phages and transferred at high frequencies. Quiles-Puchalt et al report that one of the non-terS-coding SaPIs, SaPIbov5, and found that it uses two different, undescribed packaging strategies. SaPIbov5 is packaged in full-sized phage-like particles either by typical pac-type helper phages, or by cos-type phages—i.e., it has both pac and cos sites and uses the two different phage-coded TerSs. This is an example of SaPI packaging by a cos phage, and in this, it resembles the P4 plasmid of Escherichia coli. Cos-site packaging in Staphylococcus aureus is additionally unique in that it requires the HNH nuclease, carried only by cos phages, in addition to the large terminase subunit, for cos-site cleavage and melting.
Characterization of several of the phage-inducible SaPIs and their helper phages has established that the pac (or headful) mechanism is used for encapsidation. In keeping with this concept, some SaPIs encode a homolog of TerS, which complexes with the phage-coded large terminase subunit TerL to enable packaging of the SaPI DNA in infectious particles composed of phage proteins. These also contain a morphogenesis (cpm) module that causes the formation of small capsids commensurate with the small SaPI genomes. Among the SaPI sequences first characterized, there were several that did not include either a TerS homolog or a cpm homolog, and the same is true of several subsequently identified SaPIs from bovine sources and for many phage-inducible chromosomal islands from other species. It was assumed, for these several islands, either that they were defective derivatives of elements that originally possessed these genes, or that terS and cpm genes were present but not recognized by homology.
Quiles-Puchalt et al observed that an important feature of ϕSLT/SaPIbov5 packaging is the requirement for an HNH nuclease, which is encoded next to the ϕSLT terminase module. Proteins carrying HNH domains are widespread in nature, being present in organisms of all kingdoms. The HNH motif is a degenerate small nucleic acid-binding and cleavage module of about 30-40 aa residues and is bound by a single divalent metal ion. The HNH motif has been found in a variety of enzymes playing important roles in many different cellular processes, including bacterial killing; DNA repair, replication, and recombination; and processes related to RNA. HNH endonucleases are present in a number of cos-site bacteriophages of Gram-positive and -negative bacteria, always adjacent to the genes encoding the terminases and other morphogenetic proteins. Quiles-Puchalt et al have demonstrated that the HNH nucleases encoded by ϕ12 and the closely related ϕSLT have nonspecific nuclease activity and are required for the packaging of these phages and of SaPIbov5. Quiles-Puchalt et al have shown that HNH and TerL are jointly required for cos-site cleavage. Quiles-Puchalt et al have also observed that only cos phages of Gram-negative as well as of Gram-positive bacteria encode HNH nucleases, consistent with a special requirement for cos-site cleavage as opposed to pac-site cleavage, which generates flush-ended products. The demonstration that HNH nuclease activity is required for some but not other cos phages suggests that there is a difference between the TerL proteins of the two types of phages—one able to cut both strands and the other needing a second protein to enable the generation of a double-stranded cut.
The invention, also involves, in certain configurations the use of mobile genetic elements (MGEs). Thus, there are provided the following Clauses. Any of the other configurations, Aspects, Examples or description of the invention above or elsewhere herein are combinable mutatis mutandis with any of these Clauses:—
The present invention is optionally for an industrial or domestic use, or is used in a method for such use. For example, it is for or used in agriculture, oil or petroleum industry, food or drink industry, clothing industry, packaging industry, electronics industry, computer industry, environmental industry, chemical industry, aerospace industry, automotive industry, biotechnology industry, medical industry, healthcare industry, dentistry industry, energy industry, consumer products industry, pharmaceutical industry, mining industry, cleaning industry, forestry industry, fishing industry, leisure industry, recycling industry, cosmetics industry, plastics industry, pulp or paper industry, textile industry, clothing industry, leather or suede or animal hide industry, tobacco industry or steel industry.
The present invention is optionally for use in an industry or the environment is an industrial environment, wherein the industry is an industry of a field selected from the group consisting of the medical and healthcare; pharmaceutical; human food; animal food; plant fertilizers; beverage; dairy; meat processing; agriculture; livestock farming; poultry farming; fish and shellfish farming; veterinary; oil; gas; petrochemical; water treatment; sewage treatment; packaging; electronics and computer; personal healthcare and toiletries; cosmetics; dental; non-medical dental; ophthalmic; non-medical ophthalmic; mineral mining and processing; metals mining and processing; quarrying; aviation; automotive; rail; shipping; space; environmental; soil treatment; pulp and paper; clothing manufacture; dyes; printing; adhesives; air treatment; solvents; biodefence; vitamin supplements; cold storage; fibre retting and production; biotechnology; chemical; industrial cleaning products; domestic cleaning products; soaps and detergents; consumer products; forestry; fishing; leisure; recycling; plastics; hide, leather and suede; waste management; funeral and undertaking; fuel; building; energy; steel; and tobacco industry fields.
In an example, the first DNA, first phage or vector comprises a CRISPR array that targets target bacteria, wherein the array comprises one, or two or more spacers (eg, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50 or more spacers) for targeting the genome of target bacteria.
In an example, the target bacteria are comprised by an environment as follows. In an example, the environment is a microbiome of a human, eg, the oral cavity microbiome or gut microbiome or the bloodstream. In an example, the environment is not an environment in or on a human. In an example, the environment is not an environment in or on a non-human animal. In an embodiment, the environment is an air environment. In an embodiment, the environment is an agricultural environment. In an embodiment, the environment is an oil or petroleum recovery environment, eg, an oil or petroleum field or well. In an example, the environment is an environment in or on a foodstuff or beverage for human or non-human animal consumption.
In an example, the environment is a a human or animal microbiome (eg, gut, vaginal, scalp, armpit, skin or oral cavity microbiome). In an example, the target bacteria are comprised by a human or animal microbiome (eg, gut, vaginal, scalp, armpit, skin or oral cavity microbiome).
In an example, the DNAs, phage or composition of the invention are administered intranasally, topically or orally to a human or non-human animal, or is for such administration. The skilled person aiming to treat a microbiome of the human or animal will be able to determine the best route of administration, depending upon the microbiome of interest. For example, when the microbiome is a gut microbiome, administration can be intranasally or orally. When the microbiome is a scalp or armpit microbiome, administration can be topically. When the microbiome is in the mouth or throat, the administration can be orally.
In an example, the environment is harboured by a beverage or water (eg, a waterway or drinking water for human consumption) or soil. The water is optionally in a heating, cooling or industrial system, or in a drinking water storage container.
In an example, the host and/or target bacteria are Firmicutes selected from Anaerotruncus, Acetanaerobacterium, Acetitomaculum, Acetivibrio, Anaerococcus, Anaerofilum, Anaerosinus, Anaerostipes, Anaerovorax, Butyrivibrio, Clostridium, Capracoccus, Dehalobacter, Dialister, Dorea, Enterococcus, Ethanoligenens, Faecalibacterium, Fusobacterium, Gracilibacter, Guggenheimella, Hespellia, Lachnobacterium, Lachnospira, Lactobacillus, Leuconostoc, Megamonas, Moryella, Mitsuokella, Oribacterium, Oxobacter, Papillibacter, Proprionispira, Pseudobutyrivibrio, Pseudoramibacter, Roseburia, Ruminococcus, Sarcina, Seinonella, Shuttleworthia, Sporobacter, Sporobacterium, Streptococcus, Subdoligranulum, Syntrophococcus, Thermobacillus, Turibacter and Weissella.
In an example, the kit, DNA(s), first phage, helper phage, composition, use or method is for reducing pathogenic infections or for re-balancing gut or oral microbiota eg, for treating or preventing obesity or disease in a human or animal. For example, the first phage, helper phage, composition, use or method is for knocking-down Clostridium difficile or E coli bacteria in a gut microbiota of a human or animal.
In an example, the packaging signal, NPF and/or HPF consists or comprises SEQ ID NO: 1 or a structural or functional homologue thereof.
In an example, the packaging signal, NPF and/or HPF consists or comprises SEQ ID NO: 1 or a nucleotide sequence that is at least 70, 75, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99% identical thereto.
In an example, the disease or condition is a cancer, inflammatory or autoimmune disease or condition, eg, obesity, diabetes IBD, a GI tract condition or an oral cavity condition.
Optionally, the environment is comprised by, or the target bacteria are comprised by, a gut microbiota, skin microbiota, oral cavity microbiota, throat microbiota, hair microbiota, armpit microbiota, vaginal microbiota, rectal microbiota, anal microbiota, ocular microbiota, nasal microbiota, tongue microbiota, lung microbiota, liver microbiota, kidney microbiota, genital microbiota, penile microbiota, scrotal microbiota, mammary gland microbiota, ear microbiota, urethra microbiota, labial microbiota, organ microbiota or dental microbiota. Optionally, the environment is comprised by, or the target bacteria are comprised by, a plant (eg, a tobacco, crop plant, fruit plant, vegetable plant or tobacco, eg on the surface of a plant or contained in a plant) or by an environment (eg, soil or water or a waterway or aqueous liquid).
Optionally, the disease or condition of a human or animal subject is selected from
Neurodegenerative or CNS Diseases or Conditions for Treatment or Prevention by the Invention
In an example, the neurodegenerative or CNS disease or condition is selected from the group consisting of Alzheimer disease, geriopsychosis, Down syndrome, Parkinson's disease, Creutzfeldt-jakob disease, diabetic neuropathy, Parkinson syndrome, Huntington's disease, Machado-Joseph disease, amyotrophic lateral sclerosis, diabetic neuropathy, and Creutzfeldt Creutzfeldt-Jakob disease. For example, the disease is Alzheimer disease. For example, the disease is Parkinson syndrome.
In an example, wherein the method of the invention is practised on a human or animal subject for treating a CNS or neurodegenerative disease or condition, the method causes downregulation of Treg cells in the subject, thereby promoting entry of systemic monocyte-derived macrophages and/or Treg cells across the choroid plexus into the brain of the subject, whereby the disease or condition (eg, Alzheimer's disease) is treated, prevented or progression thereof is reduced. In an embodiment the method causes an increase of IFN-gamma in the CNS system (eg, in the brain and/or CSF) of the subject. In an example, the method restores nerve fibre and/or reduces the progression of nerve fibre damage. In an example, the method restores nerve myelin and/or reduces the progression of nerve myelin damage. In an example, the method of the invention treats or prevents a disease or condition disclosed in WO2015136541 and/or the method can be used with any method disclosed in WO2015136541 (the disclosure of this document is incorporated by reference herein in its entirety, eg, for providing disclosure of such methods, diseases, conditions and potential therapeutic agents that can be administered to the subject for effecting treatment and/or prevention of CNS and neurodegenerative diseases and conditions, eg, agents such as immune checkpoint inhibitors, eg, anti-PD-1, anti-PD-L1, anti-TIM3 or other antibodies disclosed therein).
Cancers for Treatment or Prevention by the Method
Cancers that may be treated include tumours that are not vascularized, or not substantially vascularized, as well as vascularized tumours. The cancers may comprise non-solid tumours (such as haematological tumours, for example, leukaemias and lymphomas) or may comprise solid tumours. Types of cancers to be treated with the invention include, but are not limited to, carcinoma, blastoma, and sarcoma, and certain leukaemia or lymphoid malignancies, benign and malignant tumours, and malignancies e.g., sarcomas, carcinomas, and melanomas. Adult tumours/cancers and paediatric tumours/cancers are also included.
Haematologic cancers are cancers of the blood or bone marrow. Examples of haematological (or haematogenous) cancers include leukaemias, including acute leukaemias (such as acute lymphocytic leukaemia, acute myelocytic leukaemia, acute myelogenous leukaemia and myeloblasts, promyelocytic, myelomonocytic, monocytic and erythroleukemia), chronic leukaemias (such as chronic myelocytic (granulocytic) leukaemia, chronic myelogenous leukaemia, and chronic lymphocytic leukaemia), polycythemia vera, lymphoma, Hodgkin's disease, non-Hodgkin's lymphoma (indolent and high grade forms), multiple myeloma, Waldenstrom's macroglobulinemia, heavy chain disease, myelodysplastic syndrome, hairy cell leukaemia and myelodysplasia.
Solid tumours are abnormal masses of tissue that usually do not contain cysts or liquid areas. Solid tumours can be benign or malignant. Different types of solid tumours are named for the type of cells that form them (such as sarcomas, carcinomas, and lymphomas). Examples of solid tumours, such as sarcomas and carcinomas, include fibrosarcoma, myxosarcoma, liposarcoma, chondrosarcoma, osteosarcoma, and other sarcomas, synovioma, mesothelioma, Ewing's tumour, leiomyosarcoma, rhabdomyosarcoma, colon carcinoma, lymphoid malignancy, pancreatic cancer, breast cancer, lung cancers, ovarian cancer, prostate cancer, hepatocellular carcinoma, squamous eel! carcinoma, basal cell carcinoma, adenocarcinoma, sweat gland carcinoma, medullary thyroid carcinoma, papillary thyroid carcinoma, pheochromocytomas sebaceous gland carcinoma, papillary carcinoma, papillary adenocarcinomas, medullary carcinoma, bronchogenic carcinoma, renal cell carcinoma, hepatoma, bile duct carcinoma, choriocarcinoma, Wilms' tumour, cervical cancer, testicular tumour, seminoma, bladder carcinoma, melanoma, and CNS tumours (such as a glioma (such as brainstem glioma and mixed gliomas), glioblastoma (also known as glioblastoma multiforme) astrocytoma, CNS lymphoma, germinoma, medu!loblastoma, Schwannoma craniopharyngioma, ependymoma, pinealoma, hemangioblastoma, acoustic neuroma, oligodendroglioma, menangioma, neuroblastoma, retinoblastoma and brain metastases).
Autoimmune Diseases for Treatment or Prevention by the Method
Inflammatory Diseases for Treatment or Prevention by the Method
Background
We designed a strategy for efficient production of phage particles comprising components of a CRISPR/Cas system for killing target E coli Nissle strain bacteria. So our phage composition will consist of a lysate primarily containing CRISPR/Cas system components packaged in phage particles which will be devoid of phage protein-encoding sequences and which will have no or a very low proportion of helper phage. Also the strategy will work alternatively in less well characterised phage/bacterial strain combinations.
Outline of Strategy for CRISPR/Cas Component Packaging in Hitherto Unknown Phages
Example of the Above Specifically for E coli Nissle Using Phage P2:
Nissle is useful due to its GRAS (Generally Regarded as Safe) status and P2 has a relatively broad host range (most E coli, Shigella, Klebsiella, Salmonella in addition to DNA delivery into e.g. Pseudomonas; Kahn et al 1991).
We will use pUC19 or other high copy number cloning vector. Temperate phage P2 can lysogenize Nissle. Most E coli K strains have an inactive CRISPR/Cas system and can be infected by P2 and thus all regular cloning hosts can be used (here exemplified by E coli TOP10).
P2 is introduced into TOP10 to produce a lysogen. P2 cannot be induced with mitomycin C or UV but we will use the epsilon anti-repressor from the parasite phage P4 that derepresses P2 and makes it go into lytic phase. We will express this gene from an inducible promoter in the production host strain.
The 325 bp packaging signal sequence as follows will be used
The packaging sequence will be deleted in the P2 prophage of the lysogenic production TOP10 strain.
A pUC19 shuttle vector encoding a guide RNA that targets the genome of the target Nissle strain (or alternatively comprising a CRISPR array for producing such a guide RNA) will be constructed and the packaging signal will be added. If the target Nissle harbours it own endogenous CRISPR/Cas system, we will use an activation strategy to activate the endogenous Cas3 by including Cas activating genes in the vector. If not, we will include an exogenous Cas3-encoding nucleotide sequence (and optionally one or more nucleotide sequences encoding one or more required Cascade components) in the vector for expression in the target Nissle. We will transform the vector into the TOP10 production strain, induce the P4 anti-repressor and harvest phage comprising the CRISPR/Cas component(s).
Since the induced (helper) phage DNA does not contain a packaging signal we will be able to isolate particles with only the vector DNA packaged. Thus, we will obtain a composition comprising such phage which can be used to infect target Nissle bacteria and introduce the CRISPR/Cas component(s) therein for killing the target bacteria.
Overview of possible different MGE packaging strategies follow.
Applicable to different types of phages:
For using parasitic mobile elements (P4 phage or SaPI etc) activation of helper phage structural genes is done by induction of a helper phage activator obtained from the parasitic element Delta in P4 or one, more or al of ptiA/B/M in SaPI.
If one wants smaller size particle one can choose to package in a parasite-size capsid (typically 10-20 kb) by including in the MGE or vector P4 Sid and psu or cpmA/B from a SaPI.
One can use defective helper phages where at least the packaging signal has been removed and structural genes are either on a plasmid or integrated as a cryptic prophage in the production host. If for some reason one cannot use this approach and need to use functional helper phages, one will include in the MGE or vector the genes on the parasite that hijack the phage packaging machinery to preferentially package parasite DNA (in our case CGV) over phage DNA.
List of the Minimal Genes One could Include on a Plasmid Vector from P4.
P4 sequence: see world wide web.ncbi.nlm.nih.gov/nuccore/x51522
The homology between P2 and P4 pasted below; this may be used as a packaging signal in the MGE or vector:
For small capsid size (packages 11.4 kb instead of 33.5 kb) Sid and/or Psu can be included in the MGE or vector:—
To activate helper phage P2, Delta can be included in a host cell genome (provided separately in a host cell, not on the MGE or vector to be packaged)
Minimum Genes to Include in the Host Chromosome/Episome from P2.
P2 sequence (acc. number: NC_001895)
Minimal Genes to Include from a SaPI on a Vector or MGE.
Several different SaPI systems exist.
If one uses a defective helper phage with deleted packaging signal one can use that signal from the helper phage. In this example from S. aureus phi11 (acc. number: AF424781), as follows:
For small capsid size (packages 15.8 kb instead of 43.6 kb), one can include cpmA and/or cpmB in the MGE or vector.
To activate helper phage phi11 one can include one, more or all of ptiA, B and M (provided separately in a host cell and not on the MGE or vector to be packaged)
Minimum Genes to Include in the Host Chromosome/Episome from Phi11.
A List of Phage that Work with SaPIs
Different SaPIs are linked to different helper phages (see
One can mutates the helper phage to only contain structural genes to direct the phage to package in smaller capsids. If only looking at the genes responsible for small capsid packaging (cpmA and cpmB) these are highly conserved among staphylococci indicating that they will function to redirect packaging in a variety of phages broader than the list below (
C dificile, E coli, Akkermansia, Enterobacteriacea, Ruminococcus, Faecalibacterium, Firmicutes, Bacteroides, Salmonella, Klebsiella, Pseudomonas, Acinterobacter or Streptococcus cells.
Abiotrophia
Acidocella
Actinomyces
Alkalilimnicola
Aquaspirillum
Abiotrophia defectiva
Acidocella aminolytica
Actinomyces bovis
Alkalilimnicola ehrlichii
Aquaspirillum polymorphum
Acaricomes
Acidocella facilis
Actinomyces denticolens
Alkaliphilus
Aquaspirillum
Acaricomes phytoseiuli
Acidomonas
Actinomyces europaeus
Alkaliphilus oremlandii
putridiconchylium
Acetitomaculum
Acidomonas methanolica
Actinomyces georgiae
Alkaliphilus transvaalensis
Aquaspirillum serpens
Acetitomaculum ruminis
Acidothermus
Actinomyces gerencseriae
Allochromatium
Aquimarina
Acetivibrio
Acidothermus cellulolyticus
Actinomyces
Allochromatium vinosum
Aquimarina latercula
Acetivibrio cellulolyticus
Acidovorax
hordeovulneris
Alloiococcus
Arcanobacterium
Acetivibrio ethanolgignens
Acidovorax anthurii
Actinomyces howellii
Alloiococcus otitis
Arcanobacterium
Acetivibrio multivorans
Acidovorax caeni
Actinomyces hyovaginalis
Allokutzneria
haemolyticum
Acetoanaerobium
Acidovorax cattleyae
Actinomyces israelii
Allokutzneria albata
Arcanobacterium pyogenes
Acetoanaerobium noterae
Acidovorax citrulli
Actinomyces johnsonii
Altererythrobacter
Archangium
Acetobacter
Acidovorax defluvii
Actinomyces meyeri
Altererythrobacter ishigakiensis
Archangium gephyra
Acetobacter aceti
Acidovorax delafieldii
Actinomyces naeslundii
Altermonas
Arcobacter
Acetobacter cerevisiae
Acidovorax facilis
Actinomyces neuii
Altermonas haloplanktis
Arcobacter butzleri
Acetobacter cibinongensis
Acidovorax konjaci
Actinomyces odontolyticus
Altermonas macleodii
Arcobacter cryaerophilus
Acetobacter estunensis
Acidovorax temperans
Actinomyces oris
Alysiella
Arcobacter halophilus
Acetobacter fabarum
Acidovorax valerianellae
Actinomyces radingae
Alysiella crassa
Arcobacter nitrofigilis
Acetobacter ghanensis
Acinetobacter
Actinomyces slackii
Alysiella filiformis
Arcobacter skirrowii
Acetobacter indonesiensis
Acinetobacter baumannii
Actinomyces turicensis
Aminobacter
Arhodomonas
Acetobacter lovaniensis
Acinetobacter baylyi
Actinomyces viscosus
Aminobacter aganoensis
Arhodomonas aquaeolei
Acetobacter malorum
Acinetobacter bouvetii
Actinoplanes
Aminobacter aminovorans
Arsenophonus
Acetobacter nitrogenifigens
Acinetobacter calcoaceticus
Actinoplanes auranticolor
Aminobacter niigataensis
Arsenophonus
Acetobacter oeni
Acinetobacter gerneri
Actinoplanes brasiliensis
Aminobacterium
nasoniae
Acetobacter orientalis
Acinetobacter haemolyticus
Actinoplanes consettensis
Aminobacterium mobile
Arthrobacter
Acetobacter orleanensis
Acinetobacter johnsonii
Actinoplanes deccanensis
Aminomonas
Arthrobacter agilis
Acetobacter pasteurianus
Acinetobacter junii
Actinoplanes derwentensis
Aminomonas paucivorans
Arthrobacter albus
Acetobacter pornorurn
Acinetobacter lwoffi
Actinoplanes digitatis
Ammoniphilus
Arthrobacter aurescens
Acetobacter senegalensis
Acinetobacter parvus
Actinoplanes durhamensis
Ammoniphilus oxalaticus
Arthrobacter chlorophenolicus
Acetobacter xylinus
Acinetobacter radioresistens
Actinoplanes ferrugineus
Ammoniphilus oxalivorans
Arthrobacter citreus
Acetobacterium
Acinetobacter schindleri
Actinoplanes globisporus
Amphibacillus
Arthrobacter crystallopoietes
Acetobacterium bakii
Acinetobacter soli
Actinoplanes humidus
Amphibacillus xylanus
Arthrobacter cumminsii
Acetobacterium carbinolicum
Acinetobacter tandoii
Actinoplanes italicus
Amphritea
Arthrobacter globiformis
Acetobacterium dehalogenans
Acinetobacter tjernbergiae
Actinoplanes liguriensis
Amphritea balenae
Arthrobacter
Acetobacterium fimetarium
Acinetobacter towneri
Actinoplanes lobatus
Amphritea japonica
histidinolovorans
Acetobacterium malicum
Acinetobacter ursingii
Actinoplanes missouriensis
Amycolatopsis
Arthrobacter ilicis
Acetobacterium paludosum
Acinetobacter venetianus
Actinoplanes palleronii
Amycolatopsis alba
Arthrobacter luteus
Acetobacterium tundrae
Acrocarpospora
Actinoplanes philippinensis
Amycolatopsis albidoflavus
Arthrobacter methylotrophus
Acetobacterium wieringae
Acrocarpospora corrugata
Actinoplanes rectilineatus
Amycolatopsis azurea
Arthrobacter mysorens
Acetobacterium woodii
Acrocarpospora
Actinoplanes regularis
Amycolatopsis coloradensis
Arthrobacter nicotianae
Acetofilamentum
macrocephala
Actinoplanes
Amycolatopsis lurida
Arthrobacter nicotinovorans
Acetofilamentum rigidum
Acrocarpospora pleiomorpha
teichomyceticus
Amycolatopsis mediterranei
Arthrobacter oxydans
Acetohalobium
Actibacter
Actinoplanes utahensis
Amycolatopsis rifamycinica
Arthrobacter pascens
Acetohalobium arabaticum
Actibacter sediminis
Actinopolyspora
Amycolatopsis rubida
Arthrobacter
Acetomicrobium
Actinoalloteichus
Actinopolyspora halophila
Amycolatopsis sulphurea
phenanthrenivorans
Acetomicrobium faecale
Actinoalloteichus
Actinopolyspora mortivallis
Amycolatopsis tolypomycina
Arthrobacter
Acetomicrobium flavidum
cyanogriseus
Actinosynnema
Anabaena
polychromogenes
Acetonema
Actinoalloteichus
Actinosynnema mirum
Anabaena cylindrica
Atrhrobacter protophormiae
Acetonema longum
hymeniacidonis
Actinotalea
Anabaena flos-aquae
Arthrobacter
Acetothermus
Actinoalloteichus spitiensis
Actinotalea fermentans
Anabaena variabilis
psychrolactophilus
Acetothermus paucivorans
Actinobaccillus
Aerococcus
Anaeroarcus
Arthrobacter ramosus
Acholeplasma
Actinobacillus capsulatus
Aerococcus sanguinicola
Anaeroarcus burkinensis
Arthrobacter sulfonivorans
Acholeplasma axanthum
Actinobacillus delphinicola
Aerococcus urinae
Anaerobaculum
Arthrobacter sulfureus
Acholeplasma brassicae
Actinobacillus hominis
Aerococcus urinaeequi
Anaerobaculum mobile
Arthrobacter uratoxydans
Acholeplasma cavigenitalium
Actinobacillus indolicus
Aerococcus urinaehominis
Anaerobiospirillum
Arthrobacter ureafaciens
Acholeplasma equifetale
Actinobacillus lignieresii
Aerococcus viridans
Anaerobiospirillum
Arthrobacter viscosus
Acholeplasma granularum
Actinobacillus minor
Aeromicrobium
succiniciproducens
Arthrobacter woluwensis
Acholeplasma hippikon
Actinobacillus muris
Aeromicrobium erythreum
Anaerobiospirillum thomasii
Asaia
Acholeplasma laidlawii
Actinobacillus
Aeromonas
Anaerococcus
Asaia bogorensis
Acholeplasma modicum
pleuropneumoniae
Aeromonas
Anaerococcus hydrogenalis
Asanoa
Acholeplasma morum
Actinobacillus porcinus
allosaccharophila
Anaerococcus lactolyticus
Asanoa ferruginea
Acholeplasma multilocale
Actinobacillus rossii
Aeromonas bestiarum
Anaerococcus prevotii
Asticcacaulis
Acholeplasma oculi
Actinobacillus scotiae
Aeromonas caviae
Anaerococcus tetradius
Asticcacaulis biprosthecium
Acholeplasma palmae
Actinobacillus seminis
Aeromonas encheleia
Anaerococcus vaginalis
Asticcacaulis excentricus
Acholeplasma parvum
Actinobacillus succinogenes
Aeromonas
Anaerofustis
Atopobacter
Acholeplasma pleciae
Actinobaccillus suis
enteropelogenes
Anaerofustis stercorihominis
Atopobacter phocae
Acholeplasma vituli
Actinobacillus ureae
Aeromonas eucrenophila
Anaeromusa
Atopobium
Achromobacter
Actinobaculum
Aeromonas ichthiosmia
Anaeromusa acidaminophila
Atopobium fossor
Achromobacter denitrificans
Actinobaculum massiliense
Aeromonas jandaei
Anaeromyxobacter
Atopobium minutum
Achromobacter insolitus
Actinobaculum schaalii
Aeromonas media
Anaeromyxobacter
Atopobium parvulum
Achromobacter piechaudii
Actinobaculum suis
Aeromonas popoffii
dehalogenans
Atopobium rimae
Achromobacter ruhlandii
Actinomyces urinale
Aeromonas sobria
Anaerorhabdus
Atopobium vaginae
Achromobacter spanius
Actinocatenispora
Aeromonas veronii
Anaerorhabdus furcosa
Aureobacterium
Acidaminobacter
Actinocatenispora rupis
Agrobacterium
Anaerosinus
Aureobacterium barkeri
Acidaminobacter
Actinocatenispora
Agrobacterium
Anaerosinus glycerini
Aurobacterium
hydrogenoformans
thailandica
gelatinovorum
Anaerovirgula
Aurobacterium liquefaciens
Acidaminococcus
Actinocatenispora sera
Agrococcus
Anaerovirgula multivorans
Avibacterium
Acidaminococcus fermentans
Actinocorallia
Agrococcus citreus
Ancalomicrobium
Avibacterium avium
Acidaminococcus intestini
Actinocorallia aurantiaca
Agrococcus jenensis
Ancalomicrobium adetum
Avibacterium gallinarum
Acidicaldus
Actinocorallia aurea
Agromonas
Ancylobacter
Avibacterium paragallinarum
Acidicaldus organivorans
Actinocorallia cavernae
Agromonas oligotrophica
Ancylobacter aquaticus
Avibacterium volantium
Acidimicrobium
Actinocorallia glomerata
Agromyces
Aneurinibacillus
Azoarcus
Acidimicrobium ferrooxidans
Actinocorallia herbida
Agromyces fucosus
Aneurinibacillus aneurinilyticus
Azoarcus indigens
Acidiphilium
Actinocorallia libanotica
Agromyces hippuratus
Aneurinibacillus migulanus
Azoarcus tolulyticus
Acidiphilium acidophilum
Actinocorallia longicatena
Agromyces luteolus
Aneurinibacillus
Azoarcus toluvorans
Acidiphilium angustum
Actinomadura
Agromyces mediolanus
thermoaerophilus
Azohydromonas
Acidiphilium cryptum
Actinomadura alba
Agromyces ramosus
Angiococcus
Azohydromonas australica
Acidiphilium multivorum
Actinomadura atramentaria
Agromyces rhizospherae
Angiococcus disciformis
Azohydromonas lata
Acidiphilium organovorum
Actinomadura
Akkermansia
Angulomicrobium
Azomonas
Acidiphilium rubrum
bangladeshensis
Akkermansia muciniphila
Angulomicrobium tetraedrale
Azomonas agilis
Acidisoma
Actinomadura catellatispora
Albidiferax
Anoxybacillus
Azomonas insignis
Acidisoma sibiricum
Actinomadura chibensis
Albidiferax ferrireducens
Anoxybacillus pushchinoensis
Azomonas macrocytogenes
Acidisoma tundrae
Actinomadura chokoriensis
Albidovulum
Aquabacterium
Azorhizobium
Acidisphaera
Actinomadura citrea
Albidovulum inexpectatum
Aquabacterium commune
Azorhizobium caulinodans
Acidisphaera rubrifaciens
Actinomadura coerulea
Alcaligenes
Aquabacterium parvum
Azorhizophilus
Acidithiobacillus
Actinomadura echinospora
Alcaligenes denitrificans
Azorhizophilus paspali
Acidithiobacillus albertensis
Actinomadura fibrosa
Alcaligenes faecalis
Azospirillum
Acidithiobacillus caldus
Actinomadura formosensis
Alcanivorax
Azospirillum brasilense
Acidithiobacillus ferrooxidans
Actinomadura hibisca
Alcanivorax borkumensis
Azospirillum halopraeferens
Acidithiobacillus thiooxidans
Actinomadura kijaniata
Alcanivorax jadensis
Azospirillum irakense
Acidobacterium
Actinomadura latina
Algicola
Azotobacter
Acidobacterium capsulatum
Actinomadura livida
Algicola bacteriolytica
Azotobacter beijerinckii
Actinomadura
Alicyclobacillus
Azotobacter chroococcum
luteofluorescens
Alicyclobacillus
Azotobacter nigricans
Actinomadura macra
disulfidooxidans
Azotobacter salinestris
Actinomadura madurae
Alicyclobacillus
Azotobacter vinelandii
Actinomadura oligospora
sendaiensis
Actinomadura pelletieri
Alicyclobacillus vulcanalis
Actinomadura rubrobrunea
Alishewanella
Actinomadura rugatobispora
Alishewanella fetalis
Actinomadura umbrina
Alkalibacillus
Actinomadura
Alkalibacillus
verrucosospora
haloalkaliphilus
Actinomadura vinacea
Actinomadura viridilutea
Actinomadura viridis
Actinomadura yumaensis
Bacillus
Bacteroides
Bibersteinia
Borrelia
Brevinema
Bacteroides caccae
Bibersteinia trehalosi
Borrelia afzelii
Brevinema andersonii
Bacteriovorax
Bacteroides coagulans
Bifidobacterium
Borrelia americana
Brevundimonas
Bacteriovorax stolpii
Bacteroides eggerthii
Bifidobacterium adolescentis
Borrelia burgdorferi
Brevundimonas alba
Bacteroides fragilis
Bifidobacterium angulatum
Borrelia carolinensis
Brevundimonas aurantiaca
Bacteroides galacturonicus
Bifidobacterium animalis
Borrelia coriaceae
Brevundimonas diminuta
Bacteroides helcogenes
Bifidobacterium asteroides
Borrelia garinii
Brevundimonas intermedia
Bacteroides ovatus
Bifidobacterium bifidum
Borrelia japonica
Brevundimonas subvibrioides
Bacteroides pectinophilus
Bifidobacterium boum
Bosea
Brevundimonas vancanneytii
Bacteroides pyogenes
Bifidobacterium breve
Bosea minatitlanensis
Brevundimonas variabilis
Bacteroides salyersiae
Bifidobacterium catenulatum
Bosea thiooxidans
Brevundimonas vesicularis
Bacteroides stercoris
Bifidobacterium choerinum
Brachybacterium
Brochothrix
Bacteroides suis
Bifidobacterium coryneforme
Brachybacterium
Brochothrix campestris
Bacteroides tectus
Bifidobacterium cuniculi
alimentarium
Brochothrix thermosphacta
Bacteroides thetaiotaomicron
Bifidobacterium dentium
Brachybacterium faecium
Brucella
Bacteroides uniformis
Bifidobacterium gallicum
Brachybacterium
Brucella canis
Bacteroides ureolyticus
Bifidobacterium gallinarum
paraconglomeratum
Brucella neotomae
Bacteroides vulgatus
Bifidobacterium indicum
Brachybacterium rhamnosum
Bryobacter
Balnearium
Bifidobacterium longum
Brachybacterium
Bryobacter aggregatus
Balnearium lithotrophicum
Bifidobacterium
tyrofermentans
Burkholderia
Balneatrix
magnumBifidobacterium
Brachyspira
Burkholderia ambifaria
Balneatrix alpica
merycicum
Brachyspira alvinipulli
Burkholderia andropogonis
Balneola
Bifidobacterium minimum
Brachyspira hyodysenteriae
Burkholderia anthina
Balneola vulgaris
Bifidobacterium
Brachyspira innocens
Burkholderia caledonica
Barnesiella
pseudocatenulatum
Brachyspira murdochii
Burkholderia caryophylli
Barnesiella viscericola
Bifidobacterium
Brachyspira
Burkholderia cenocepacia
Bartonella
pseudolongum
pilosicoli
Burkholderia cepacia
Bartonella alsatica
Bifidobacterium pullorum
Bradyrhizobium
Burkholderia cocovenenans
Bartonella bacilliformis
Bifidobacterium ruminantium
Bradyrhizobium canariense
Burkholderia dolosa
Bartonella clarridgeiae
Bifidobacterium saeculare
Bradyrhizobium elkanii
Burkholderia fungorum
Bartonella doshiae
Bifidobacterium subtile
Bradyrhizobium japonicum
Burkholderia glathei
Bartonella elizabethae
Bifidobacterium
Bradyrhizobium liaoningense
Burkholderia glumae
Bartonella grahamii
thermophilum
Brenneria
Burkholderia graminis
Bartonella henselae
Bilophila
Brenneria alni
Burkholderia kururiensis
Bartonella rochalimae
Bilophila wadsworthia
Brenneria nigrifluens
Burkholderia multivorans
Bartonella vinsonii
Biostraticola
Brenneria quercina
Burkholderia phenazinium
Bavariicoccus
Biostraticola tofi
Brenneria quercina
Burkholderia plantarii
Bavariicoccus seileri
Bizionia
Brenneria salicis
Burkholderia pyrrocinia
Bdellovibrio
Bizionia argentinensis
Brevibacillus
Burkholderia silvatlantica
Bdellovibrio bacteriovorus
Blastobacter
Brevibacillus agri
Burkholderia stabilis
Bdellovibrio exovorus
Blastobacter capsulatus
Brevibacillus borstelensis
Burkholderia thailandensis
Beggiatoa
Blastobacter denitrificans
Brevibacillus brevis
Burkholderia tropica
Beggiatoa alba
Blastococcus
Brevibacillus centrosporus
Burkholderia unamae
Beijerinckia
Blastococcus aggregatus
Brevibacillus choshinensis
Burkholderia vietnamiensis
Beijerinckia derxii
Blastococcus saxobsidens
Brevibacillus invocatus
Buttiauxella
Beijerinckia fluminensis
Blastochloris
Brevibacillus laterosporus
Buttiauxella agrestis
Beijerinckia indica
Blastochloris viridis
Brevibacillus parabrevis
Buttiauxella brennerae
Beijerinckia mobilis
Blastomonas
Brevibacillus reuszeri
Buttiauxella ferragutiae
Belliella
Blastomonas natatoria
Brevibacterium
Buttiauxella gaviniae
Belliella baltica
Blastopirellula
Brevibacterium abidum
Buttiauxella izardii
Bellilinea
Blastopirellula marina
Brevibacterium album
Buttiauxella noackiae
Bellilinea caldifistulae
Blautia
Brevibacterium aurantiacum
Buttiauxella warmboldiae
Belnapia
Blautia coccoides
Brevibacterium celere
Butyrivibrio
Belnapia moabensis
Blautia hansenii
Brevibacterium epidermidis
Butyrivibrio fibrisolvens
Bergeriella
Blautia producta
Brevibacterium
Butyrivibrio hungatei
Bergeriella denitrificans
Blautia wexlerae
frigoritolerans
Butyrivibrio proteoclasticus
Beutenbergia
Bogoriella
Brevibacterium halotolerans
Beutenbergia cavernae
Bogoriella caseilytica
Brevibacterium iodinum
Bordetella
Brevibacterium linens
Bordetella avium
Brevibacterium lyticum
Bordetella bronchiseptica
Brevibacterium mcbrellneri
Bordetella hinzii
Brevibacterium otitidis
Bordetella holmesii
Brevibacterium oxydans
Bordetella parapertussis
Brevibacterium paucivorans
Bordetella pertussis
Brevibacterium stationis
Bordetella petrii
Bordetella trematum
Bacillus
B. acidiceler
B. aminovorans
B. glucanolyticus
B. taeanensis
B. lautus
B. acidicola
B. amylolyticus
B. gordonae
B. tequilensis
B. lehensis
B. acidiproducens
B. andreesenii
B. gottheilii
B. thermantarcticus
B. lentimorbus
B. acidocaldarius
B. aneurinilyticus
B. graminis
B. thermoaerophilus
B. lentus
B. acidoterrestris
B. anthracis
B. halmapalus
B. thermoamylovorans
B. licheniformis
B. aeolius
B. aquimaris
B. haloalkaliphilus
B. thermocatenulatus
B. ligniniphilus
B. aerius
B. arenosi
B. halochares
B. thermocloacae
B. litoralis
B. aerophilus
B. arseniciselenatis
B. halodenitrificans
B. thermocopriae
B. locisalis
B. agaradhaerens
B. arsenicus
B. halodurans
B. thermodenitrificans
B. luciferensis
B. agri
B. aurantiacus
B. halophilus
B. thermoglucosidasius
B. luteolus
B. aidingensis
B. arvi
B. halosaccharovorans
B. thermolactis
B. luteus
B. akibai
B. aryabhattai
B. hemicellulosilyticus
B. thermoleovorans
B. macauensis
B. alcalophilus
B. asahii
B. hemicentroti
B. thermophilus
B. macerans
B. algicola
B. atrophaeus
B. herbersteinensis
B. thermoruber
B. macquariensis
B. alginolyticus
B. axarquiensis
B. horikoshii
B. thermosphaericus
B. macyae
B. alkalidiazotrophicus
B. azotofixans
B. horneckiae
B. thiaminolyticus
B. malacitensis
B. alkalinitrilicus
B. azotoformans
B. horti
B. thioparans
B. mannanilyticus
B. alkalisediminis
B. badius
B. huizhouensis
B. thuringiensis
B. marisflavi
B. alkalitelluris
B. barbaricus
B. humi
B. tianshenii
B. marismortui
B. altitudinis
B. bataviensis
B. hwajinpoensis
B. trypoxylicola
B. marmarensis
B. alveayuensis
B. beijingensis
B. idriensis
B. tusciae
B. massiliensis
B. alvei
B. benzoevorans
B. indicus
B. validus
B. megaterium
B. amyloliquefaciens
B. beringensis
B. infantis
B. vallismortis
B. mesonae
B. berkeleyi
B. infernus
B. vedderi
B. methanolicus
B. beveridgei
B. insolitus
B. velezensis
B. methylotrophicus
B. bogoriensis
B. invictae
B. vietnamensis
B. migulanus
B. boroniphilus
B. iranensis
B. vireti
B. mojavensis
B. dipsosauri
B. borstelensis
B. isabeliae
B. vulcani
B. mucilaginosus
B. drentensis
B. brevis Migula
B. isronensis
B. wakoensis
B. muralis
B. edaphicus
B. butanolivorans
B. jeotgali
B. weihenstephanensis
B. murimartini
B. ehimensis
B. canaveralius
B. kaustophilus
B. xiamenensis
B. mycoides
B. eiseniae
B. carboniphilus
B. kobensis
B. xiaoxiensis
B. naganoensis
B. enclensis
B. cecembensis
B. kochii
B. zhanjiangensis
B. nanhaiensis
B. endophyticus
B. cellulosilyticus
B. kokeshiiformis
B. peoriae
B. nanhaiisediminis
B. endoradicis
B. centrosporus
B. koreensis
B. persepolensis
B. nealsonii
B. farraginis
B. cereus
B. korlensis
B. persicus
B. neidei
B. fastidiosus
B. chagannorensis
B. kribbensis
B. pervagus
B. neizhouensis
B. fengqiuensis
B. chitinolyticus
B. krulwichiae
B. plakortidis
B. niabensis
B. firmus
B. chondroitinus
B. laevolacticus
B. pocheonensis
B. niacini
B. flexus
B. choshinensis
B. larvae
B. polygoni
B. novalis
B. foraminis
B. chungangensis
B. laterosporus
B. polymyxa
B. oceanisediminis
B. fordii
B. cibi
B. salexigens
B. popilliae
B. odysseyi
B. formosus
B. circulans
B. saliphilus
B. pseudalcalophilus
B. okhensis
B. fortis
B. clarkii
B. schlegelii
B. pseudofirmus
B. okuhidensis
B. fumarioli
B. clausii
B. sediminis
B. pseudomycoides
B. oleronius
B. funiculus
B. coagulans
B. selenatarsenatis
B. psychrodurans
B. oryzaecorticis
B. fusiformis
B. coahuilensis
B. selenitireducens
B. psychrophilus
B. oshimensis
B. galactophilus
B. cohnii
B. seohaeanensis
B. psychrosaccharolyticus
B. pabuli
B. galactosidilyticus
B. composti
B. shacheensis
B. psychrotolerans
B. pakistanensis
B. galliciensis
B. curdlanolyticus
B. shackletonii
B. pulvifaciens
B. pallidus
B. gelatini
B. cycloheptanicus
B. siamensis
B. pumilus
B. pallidus
B. gibsonii
B. cytotoxicus
B. silvestris
B. purgationiresistens
B. panacisoli
B. ginsengi
B. daliensis
B. simplex
B. pycnus
B. panaciterrae
B. ginsengihumi
B. decisifrondis
B. siralis
B. qingdaonensis
B. pantothenticus
B. ginsengisoli
B. decolorationis
B. smithii
B. qingshengii
B. parabrevis
B. globisporus (eg, B.
B. deserti
B. soli
B. reuszeri
B. paraflexus
B. solimangrovi
B. rhizosphaerae
B. pasteurii
B. solisalsi
B. rigui
B. patagoniensis
B. songklensis
B. ruris
B. sonorensis
B. safensis
B. sphaericus
B. salarius
B. sporothermodurans
B. stearothermophilus
B. stratosphericus
B. subterraneus
B. subtilis (eg, B.
Caenimonas
Campylobacter
Cardiobacterium
Catenuloplanes
Curtobacterium
Caenimonas koreensis
Campylobacter coli
Cardiobacterium hominis
Catenuloplanes atrovinosus
Curtobacterium albidum
Caldalkalibacillus
Campylobacter concisus
Carnimonas
Catenuloplanes castaneus
Curtobacterium citreus
Caldalkalibacillus uzonensis
Campylobacter curvus
Carnimonas nigrificans
Catenuloplanes crispus
Caldanaerobacter
Campylobacter fetus
Carnobacterium
Catenuloplanes indicus
Caldanaerobacter subterraneus
Campylobacter gracilis
Carnobacterium alterfunditum
Catenuloplanes japonicus
Caldanaerobius
Campylobacter helveticus
Carnobacterium divergens
Catenuloplanes nepalensis
Caldanaerobius fijiensis
Campylobacter hominis
Carnobacterium funditum
Catenuloplanes niger
Caldanaerobius
Campylobacter hyointestinalis
Carnobacterium gallinarum
Chryseobacterium
polysaccharolyticus
Campylobacter jejuni
Carnobacterium
Chryseobacterium
Caldanaerobius zeae
Campylobacter lari
maltaromaticum
balustinum
Caldanaerovirga
Campylobacter mucosalis
Carnobacterium mobile
Citrobacter
Caldanaerovirga acetigignens
Campylobacter rectus
Carnobacterium viridans
C. amalonaticus
Caldicellulosiruptor
Campylobacter showae
Caryophanon
C. braakii
Caldicellulosiruptor bescii
Campylobacter sputorum
Caryophanon latum
C. diversus
Caldicellulosiruptor kristjanssonii
Campylobacter upsaliensis
Caryophanon tenue
C. farmeri
Caldicellulosiruptor owensensis
Capnocytophaga
Catellatospora
C. freundii
Capnocytophaga canimorsus
Catellatospora citrea
C. gillenii
Capnocytophaga cynodegmi
Catellatospora
C. koseri
Capnocytophaga gingivalis
methionotrophica
C. murliniae
Capnocytophaga granulosa
Catenococcus
C. pasteurii
[1]
Capnocytophaga haemolytica
Catenococcus thiocycli
C. rodentium
Capnocytophaga ochracea
C. sedlakii
Capnocytophaga sputigena
C. werkmanii
C. youngae
Clostridium
Coccochloris
Coccochloris elabens
Corynebacterium
Corynebacterium flavescens
Corynebacterium variabile
Clostridium
Clostridium absonum, Clostridium aceticum, Clostridium acetireducens, Clostridium acetobutylicum, Clostridium acidisoli, Clostridium aciditolerans, Clostridium acidurici, Clostridium aerotolerans, Clostridium
aestuarii, Clostridium akagii, Clostridium aldenense, Clostridium aldrichii, Clostridium algidicarni, Clostridium algidixylanolyticum, Clostridium algifaecis, Clostridium algoriphilum, Clostridium alkalicellulosi,
Clostridium aminophilum, Clostridium aminovalericum, Clostridium amygdalinum, Clostridium amylolyticum, Clostridium arbusti, Clostridium arcticum, Clostridium argentinense, Clostridium asparagiforme,
Clostridium aurantibutyricum, Clostridium autoethanogenum, Clostridium baratii, Clostridium barkeri, Clostridium bartlettii, Clostridium beijerinckii, Clostridium bifermentans, Clostridium bolteae, Clostridium
bornimense, Clostridium botulinum, Clostridium bowmanii, Clostridium bryantii, Clostridium butyricum, Clostridium cadaveris, Clostridium caenicola, Clostridium caminithermale, Clostridium carboxidivorans,
Clostridium carnis, Clostridium cavendishii, Clostridium celatum, Clostridium celerecrescens, Clostridium cellobioparum, Clostridium cellulofermentans, Clostridium cellulolyticum, Clostridium cellulosi,
Clostridium cellulovorans, Clostridium chartatabidum, Clostridium chauvoei, Clostridium chromiireducens, Clostridium citroniae, Clostridium clariflavum, Clostridium clostridioforme, Clostridium coccoides,
Clostridium cochlearium, Clostridium colletant, Clostridium colicanis, Clostridium colinum, Clostridium collagenovorans, Clostridium cylindrosporum, Clostridium difficile, Clostridium diolis, Clostridium
disporicum, Clostridium drakei, Clostridium durum, Clostridium estertheticum, Clostridium estertheticum estertheticum, Clostridium estertheticum laramiense, Clostridium fallax, Clostridium felsineum, Clostridium
fervidum, Clostridium fimetarium, Clostridium formicaceticum, Clostridium frigidicarnis, Clostridium frigoris, Clostridium ganghwense, Clostridium gasigenes, Clostridium ghonii, Clostridium glycolicum,
Clostridium glycyrrhizinilyticum, Clostridium grantii, Clostridium haemolyticum, Clostridium halophilum, Clostridium hastiforme, Clostridium hathewayi, Clostridium herbivorans, Clostridium hiranonis,
Clostridium histolyticum, Clostridium homopropionicum, Clostridium huakuii, Clostridium hungatei, Clostridium hydrogeniformans, Clostridium hydroxybenzoicum, Clostridium hylemonae, Clostridium jejuense,
Clostridium indolis, Clostridium innocuum, Clostridium intestinale, Clostridium irregulare, Clostridium isatidis, Clostridium josui, Clostridium kluyveri, Clostridium lactatifermentans, Clostridium lacusfryxellense,
Clostridium laramiense, Clostridium lavalense, Clostridium lentocellum, Clostridium lentoputrescens, Clostridium leptum, Clostridium limosum, Clostridium litorale, Clostridium lituseburense, Clostridium ljungdahlii,
Clostridium lortetii, Clostridium lundense, Clostridium magnum, Clostridium malenominatum, Clostridium mangenotii, Clostridium mayombei, Clostridium methoxybenzovorans, Clostridium methylpentosum,
Clostridium neopropionicum, Clostridium nexile, Clostridium nitrophenolicum, Clostridium novyi, Clostridium oceanicum, Clostridium orbiscindens, Clostridium oroticum, Clostridium oxalicum, Clostridium
papyrosolvens, Clostridium paradoxum, Clostridium paraperfringens (Alias: C. welchii), Clostridium paraputrificum, Clostridium pascui, Clostridium pasteurianum, Clostridium peptidivorans, Clostridium perenne,
Clostridium perfringens, Clostridium pfennigii, Clostridium phytofermentans, Clostridium piliforme, Clostridium polysaccharolyticum, Clostridium populeti, Clostridium propionicum, Clostridium proteoclasticum,
Clostridium proteolyticum, Clostridium psychrophilum, Clostridium puniceum, Clostridium purinilyticum, Clostridium putrefaciens, Clostridium putrificum, Clostridium quercicolum, Clostridium quinii,
Clostridium ramosum, Clostridium rectum, Clostridium roseum, Clostridium saccharobutylicum, Clostridium saccharogumia, Clostridium saccharolyticum, Clostridium saccharoperbutylacetonicum, Clostridium
sardiniense, Clostridium sartagoforme, Clostridium scatologenes, Clostridium schirmacherense, Clostridium scindens, Clostridium septicum, Clostridium sordellii, Clostridium sphenoides, Clostridium spiroforme,
Clostridium sporogenes, Clostridium sporosphaeroides, Clostridium stercorarium, Clostridium stercorarium leptospartum, Clostridium stercorarium stercorarium, Clostridium stercorarium thermolacticum,
Clostridium sticklandii, Clostridium straminisolvens, Clostridium subterminale, Clostridium sufflavum, Clostridium sulfidigenes, Clostridium symbiosum, Clostridium tagluense, Clostridium
tepidiprofundi, Clostridium termitidis, Clostridium tertium, Clostridium tetani, Clostridium tetanomorphum, Clostridium thermaceticum, Clostridium thermautotrophicum, Clostridium thermoalcaliphilum,
Clostridium thermobutyricum, Clostridium thermocellum, Clostridium thermocopriae, Clostridium thermohydrosulfuricum, Clostridium thermolacticum, Clostridium thermopalmarium,
Clostridium thermopapyrolyticum, Clostridium thermosaccharolyticum, Clostridium thermosuccinogenes, Clostridium thermosulfurigenes, Clostridium thiosulfatireducens, Clostridium tyrobutyricum,
Clostridium uliginosum, Clostridium ultunense, Clostridium villosum, Clostridium vincentii, Clostridium viride, Clostridium xylanolyticum, Clostridium xylanovorans
Dactylosporangium
Deinococcus
Delftia
Echinicola
Dactylosporangium aurantiacum
Deinococcus aerius
Delftia acidovorans
Echinicola pacifica
Dactylosporangium fulvum
Deinococcus apachensis
Desulfovibrio
Echinicola vietnamensis
Dactylosporangium matsuzakiense
Deinococcus aquaticus
Desulfovibrio desulfuricans
Dactylosporangium roseum
Deinococcus aquatilis
Diplococcus
Dactylosporangium thailandense
Deinococcus caeni
Diplococcus pneumoniae
Dactylosporangium vinaceum
Deinococcus radiodurans
Deinococcus radiophilus
Enterobacter
Enterobacter kobei
Faecalibacterium
Flavobacterium
E. aerogenes
E. ludwigii
Faecalibacterium prausnitzii
Flavobacterium antarcticum
E. amnigemis
E. mori
Fangia
Flavobacterium aquatile
E. agglomerans
E. nimipressuralis
Fangia hongkongensis
Flavobacterium aquidurense
E. arachidis
E. oryzae
Fastidiosipila
Flavobacterium balustinum
E. asburiae
E. pulveris
Fastidiosipila sanguinis
Flavobacterium croceum
E. cancerogenous
E. pyrinus
Fusobacterium
Flavobacterium cucumis
E. cloacae
E. radicincitans
Fusobacterium nucleatum
Flavobacterium daejeonense
E. cowanii
E. taylorae
Flavobacterium defluvii
E. dissolvens
E. turicensis
Flavobacterium degerlachei
E. gergoviae
E. sakazakii Enterobacter soli
Flavobacterium
E. helveticus
Enterococcus
denitrificans
E. hormaechei
Enterococcus durans
Flavobacterium filum
E. intermedins
Enterococcus faecalis
Flavobacterium flevense
Enterococcus faecium
Flavobacterium frigidarium
Erwinia
Flavobacterium mizutaii
Erwinia hapontici
Flavobacterium
Escherichia
okeanokoites
Escherichia coli
Gaetbulibacter
Haemophilus
Ideonella
Janibacter
Gaetbulibacter saemankumensis
Haemophilus aegyptius
Ideonella azotifigens
Janibacter anophelis
Gallibacterium
Haemophilus aphrophilus
Idiomarina
Janibacter corallicola
Gallibacterium anatis
Haemophilus felis
Idiomarina abyssalis
Janibacter limosus
Gallicola
Haemophilus gallinarum
Idiomarina baltica
Janibacter melonis
Gallicola barnesae
Haemophilus haemolyticus
Idiomarina fontislapidosi
Janibacter terrae
Garciella
Haemophilus influenzae
Idiomarina loihiensis
Jannaschia
Garciella nitratireducens
Haemophilus paracuniculus
Idiomarina ramblicola
Jannaschia cystaugens
Geobacillus
Haemophilus parahaemolyticus
Idiomarina seosinensis
Jannaschia helgolandensis
Geobacillus thermoglucosidasius
Haemophilus parainfluenzae
Idiomarina zobellii
Jannaschia
Geobacillus stearothermophilus
Haemophilus
Ignatzschineria
pohangensis
Geobacter
paraphrohaemolyticus
Ignatzschineria
Jannaschia rubra
Geobacter bemidjiensis
Haemophilus parasuis
larvae
Janthinobacterium
Geobacter bremensis
Haemophilus pittmaniae
Ignavigranum
Janthinobacterium
Geobacter chapellei
Hafnia
Ignavigranum ruoffiae
agaricidamnosum
Geobacter grbiciae
Hafnia alvei
Ilumatobacter
Janthinobacterium lividum
Geobacter hydrogenophilus
Hahella
Ilumatobacter fluminis
Jejuia
Geobacter lovleyi
Hahella ganghwensis
Ilyobacter
Jejuia pallidilutea
Geobacter metallireducens
Halalkalibacillus
Ilyobacter delafieldii
Jeotgalibacillus
Geobacter pelophilus
Halalkalibacillus halophilus
Ilyobacter insuetus
Jeotgalibacillus
Geobacter pickeringii
Helicobacter
Ilyobacter polytropus
alimentarius
Geobacter sulfurreducens
Helicobacter pylori
Ilyobacter tartaricus
Jeotgalicoccus
Geodermatophilus
Jeotgalicoccus halotolerans
Geodermatophilus obscurus
Gluconacetobacter
Gluconacetobacter xylinus
Gordonia
Gordonia rubripertincta
Kaistia
Labedella
Listeria ivanovii
Micrococcus
Nesterenkonia
Kaistia adipata
Labedella gwakjiensis
L. marthii
Micrococcus luteus
Nesterenkonia holobia
Kaistia soli
Labrenzia
L. monocytogenes
Micrococcus lylae
Nocardia
Kangiella
Labrenzia aggregata
L. newyorkensis
Moraxella
Nocardia argentinensis
Kangiella aquimarina
Labrenzia alba
L. riparia
Moraxella bovis
Nocardia corallina
Kangiella
Labrenzia alexandrii
L. rocourtiae
Moraxella nonliquefaciens
Nocardia
koreensis
Labrenzia marina
L. seeligeri
Moraxella osloensis
otitidiscaviarum
Kerstersia
Labrys
L. weihenstephanensis
Nakamurella
Kerstersia gyiorum
Labrys methylaminiphilus
L. welshimeri
Nakamurella multipartita
Kiloniella
Labrys miyagiensis
Listonella
Nannocystis
Kiloniella laminariae
Labrys monachus
Listonella anguillarum
Nannocystis pusilia
Klebsiella
Labrys okinawensis
Macrococcus
Natranaerobius
K. gramilomatis
Labrys
Macrococcus bovicus
Natranaerobius
K. oxytoca
portucalensis
Marinobacter
thermophilus
K. pneumoniae
Lactobacillus
Marinobacter algicola
Natranaerobius trueperi
K. terrigena
Marinobacter bryozoorum
Naxibacter
K. variicola
Laceyella
Marinobacter flavimaris
Naxibacter alkalitolerans
Kluyvera
Laceyella putida
Meiothermus
Neisseria
Kluyvera ascorbata
Lechevalieria
Meiothermus ruber
Neisseria cinerea
Kocuria
Lechevalieria aerocolonigenes
Methylophilus
Neisseria denitrificans
Kocuria roasea
Legionella
Methylophilus methylotrophus
Neisseria gonorrhoeae
Kocuria varians
Microbacterium
Neisseria lactamica
Kurthia
Listeria
Microbacterium
Neisseria mucosa
Kurthia zopfii
L. aquatica
ammoniaphilum
Neisseria sicca
L. booriae
Microbacterium arborescens
Neisseria subflava
L. cornellensis
Microbacterium liquefaciens
Neptunomonas
L. fleischmannii
Microbacterium oxydans
Neptunomonas japonica
L. floridensis
L. grandensis
L. grayi
L. innocua
Lactobacillus
L. acetotolerans
L. catenaformis
L. mali
L. parakefiri
L. sakei
L. acidifarinae
L. ceti
L. manihotivorans
L. paralimentarius
L. salivarius
L. acidipiscis
L. coleohominis
L. mindensis
L. paraplantarum
L. sanfranciscensis
L. acidophilus
L. collinoides
L. mucosae
L. pentosus
L. satsumensis
Lactobacillus agilis
L. composti
L. murinus
L. perolens
L. secaliphilus
L. algidus
L. concavus
L. nagelii
L. plantarum
L. sharpeae
L. alimentarius
L. coryniformis
L. namurensis
L. pontis
L. siliginis
L. amylolyticus
L. crispatus
L. nantensis
L. protectus
L. spicheri
L. amylophilus
L. crustorum
L. oligofermentans
L. psittaci
L. suebicus
L. amylotrophicus
L. curvatus
L. oris
L. rennini
L. thailandensis
L. amylovorus
L. delbrueckii subsp. bulgaricus
L. panis
L. reuteri
L. ultunensis
L. animalis
L. delbrueckii subsp.
L. pantheris
L. rhamnosus
L. vaccinostercus
L. antri
delbrueckii
L. parabrevis
L. rimae
L. vaginalis
L. apodemi
L. delbrueckii subsp. lactis
L. parabuchneri
L. rogosae
L. versmoldensis
L. aviarius
L. dextrinicus
L. paracasei
L. rossiae
L. vini
L. bifermentans
L. diolivorans
L. paracollinoides
L. ruminis
L. vitulinus
L. brevis
L. equi
L. parafarraginis
L. saerimneri
L. zeae
L. buchneri
L. equigenerosi
L. homohiochii
L. jensenii
L. zymae
L. camelliae
L. farraginis
L. iners
L. johnsonii
L. gastricus
L. casei
L. farciminis
L. ingluviei
L. kalixensis
L. ghanensis
L. kitasatonis
L. fermentum
L. intestinalis
L. kefiranofaciens
L. graminis
L. kunkeei
L. fornicalis
L. fuchuensis
L. kefiri
L. hammesii
L. leichmannii
L. fructivorans
L. gallinarum
L. kimchii
L. hamsteri
L. lindneri
L. frumenti
L. gasseri
L. helveticus
L. harbinensis
L. malefermentans
L. hilgardii
L. hayakitensis
Legionella
Legionella adelaidensis
Legionella drancourtii
Candidatus Legionella jeonii
Legionella quinlivanii
Legionella anisa
Legionella dresdenensis
Legionella jordanis
Legionella rowbothamii
Legionella beliardensis
Legionella drozanskii
Legionella lansingensis
Legionella rubrilucens
Legionella birminghamensis
Legionella dumoffii
Legionella londiniensis
Legionella sainthelensi
Legionella bozemanae
Legionella erythra
Legionella longbeachae
Legionella santicrucis
Legionella brunensis
Legionella fairfieldensis
Legionella lytica
Legionella shakespearei
Legionella busanensis
Legionella fallonii
Legionella maceachernii
Legionella spiritensis
Legionella cardiaca
Legionella feeleii
Legionella massiliensis
Legionella steelei
Legionella cherrii
Legionella geestiana
Legionella micdadei
Legionella steigerwaltii
Legionella cincinnatiensis
Legionella genomospecies
Legionella monrovica
Legionella taurinensis
Legionella clemsonensis
Legionella gormanii
Legionella moravica
Legionella tucsonensis
Legionella donaldsonii
Legionella gratiana
Legionella nagasakiensis
Legionella tunisiensis
Legionella gresilensis
Legionella nautarum
Legionella wadsworthii
Legionella hackeliae
Legionella norrlandica
Legionella waltersii
Legionella impletisoli
Legionella oakridgensis
Legionella worsleiensis
Legionella israelensis
Legionella parisiensis
Legionella yabuuchiae
Legionella jamestowniensis
Legionella pittsburghensis
Legionella pneumophila
Legionella quateirensis
Oceanibulbus
Paenibacillus
Prevotella
Quadrisphaera
Oceanibulbus indolifex
Paenibacillus thiaminolyticus
Prevotella albensis
Quadrisphaera
Oceanicaulis
Pantoea
Prevotella amnii
granulorum
Oceanicaulis alexandrii
Pantoea
Prevotella bergensis
Quatrionicoccus
Oceanicola
agglomerans
Prevotella bivia
Quatrionicoccus
Oceanicola batsensis
Paracoccus
Prevotella brevis
australiensis
Oceanicola granulosus
Paracoccus alcaliphilus
Prevotella bryantii
Quinella
Oceanicola nanhaiensis
Paucimonas
Prevotella buccae
Quinella
Oceanimonas
Paucimonas lemoignei
Prevotella buccalis
ovalis
Oceanimonas baumannii
Pectobacterium
Prevotella copri
Ralstonia
Oceaniserpentilla
Pectobacterium aroidearum
Prevotella dentalis
Ralstonia eutropha
Oceaniserpentilla haliotis
Pectobacterium atrosepticum
Prevotella denticola
Ralstonia insidiosa
Oceanisphaera
Pectobacterium betavasculorum
Prevotella disiens
Ralstonia mannitolilytica
Oceanisphaera donghaensis
Pectobacterium cacticida
Prevotella histicola
Ralstonia pickettii
Oceanisphaera litoralis
Pectobacterium carnegieana
Prevotella intermedia
Ralstonia
Oceanithermus
Pectobacterium carotovorum
Prevotella maculosa
pseudosolanacearum
Oceanithermus desulfurans
Pectobacterium chrysanthemi
Prevotella marshii
Ralstonia syzygii
Oceanithermus profundus
Pectobacterium cypripedii
Prevotella melaninogenica
Ralstonia solanacearum
Oceanobacillus
Pectobacterium rhapontici
Prevotella micans
Ramlibacter
Oceanobacillus caeni
Pectobacterium wasabiae
Prevotella multiformis
Ramlibacter henchirensis
Oceanospirillum
Planococcus
Prevotella nigrescens
Ramlibacter
Oceanospirillum linum
Planococcus citreus
Prevotella oralis
tataouinensis
Planomicrobium
Prevotella oris
Raoultella
Planomicrobium okeanokoites
Prevotella oulorum
Raoultella ornithinolytica
Plesiomonas
Prevotella pallens
Raoultella planticola
Plesiomonas shigelloides
Prevotella salivae
Raoultella terrigena
Proteus
Prevotella stercorea
Rathayibacter
Proteus vulgaris
Prevotella tannerae
Rathayibacter caricis
Prevotella timonensis
Rathayibacter festucae
Prevotella veroralis
Rathayibacter iranicus
Providencia
Rathayibacter rathayi
Providencia stuartii
Rathayibacter toxicus
Pseudomonas
Rathayibacter tritici
Pseudomonas aeruginosa
Rhodobacter
Pseudomonas alcaligenes
Rhodobacter sphaeroides
Pseudomonas anguillispetica
Ruegeria
Pseudomonas fluorescens
Ruegeria gelatinovorans
Pseudoalteromonas
haloplanktis
Pseudomonas mendocina
Pseudomonas
pseudoalcaligenes
Pseudomonas putida
Pseudomonas tutzeri
Pseudomonas syringae
Psychrobacter
Psychrobacter faecalis
Psychrobacter
phenylpyruvicus
Saccharococcus
Sagittula
Sanguibacter
Stenotrophomonas
Tatlockia
Saccharococcus thermophilus
Sagittula stellata
Sanguibacter keddieii
Stenotrophomonas
Tatlockia maceachernii
Saccharomonospora
Salegentibacter
Sanguibacter suarezii
maltophilia
Tatlockia micdadei
Saccharomonospora azurea
Salegentibacter salegens
Saprospira
Streptococcus
Tenacibaculum
Saccharomonospora cyanea
Salimicrobium
Saprospira grandis
Tenacibaculum
Saccharomonospora viridis
Salimicrobium album
Sarcina
Streptomyces
amylolyticum
Saccharophagus
Salinibacter
Sarcina maxima
Streptomyces
Tenacibaculum discolor
Saccharophagus degradans
Salinibacter ruber
Sarcina ventriculi
achromogenes
Tenacibaculum
Saccharopolyspora
Salinicoccus
Sebaldella
Streptomyces
gallaicum
Saccharopolyspora erythraea
Salinicoccus alkaliphilus
Sebaldella
cesalbus
Tenacibaculum
Saccharopolyspora gregorii
Salinicoccus hispanicus
termitidis
Streptomyces cescaepitosus
lutimaris
Saccharopolyspora hirsuta
Salinicoccus roseus
Serratia
Streptomyces cesdiastaticus
Tenacibaculum
Saccharopolyspora hordei
Salinispora
Serratia fonticola
Streptomyces cesexfoliatus
mesophilum
Saccharopolyspora rectivirgula
Salinispora arenicola
Serratia marcescens
Streptomyces fimbriatus
Tenacibaculum
Saccharopolyspora spinosa
Salinispora tropica
Sphaerotilus
Streptomyces fradiae
skagerrakense
Saccharopolyspora taberi
Salinivibrio
Sphaerotilus natans
Streptomyces fulvissimus
Tepidanaerobacter
Saccharothrix
Salinivibrio costicola
Sphingobacterium
Streptomyces griseoruber
Tepidanaerobacter
Saccharothrix australiensis
Salmonella
Sphingobacterium multivorum
Streptomyces griseus
syntrophicus
Saccharothrix coeruleofusca
Salmonella bongori
Staphylococcus
Streptomyces lavendulae
Tepidibacter
Saccharothrix espanaensis
Salmonella enterica
Streptomyces
Tepidibacter
Saccharothrix longispora
Salmonella subterranea
phaeochromogenes
formicigenes
Saccharothrix mutabilis
Salmonella typhi
Streptomyces
Tepidibacter thalassicus
Saccharothrix syringae
thermodiastaticus
Thermus
Saccharothrix tangerinus
Streptomyces tubercidicus
Thermus aquaticus
Saccharothrix texasensis
Thermus filiformis
Thermus thermophilus
Staphylococcus
S. arlettae
S. equorum
S. microti
S. schleiferi
S. agnetis
S. felis
S. muscae
S. sciuri
S. aureus
S. fleurettii
S. nepalensis
S. simiae
S. auricularis
S. gallinarum
S. pasteuri
S. simulans
S. capitis
S. haemolyticus
S. petrasii
S. stepanovicii
S. caprae
S. hominis
S. pettenkoferi
S. succinus
S. carnosus
S. hyicus
S. piscifermentans
S. vitulinus
S. caseolyticus
S. intermedius
S. pseudintermedius
S. warneri
S. chromogenes
S. kloosii
S. pseudolugdunensis
S. xylosus
S. cohnii
S. leei
S. pulvereri
S. condimenti
S. lentus
S. rostri
S. delphini
S. lugdunensis
S. saccharolyticus
S. devriesei
S. lutrae
S. saprophyticus
S. epidermidis
S. lyticans
S. massiliensis
Streptococcus
Streptococcus agalactiae
Streptococcus infantarius
Streptococcus orisratti
Streptococcus thermophilus
Streptococcus anginosus
Streptococcus iniae
Streptococcus parasanguinis
Streptococcus sanguinis
Streptococcus bovis
Streptococcus intermedius
Streptococcus peroris
Streptococcus sobrinus
Streptococcus canis
Streptococcus lactarius
Streptococcus pneumoniae
Streptococcus suis
Streptococcus constellatus
Streptococcus milleri
Streptococcus
Streptococcus uberis
Streptococcus downei
Streptococcus mitis
pseudopneumoniae
Streptococcus vestibularis
Streptococcus dysgalactiae
Streptococcus mutans
Streptococcus pyogenes
Streptococcus viridans
Streptococcus equines
Streptococcus oralis
Streptococcus ratti
Streptococcus
Streptococcus faecalis
Streptococcus tigurinus
Streptococcus salivariu
zooepidemicus
Streptococcus ferus
Uliginosibacterium
Vagococcus
Vibrio
Virgibacillus
Xanthobacter
Uliginosibacterium
Vagococcus carniphilus
Vibrio aerogenes
Virgibacillus
Xanthobacter agilis
gangwonense
Vagococcus elongatus
Vibrio aestuarianus
halodenitrificans
Xanthobacter
Ulvibacter
Vagococcus fessus
Vibrio albensis
Virgibacillus
aminoxidans
Ulvibacter litoralis
Vagococcus fluvialis
Vibrio alginolyticus
pantothenticus
Xanthobacter
Umezawaea
Vagococcus lutrae
Vibrio campbellii
Weissella
autotrophicus
Umezawaea tangerina
Vagococcus salmoninarum
Vibrio cholerae
Weissella cibaria
Xanthobacter flavus
Undibacterium
Variovorax
Vibrio cincinnatiensis
Weissella confusa
Xanthobacter tagetidis
Undibacterium pigrum
Variovorax boronicumulans
Vibrio coralliilyticus
Weissella halotolerans
Xanthobacter viscosus
Ureaplasma
Variovorax dokdonensis
Vibrio cyclitrophicus
Weissella hellenica
Xanthomonas
Ureaplasma
Variovorax paradoxus
Vibrio diazotrophicus
Weissella kandleri
Xanthomonas
urealyticum
Variovorax soli
Vibrio fluvialis
Weissella koreensis
albilineans
Ureibacillus
Veillonella
Vibrio furnissii
Weissella minor
Xanthomonas alfalfae
Ureibacillus composti
Veillonella atypica
Vibrio gazogenes
Weissella
Xanthomonas
Ureibacillus suwonensis
Veillonella caviae
Vibrio halioticoli
paramesenteroides
arboricola
Ureibacillus terrenus
Veillonella criceti
Vibrio harveyi
Weissella soli
Xanthomonas
Ureibacillus thermophilus
Veillonella dispar
Vibrio ichthyoenteri
Weissella thailandensis
axonopodis
Ureibacillus thermosphaericus
Veillonella montpellierensis
Vibrio mediterranei
Weissella viridescens
Xanthomonas
Veillonella parvula
Vibrio metschnikovii
Williamsia
campestris
Veillonella ratti
Vibrio mytili
Williamsia marianensis
Xanthomonas citri
Veillonella rodentium
Vibrio natriegens
Williamsia maris
Xanthomonas codiaei
Venenivibrio
Vibrio navarrensis
Williamsia serinedens
Xanthomonas
Venenivibrio stagnispumantis
Vibrio nereis
Winogradskyella
cucurbitae
Verminephrobacter
Vibrio nigripulchritudo
Winogradskyella
Xanthomonas
Verminephrobacter eiseniae
Vibrio ordalii
thalassocola
euvesicatoria
Verrucomicrobium
Vibrio orientalis
Wolbachia
Xanthomonas fragariae
Verrucomicrobium spinosum
Vibrio parahaemolyticus
Wolbachia persica
Xanthomonas fuscans
Vibrio pectenicida
Wolinella
Xanthomonas gardneri
Vibrio penaeicida
Wolinella succinogenes
Xanthomonas hortorum
Vibrio proteolyticus
Zobellia
Xanthomonas hyacinthi
Vibrio shilonii
Zobellia galactanivorans
Xanthomonas perforans
Vibrio splendidus
Zobellia uliginosa
Xanthomonas phaseoli
Vibrio tubiashii
Zoogloea
Xanthomonas pisi
Vibrio vulnificus
Zoogloea ramigera
Xanthomonas populi
Zoogloea resiniphila
Xanthomonas theicola
Xanthomonas
translucens
Xanthomonas
vesicatoria
Xylella
Xylella fastidiosa
Xylophilus
Xylophilus ampelinus
Xenophilus
Yangia
Yersinia mollaretii
Zooshikella
Zobellella
Xenophilus azovorans
Yangia pacifica
Yersinia philomiragia
Zooshikella ganghwensis
Zobellella denitrificans
Xenorhabdus
Yaniella
Yersinia pestis
Zunongwangia
Zobellella taiwanensis
Xenorhabdus beddingii
Yaniella flava
Yersinia pseudotuberculosis
Zunongwangia profunda
Zeaxanthinibacter
Xenorhabdus bovienii
Yaniella halotolerans
Yersinia rohdei
Zymobacter
Zeaxanthinibacter
Xenorhabdus cabanillasii
Yeosuana
Yersinia ruckeri
Zymobacter palmae
enoshimensis
Xenorhabdus doucetiae
Yeosuana aromativorans
Yokenella
Zymomonas
Zhihengliuella
Xenorhabdus griffiniae
Yersinia
Yokenella regensburgei
Zymomonas mobilis
Zhihengliuella
Xenorhabdus hominickii
Yersinia aldovae
Yonghaparkia
Zymophilus
halotolerans
Xenorhabdus koppenhoeferi
Yersinia bercovieri
Yonghaparkia alkaliphila
Zymophilus paucivorans
Xylanibacterium
Xenorhabdus nematophila
Yersinia enterocolitica
Zavarzinia
Zymophilus raffinosivorans
Xylanibacterium ulmi
Xenorhabdus poinarii
Yersinia entomophaga
Zavarzinia compransoris
Xylanibacter
Yersinia frederiksenii
Xylanibacter oryzae
Yersinia intermedia
Yersinia kristensenii
| Number | Date | Country | Kind |
|---|---|---|---|
| 1719896.1 | Nov 2017 | GB | national |
| 1808063.0 | May 2018 | GB | national |
| Number | Date | Country | |
|---|---|---|---|
| Parent | 16839164 | Apr 2020 | US |
| Child | 18314755 | US | |
| Parent | 15985658 | May 2018 | US |
| Child | 16839164 | US |
