TARGETED ANTIMICROBIAL MOIETIES

STATEMENT OF GOVERNMENTAL SUPPORT

[Not Applicable]

FIELD OF THE INVENTION

The present invention relates to novel targeting peptides, novel antimicrobial peptides, chimeric moieties comprising novel targeting and/or novel antimicrobial peptides and uses thereof.

BACKGROUND OF THE INVENTION

Antibiotic research at the industrial level was originally focused on the identification of refined variants of already existing drugs. This resulted example, in the development of antibiotics such as newer penicillins, cephalosporins, macrolides, and fluoroquinolones.

However, resistance to old and newer antibiotics among bacterial pathogens is evolving rapidly, as exemplified by extended beta-lactamase (ESBL) and quinolone resistant gram-negatives, multi-resistant gonococci, methicillin resistant Staphylococcus aureus (MRSA), vancomycin resistant enterococci (VRE), penicillin non-susceptible pneumococci (PNSP) and macrolide resistant pneumococci and streptococci (see, e.g., Panlilo et al. (1992) Infect Control Hosp Epidemio., 13: 582-586; Morris et al. (1995) Ann Intern Me., d 123: 250-259, and the like). An overuse, or improper use, of antibiotics is believed to be of great importance for triggering and spread of drug resistant bacteria. Microbes have, in many cases, adapted and are resistant to antibiotics due to constant exposure and improper use of the drugs.

Drug resistant pathogens represent a major economic burden for health-care systems. For example, postoperative and other nosocomial infections will prolong the need for hospital care and increase antibiotic drug expenses. It is estimated that the annual cost of treating drug resistant infections in the United States is approximately $5 billion.

SUMMARY OF THE INVENTION

In certain embodiments, novel targeting moieties (e.g., peptides) that specifically/preferentially bind to microorganisms (e.g., certain bacteria, yeasts, fungi, molds, viruses, algae, protozoa, and the like) are provided. The targeting moieties can be attached to effectors (e.g., detectable labels, drugs, antimicrobial peptides, etc.) to form chimeric constructs for specifically/preferentially delivering the effector to and/or into the target organism. In certain embodiments novel antimicrobial peptides that can be used to inhibit (e.g., kill and/or inhibit growth and/or proliferation) of certain microorganisms (e.g., certain bacteria, yeasts, fungi, molds, viruses, algae, protozoa, and the like) are provided.

Accordingly, in certain embodiments, a chimeric construct (chimeric moiety) is provided comprising: an effector attached to a peptide targeting moiety comprising an amino acid sequence found in Table 3 and/or Table 12; and/or an antimicrobial peptide comprising an amino acid sequence found in Table 4 and/or Table 5 attached to a targeting moiety. In certain embodiments the targeting moiety is a peptide comprising an amino acid sequence of a peptide found one or more of Table 3 and Table 12. In certain embodiments the targeting moiety is a peptide comprising two or more amino acid sequences of a peptide found one or more of Table 3 and Table 12. In certain embodiments the targeting moiety is a peptide whose amino acid sequence consists of the amino acid sequence of a peptide found in Table 3.

In various embodiments the effector comprises a moiety selected from the group consisting of an antimicrobial peptide, an antibiotic, a ligand, a lipid or liposome, a agent that physically disrupts the extracellular matrix within a community of microorganisms, and a polymeric particle. In certain embodiments the effector comprises an antimicrobial peptide comprising an amino acid sequence found in one or more of Tables 4, 5, 14, and Table 15. In certain embodiments the effector comprises an antimicrobial peptide comprising an amino acid sequence found in one or more of Tables 4, and 5. In certain embodiments the effector comprises an antimicrobial peptide comprising an amino acid sequence characterized by a motif selected from the group consisting of KIF, FIK, KIH, HIK, and KIV (e.g., as identified in Table 7). In certain embodiments the construct comprises a targeting peptide comprising an amino acid sequence found in Table 3 attached to an antimicrobial peptide comprising an amino acid sequence found in Table 4 and/or Table 5. In certain embodiments the construct comprises an antimicrobial peptide comprising an amino acid sequence found in Table 4 attached to a targeting moiety comprising an amino acid sequence found in Table 3 and/or Table 10, and/or Table 12. In certain embodiments the construct comprises a targeting peptide comprising an amino acid sequence found in Table 3 attached to an antimicrobial peptide comprising an amino acid sequence found in Table 4.

In various embodiments the targeting moiety is chemically conjugated to the effector (directly or via a linker). In certain embodiments the liker comprises a polyethylene glycol (PEG). In certain embodiments the targeting moiety is chemically conjugated to the effector via a non-peptide linker found in Table 16. In certain embodiments the targeting moiety is linked to the effector via a peptide linkage. In certain embodiments the effector comprises an antimicrobial peptide and the construct is a fusion protein. In certain embodiments the targeting moiety is attached to the effector by a peptide linker comprising or consisting of an amino acid sequence found in Table 16. In certain embodiments any of the constructs and/or peptides described herein bears one or more protecting groups. In certain embodiments the one or more protecting groups are independently selected from the group consisting of acetyl, amide, 3 to 20 carbon alkyl groups, fmoc, tBoc, 9-fluoreneacetyl group, 1-fluorenecarboxylic group, 9-florenecarboxylic group, 9-fluorenone-1-carboxylic group, benzyloxycarbonyl, xanthyl (Xan), trityl (Trt), 4-methyltrityl (Mtt), 4-methoxytrityl (Mmt), 4-methoxy-2,3,6-trimethyl-benzenesulphonyl (Mtr), mesitylene-2-sulphonyl (Mts), 4,4-dimethoxybenzhydryl (Mbh), tosyl (Tos), 2,2,5,7,8-pentamethyl chroman-6-sulphonyl (Pmc), 4-methylbenzyl (MeBzl), 4-methoxybenzyl (MeOBzl), benzyloxy (BzlO), benzyl (Bzl), benzoyl (Bz), 3-nitro-2-pyridinesulphenyl (Npys), 1-(4,4-dimentyl-2,6-diaxocyclohexylidene)ethyl (Dde), 2,6-dichlorobenzyl (2,6-DiCl—Bzl), 2-chlorobenzyloxycarbonyl (2-Cl—Z), 2-bromobenzyloxycarbonyl (2-Br—Z), benzyloxymethyl (Bom), t-butoxycarbonyl (Boc), cyclohexyloxy (cHxO), t-butoxymethyl (Bum), t-butoxy (tBuO), t-Butyl (tBu), and trifluoroacetyl (TFA). In certain embodiments the peptide and/or construct comprises a protecting group at a carboxyl and/or amino terminus. In certain embodiments the carboxyl terminus is amidated and/or the amino terminus is acetylated. In various embodiments the chimeric construct and/or peptide is functionalized with a polymer (e.g., comprises polyethylene glycol, cellulose, modified cellulose, dextrin, etc.) to increase serum halflife.

In certain embodiments pharmaceutical compositions are provided. In various embodiments the pharmaceutical compositions comprise a chimeric construct as described herein (e.g., a chimeric construct according to any of claims 1-26) and/or an antimicrobial peptide as described herein, in a pharmaceutically acceptable carrier. In certain embodiments the composition is formulated as a unit dosage formulation. In certain embodiments the composition is formulated for administration by a modality selected from the group consisting of intraperitoneal administration, topical administration, oral administration, inhalation administration, transdermal administration, subdermal depot administration, systemic IV application, ocular administration, and rectal administration.

In certain embodiments isolated antimicrobial peptides are provided. In various embodiments the peptides comprise one or more sequences selected from the amino acid sequences listed in Table 4 and/or Table 5 (and/or the retro, inverso, retroinverso, or beta forms). In various embodiments the antimicrobial peptide bears one or more protecting groups e.g., as described herein.

In certain embodiments a composition effective to kill or to inhibit the growth and/or of a microorganism and/or the formation and/or maintenance of a biofilm is provided. The composition typically comprises one or more isolated antimicrobial peptides, the amino acid sequences of the peptides comprising one or more sequences selected from the amino acid sequences listed in Table 4 and/or Table 5 (and/or their retro, inverso, or retroinverso forms). In certain embodiments the composition is effective to kill or inhibit the growth and/or proliferation of a yeast or fungus, and the composition comprises one or more peptides, the amino acid sequences of the peptides comprising one or more sequences selected from the group of amino acid sequences listed in Table 4 and/or Table 5 identified (e.g., in those tables) as effective to effective to kill or inhibit the growth and/or proliferation of a yeast or fungus. In certain embodiments the composition is effective to kill or inhibit the growth and/or proliferation of Aspergillus niger and the composition comprises one or more peptides, the amino acid sequences of the peptides comprising one or more sequences selected from the group of amino acid sequences listed in Table 4 and/or Table 5 identified as effective to effective to kill or inhibit the growth and/or proliferation of Aspergillus niger. In certain embodiments the composition is effective to kill or inhibit the growth and/or proliferation of C. albicans and the composition comprises one or more peptides, the amino acid sequences of the peptides comprising one or more sequences selected from the group of amino acid sequences listed in Table 4 and/or Table 5 identified as effective to effective to kill or inhibit the growth and/or proliferation of C. albicans. In certain embodiments the composition is effective to kill or inhibit the growth and/or proliferation of T. rubrum and the composition comprises one or more peptides, the amino acid sequences of the peptides comprising one or more sequences selected from the group of amino acid sequences listed in Table 4 and/or Table 5 identified as effective to effective to kill or inhibit the growth and/or proliferation of T. rubrum. In certain embodiments the composition is effective to kill or inhibit the growth and/or proliferation of a bacterium, and the composition comprises one or more peptides, the amino acid sequences of the peptides comprising one or more sequences selected from the group of amino acid sequences listed in Table 4 and/or Table 5 identified as effective to effective to kill or inhibit the growth and/or proliferation of a bacterium. In certain embodiments the composition is effective to kill or inhibit the growth and/or proliferation of a gram positive bacterium, and the composition comprises one or more peptides, the amino acid sequences of the peptides comprising one or more sequences selected from the group of amino acid sequences listed in Table 4 and/or Table 5 identified as effective to effective to kill or inhibit the growth and/or proliferation of a gram positive bacterium. In certain embodiments the composition is effective to kill or inhibit the growth and/or proliferation of A. naeslundii, and the composition comprises one or more peptides, the amino acid sequences of the peptides comprising one or more sequences selected from the group of amino acid sequences listed in Table 4 and/or Table 5 identified as effective to effective to kill or inhibit the growth and/or proliferation of A. naeslundii. In certain embodiments the composition is effective to kill or inhibit the growth and/or proliferation of B. subtilis, and the composition comprises one or more peptides, the amino acid sequences of the peptides comprising one or more sequences selected from the group of amino acid sequences listed in Table 4 and/or Table 5 identified as effective to effective to kill or inhibit the growth and/or proliferation of B. subtilis. In certain embodiments the composition is effective to kill or inhibit the growth and/or proliferation of C. difficile, and the composition comprises one or more peptides, the amino acid sequences of the peptides comprising one or more sequences selected from the group of amino acid sequences listed in Table 4 and/or Table 5 identified as effective to effective to kill or inhibit the growth and/or proliferation of C. difficile. In certain embodiments the composition is effective to kill or inhibit the growth and/or proliferation of C. jeikeium, and the composition comprises one or more peptides, the amino acid sequences of the peptides comprising one or more sequences selected from the group of amino acid sequences listed in Table 4 and/or Table 5 identified as effective to effective to kill or inhibit the growth and/or proliferation of C. jeikeium. In certain embodiments the composition is effective to kill or inhibit the growth and/or proliferation of E. faecalis, and the composition comprises one or more peptides, the amino acid sequences of the peptides comprising one or more sequences selected from the group of amino acid sequences listed in Table 4 and/or Table 5 identified as effective to effective to kill or inhibit the growth and/or proliferation of E. faecalis. In certain embodiments the composition is effective to kill or inhibit the growth and/or proliferation of M. luteus, and the composition comprises one or more peptides, the amino acid sequences of the peptides comprising one or more sequences selected from the group of amino acid sequences listed in Table 4 and/or Table 5 identified as effective to effective to kill or inhibit the growth and/or proliferation of M. luteus. In certain embodiments the composition is effective to kill or inhibit the growth and/or proliferation of MRSA, and the composition comprises one or more peptides, the amino acid sequences of the peptides comprising one or more sequences selected from the group of amino acid sequences listed in Table 4 and/or Table 5 identified as effective to effective to kill or inhibit the growth and/or proliferation of MRSA. In certain embodiments composition is effective to kill or inhibit the growth and/or proliferation of S. epidermidis, and the composition comprises one or more peptides, the amino acid sequences of the peptides comprising one or more sequences selected from the group of amino acid sequences listed in Table 4 and/or Table 5 identified as effective to effective to kill or inhibit the growth and/or proliferation of S. epidermidis. In certain embodiments the composition is effective to kill or inhibit the growth and/or proliferation of S. mutans, and the composition comprises one or more peptides, the amino acid sequences of the peptides comprising one or more sequences selected from the group of amino acid sequences listed in Table 4 and/or Table 5 identified as effective to effective to kill or inhibit the growth and/or proliferation of S. mutans. In certain embodiments the composition is effective to kill or inhibit the growth and/or proliferation of S. pneumoniae, and the composition comprises one or more peptides, the amino acid sequences of the peptides comprising one or more sequences selected from the group of amino acid sequences listed in Table 4 and/or Table 5 identified as effective to effective to kill or inhibit the growth and/or proliferation of S. pneumoniae. In certain embodiments the composition is effective to kill or inhibit the growth and/or proliferation of a gram negative bacterium, and the composition comprises one or more peptides, the amino acid sequences of the peptides comprising one or more sequences selected from the group of amino acid sequences listed in Table 4 and/or Table 5 identified as effective to effective to kill or inhibit the growth and/or proliferation of a gram negative bacterium. In certain embodiments the composition is effective to kill or inhibit the growth and/or proliferation of A. baumannii, and the composition comprises one or more peptides, the amino acid sequences of the peptides comprising one or more sequences selected from the group of amino acid sequences listed in Table 4 and/or Table 5 identified as effective to effective to kill or inhibit the growth and/or proliferation of A. baumannii. In certain embodiments the composition is effective to kill or inhibit the growth and/or proliferation of C. jejuni, and the composition comprises one or more peptides, the amino acid sequences of the peptides comprising one or more sequences selected from the group of amino acid sequences listed in Table 4 and/or Table 5 identified as effective to effective to kill or inhibit the growth and/or proliferation of C. jejuni. In certain embodiments the composition is effective to kill or inhibit the growth and/or proliferation of E. coli, and the composition comprises one or more peptides, the amino acid sequences of the peptides comprising one or more sequences selected from the group of amino acid sequences listed in Table 4 and/or Table 5 identified as effective to effective to kill or inhibit the growth and/or proliferation of E. coli. In certain embodiments the composition is effective to kill or inhibit the growth and/or proliferation of F. nucleatum, and the composition comprises one or more peptides, the amino acid sequences of the peptides comprising one or more sequences selected from the group of amino acid sequences listed in Table 4 and/or Table 5 identified as effective to effective to kill or inhibit the growth and/or proliferation of F. nucleatum. In certain embodiments the composition is effective to kill or inhibit the growth and/or proliferation of E. coli, and the composition comprises one or more peptides, the amino acid sequences of the peptides comprising one or more sequences selected from the group of amino acid sequences listed in Table 4 and/or Table 5 identified as effective to effective to kill or inhibit the growth and/or proliferation of M. xanthus. In certain embodiments the composition is effective to kill or inhibit the growth and/or proliferation of P. aeruginosa, and the composition comprises one or more peptides, the amino acid sequences of the peptides comprising one or more sequences selected from the group of amino acid sequences listed in Table 4 and/or Table 5 identified as effective to effective to kill or inhibit the growth and/or proliferation of P. aeruginosa. In certain embodiments the composition is effective to kill or inhibit the growth and/or proliferation of P. gingivalis, and the composition comprises one or more peptides, the amino acid sequences of the peptides comprising one or more sequences selected from the group of amino acid sequences listed in Table 4 and/or Table 5 identified as effective to effective to kill or inhibit the growth and/or proliferation of P. gingivalis. In certain embodiments the composition is effective to kill or inhibit the growth and/or proliferation of P. mirabilis, and the composition comprises one or more peptides, the amino acid sequences of the peptides comprising one or more sequences selected from the group of amino acid sequences listed in Table 4 and/or Table 5 identified as effective to effective to kill or inhibit the growth and/or proliferation of P. mirabilis.

In various embodiments one or more of the peptides comprising the composition comprise all “L” amino acids or all “D” amino acids, or a mixture of “L” and “D” amino acids. In various embodiments one or more of the peptides comprising the composition are β peptides. In various embodiments one or more of the peptides comprising the composition comprise one or more protecting groups (e.g. protected carboxyl and/or amino termini). In various embodiments one or more of the peptides comprising the composition comprise an amide on the carboxyl terminus and/or an acetyl on the amino terminus. In various embodiments the peptides comprising the composition are in a pharmaceutically acceptable carrier. In certain embodiments the carrier is suitable for administration via a route selected from the group consisting of topical administration, aerosol administration, administration via inhalation, oral administration, and/or rectal administration.

In various embodiments methods are provided for killing and/or inhibiting the growth and/or proliferation of a microorganism and or for disrupting and/or inhibiting the growth and/or maintenance of a biofilm, the method comprising contacting the microorganism (or a biofilm comprising the microorganism) with a chimeric construct as described herein (e.g., see description above, and/or a chimeric construct according to any one of claims 1-29), or with an antimicrobial peptide as described herein, and/or with a composition as described herein (e.g., a composition according to any one of claims 30-65). In certain embodiments the microorganism is a yeast or fungus and the chimeric construct or composition is a chimeric construct comprising an effector identified as killing a yeast or fungus, or a composition comprising an antimicrobial peptide described herein as killing a yeast or fungus. In certain embodiments the microorganism is a bacterium (e.g., gram negative and/or gram positive bacterium) and the chimeric construct or composition is a chimeric construct comprising an effector identified as killing a bacterium (e.g., gram negative and/or gram positive bacterium), or a composition comprising an antimicrobial peptide described herein as killing a gram negative and/or gram positive bacterium. In certain embodiments the effector is an antimicrobial peptide. In certain embodiments the microorganism is S. mutans, and the chimeric construct or composition is applied to the oral cavity of an animal or human, e.g., to reduces the incidence or severity of dental caries and/or periodontal disease). In certain embodiments the chimeric construct or composition preferentially targets Corynebacterium spp. and the chimeric construct or composition is applied to the skin surface of an animal or human (e.g., to reduce body odor).

Methods are also provided for disinfecting a surface. The methods typically involve contacting the surface with one or more chimeric constructs described herein (e.g. a construct according to any one of claims 1-29), or a composition as described herein (e.g., a composition according to any one of claims 30-65). In certain embodiments, the surface comprises a surface of a prosthesis or medical implant. In certain embodiments the surface comprises a surface of a medical device. In certain embodiments the surface comprises a surface of a plant or foodstuff. In certain embodiments the chimeric construct and/or the antimicrobial peptide(s) are combined with a second disinfectant selected from the group consisting of other antimicrobial agent is a disinfectant selected from the group consisting of acetic acid, phosphoric acid, citric acid, lactic, formic, propionic acid, hydrochloric acid, sulfuric acid, nitric acid, sodium hydroxide, potassium hydroxide, sodium carbonate, ammonium hydroxide, ethyl alcohol, isopropyl alcohol, phenol, formaldehyde, glutaraldehyde, hypochlorites, chlorine dioxide, sodium dichloroisocyanurate, chloramine-T, iodine, povidone-iodine, chlorhexidine, hydrogen peroxide, peracetic acid, and benzalkonium chloride.

In various embodiments the use of a chimeric construct described herein and/or an antimicrobial composition as described herein (e.g., a chimeric construct according to any one of claims 1-29, or a composition according to any one of claims 30-65) in the manufacture of a medicament for killing and/or inhibiting the growth and/or proliferation of a microorganism and/or inhibiting the growth and/or maintenance of a biofilm comprising the microorganism is provided. In certain embodiments the microorganism is a yeast or fungus and the chimeric construct or composition is a chimeric construct comprising an effector identified as killing a yeast or fungus, or a composition comprising an antimicrobial peptide described herein as killing a yeast or fungus. In certain embodiments the microorganism is a bacterium (e.g., gram negative and/or gram positive bacterium) and the chimeric construct or composition is a chimeric construct comprising an effector identified as killing a bacterium (e.g., gram negative and/or gram positive bacterium), or a composition comprising an antimicrobial peptide described herein as killing a gram negative and/or gram positive bacterium. In certain embodiments the effector is an antimicrobial peptide.

In various embodiments methods are also provided for of detecting a bacterium and/or a bacterial film (e.g., a biofilm comprising the bacteria). The methods typically involve contacting the bacterium or bacterial film with a composition comprising a detectable label attached to a targeting peptide comprising one or more amino acid sequences found Table 3 and/or Table 12; and detecting the detectable label where the quantity and/or location of the detectable label is an indicator of the presence of the bacterium and/or bacterial film. In certain embodiments the targeting peptide comprises or consists of an amino acid sequence of a peptide found in Table 3 (and/or the retro, inverso, retroinverso form of the sequence). In certain embodiments the detectable label is a label selected from the group consisting of a radioactive label, a radio-opaque label, a fluorescent dye, a fluorescent protein, an enzymatic label, a colorimetric label, and a quantum dot.

Certain compositions are also provided comprising a photosensitizing or photoactivatable agent attached to a targeting peptide (e.g., a peptide comprising an amino acid sequence of a peptide found in Table 3 and/or Table 12). In certain embodiments the targeting peptide comprises or consists of an amino acid sequence of a peptide found in Table 3. In certain embodiments the photosensitizing agent is an agent selected from the group consisting of a porphyrinic macrocycle, a porphyrin, a chlorine, a crown ether, an acridine, an azine, a phthalocyanine, a cyanine, a psoralen, a cucumin, and a perylenequinonoid. In certain embodiments the photosensitizing agent comprises one or more agents agent shown in any of FIGS. 1-12. In certain embodiments the photosensitizing agent is attached to the targeting peptide by a non-peptide linker (e.g., a polyethylene glycol (PEG)). In certain embodiments the photosensitizing agent is attached to the targeting peptide by a non-peptide linker found in Table 16.

In various embodiments methods are provided for killing and/or for inhibiting the growth and/or proliferation of a microorganism or a biofilm comprising a microorganism, where the methods involve contacting the microorganism or biofilm with a composition comprising a photosensitizing or photoactivatable agent attached to a targeting peptide (e.g., a peptide comprising an amino acid sequence of a peptide found in Table 3 and/or Table 12). In certain embodiments the targeting peptide comprises or consists of an amino acid sequence of a peptide found in Table 3. In certain embodiments the photosensitizing agent is an agent selected from the group consisting of a porphyrinic macrocycle, a porphyrin, a chlorine, a crown ether, an acridine, an azine, a phthalocyanine, a cyanine, a psoralen, a cucumin, and a perylenequinonoid. In certain embodiments the photosensitizing agent comprises one or more agents agent shown in any of FIGS. 1-12. In certain embodiments the photosensitizing agent is attached to the targeting peptide by a non-peptide linker (e.g., a polyethylene glycol (PEG)). In certain embodiments the photosensitizing agent is attached to the targeting peptide by a non-peptide linker found in Table 16. In certain embodiments the method further comprises exposing the microorganism or biofilm to a light source. In certain embodiments the microorganism is a microorganism selected from the group consisting of a bacterium (e.g., a gram positive and/or a gram negative bacterium), a yeast, a fungus, a protozoan, and a virus. In certain embodiments the biofilm comprises a bacterial film. In certain embodiments the biofilm is a biofilm on an implanted or implantable medical device. In certain embodiments the microorganism or biofilm is an organism or biofilm in an oral cavity.

In various embodiments certain formulations are provided. Typical formulations include, but are not limited to a targeting peptide, an antimicrobial peptide, and/or a STAMP; and a salt at a concentration comparable to that found in phosphate buffered saline (PBS) ranging from about 0.5×PBS to about 2.5×PBS. In certain embodiments the formulation comprises a targeting peptide found in Tables 3 or 10. In certain embodiments the formulation comprises an anti-S. mutans peptide targeting peptide (e.g., as identified in Tables 3 or 12). In certain embodiments the anti-S. mutans targeting peptide has the amino acid sequence TFFRLFNRSFTQALGK (SEQ ID NO:1). In certain embodiments the anti-S. mutans targeting peptide is attached to an antimicrobial peptide. In certain embodiments the antimicrobial peptide is a peptide found in Tables 4, 5, or 14. In certain embodiments the antimicrobial peptide has the amino acid sequence KNLRIIRKGIHIIKKY (SEQ ID NO:3080). In certain embodiments the formulation comprises the amino acid sequence of the C16G2 STAMP (TFFRLFNRSFTQALGKGGGKNLRIIRKGIHIIKKY, (SEQ ID NO:2). In various embodiments the targeting peptide, antimicrobial peptide, and/or a STAMP bears one or more protecting groups. In certain embodiments the protecting group(s) are independently selected from the group consisting of acetyl, amide, 3 to 20 carbon alkyl groups, Fmoc, Tboc, 9-fluoreneacetyl group, 1-fluorenecarboxylic group, 9-florenecarboxylic group, 9-fluorenone-1-carboxylic group, benzyloxycarbonyl, Xanthyl (Xan), Trityl (Trt), 4-methyltrityl (Mtt), 4-methoxytrityl (Mmt), 4-methoxy-2,3,6-trimethyl-benzenesulphonyl (Mtr), Mesitylene-2-sulphonyl (Mts), 4,4-dimethoxybenzhydryl (Mbh), Tosyl (Tos), 2,2,5,7,8-pentamethyl chroman-6-sulphonyl (Pmc), 4-methylbenzyl (MeBzl), 4-methoxybenzyl (MeOBzl), Benzyloxy (BzlO), Benzyl (Bzl), Benzoyl (Bz), 3-nitro-2-pyridinesulphenyl (Npys), 1-(4,4-dimentyl-2,6-diaxocyclohexylidene)ethyl (Dde), 2,6-dichlorobenzyl (2,6-DiCl—Bzl), 2-chlorobenzyloxycarbonyl (2-Cl—Z), 2-bromobenzyloxycarbonyl (2-Br—Z), Benzyloxymethyl (Bon), t-butoxycarbonyl (Boc), cyclohexyloxy (cHxO), t-butoxymethyl (Bum), t-butoxy (tBuO), t-Butyl (tBu), and Trifluoroacetyl (TFA). In certain embodiments the targeting peptide, antimicrobial peptide, and/or a STAMP is amidated at the carboxyl terminus and/or bears an acetyl group at the amino terminus. In certain embodiments the pH of the formulation ranges from about pH 5.0 to about pH 8.5. In certain embodiments the pH is about pH 7.4. In various embodiments the salt is at a concentration comparable to that found in 1×PBS. In certain embodiments the formulation comprises PBS. In certain embodiments the formulation of further comprising ethanol, and/or glycerin, and/or polyethylene glycol, and/or fluoride.

DEFINITIONS

The term “peptide” as used herein refers to a polymer of amino acid residues typically ranging in length from 2 to about 50 or about 60 residues. In certain embodiments the peptide ranges in length from about 2, 3, 4, 5, 7, 9, 10, or 11 residues to about 60, 50, 45, 40, 45, 30, 25, 20, or 15 residues. In certain embodiments the peptide ranges in length from about 8, 9, 10, 11, or 12 residues to about 15, 20 or 25 residues. In certain embodiments the amino acid residues comprising the peptide are “L-form” amino acid residues, however, it is recognized that in various embodiments, “D” amino acids can be incorporated into the peptide. Peptides also include amino acid polymers in which one or more amino acid residues is an artificial chemical analogue of a corresponding naturally occurring amino acid, as well as to naturally occurring amino acid polymers. In addition, the term applies to amino acids joined by a peptide linkage or by other, “modified linkages” (e.g., where the peptide bond is replaced by an α-ester, a β-ester, a thioamide, phosphonamide, carbonate, hydroxylate, and the like (see, e.g., Spatola, (1983) Chem. Biochem. Amino Acids and Proteins 7: 267-357), where the amide is replaced with a saturated amine (see, e.g., Skiles et al., U.S. Pat. No. 4,496,542, which is incorporated herein by reference, and Kaltenbronn et al., (1990) Pp. 969-970 in Proc. 11th American Peptide Symposium, ESCOM Science Publishers, The Netherlands, and the like)).

The term “residue”” as used herein refers to natural, synthetic, or modified amino acids. Various amino acid analogues include, but are not limited to 2-aminoadipic acid, 3-aminoadipic acid, beta-alanine (beta-aminopropionic acid), 2-aminobutyric acid, 4-aminobutyric acid, piperidinic acid, δ-aminocaproic acid, 2-aminoheptanoic acid, 2-aminoisobutyric acid, 3-aminoisobutyric acid, 2-aminopimelic acid, 2,4 diaminobutyric acid, desmosine, 2,2′-diaminopimelic acid, 2,3-diaminopropionic acid, n-ethylglycine, n-ethylasparagine, hydroxylysine, allo-hydroxylysine, 3-hydroxyproline, 4-hydroxyproline, isodesmosine, allo-isoleucine, n-methylglycine, sarcosine, n-methylisoleucine, 6-n-methyllysine, n-methylvaline, norvaline, norleucine, ornithine, and the like. These modified amino acids are illustrative and not intended to be limiting.

“β-peptides” comprise of “β amino acids”, which have their amino group bonded to the β carbon rather than the α-carbon as in the 20 standard biological amino acids. The only commonly naturally occurring β amino acid is β-alanine.

Peptoids, or N-substituted glycines, are a specific subclass of peptidomimetics. They are closely related to their natural peptide counterparts, but differ chemically in that their side chains are appended to nitrogen atoms along the molecule's backbone, rather than to the α-carbons (as they are in natural amino acids).

The terms “conventional” and “natural” as applied to peptides herein refer to peptides, constructed only from the naturally-occurring amino acids: Ala, Cys, Asp, Glu, Glu, Phe, Gly, His, Ile, Lys, Leu, Met, Asn, Pro, Gln, Arg, Ser, Thr, Val, Trp, and Tyr. A compound of the invention “corresponds” to a natural peptide if it elicits a biological activity (e.g., antimicrobial activity) related to the biological activity and/or specificity of the naturally occurring peptide. The elicited activity may be the same as, greater than or less than that of the natural peptide. In general, such a peptoid will have an essentially corresponding monomer sequence, where a natural amino acid is replaced by an N-substituted glycine derivative, if the N-substituted glycine derivative resembles the original amino acid in hydrophilicity, hydrophobicity, polarity, etc. The following are illustrative, but non-limiting N-substituted glycine replacements: N-(1-methylprop-1-yl)glycine substituted for isoleucine (Ile), N-(prop-2-yl)glycine for valine (Val), N-benzylglycine for phenylanlaine (Phe), N-(2-hydroxyethyl)glycine for serine (Ser), and the like. In certain embodiments substitutions need not be “exact”. Thus for example, in certain embodiments N-(2-hydroxyethyl)glycine may substitute for Ser, Thr, Cys, and/or Met; N-(2-methylprop-1-yl)glycine may substitute for Val, Leu, and/or Ile. In certain embodiments N-(2-hydroxyethyl)glycine can be used to substitute for Thr and Ser, despite the structural differences: the side chain in N-(2-hydroxyethyl)glycine is one methylene group longer than that of Ser, and differs from Thr in the site of hydroxy-substitution. In general, one may use an N-hydroxyalkyl-substituted glycine to substitute for any polar amino acid, an N-benzyl- or N-aralkyl-substituted glycine to replace any aromatic amino acid (e.g., Phe, Trp, etc.), an N-alkyl-substituted glycine such as N-butylglycine to replace any nonpolar amino acid (e.g., Leu, Val, Ile, etc.), and an N-(aminoalkyl)glycine derivative to replace any basic polar amino acid (e.g., Lys and Arg).

Where an amino acid sequence is provided herein, L-, D-, or beta amino acid versions of the sequence are also contemplated as well as retro, inversion, and retro-inversion isoforms. In addition, conservative substitutions (e.g., in the binding peptide, and/or antimicrobial peptide, and/or linker peptide) are contemplated. Non-protein backbones, such as PEG, alkane, ethylene bridged, ester backbones, and other backbones are also contemplated. Also fragments ranging in length from about 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25 amino acids up to the full length minus one amino acid of the peptide are contemplated where the fragment retains at least 50%, preferably at least 60% 70% or 80%, more preferably at least 90%, 95%, 98%, 99%, or at least 100% of the activity (e.g., binding specificity and/or avidity, antimicrobial activity, etc.) of the full length peptide are contemplated.

A “compound antimicrobial peptide” or “compound AMP” refers to a construct comprising two or more AMPs joined together. The AMPs can be joined directly or through a linker. They can be chemically conjugated or, where joined directly together or through a peptide linker can comprise a fusion protein.

In certain embodiments, conservative substitutions of the amino acids comprising any of the sequences described herein are contemplated. In various embodiments one, two, three, four, or five different residues are substituted. The term “conservative substitution” is used to reflect amino acid substitutions that do not substantially alter the activity (e.g., antimicrobial activity and/or specificity) of the molecule. Typically conservative amino acid substitutions involve substitution one amino acid for another amino acid with similar chemical properties (e.g. charge or hydrophobicity). Certain conservative substitutions include “analog substitutions” where a standard amino acid is replaced by a non-standard (e.g., rare, synthetic, etc) amino acid differing minimally from the parental residue. Amino acid analogs are considered to be derived synthetically from the standard amino acids without sufficient change to the structure of the parent, are isomers, or are metabolite precursors. Examples of such “analog substitutions” include, but are not limited to, 1) Lys-Orn, 2) Leu-Norleucine, 3) Lys-Lys[TFA], 4) Phe-Phe[Gly], and 5) δ-amino butylglycine-ξ-amino hexylglycine, where Phe[gly] refers to phenylglycine (a Phe derivative with a H rather than CH₃component in the R group), and Lys[TFA] refers to a Lys where a negatively charged ion (e.g., TFA) is attached to the amine R group. Other conservative substitutions include “functional substitutions” where the general chemistries of the two residues are similar, and can be sufficient to mimic or partially recover the function of the native peptide. Strong functional substitutions include, but are not limited to 1) Gly/Ala, 2) Arg/Lys, 3) Ser/Tyr/Thr, 4) Leu/Ile/Val, 5) Asp/Glu, 6) Gln/Asn, and 7) Phe/Trp/Tyr, while other functional substitutions include, but are not limited to 8) Gly/Ala/Pro, 9) Tyr/His, 10) Arg/Lys/His, 11) Ser/Thr/Cys, 12) Leu/Ile/Val/Met, and 13) Met/Lys (special case under hydrophobic conditions). Various “broad conservative substations” include substitutions where amino acids replace other amino acids from the same biochemical or biophysical grouping. This is similarity at a basic level and stems from efforts to classify the original 20 natural amino acids. Such substitutions include 1) nonpolar side chains: Gly/Ala/Val/Leu/Ile/Met/Pro/Phe/Trp, and/or 2) uncharged polar side chains Ser/Thr/Asn/Gln/Tyr/Cys. In certain embodiments broad-level substitutions can also occur as paired substitutions. For example, Any hydrophilic neutral pair [Ser, Thr, Gln, Asn, Tyr, Cys]+[Ser, Thr, Gln, Asn, Tyr, Cys] can may be replaced by a charge-neutral charged pair [Arg, Lys, His]+[Asp, Glu]. The following six groups each contain amino acids that, in certain embodiments, are typical conservative substitutions for one another: 1) Alanine (A), Serine (S), Threonine (T); 2) Aspartic acid (D), Glutamic acid (E); 3) Asparagine (N), Glutamine (Q); 4) Arginine (R), Lysine (K), Histidine (H); 5) Isoleucine (I), Leucine (L), Methionine (M), Valine (V); and 6) Phenylalanine (F), Tyrosine (Y), Tryptophan (W). Where amino acid sequences are disclosed herein, amino acid sequences comprising, one or more of the above-identified conservative substitutions are also contemplated.

In certain embodiments, targeting peptides, antimicrobial peptides, and/or STAMPs compromising at least 80%, preferably at least 85% or 90%, and more preferably at least 95% or 98% sequence identity with any of the sequences described herein are also contemplated. The terms “identical” or percent “identity,” refer to two or more sequences that are the same or have a specified percentage of amino acid residues that are the same, when compared and aligned for maximum correspondence, as measured using one of the following sequence comparison algorithms or by visual inspection. With respect to the peptides of this invention sequence identity is determined over the full length of the peptide. For sequence comparison, typically one sequence acts as a reference sequence, to which test sequences are compared. When using a sequence comparison algorithm, test and reference sequences are input into a computer, subsequence coordinates are designated, if necessary, and sequence algorithm program parameters are designated. The sequence comparison algorithm then calculates the percent sequence identity for the test sequence(s) relative to the reference sequence, based on the designated program parameters. Optimal alignment of sequences for comparison can be conducted, e.g., by the local homology algorithm of Smith & Waterman (1981) Adv. Appl. Math. 2: 482, by the homology alignment algorithm of Needleman & Wunsch (1970) J. Mol. Biol. 48: 443, by the search for similarity method of Pearson & Lipman (1988) Proc. Natl. Acad. Sci., USA, 85: 2444, by computerized implementations of these algorithms (GAP, BESTFIT, FASTA, and TFASTA in the Wisconsin Genetics Software Package, Genetics Computer Group, 575 Science Dr., Madison, Wis.), or by visual inspection.

The term “specificity” when used with respect to the antimicrobial activity of a peptide indicates that the peptide preferentially inhibits growth and/or proliferation and/or kills a particular microbial species as compared to other related and/or unrelated microbes. In certain embodiments the preferential inhibition or killing is at least 10% greater (e.g., LD₅₀is 10% lower), preferably at least 20%, 30%, 40%, or 50%, more preferably at least 2-fold, at least 5-fold, or at least 10-fold greater for the target species.

“Treating” or “treatment” of a condition as used herein may refer to preventing the condition, slowing the onset or rate of development of the condition, reducing the risk of developing the condition, preventing or delaying the development of symptoms associated with the condition, reducing or ending symptoms associated with the condition, generating a complete or partial regression of the condition, or some combination thereof.

The term “consisting essentially of” when used with respect to an antimicrobial peptide (AMP) or AMP motif as described herein, indicates that the peptide or peptides encompassed by the library or variants, analogues, or derivatives thereof possess substantially the same or greater antimicrobial activity and/or specificity as the referenced peptide. In certain embodiments substantially the same or greater antimicrobial activity indicates at least 80%, preferably at least 90%, and more preferably at least 95% of the anti microbial activity of the referenced peptide(s) against a particular bacterial species (e.g., S. mutans).

The term “porphyrinic macrocycle” refers to a porphyrin or porphyrin derivative. Such derivatives include porphyrins with extra rings ortho-fused, or orthoperifused, to the porphyrin nucleus, porphyrins having a replacement of one or more carbon atoms of the porphyrin ring by an atom of another element (skeletal replacement), derivatives having a replacement of a nitrogen atom of the porphyrin ring by an atom of another element (skeletal replacement of nitrogen), derivatives having substituents other than hydrogen located at the peripheral (meso-, .beta.-) or core atoms of the porphyrin, derivatives with saturation of one or more bonds of the porphyrin (hydroporphyrins, e.g., chlorins, bacteriochlorins, isobacteriochlorins, decahydroporphyrins, corphins, pyrrocorphins, etc.), derivatives obtained by coordination of one or more metals to one or more porphyrin atoms (metalloporphyrins), derivatives having one or more atoms, including pyrrolic and pyrromethenyl units, inserted in the porphyrin ring (expanded porphyrins), derivatives having one or more groups removed from the porphyrin ring (contracted porphyrins, e.g., corrin, corrole) and combinations of the foregoing derivatives (e.g. phthalocyanines, porphyrazines, naphthalocyanines, subphthalocyanines, and porphyrin isomers). Certain porphyrinic macrocycles comprise at least one 5-membered ring.

As used herein, an “antibody” refers to a protein consisting of one or more polypeptides substantially encoded by immunoglobulin genes or fragments of immunoglobulin genes. The recognized immunoglobulin genes include the kappa, lambda, alpha, gamma, delta, epsilon and mu constant region genes, as well as myriad immunoglobulin variable region genes. Light chains are classified as either kappa or lambda. Heavy chains are classified as gamma, mu, alpha, delta, or epsilon, which in turn define the immunoglobulin classes, IgG, IgM, IgA, IgD and IgE, respectively.

A typical immunoglobulin (antibody) structural unit is known to comprise a tetramer. Each tetramer is composed of two identical pairs of polypeptide chains, each pair having one “light” (about 25 kD) and one “heavy” chain (about 50-70 kD). The N-terminus of each chain defines a variable region of about 100 to 110 or more amino acids primarily responsible for antigen recognition. The terms variable light chain (V_L) and variable heavy chain (V_H) refer to these light and heavy chains respectively.

Antibodies exist as intact immunoglobulins or as a number of well characterized fragments produced by digestion with various peptidases. Thus, for example, pepsin digests an antibody below the disulfide linkages in the hinge region to produce F(ab)′₂, a dimer of Fab which itself is a light chain joined to V_H-C_H1 by a disulfide bond. The F(ab)′₂may be reduced under mild conditions to break the disulfide linkage in the hinge region thereby converting the (Fab′)₂dimer into an Fab′ monomer. The Fab′ monomer is essentially an Fab with part of the hinge region (see, Fundamental Immunology, W. E. Paul, ed., Raven Press, N.Y. (1993), for a more detailed description of other antibody fragments). While various antibody fragments are defined in terms of the digestion of an intact antibody, one of skill will appreciate that such Fab′ fragments may be synthesized de novo either chemically or by utilizing recombinant DNA methodology. Thus, the term antibody, as used herein also includes antibody fragments either produced by the modification of whole antibodies or synthesized de novo using recombinant DNA methodologies, including, but are not limited to, Fab′₂, IgG, IgM, IgA, scFv, dAb, nanobodies, unibodies, and diabodies.

In certain embodiments antibodies and fragments of the present invention can be bispecific. Bispecific antibodies or fragments can be of several configurations. For example, bispecific antibodies may resemble single antibodies (or antibody fragments) but have two different antigen binding sites (variable regions). In various embodiments bispecific antibodies can be produced by chemical techniques (Kranz et al. (1981)Proc. Natl. Acad. Sci., USA, 78: 5807), by “polydoma” techniques (see, e.g., U.S. Pat. No. 4,474,893), or by recombinant DNA techniques. In certain embodiments bispecific antibodies of the present invention can have binding specificities for at least two different epitopes, at least one of which is an epitope of a microbial organism. The microbial binding antibodies and fragments can also be heteroantibodies. Heteroantibodies are two or more antibodies, or antibody binding fragments (e.g., Fab) linked together, each antibody or fragment having a different specificity.

The term “STAMP” refers to Specifically Targeted Anti-Microbial Peptides. In various embodiments, a STAMP comprises one or more peptide targeting moieties attached to one or more antimicrobial moieties (e.g., antimicrobial peptides (AMPs)). An MH-STAMP is a STAMP bearing two or more targeting domains (i.e., a multi-headed STAMP).

The terms “isolated” “purified” or “biologically pure” refer to material which is substantially or essentially free from components that normally accompany it as found in its native state. In the case of a peptide, an isolated (naturally occurring) peptide is typically substantially free of components with which it is associated in the cell, tissue, or organism. The term isolated also indicates that the peptide is not present in a phage display, yeast display, or other peptide library.

In various embodiments the amino acid abbreviations shown in Table 1 are used herein.

TABLE 1

Amino acid abbreviations.

Abbreviation

Name
3 Letter
1 Letter

Alanine
Ala
A

βAlanine (NH₂—CH₂—CH₂—COOH)
βAla

Arginine
Arg
R

Asparagine
Asn
N

Aspartic Acid
Asp
D

Cysteine
Cys
C

Glutamic Acid
Glu
E

Glutamine
Gln
Q

Glycine
Gly
G

Histidine
His
H

Homoserine
Hse
—

Isoleucine
Ile
I

Leucine
Leu
L

Lysine
Lys
K

Methionine
Met
M

Methionine sulfoxide
Met (O)
—

Methionine methylsulfonium
Met (S-Me)
—

Norleucine
Nle
—

Phenylalanine
Phe
F

Proline
Pro
P

Serine
Ser
S

Threonine
Thr
T

Tryptophan
Trp
W

Tyrosine
Tyr
Y

Valine
Val
V

episilon-aminocaproic acid
Ahx
J

(NH²—(CH₂)₅—COOH)

4-aminobutanoic acid
gAbu

(NH₂—(CH₂)₃—COOH)

tetrahydroisoquinoline-3-

O

carboxylic acid

Lys(N(epsilon)-trifluoroacetyl)

K[TFA]

α-aminoisobutyric acid
Aib
B

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows some illustrative porphyrins (compounds 92-99) suitable for use as targeting moieties and/or antimicrobial effectors.

FIG. 2 shows some illustrative porphyrins (compounds 100-118) suitable for use as targeting moieties and/or antimicrobial effectors.

FIG. 3 shows some illustrative porphyrins (in particular phthalocyanines) (compounds 119-128) suitable for use as targeting moieties and/or antimicrobial effectors.

FIG. 4 illustrates the structures of two phthalocyanines, Monoastral Fast Blue B and Monoastral Fast Blue G suitable for use as targeting moieties and/or antimicrobial effectors.

FIG. 5 illustrates certain azine photosensitizers suitable for use as targeting moieties and/or antimicrobial effectors in the compositions and methods described herein.

FIG. 6 shows illustrative cyanine suitable for use as targeting moieties and/or antimicrobial effectors in the compositions and methods described herein.

FIG. 7 shows illustrative psoralen (angelicin) photosensitizers suitable for use as targeting moieties and/or antimicrobial effectors in the compositions and methods described herein.

FIG. 8 shows illustrative hypericin and the perylenequinonoid pigments suitable for use as targeting moieties and/or antimicrobial effectors in the compositions and methods described herein.

FIG. 9 shows illustrative acridines suitable for use as targeting moieties and/or antimicrobial effectors in the compositions and methods described herein.

FIG. 10 illustrates the structure of the acridine Rose Bengal.

FIG. 11 illustrates various crown ethers suitable for use as targeting moieties and/or antimicrobial effectors in the compositions and methods described herein.

FIG. 12 illustrates the structure of cumin.

FIG. 13 illustrates an example of a targeted light-activated porphyrin we have constructed: C16-P18 comprising a porphyrin coupled to a C16 (SEQ ID NO:3) targeting sequence.

FIG. 14 schematically shows some illustrative configurations for chimeric constructs described herein. A: Shows a single targeting moiety T1 attached to a single effector E1 by a linker/spacer L. B: Shows multiple targeting moieties T1, T2, T3 attached directly to each other and attached by a linker L to a single effector E1. In various embodiments T1, T2, and T3, can be domains in a fusion protein. C: Shows multiple targeting moieties T1, T2, T3 attached to each other by linkers L and attached by a linker L to a single effector E1. In various embodiments T1, T2, and T3, can be domains in a fusion protein. D: Shows a single targeting moiety T1 attached by a linker L to multiple effectors E1, E2, and E3 joined directly to each other. E: Shows a single targeting moiety T1 attached by a linker L to multiple effectors E1, E2, and E3 joined to each other by linkers L. F: Shows multiple targeting moieties joined directly to each other and by a linker L to multiple effectors joined to each other by linkers L. G: Shows multiple targeting moieties joined to each other by linkers L and by a linker L to multiple effectors joined to each other by linkers L. In various embodiments T1, T2, and T3, and/or E1, E2, and E3 can be domains in a fusion protein. H: Illustrates a branched configuration where multiple targeting moieties are linked to a single effector. I: Illustrates a dual branched configuration where multiple targeting moieties are linked to multiple effectors. J: Illustrates a branched configuration where multiple targeting moieties are linked to multiple effectors where the effectors are joined to each other in a linear configuration.

FIG. 15 illustrates various MH-STAMPs used in Example 1. The design, sequence, and observed mass (m/z) for M8(KH)-20 (SEQ ID NOs:4, 5, and 6), BL(KH)-20 (SEQ ID 7, 8, and 9), and M8(BL)-20 (SEQ ID 10, 11, and 12).

FIGS. 16A and 16B show HPLC and MS spectra of M8(KH)-20. The quality of the completed MH-STAMP was analyzed by HPLC (FIG. 16A) and MALDI mass spectroscopy (FIG. 16B). At UV absorbance 215 nm (260 and 280 nm are also plotted), a single major product was detected by HPLC (* retention volume 11.04 mL). After fraction collection, the correct mass (m/z) for single-charged M8(KH)-20, 4884.91 (marked by *), was observed for this peak. Y-axis: 16A, mAU miliabsorbance units; 16B, percent intensity.

FIG. 17A-17E show growth inhibitory activity of MH-STAMPs. Monocultures of S. mutans (FIG. 17A); P. aeruginosa (FIG. 17B); S. epidermidis (FIG. 17C); S. aureus (FIG. 17D); or E. coli (FIG. 17E); were treated with peptides (as indicated in the figure) for 10 min. Agent was then removed and fresh media returned. Culture recovery was measured over time (OD600). Plots represent the average of at least 3 independent experiments with standard deviations.

FIG. 18 illustrates the selective activity of dual-targeted and single-targeted MH-STAMPs in mixed culture. A mixture of P. aeruginosa (Pa), S. mutans (Sm), E. coli (Ec), and S. epidermidis (Se) planktonic cells were mixed with MH-STAMPs (as indicated in the figure) and treated 24 h. After incubation, cfu/mL of remaining constituent species were quantitated after plating to selective media. * indicates under 200 surviving cfu/mL recovered.

FIGS. 19A and 19B illustrate Rose Bengal (FIG. 19A) and synthesis scheme for C16-RB, halides and side-chains omitted for clarity (FIG. 19B).

FIG. 20 shows LC/MS profile C16-RB. Purity and molecular mass of C16-RB was confirmed by LC/MS. A single product was observed at 11.92 min with mass species at 1040.8 and 1560.25 daltons. Expected C16-RB mas: m/z=3118, m²⁺/z=1559, m³⁺/Z=1039.

FIG. 21 illustrates activity of RB and C16-RB against single-species S. mutans biofilms. * indicates fewer than 100 cfu/mL recovered

FIG. 22 shows S. mutans-specific C16-RB activity. C16-RB, and not RB alone, preferentially eliminated S. mutans, and not other oral streptococci, after blue light illumination.

DETAILED DESCRIPTION

In various embodiments, novel “targeting” peptides are identified that specifically or preferentially bind particular microorganisms (e.g., bacteria, yeasts, fungi, etc.). These peptides can be used alone to bind/capture and thereby identify and/or isolate particular target microorganisms, or they can be attached to one or more effectors (e.g., drugs, labels, etc.) and used as targeting moieties thereby providing a chimeric moiety that preferentially or specifically delivers the effector to a target microorganism, a population of target microorganisms, a microbial film, a biofilm, and the like.

In various embodiments novel peptides having antimicrobial activity against certain bacteria, fungi, yeasts, and/or viruses and/or having activity that inhibits the growth or maintenance of biofilms comprising such microorganisms are provided. The AMPs can be used to inhibit the growth and/or proliferation of a microbial species and/or the growth and/formation and/or maintenance of a biofilm comprising the microbial species.

In certain embodiments, the targeting moieties can be attached to antimicrobial peptides to form Specifically Targeted Anti-Microbial Peptides (STAMPs). In certain embodiments attachment of one or more targeting moieties/peptides to one or more antimicrobial peptides can narrow the spectrum of activity of the AMP(s) to provide efficacy against one or a few target microorganisms without substantially disrupting the remaining microbial ecology and thereby provide increased efficacy with fewer side effects.

In certain embodiments STAMPs or effector peptides can be delivered against pathogenic bacteria by being cloned and expressed in probiotic organisms for therapeutic delivery in vivo. Recombinant expression (and overexpression) and export of antimicrobial peptides and other peptides are well documented in bacteria, including species that are also utilized as probiotics.

In various embodiments the targeting peptides, antimicrobial peptides, and/or STAMPs can be formulated individually, in combination with each other, in combination with other antimicrobial peptides, and/or in combination with various antibacterial agents to provide antimicrobial reagents and/or pharmaceuticals.

Accordingly, in certain embodiments this invention provides peptides having antimicrobial activity, compositions comprising the peptides, methods of using the peptides (or compositions thereof) to inhibit the growth of or kill a wide variety of microbial targets and methods of using the peptides (or compositions thereof) to treat or prevent microbial infections and diseases related thereto in both plants and animals.

The various peptides (targeting peptides, AMPs, STAMPs, etc.) described herein exhibit antimicrobial activity, being biostatic or biocidal against a certain microbial targets, including but not limited to, Gram-negative bacteria such as Acinetobacter baumannii, Escherichia coli, Fusobacterium nucleatum, Pseudomonas aeruginosa, Porphyromonas gingivalis; Gram-positive bacteria such as Actinomyces naeslundii, Bacillus subtilis, Clostridium difficile, Enterococcus faecalis, Staphylococcus aureus (and MRSA), S. epidermidis, Streptococcus mutans, Streptococcus pneumoniae; and yeast or fungi such as Aspergillus niger, Candida albicans, Malassezia furfur, and Trichophyton rubrum (see, e.g., Table 2). Significantly, various peptides described herein are biostatic or biocidal against clinically relevant pathogens exhibiting multi-drug resistance such as, for example, methicillin-resistant Staphylococcus aureus (“MRSA”).

TABLE 2

Illustrative target microorganisms and associated pathology.

Acinetobacter baumannii

Pathogenic gram-negative bacillus that is naturally sensitive

(A. baumannii)
to relatively few antibiotics.

Actinomyces naeslundii

Gram positive rod shaped bacteria that occupy the oral

(A. naeslundii)
cavity and are implicated in periodontal disease and root

caries.

Aspergillus niger

A fungal infection that often causes a black mould to appear

(A. niger)
on some fruit and vegetables but may also infect humans

through inhalation of fungal spores.

Bacteroides fragilis

Gram positive bacilli that are opportunistic human

(B. fragilis)
pathogens, causing infections of the peritoneal cavity,

gastrointestinal surgery, and appendicitis via abscess

formation, inhibiting phagocytosis. Resistant to a wide

variety of antibiotics - β-lactams, aminoglycosides, and

recently many species have acquired resistance to

erythromycin and tetracycline.

Bacillus subtilis

Gram-positive, catalase-positive bacterium.

(B. subtilis)

Candida albicans

Causal agent of opportunistic oral and genital fungal

(C. albicans)
infections in humans.

Clostridium difficile

A gram-positive, anaerobic, spore-forming bacillus that is

(C. difficile)
responsible for the development of antibiotic-associated

diarrhea and colitis.

Corynebacterium jeikeium

Gram positive, opportunistic pathogen primarily of

(C. jeikeium)
immunocompromised (neutropenic) patients. Highly

resistant to antibiotics

Campylobacter jejuni

Gram negative cause of human gastroenteritis/food

(C. jejuni)
poisoning.

Escherichia coli

Gram negative rod-shaped bacterium commonly found in the

(E. coli)
lower intestine of warm-blooded organisms. Certain strains

cause serious food poisoning in humans.

Enterococcus faecalis

Gram-positive commensal bacterium

(E. faecalis)

Fusobacterium nucleatum

Gram negative schizomycetes bacterium often seen in

(F. nucleatum)
necrotic tissue and implicated, but not conclusively, with

other organisms in the causation and perpetuation of

periodontal disease.

Lactobacillus acidophilus

Gram-positive commensal bacterium.

(L. acidophilus)

Legionella pneumophila

Gram negative bacterium that is the causative agent of

(L. pneumophila)
legionellosis or Legionnaires' disease.

(Micrococcus luteus)
Gram positive, spherical, saprotrophic bacterium found in

M. luteus

soil, dust, water and air, and as part of the normal flora of the

mammalian skin. The bacterium also colonizes the human

mouth, mucosae, oropharynx and upper respiratory tract.

Considered an emerging nosocomial pathogen in

immunocompromised patients.

Mycobacterium smegmatis

Gram-variable (acid-fast) soil-dwelling organism utilized as

(M. smegmatis)
a proxy for Mycobacterium tuberculosis during research and

development.

Malassezia furfur

Yeast - cutaneous pathogen.

(M. furfur)

Methicillin-resistant
Any strain of Staphylococcus aureus bacteria (gram positive)

Staphylococcus aureus

that is resistant to a one or more members of a large group of

(MRSA)
antibiotics called the beta-lactams. Responsible for skin and

systemic infections.

Myxococcus xanthus

Gram negative cells that form biofilms and display primitive

(M. xanthus)
social motility and fruiting body organization.

Pseudomonas aeruginosa

Gram-negative rod. Frequent opportunistic pathogen and

P. aeruginosa

infects burn wounds. Causes ear infections in children.

Infects the lungs of cystic fibrosis patients.

Porphyromonas gingivalis

Non-motile, gram-negative, rod-shaped, anaerobic

(P. gingivalis)
pathogenic bacterium (periodontal disease)

Progeussmirabilis

Gram-negative, facultatively anaerobic bacterium. Causes

(P. mirabilis)
90% of all ‘Proteus’ infections in humans.

S. epidermidis

Gram-positive, coagulase-negative cocci. Nosocomial

(S. epidermidis)
pathogen associated with infection (biofilm) of implanted

medical device.

Streptococcus mutans

Gram-positive, facultatively anaerobic bacterium commonly

(S. mutans)
found in the human oral cavity and is a significant

contributor to tooth decay

Streptococcus pneumoniae

Gram-positive, alpha-hemolytic, bile soluble aerotolerant

(S. pneumoniae)
anaerobe. Causal agent for streptococcal pneumonia.

Treponema denticola

Gram-negative oral spirochete associated with the incidence

(T. denticola)
and severity of human periodontal disease.

Trichophyton rubrum

Most common cause of athlete's foot, jock itch and

(T. rubrum)
ringworm.

The various agents described herein (targeting peptides, compound targeting peptides, antimicrobial peptides (AMPs) and/or compound AMPs, STAMPs and/or other chimeric moieties). or compositions thereof, are useful as biocidal or biostatic or fungicidal or fungistatic agents and/or virucidal agents in a wide variety of applications. For example, the agents can be used to disinfect or preserve a variety of materials including medical instruments, foodstuffs, medicaments, cosmetics and other nutrient-containing materials. Various peptides described herein are particularly useful as bacteriostatic or bactericidal agents against multi-drug-resistant pathogens such as MRSA in a variety of clinical settings.

The agents described herein, or compositions thereof, are also useful for the prophylaxis or treatment of microbial infections and diseases related thereto in both plants and animals. Such diseases include, but are not limited to, Gram-negative and Gram-positive bacterial infections, endocarditis, pneumonia and other respiratory infections, urinary tract infections, systemic candidiasis, oral mucositis, fungal infections, biofilm formation or maintenance (e.g., on medical implants), and the like.

In various embodiments, the agents described herein can be formulated individually, in combination with each other, in combination with other antimicrobial peptides, and/or in combination with various antibiotic (e.g., antibacterial) agents in “home healthcare” formulations. Such formulations include, but are not limited to toothpaste, mouthwash, tooth whitening strips or solutions, contact lens storage, wetting, or cleaning solutions, dental floss, toothpicks, toothbrush bristles, oral sprays, oral lozenges, nasal sprays, aerosolizers for oral and/or nasal application, wound dressings (e.g., bandages), and the like.

Such applications are illustrative and not limiting. Using the teachings provided herein other uses of the AMPs and compositions described herein will be recognized by one of

I. Targeting Peptides.

A) Uses of Targeting Peptides.

The novel microorganism-binding peptides (targeting peptides) described herein can be used to preferentially or specifically deliver an effector to a microorganism (e.g., a bacterium, a fungus, a protozoan, an algae, etc.), to a bacterial film, to a biofilm, and the like. The targeting peptides described herein can be used to bind to and thereby label particular targets, and/or as capture reagents to bind target microorganisms and thereby provide an indicator of the presence and/or quantity of the target microorganism(s). In certain embodiments the targeting peptide can be attached to an effector such as an epitope tag and/or a detectable label and thereby facilitate the identification of the presence and/or location, and/or quantity of the target (e.g., target organism). Thus targeting moieties are thus readily adapted for use in in vivo diagnostics, and/or ex vivo assays. Moreover, because of small size and good stability, microorganism binding peptides are well suited for microassay systems (e.g., microfluidic assays (Lab on a Chip), microarray assays, and the like).

In certain embodiments the microorganism binding peptides (targeting peptides) can be attached to an effector that has antimicrobial activity (e.g., an antimicrobial peptide, an antibacterial and/or antifungal, a vehicle that contains an antibacterial or antifungal, etc. In various embodiments these chimeric moieties can be used in vivo, or ex vivo to preferentially inhibit or kill the target organism(s).

In certain embodiments the targeting peptides can be recombinantly expressed as part of a yeast or phage tail fiber or coat protein to enhance binding of the yeast or phage to a specific bacterial Gram-designation, genus, species, or strain. Phage with expressed peptides will then display altered infection selectivity towards a designed target bacteria for use in phage therapy. Cloning the DNA encoding a peptide of interest into the major or minor coat proteins of a bacteriophage, for example in Proteins I through VIII of phages SAP-2, M13, or T7, will result in a targeted phage expressing 1-200 copies of the targeting peptide on the phage surface.

In certain embodiments the targeting peptides can be used in various pre-targeting protocols. In pre-targeting protocols, a chimeric molecule is utilized comprising a primary targeting species (e.g. a microorganism-binding peptide) that specifically binds the desired target (e.g. a bacterium) and an effector that provides a binding site that is available for binding by a subsequently administered second targeting species. Once sufficient accretion of the primary targeting species (the chimeric molecule) is achieved, a second targeting species comprising (i) a diagnostic or therapeutic agent and (ii) a second targeting moiety, that recognizes the available binding site of the primary targeting species, is administered.

An illustrative example of a pre-targeting protocol is the biotin-avidin system for administering a cytotoxic radionuclide to a tumor. In a typical procedure, a monoclonal antibody targeted against a tumor-associated antigen is conjugated to avidin and administered to a patient who has a tumor recognized by the antibody. Then the therapeutic agent, e.g., a chelated radionuclide covalently bound to biotin, is administered. The radionuclide, via its attached biotin is taken up by the antibody-avidin conjugate pretargeted at the tumor. Examples of pre-targeting biotin/avidin protocols are described, for example, in Goodwin et al., U.S. Pat. No. 4,863,713; Goodwin et al. (1988) J. Nucl. Med. 29: 226; Hnatowich et al. (1987) J. Nucl. Med. 28: 1294; Oehr et al. (1988) J. Nucl. Med. 29: 728; Klibanov et al. (1988) J. Nucl. Med. 29: 1951; Sinitsyn et al. (1989) J. Nucl. Med. 30: 66; Kalofonos et al. (1990) J. Nucl. Med. 31: 1791; Schechter et al. (1991) Int. J. Cancer 48:167; Paganelli et al. (1991) Cancer Res. 51: 5960; Paganelli et al. (1991) Nucl. Med. Commun. 12: 211; Stickney et al. (1991) Cancer Res. 51: 6650; and Yuan et al. (1991) Cancer Res. 51:3119.

It will be recognized that the tumor-specific antibody used for cancer treatments can be replaced with a microorganism binding peptide of the present invention and similar pre-targeting strategies can be used to direct labels, antibiotics, and the like to the target organism(s).

Three-step pre-targeting protocols in which a clearing agent is administered after the first targeting composition has localized at the target site also have been described. The clearing agent binds and removes circulating primary conjugate which is not bound at the target site, and prevents circulating primary targeting species (antibody-avidin or conjugate, for example) from interfering with the targeting of active agent species (biotin-active agent conjugate) at the target site by competing for the binding sites on the active agent-conjugate. When antibody-avidin is used as the primary targeting moiety, excess circulating conjugate can be cleared by injecting a biotinylated polymer such as biotinylated human serum albumin. This type of agent forms a high molecular weight species with the circulating avidin-antibody conjugate which is quickly recognized by the hepatobiliary system and deposited primarily in the liver.

Examples of these protocols are disclosed, e.g., in PCT Application No. WO 93/25240; Paganelli et al. (1991) Nucl. Med. Comm., 12: 211-234; Oehr et al. (1988) J. Nucl. Med., 29: 728-729; Kalofonos et al. (1990) J. Nucl. Med., 31: 1791-1796; Goodwin et al. (1988) J. Nucl. Med., 29: 226-234; and the like).

These applications of microorganism binding peptides of this invention are intended to be illustrative and not limiting. Using the teaching provided herein, other uses will be recognized by one of skill in the art.

B) Illustrative Novel Targeting Peptides.

In certain embodiments, the targeting moiety comprises one or more targeting peptides that bind particular bacteria, fungi, and/or yeasts, and/or algae, and/or viruses and/or that bind particular groups of bacteria, and/or groups of fungi, and/or groups of yeasts, and/or groups of algae.

In certain embodiments the targeting peptides include peptides comprising or consisting of one or more of the amino acid sequences shown in Table 3 (SEQ ID NOs:13-1566). In various embodiments the peptides include peptides comprising or consisting of the retro, inverso, retro-inverso, and/or beta form of one or more of the amino acid sequences shown in Table 3. Also contemplated are circular permutations of these sequences as well as peptides comprising or consisting of the retro, inverso, retro-inverso, and/or beta form of such circular permutations.

It will also be recognized, that in certain embodiments, any peptide or compound AMP described herein can be circularized.

In various embodiments the peptides can optionally bear one or more protecting groups, e.g., and the amino and/or carboxyl termini, and/or on side chains.

Also contemplated are peptides comprising one, two, three four, or five conservative substitutions of these amino acid sequences.

TABLE 3

Illustrative list of novel targeting peptides.

SEQ ID

ID
Target(s)
Targeting Peptide Sequence
NO

1T-3

S. mutans

VLGIAGGLDAYGELVGGN
13

S. gordonii

1T-4

S. mutans

LDAYGELVGGN
14

S. gordonii

S. sanguinis

S. oxalis

V. atypica

L. casei

1T-6

S. mutans

KFINGVLSQFVLERK
15

1T-7

M. xanthus

SQRIIEPVKSPQPYPGFSVS
16

1T-8

M. xanthus

FSVAACGEQRAVTFVLLIEDLI
17

1T-9

M. xanthus

WAWAESPRCVSTRSNIHALAFRVEVAA
18

LT

1T-10

M. xanthus

SPAGLPGDGDEA
19

1T-11

S. mutans

RISE
20

S. epidermidis

P. aeruginosa

1T-12

C. xerosis

FGNIFKGLKDVIETIVKWTAAK
21

C. striatum

S. epidermidis

S. mutans

1T-13

S. aureus

FRSPCINNNSLQPPGVYPAR
22

S. epidermidis

P. aeruginosa

1T-14

S. mutans

ALAGLAGLISGK
23

S. aureus

S. epidermidis

C. xerosis

1T-15

S. mutans

DVILRVEAQ
24

1T-16

P. aeruginosa

IDMR
25

1T-17

S. mutans

NNAIVYIS
26

1T-18

S. aureus

YSKTLHFAD
27

S. epidermidis

C. striatum

P. aeruginosa

1T-19

S. aureus

PGAFRNPQMPRG
28

S. epidermidis

P. aeruginosa

1T-20

S. mutans

PALVDLSNKEAVWAVLDDHS
29

P. aeruginosa

1T-21

S. mutans

YVEEAVRAALKKEARISTEDTPVNLPSF
30

P. aeruginosa

DC

1T-22

S. epidermidis

VPLDDGTRRPEVARNRDKDRED
31

P. aeruginosa

1T-23

S. mutans

PALVDLSNKEAVWAVLDDHS
32

P. aeruginosa

1T-24

P. aeruginosa

EEAEEKLAEVSQAVKRLVR
33

1T-25

S. aureus

VGLDVSVLVLFFGLQLLSVLLGAMIR
34

S. epidermidis

C. xerosis

C. striatum

P. aeruginosa

1T-26

S. mutans

LTILPTTFFAIIVPILAVAFIAYSGFKIKGI
35

S. aureus

VEHKDQW

S. epidermidis

C. jeikeium

C. xerosis

C. striatum

P. aeruginosa

1T-27

S. mutans

ALFVSLEQFLVVVAKSVFALCHSGTLS
36

S. aureus

S. epidermidis

C. jeikeium

C. xerosis

C. striatum

P. aeruginosa

1T-28

P. aeruginosa

VSRDEAMEFIDREWTTLQPAGKSHA
37

1T-29

S. mutans

GSVIKKRRKRMSKKKHRKMLRRTRVQ
38

S. aureus

RRKLGK

S. epidermidis

C. jeikeium

C. xerosis

C. striatum

P. aeruginosa

1T-30

S. aureus

GKAKPYQVRQVLRAVDKLETRRKKGGR
39

S. epidermidis

C. xerosis

C. striatum

P. aeruginosa

1T-31

S. mutans

NATGTDIGEVTLTLGRFS
40

P. aeruginosa

1T-32

S. mutans

VSFLAGWLCLGLAAWRLGNA
41

1T-33

S. aureus

VRTLTILVIFIFNYLKSISYKLKQPFENNL
42

S. epidermidis

AQSMISI

C. jeikeium

C. xerosis

C. striatum

P. aeruginosa

1T-34

S. aureus

AFWLNILLTLLGYIPGIVHAVYIIAKR
43

S. epidermidis

C. jeikeium

C. xerosis

C. striatum

P. aeruginosa

1T-35

P. aeruginosa

EICLTLVFPIRGSYSEAAKFPVPIHIVEDG
44

TVELPK

1T-36

S. aureus

VYRHLRFIDGKLVEIRLERK
45

S. epidermidis

C. jeikeium

C. xerosis

C. striatum

P. aeruginosa

1T-37

S. mutans

YIVGALVILAVAGLIYSMLRKA
46

S. aereus

S. epidermidis

C. jeikeium

C. xerosis

C. striatum

P. aeruginosa

1T-38

S. mutans

VMFVLTRGRSPRPMIPAY
47

S. aereus

S. epidermidis

C. jeikeium

C. xerosis

C. striatum

P. aeruginosa

1T-39

S. mutans

FGFCVWMYQLLAGPPGPPA
48

P. aeruginosa

1T-40

S. mutans

QRVSLWSEVEHEFR
49

P. aeruginosa

1T-41

S. mutans

KRGSKIVIAIAVVLIVLAGVWVW
50

S. aureus

S. epidermidis

C. jeikeium

C. striatum

P. aeruginosa

1T-42

S. aureus

TVLDWLSLALATGLFVYLLVALLRADRA
51

S. epidermidis

C. xerosis

C. striatum

P. aeruginosa

1T-43

C. jeikium

DRCLSVLSWSPPKVSPLI
52

P. aeruginosa

1T-44

S. mutans

DPALADFAAGMRAQVRT
53

S. aureus

S. epidermidis

C. jeikeium

C. striatum

P. aeruginosa

1T-45

S. aureus

WTKPSFTDLRLGFEVTLYFANR
54

S. epidermidis

C. striatum

P. aeruginosa

1T-46

S. aureus

FSFKQRVMFRKEVERLR
55

S. epidermidis

C. jeikeium

C. xerosis

C. striatum

P. aeruginosa

1T-47

S. mutans

VIKISVPGQVQMLIP
56

S. epidermidis

P. aeruginosa

1T-48

S. aureus

KLQVHHGRATHTLLLQPPLCAPGTIR
57

S. epidermidis

C. jeikeium

C. xerosis

C. striatum

P. aeruginosa

1T-49

S. aureus

SLVRIHDQQPWVTRGAFIDAARTCS
58

S. epidermidis

C. jeikeium

P. aeruginosa

1T-50

P. aeruginosa

HSDEPIPNILFKSDSVH
59

1T-51

S. aureus

GKPKRMPAEFIDGYGQALLAGA
60

P. aeruginosa

1T-52

S. aureus

DEYPAKLPLSDKGATEPRRH
61

C. xerosis

P. aeruginosa

1T-53

P. aeruginosa

SDILAEMFEKGELQTLVKDAAAKANA
62

1T-54

S. epidermidis

RWVSCNPSWRIQ
63

C. xerosis

C. striatum

P. aeruginosa

1T-55

C. xerosis

NHKTLKEWKAKWGPEAVESWATLLG
64

P. aeruginosa

1T-56

C. xerosis

LALIGAGIWMIRKG
65

P. aeruginosa

1T-57

P. aeruginosa

RLEYRRLETQVEENPESGRRPMRG
66

1T-58

P. aeruginosa

CDDLHALERAGKLDALLSA
67

1T-59

S. aureus

AVGNNLGKDNDSGHRGKKHRKHKHR
68

S. epidermidis

P. aeruginosa

1T-60

S. aureus

YLTSLGLDAAEQAQGLLTILKG
69

S. epidermidis

C. jeikeium

C. striatum

P. aeruginosa

1T-61

P. aeruginosa

HATLLPAVREAISRQLLPALVPRG
70

1T-62

S. epidermidis

GCKGCAQRDPCAEPEPYFRLR
71

P. aeruginosa

1T-63

S. aureus

EPLILKELVRNLFLFCYARALR
72

S. epidermidis

C. jeikeium

C. xerosis

C. striatum

P. aeruginosa

1T-64

S. aureus

QTVHHIHMHVLGQRQMHWPPG
73

S. epidermidis

C. jeikeium

C. xerosis

C. striatum

P. aeruginosa

1T-65

S. mutans

HARAAVGVAELPRGAAVEVELIAAVRP
74

S. aureus

S. epidermidis

C. jeikeium

C. xerosis

C. striatum

P. aeruginosa

1T-66

S. mutans

DTDCLSRAYAQRIDELDKQYAGIDKPL
75

S. aureus

S. epidermidis

C. jeikeium

C. xerosis

C. striatum

P. aeruginosa

1T-67

S. aureus

GQRQRLTCGRVSGCSEGPSREAAR
76

S. epidermidis

C. jeikeium

C. xerosis

C. striatum

P. aeruginosa

1T-68

S. mutans

GGTKEIVYQRG
77

S. aureus

C. jeikeium

C. xerosis

C. striatum

P. aeruginosa

1T-69

S. mutans

ILSQEADRKKLF
78

P. aeruginosa

1T-70

S. aureus

NRQAQGERAHGEQQG
79

C. jeikeium

P. aeruginosa

1T-71

P. aeruginosa

KIDTNQWPPNKEG
80

1T-72

P. aeruginosa

EPTDGVACKER
81

1T-73

S. pneumoniae

GWWEELLHETILSKFKITKALELPIQL
82

1T-74

S. pneumoniae

DIDWGRKISCAAGVAYGAIDGCATTV
83

1T-75

S. pneumoniae

GVARGLQLGIKTRTQWGAATGAA
84

1T-76

S. pneumoniae

EMRLSKFFRDFILWRKK
85

1T-77

S. pneumoniae

EMRISRIILDFLFLRKK
86

1T-78

S. pneumoniae

FFKTIFVLILGALGVAAGLYIEKNYIDK
87

1T-79

S. pneumoniae

FGTPWSITNFWKKNFNDRPDFDSDRRRY
88

1T-80

S. pneumoniae

GGNLGPGFGVIIP
89

1T-81

S. pneumoniae

AIATGLDIVDGKFDGYLWA
90

1T-82

S. pneumoniae

FGVGVGIALFMAGYAIGKDLRKKFGKSC
91

1T-83

S. pneumoniae

QKPRKNETFIGYIQRYDIDGNGYQSLPC
92

PQN

1T-84

S. pneumoniae

FRKKRYGLSILLWLNAFTNLVNSIHAFY
93

MTLF

1T-85

A. naeslundii

VMASLTWRMRAASASLPTHSRTDA
94

F. nucleatum

P. gingivalis

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-86

S. mitis

HRKNPVLGVGRRHRAHNVA
95

S. oralis

S. salivarious

1T-87

S. mitis

EAVGQDLVDAHHP
96

S. mutans

S. oralis

1T-89

S. mitis

HEDDKRRGMSVEVLGFEVVQHEE
97

S. mutans

1T-90

S. gordonii

RNVIGQVL
98

S. mitis

S. mutans

S. oralis

S. sanguinis

1T-91

S. mitis

TSVRPGAAGAAVPAGAAGAAGAGWR
99

S. mutans

WP

S. oralis

S. sanguinis

1T-92

S. mitis

GQDEGQRRAGVGEGQGVDG
100

S. mutans

1T-93

S. epidermidis

AMRSVNQA
101

S. gordonii

S. mitis

S. mutans

S. oralis

S. sanguinis

1T-94

S. mitis

DQVAHSGDMLVQARRRDS
102

S. mutans

S. oralis

1T-95

S. gordonii

GHLLRVGGRVGGVGGVAGACAQPFGGQ
103

S. mitis

S. mutans

S. oralis

S. sanguinis

1T-96

S. gordonii

VAGACAQPFGGQ
104

S. mitis

S. mutans

S. oralis

S. sanguinis

1T-97

A. naeslundii

GVAERNLDRITVAVAIIWTITIVGLGLV
105

F. nucleatum

AKLG

P. gingivalis

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-98

A. naeslundii

VRSAKAVKALTAAGYTGELVNVSGGM
106

F. nucleatum

KAWLGQ

P. gingivalis

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-99

S. gordonii

MKAWLGQ
107

S. mitis

S. mutans

S. oralis

S. sanguinis

1T-100

S. gordonii

LDPLEPRIAPPGDRSHQGAPACHRDPLR
108

S. mitis

GRSARDAER

S. mutans

1T-101

A. naeslundii

RLRVGRATDLPLTSFAVGVVRNLPDAP
109

P. gingivalis

AH

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. sanguinis

1T-102

A. naeslundii

WKRLWPARILAGHSRRRMRWMVVWR
110

F. nucleatum

YFAAT

P. gingivalis

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-103

A. naeslundii

AQFYEAIITGYALGAGQRIGQL
111

F. nucleatum

P. gingivalis

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. sanguinis

1T-104

S. mitis

RAVAAHLQGRHHGHQVRRQRHGQR
112

1T-105

S. epidermidis

GEGLPPPVLHLPPPRMSGR
113

S. gordonii

S. mitis

S. mutans

S. oralis

1T-106

S. gordonii

DALRRSRSQGRRHR
114

S. mitis

S. mutans

S. oralis

S. salivarious

1T-107

A. naeslundii

SPVPRFTAVGGVSRGSP
115

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-108

S. gordonii

WGPLGPERPLW
116

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-109

A. naeslundii

VTTNVRQGAGS
117

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-110

A. naeslundii

LAAKTAVCVGRAFM
118

P. gingivalis

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. sanguinis

1T-111

A. naeslundii

GRLSRREEDPATSIILLRGAYRMAVF
119

F. nucleatum

P. gingivalis

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-112

S. gordonii

SDNDGKLILGTSQ
120

1T-113

S. mitis

HGAHQRTGQRLHHHRGRTVSGCRQNP
121

VAGVDPDEHR

1T-114

A. naeslundii

RQAPGPGLVTITAACSAPGSRSR
122

P. gingivalis

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. sanguinis

1T-115

A. naeslundii

LLIERFSNHH
123

F. nucleatum

P. gingivalis

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-116

A. naeslundii

MILHRRRDR
124

P. gingivalis

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-117

S. mutans

GPGVVGPAPFSRLPAHALNL
125

1T-118

A. naeslundii

TASPPAPSDQGLRTAFPATLLIALAALA
126

F. nucleatum

RISR

P. gingivalis

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-119

S. gordonii

SPATQKAPTRAQPSRAPVQDCGDGRPT
127

S. mitis

AAPDDVERLSPR

S. mutans

S. oralis

1T-120

A. naeslundii

DVRDRVDLAGADLCAAHATR
128

F. nucleatum

P. gingivalis

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-121

S. gordonii

FAKETGFGIGGAQEGWWIIADIYGPNPF
129

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-122

S. mitis

GAIPDPVTHRVDWEEDHQTRPSR
130

1T-123

S. gordonii

LVRRNAVAGRSDGLAGAEQLDLVRLQ
131

GVL

1T-124

S. mitis

LFDERNKIA
132

S. mutans

S. oralis

1T-125

S. epidermidis

DAITGGNPPLSDTDGLRP
133

S. gordonii

S. mutans

S. oralis

1T-126

S. gordonii

QGLARPVLRRIPL
134

S. mitis

S. mutans

1T-127

A. naeslundii

YDPVPKRKNKNSEGKREE
135

F. nucleatum

P. gingivalis

T. denticola

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-128

A. naeslundii

SGSAIRMLEIATKMLKR
136

P. gingivalis

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-129

A. naeslundii

YDKYIKYLSIQPPFIVYFI
137

P. gingivalis

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-130

A. naeslundii

QKIIDMSKFLFSLILFIMIVVIYIGKSIGG
138

F. nucleatum

YSAIVSSIMLELDTVLYNKKIFFIYK

P. gingivalis

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-131

A. naeslundii

DEVWKMLGI
139

F. nucleatum

P. gingivalis

T. denticola

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-132

A. naeslundii

YSKKLFEYFYFIIFILIRYLIFYKIIQNKNY
140

F. nucleatum

YINNIAYN

P. gingivalis

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-133

A. naeslundii

YFIKDDNEALSKDWEVIGNDLKGTIDK
141

P. gingivalis

YGKEFKVR

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-134

A. naeslundii

SRLVREIKKKCRKS
142

F. nucleatum

P. gingivalis

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-135

A. naeslundii

FESLLPQATKKIVNNKGSKINKIF
143

P. gingivalis

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-136

A. naeslundii

ELLTQIRLALLYSVNEW
144

F. nucleatum

P. gingivalis

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-137

A. naeslundii

PLNFYRAVKENRLPLSEKNINDFTNIKL
145

F. nucleatum

KVSPKLINLLQESSIFYNFSPKKRNTN

P. gingivalis

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-138

A. naeslundii

YPNEYCIFLENLSLEELKEIKAINGETLN
146

F. nucleatum

LEEIINERKNLKD

P. gingivalis

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-139

A. naeslundii

AVAGAAVGALLGNDARSTAVGAAIGG
147

S. gordonii

ALGAGAGELTKNK

S. mitis

S. mutans

S. oralis

1T-140

A. naeslundii

IKGTIAFVGEDYVEIRVDKGVKLTFRKS
148

F. nucleatum

AIANVINNNQQ

P. gingivalis

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-141

F. nucleatum

KKFIILLFILVQGLIFSATKTLSDIIAL
149

P. gingivalis

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. sanguinis

1T-142

A. naeslundii

FTQGIKRIVLKRLKED
150

F. nucleatum

P. gingivalis

T. denticola

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-143

A. naeslundii

MPKRHYYKLEAKALQFGLPFAYSPIQL
151

F. nucleatum

LK

P. gingivalis

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-144

A. naeslundii

IIELHPKSWTQDWRCSFL
152

F. nucleatum

P. gingivalis

T. denticola

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-145

S. mitis

VEAGKRNISLENIEKISKGLGISISELFKY
153

S. mutans

IEEGEDKIG

S. oralis

1T-146

A. naeslundii

RNSADNQTKIDKIRIDISLWDEHLNIVK
154

F. nucleatum

QGK

P. gingivalis

T. denticola

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-147

A. naeslundii

GVENRRFYERDVSKVSMMTSEAVAPR
155

F. nucleatum

GGSK

P. gingivalis

T. denticola

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-148

A. naeslundii

IVELDDTTILERALSMLGEANA
156

F. nucleatum

P. gingivalis

T. denticola

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-149

A. naeslundii

SVRAVKPIDETVARHFPGDFIVN
157

F. nucleatum

P. gingivalis

T. denticola

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-150

A. naeslundii

YINRRLKKAFSDADIKEAPAEFYEELRR
158

F. nucleatum

VQYV

P. gingivalis

T. denticola

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-151

A. naeslundii

SVRAVKPIDEIVAWHFPGDFIVN
159

F. nucleatum

P. gingivalis

T. denticola

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-152

A. naeslundii

YVSADESAYNHIVTDDIPLADRRIEAVQQ
160

F. nucleatum

P. gingivalis

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-153

A. naeslundii

YIACPGYFY
161

F. nucleatum

P. gingivalis

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-154

P. gingivalis

YFSFLEIVGMARR
162

1T-155

A. naeslundii

LKLAFGVYPFQAMSQSDTAVSERNVL
163

F. nucleatum

WR

P. gingivalis

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-156

A. naeslundii

GRFQISIRGEEKSKVKVQGKGTFTDRNTT
164

F. nucleatum

P. gingivalis

T. denticola

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-157

A. naeslundii

RRFRKTTENREKSKNKKAVLGLSTTST
165

F. nucleatum

ASY

P. gingivalis

T. denticola

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-158

A. naeslundii

WENKPSPLGSIKKLQGLVYRLIGYRHF
166

F. nucleatum

WV

P. gingivalis

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-159

P. gingivalis

IFSLHHFALICSEMGTFAVSKRAKYKWE
167

VL

1T-160

A. naeslundii

AQYKYINKLLN
168

F. nucleatum

P. gingivalis

T. denticola

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-161

A. naeslundii

NKVLQVEVMWDGSVVGRPAGVISIKSS
169

F. nucleatum

KKG

P. gingivalis

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-162

A. naeslundii

QKAKEESDRKAAVSYNGFHRVNVVSIPK
170

F. nucleatum

P. gingivalis

T. denticola

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-163

A. naeslundii

MENILIYIPMVLSPFGSGILLFLGKDRRY
171

F. nucleatum

ML

P. gingivalis

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-164

A. naeslundii

KKSHSQGKRKLKDLNSAYKIDNQLHYA
172

F. nucleatum

LR

P. gingivalis

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-165

A. naeslundii

CYDSFDFSIFVTFANRMKLSVGS
173

F. nucleatum

P. gingivalis

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-166

A. naeslundii

AQSAGQIKRKSKVRIHV
174

F. nucleatum

P. gingivalis

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-167

A. naeslundii

SRMSEHSPAGLVFEVGPMDKGSFIILDS
175

F. nucleatum

YHPTVKK

P. gingivalis

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-168

A. naeslundii

ELHRIMSTEKIGAVTKMNFDTAPIMSILP
176

F. nucleatum

IDIYPKEVGIGS

P. gingivalis

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-169

A. naeslundii

FARVRRLHQNRILTQPLTNLKYCLRQPI
177

F. nucleatum

YSD

P. gingivalis

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-170

P. gingivalis

AYGKVFSMDIMLSENDKLIVLRISHHSA
178

WH

1T-171

A. naeslundii

SVRAVKPIDKTVARHFPGDFIVN
179

F. nucleatum

P. gingivalis

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-172

A. naeslundii

FEGLKNLLGDDII
180

F. nucleatum

P. gingivalis

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-173

A. naeslundii

LFRKEDQEHVLL
181

F. nucleatum

P. gingivalis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-174

A. naeslundii

SGGSDTDGSSSGEPGSHSGDL
182

F. nucleatum

P. gingivalis

T. denticola

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-175

A. naeslundii

GEPGSHSGDL
183

F. nucleatum

P. gingivalis

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-176

A. naeslundii

PVGDIMSGFLRGANQPRFLLDHISFGS
184

P. gingivalis

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-177

P. gingivalis

GTNVPTQILGYSREERFDYEPAPEQR
185

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-178

A. naeslundii

LLASHPERLSLGVFFVYRVLHLLLENT
186

F. nucleatum

P. gingivalis

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-179

A. naeslundii

TCYPLIQRKTDRAYEA
187

F. nucleatum

P. gingivalis

T. denticola

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-180

A. naeslundii

VVFGGGDRLV
188

F. nucleatum

P. gingivalis

T. denticola

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-181

A. naeslundii

YGKESDP
189

F. nucleatum

P. gingivalis

T. denticola

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-182

A. naeslundii

LTASICRQWNDNSTPYQR
190

F. nucleatum

P. gingivalis

T. denticola

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-183

A. naeslundii

PLRSFVAEKAEHAFRVVRIADFDFGHS
191

F. nucleatum

P. gingivalis

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-184

A. naeslundii

ALLVLNLLLMQFFFGKNM
192

F. nucleatum

P. gingivalis

T. denticola

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-185

A. naeslundii

HYHFLLEFGFHKGDYLE
193

F. nucleatum

P. gingivalis

T. denticola

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-188

S. sanguinis

HRKDVYKK
194

1T-190

A. naeslundii

IQIIVNAFVEKDKTGAVIEVLYASNNHE
195

F. nucleatum

KVKAKYEELVAIS

P. gingivalis

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-192

S. sanguinis

ILVLLALQVELDSKFQY
196

1T-193

S. sanguinis

LMIFDKHANLKYKYGNRSFGVEAIM
197

1T-195

S. mutans

AASGFTYCASNGVWHPY
198

1T-196

F. nucleatum

KPEKEKLDTNTLMKVVNKALSLFDRLL
199

S. sanguinis

IKFGA

1T-197

A. naeslundii

TEILNFLITVCADRENWKIKHGLSDSVL
200

F. nucleatum

LIFFARFTGAEYW

P. gingivalis

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-198

P. gingivalis

MPVSKKRYMLSSAYATALGICYGQVAT
201

S. epidermidis

DEKESEITAIPDLLDYLSVEEYLL

S. gordonii

S. mitis

S. mutans

S. oralis

S. sanguinis

1T-199

S. sanguinis

RAGRIKKLSQKEAEPFEN
202

1T-200

A. naeslundii

MRFKRFDRDYALSGDNVFEVLTASCDV
203

F. nucleatum

IERNLSYREMCGLMQ

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-201

S. sanguinis

KRKHENVIVAEEMRVIKN
204

1T-202

A. naeslundii

LCRLEKLCKQFLRQDKVVTYYLMLPYK
205

F. nucleatum

RAIEAFYQELKERS

P. gingivalis

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-203

A. naeslundii

YPFCLATVDHLPEGLSVTDYERVQRLV
206

F. nucleatum

SQFLLNKEER

P. gingivalis

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-207

F. nucleatum

SPLEKYGTGSMTALTFLLGCCLLVLSKK
207

S. sanguinis

SR

1T-208
Unanalyzed
KRKRWAILTLFLAGLGAVGIVLATF
208

1T-215

S. sanguinis

VCFKDISVFLSPFRGQEVLFCGKAKHSL
209

IYVIGT

1T-216

S. sanguinis

FFLNVIAIRIPHF
210

1T-217

F. nucleatum

MLSNVLSRSVVSPNVDIPNSMVILSPLLI
211

S. sanguinis

SISNYH

1T-218

F. nucleatum

KLIFAALGLVFLLIGLRDSRSK
212

S. sanguinis

1T-219

S. sanguinis

RNINVSATFITEKSLV
213

1T-221

A. naeslundii

DIGRIIGKKGRTITAIRSIVYSVPTQGKK
214

F. nucleatum

VRLVIDEK

P. gingivalis

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-222

F. nucleatum

RIEASLISAIMFSMFNAIVKFLQK
215

S. sanguinis

1T-223

A. naeslundii

NQKMEINSMTSEKEKMLAGHFHNEAN
216

F. nucleatum

FAVIFKYSLFYNFF

P. gingivalis

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-225

A. naeslundii

RRSLGNSASFAEWIEYIRYLHYIIRVQFI
217

F. nucleatum

HFFSKNKKI

P. gingivalis

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-226

A. naeslundii

KLQEKQIDRNFERVSGYSTYRAVQAAK
218

F. nucleatum

AKEKGFISLEN

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-228

A. naeslundii

IFKLFEEHLLYLLDAFYYSKIFRRLKQGL
219

F. nucleatum

YRRKEQPYTQDLFRM

P. gingivalis

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-230

A. naeslundii

EFLEKFKVLKQPRKANNISKNRVAMIFL
220

F. nucleatum

TIHKSRGFLSSPY

P. gingivalis

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-233

A. naeslundii

TDQELEHLIVTELESKRLDFTYSKDITEF
221

P. gingivalis

FDEAFPEYDQNY

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-234

A. naeslundii

DNFYLILKMEERGKSKKTSQTRGFRAFF
222

F. nucleatum

DIIRKKIKKEDGK

P. gingivalis

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-237

S. sanguinis

EDPVPNHFTLRRNKKEKPSKS
223

1T-238

A. naeslundii

IFNRRKFFQYFGLSKEAMVEHIQPFILDI
224

F. nucleatum

WQIHLF

P. gingivalis

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-239

A. naeslundii

ADDLLNKRLTDLIMENAETVKTIDLDN
225

S. gordonii

SD

S. mitis

S. mutans

S. oralis

S. sanguinis

1T-240

A. naeslundii

VILGNGISNIAQTLGQLPNIAWVWIYMV
226

F. nucleatum

LIAALLEESNVC

P. gingivalis

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-242

F. nucleatum

KQVQNTTLIICGTVLLGILFKSYLKSQKSV
227

S. sanguinis

1T-243

A. naeslundii

SENIARFAAAFENEQVVSYARWFRRSW
228

P. gingivalis

RGSGSSSRF

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-248

S. sanguinis

IGGALNSCG
229

1T-249

F. nucleatum

VFSVLKHTTWPTRKQSWHDFISILEYSA
230

S. sanguinis

FFALVIFIFDKLLTLGLAELLKRF

1T-250

S. mitis

LVQGDTILIENHVGTPVKDDGKDCLIIR
231

S. mutans

EADVLAVVND

S. oralis

1T-252

F. nucleatum

MKKNLKRFYALVLGFIIGCLFVSILIFIGY
232

S. sanguinis

1T-253

A. naeslundii

KTKESLTQQEKKFLKDYDRKSLHHFRD
233

F. nucleatum

ILTYCFILDKLTNK

P. gingivalis

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-256

S. sanguinis

KGKSLMPLLKQINQWGKLYL
234

1T-257

A. naeslundii

IILAKAADLAEIERIISEDPFKINEIANYDI
235

F. nucleatum

IEFCPTKSSKAFEKVLK

P. gingivalis

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-258

A. naeslundii

TINIDDKVLDYLKKINSKAITIDLIGCAS
236

F. nucleatum

P. gingivalis

T. denticola

S. mitis

S. mutans

S. oralis

1T-259

F. nucleatum

EKLKKILLKLAVCGKAWYTL
237

P. gingivalis

T. denticola

S. mitis

S. mutans

S. oralis

S. sanguinis

1T-260

A. naeslundii

NILYFIHDENQWEPQKAEIFRGSIKHCA
238

P. gingivalis

WLSS

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. sanguinis

1T-261

F. nucleatum

SFEKNKIENNLKIAQAYIYIKPKPRICQA
239

S. mutans

S. oralis

S. sanguinis

1T-262

A. naeslundii

LSLPLIVLTKSI
240

F. nucleatum

P. gingivalis

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-263

A. naeslundii

FIAVSFTGNPATFKLVIGCKADN
241

F. nucleatum

P. gingivalis

S. epidermidis

S. gordonii

S. mitis

S. oralis

S. salivarious

S. sanguinis

1T-264

S. sanguinis

LEGKFYMAEDFDKTPECFKDYV
242

1T-265

A. naeslundii

GMFENLLMINFQIMNDLKIEIVVKDRIC
243

F. nucleatum

AV

P. gingivalis

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-266

S. sanguinis

RAGTWLVVDEIR
244

1T-267

A. naeslundii

RIKEERKNRSYKFFIWRLFDEKTGFI
245

F. nucleatum

P. gingivalis

T. denticola

S. mitis

S. mutans

S. oralis

S. sanguinis

1T-268

F. nucleatum

PITPKKEKCGLGTYAPKNPVFSKSRV
246

S. mutans

S. oralis

S. sanguinis

1T-269

F. nucleatum

PLYVAAVEKINTAKKH
247

S. mutans

S. oralis

S. sanguinis

1T-270

F. nucleatum

VHEFDIQKILQNR
248

S. mutans

S. oralis

S. sanguinis

1T-271

A. naeslundii

FLIQKFLLIKTFPPYRKKYVVIVSQTGTA
249

F. nucleatum

P. gingivalis

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-272

F. nucleatum

QLAPIDKQLKAVKKIAFYESESTAAKAV
250

S. mutans

TVA

S. oralis

S. sanguinis

1T-273

F. nucleatum

YNEPNYKWLESYKIYKQRCEDRTGMY
251

P. gingivalis

YTEET

T. denticola

S. mitis

S. mutans

S. oralis

1T-274

F. nucleatum

ETTTEINAIKLHRIKQRSPQGTRRVN
252

S. mutans

S. oralis

S. sanguinis

1T-275

A. naeslundii

QVLKNFSISRRYKINNPFFKILLFIQLRTL
253

F. nucleatum

P. gingivalis

T. denticola

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-276

A. naeslundii

ILTLLILGSIGFFILKIKLKLGRF
254

F. nucleatum

P. gingivalis

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. sanguinis

1T-277

A. naeslundii

IYYMRFVNKPLEKTFFKI
255

F. nucleatum

P. gingivalis

T. denticola

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-278

A. naeslundii

SINSSAGIQPHCLSSSFVLRTKHCFY
256

F. nucleatum

P. gingivalis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-279

A. naeslundii

FVLRTKHCFY
257

F. nucleatum

P. gingivalis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-280

A. naeslundii

TNNKNKVIIKAIKFKNKDFINLDLFIYRR
258

F. nucleatum

P. gingivalis

T. denticola

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-281

A. naeslundii

KYEKLTKENLFIRNSGNMCVFIYFLFFG
259

F. nucleatum

P. gingivalis

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-282

F. nucleatum

ISLVFPAYT
260

P. gingivalis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-283

A. naeslundii

LCTKLEDKQRGRIPAELFIISPIKILERND
261

F. nucleatum

AL

P. gingivalis

T. denticola

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-284

A. naeslundii

FQYYFSLKRV
262

F. nucleatum

P. gingivalis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-285

A. naeslundii

FFPYYLADFYKQLKFLNEYQTKNKDKV
263

F. nucleatum

VEFK

P. gingivalis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-286

S. sanguinis

LGFFNNKADLVKADTERDNRMSSLKIK
264

DL

1T-287

P. gingivalis

KGYPLPFQYRLNNH
265

T. denticola

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-288

F. nucleatum

RWVGGEPSADIYLSAKDTKT
266

S. gordonii

S. salivarious

S. sanguinis

1T-289

F. nucleatum

EPSADIYLSAKDTKT
267

P. gingivalis

S. gordonii

S. mitis

S. mutans

S. oralis

S. sanguinis

1T-290

A. naeslundii

IINQLNLILLRLMEILIL
268

F. nucleatum

P. gingivalis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-291

A. naeslundii

DMKIIKLYIKILSFLFIKYCNKKLNSVKL
269

F. nucleatum

KA

P. gingivalis

T. denticola

S. mitis

S. mutans

S. oralis

1T-292

A. naeslundii

IINQLNLILLRLMEILIL
270

F. nucleatum

P. gingivalis

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-293

A. naeslundii

HVEDCFLLSNARTTAIHGRANPARGEPR
271

F. nucleatum

TRSE

P. gingivalis

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-294

T. denticola

YDKIADGVFKIGKRGVL
272

1T-295

S. mitis

KYKLKKIIL
273

S. salivarious

S. sanguinis

1T-296

A. naeslundii

EYSQQSFKAKPCSERGVLSP
274

F. nucleatum

P. gingivalis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-297

A. naeslundii

RSLRLNNALTKLPKLWYNRIKEAFYAY
275

F. nucleatum

NDYDK

T. denticola

S. mitis

S. mutans

S. oralis

1T-298

A. naeslundii

ILNKKPKLPLWKLGKNYFRRFYVLPTFLA
276

F. nucleatum

P. gingivalis

T. denticola

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-299

A. naeslundii

SMLTSFLRSKNTRSLKMYKDVHF
277

F. nucleatum

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-300

A. naeslundii

PLIISKAQIKMSGDILGSCFKLFYLRPFF
278

F. nucleatum

P. gingivalis

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-301

F. nucleatum

SKLPRVLDASLKL
279

S. gordonii

S. sanguinis

1T-302

A. naeslundii

IIIILPKIYLVCKTV
280

P. gingivalis

S. epidermidis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-303

A. naeslundii

LDYENMDCKKRIRI
281

F. nucleatum

P. gingivalis

S. gordonii

S. mitis

S. mutans

S. oralis

S. salivarious

S. sanguinis

1T-304

P. gingivalis

STAGEASRRTASEASRRTAAKLRG
282

TT-305

F. nucleatum

ARNALNMRDVPVDAAIIGIIDGMDEE
283

TT-306

F. nucleatum

KILNEAEGKLLKVIEKNGEIDIEEI
284

TT-307

F. nucleatum

NGDKKAKEELDKWDEVIKELNIQF
285

TT-308

F. nucleatum

GLVIIPNLIALIILFSQVRQQTKDYFSNPK
286

LSSR

TT-309

F. nucleatum

EPLPLTKYDKKDTEMKKVFKEILAGKV
287

GYEKEEE

TT-310

F. nucleatum

TKLKKNNKLLSAKKENTLHTKDK
288

TT-311

S. mutans

AIFDAMHNL
289

S. sobrinus

PVCFBP2461

P. fluorescens

DLys-Dorn-Gly-DThr-Thr-Gln-Gly-DSer-
290

cDOrn

CHA0

P. fluorescens

Asp-DOrn-Lys-c(Thr-Ala-Ala-DOrn-Lys)
291

CFBP2461

P. putida

Asp-Lys-DAsp-Ser-DThr-DAla-Thr-DLys-
292

cOrn

NCPPB2192

P. tolaasii

DSer-Lys-Ser-DSer-Thr-DSer-Orn-Thr-
293

DSer-cDOrn

PyC-E

P. aeruginosa

DSer-Arg-DSer-Orn-c(Lys-Orn-Thr-Thr)
294

PyR

P. aeruginosa

DSer-Dab-Orn-DGln-Gln-DOrn-Gly
295

PyPaTII

P. aeruginosa

DSer-DOrn-Orn-Gly-DThr-Ser-cOrn
296

Py Pap

P. aptata

DAla-Lys-Thr-DSer-Orm-cOrn
297

Py Pau

P. aureofaciens

DSer-DOrn-Gly-DThr-Thr-Gln-Gly-DSer-
298

cDOrn

Ps

P. fluorescens

Lys-DAsp-Ala-DThr-Ala-cDOrn
299

Py I-III

P. fluorescens

Asn-DOrn-Lys-c(Thr-DAla-DAla-DOrn-
300

Lys)

Py Gm

P. fluorescens

DAla-Lys-Gly-Gly-Asp-DGln-DSer-Ala-
301

DAla-DAla-Ala-cOrn

Py Pf 12

P. fluorescens

DSer-Lys-Gly-Orn-DSer-Ser-Gly-c(Lys-
302

DOrn-Glu-Ser)

Py Pf

P. fluorescens

c(DSer-Dab)-Gly-Ser-Asp-Ala-Gly-DAla-
303

2798

Gly-cOrn

Py Pf

P. fluorescens

Ser-Lys-Gly-Orn-c(Lys-DOrn-Ser)
304

13525

Py Pf

P. fluorescens

DAla-DLys-Gly-Gly-Asp-DGln-Dab-Ser-
305

17400

DAla-cOrn

Py 51W

P. fluorescens

DAla-DLys-Gly-Gly-DAsp-DGln-DSer-Ala-
306

Gly-DThr-cOrn

Py 9AW

P. fluorescens

DSer-Lys-His-DThr-Ser-cOrn
307

Ps A225

P. fluorescens

DSer-DAla-DOrn-Gly-c(DSer-DAsp-DSer-
308

DThr)

Py Pf 1.3

P. fluorescens

DAla-DLys-Gly-Gly-Asp-c(DGln-Dab)-Gly-
309

Ser-cOrn

Py Pf

P. fluorescens

DSer-Lys-Gly-Orn-Ser-DSer-Gly-c(Lys-
310

18.1

DOrn-Ser)

Py Pf

P. fluorescens

DSer-DOrn-Ala-Gly-DThr-Ala-cOrn
311

PL7

Py Pf

P. fluorescens

DLys-DOrn-Ala-Gly-DThr-Ser-cOrn
312

PL8

Py Pf

P. fluorescens

DSer-DSer-Orn-DSer-DSer-c(DSer-Orn-
313

BTP7

Lys-Lys)

Ps 589A

P. putida

Asp-Lys-Asp-DSer-Thr-DAla-DGlu-DSer-
314

cOrn

Py Pp 1,2

P. putida

Ser-Thr-DSer-Orn-Asp-DGln-Dab-Ser-
315

DThr-cOrn

Py Pp

P. putida

Asp-DOrn-DDab-Thr-Gly-DSer-Ser-Asp-
316

C2,3

Thr

Py G4R

P. putida

Asp-Orn-DAsp-Dab-Gly-Ser-cOrn
317

Py

P. putida

Asp-DOrn-DDab-Thr-Gly-DSer-DSer-Thr-
318

PpBTP16

Asp

Py

P. putida

DSer-DAla-DOrn-Gly-DAla-DAsp-c(DSer-
319

Pp39167

DThr)

iPy Pp

P. putida

Asp-Ala-Asp-DOrn-Ser-cOrn
320

BTP1

Py

P. tolaasii

DSer-Lys-Ser-DSer-Thr-DSer-Orn-Thr-
321

PT2192

DSer-Orn

Ps 7SR1

Pseudomonas spp.
DSer-DAsp-DThr-c(DSer-D-Orn-Ala-Gly-
322

DSer)

Ps A214

Pseudomonas spp.
DSer-DAla-Gly-DSer-DAla-DAsp-DThr-
323

DOrn

Azoverdin

Pseudomonas spp.
Hse-DHse-Dab-DOrn-DSer-Orn
324

A. macrocytogenes

PF-S024

Corynebacteria

SKRGRKRKDRRKKKANHGKRPNS
325

spp.

PF-001

S. epidermidis

MNNWIIVAQLSVTVINEIIDIMKEKQKG
326

M. luteus

GK

P. mirabilis

E. coli

P. aeruginosa

C. albicans

MRSA

E. faecalis

C. jeikeium

PF-002

S. epidermidis

NDDAQ
327

P. mirabilis

C. albicans

C. jeikeium

C. jejuni

PF-003

S. epidermidis

MNNWIKVAQISVTVINEVIDIMKEKQN
328

M. luteus

GGK

P. mirabilis

C. albicans

MRSA

C. jeikeium

PF-004

S. epidermidis

ARLSKAIIIAVIVVYHLDVRGLF
329

B. subtilis

B. fragilis

E. coli

P. aeruginosa

C. albicans

S. pneumoniae

E. faecalis

C. jeikeium

PF-005

S. epidermidis

MESIFKIKLMNGICRSENMNMKKKNKG
330

E. coli

EKI

MRSA

S. pneumoniae

E. faecalis

PF-006

S. epidermidis

MGIIAGIIKFIKGLIEKFTGK
331

M. luteus

E. coli

P. aeruginosa

MRSA

E. faecalis

C. jeikeium

C. jejuni

PF-007

S. epidermidis

MGIIAGIIKVIKSLIEQFTGK
332

M. luteus

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

PF-008

S. epidermidis

MIEIGSIAYLNGGSKKYNHILNQENR
333

M. luteus

MRSA

C. jejuni

PF-009

M. luteus

SKKYNHILNQENR
334

P. mirabilis

C. albicans

PF-010

S. epidermidis

MDIDVNKLLQAFVYFKSFEKLRHNNS
335

M. luteus

E. coli

C. albicans

PF-011

M. luteus

MFCYYKQHKGDNFSIEEVKNIIADNEM
336

E. coli

KVN

P. aeruginosa

S. pneumoniae

C. jeikeium

PF-012

S. epidermidis

WRGPNTEAGGKSANNIVQVGGAPT
337

M. luteus

P. mirabilis

E. coli

P. aeruginosa

MRSA

S. pneumoniae

C. jeikeium

C. jejuni

PF-013

M. luteus

LIQKGLNQTFIVVIRLNNFIKKS
338

P. mirabilis

E. coli

P. aeruginosa

MRSA

S. pneumoniae

C. jeikeium

C. jejuni

PF-014

E. coli

HPTDNKHN
339

C. jeikeium

PF-015

E. faecalis

SIDKRNLYNLKYYE
340

C. jeikeium

PF-016

S. epidermidis

RKQYDDLSFNFLY
341

E. faecalis

C. jeikeium

PF-017

E. coli

ESIIE
342

PF-018

E. coli

YYKTYFKEV
343

C. jeikeium

PF-020

S. epidermidis

MKIILLLFLIFGFIVVVTLKSEHQLTLFSI
344

M. luteus

C. albicans

MRSA

S. pneumoniae

E. faecalis

PF-021

S. epidermidis

FSLNFSKQKYVTVN
345

M. luteus

P. mirabilis

E. coli

C. albicans

E. faecalis

C. jeikeium

PF-022

M. luteus

MINELKNKNSGIMNNYVVTKESKL
346

P. mirabilis

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

C. jejuni

PF-023

M. luteus

MTKNTIISLENEKTQINDSENESSDLRKAK
347

C. jeikeium

PF-024

M. luteus

DLRKAK
348

C. albicans

MRSA

E. faecalis

C. jeikeium

PF-025

S. epidermidis

LLIIFRLWLELKWKNKK
349

M. luteus

P. mirabilis

E. coli

P. aeruginosa

MRSA

E. faecalis

C. jejuni

PF-026

S. epidermidis

SIHFIN
350

M. luteus

P. mirabilis

C. albicans

MRSA

E. faecalis

C. jeikeium

PF-027

M. luteus

HNARKYLEFISQKIDGDKLTKEDSL
351

MRSA

E. faecalis

C. jejuni

PF-028

S. epidermidis

ALDCSEQSVILWYETILDKIVGVIK
352

M. luteus

MRSA

PF-029

S. epidermidis

NSTNE
353

M. luteus

C. albicans

C. jejuni

PF-030

S. epidermidis

MTCHQAPTTTHQSNMA
354

M. luteus

P. mirabilis

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

C. jejuni

PF-031

M. luteus

MPHHSTTSSRIVVPAHQSNMASTPNLSI
355

C. albicans

TP

PF-033

S. epidermidis

MFIFKTTSKSHFHNNVKSLECIKIPINKNR
356

M. luteus

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

PF-034

M. luteus

EPKKKHFPKMESASSEP
357

PF-035

S. epidermidis

SFYESY
358

M. luteus

E. coli

C. albicans

MRSA

C. jeikeium

C. jejuni

PF-036

S. epidermidis

ILNRLSRIVSNEVTSLIYSLK
359

M. luteus

P. mirabilis

E. coli

C. albicans

MRSA

S. pneumoniae

C. jejuni

PF-037

S. epidermidis

MTKKRRYDTTEFGLAHSMTAKITLHQA
360

M. luteus

LYK

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

PF-038

M. luteus

MAYKDEGKETKFAVKGYKD
361

PF-039

P. mirabilis

MLEEKNKSL
362

C. jeikeium

PF-040

S. epidermidis

MIHLTKQNTMEALHFIKQFYDMFFILNF
363

M. luteus

NV

P. mirabilis

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

C. jejuni

PF-041
MRSA
ELLVILPGFI
364

PF-042

S. epidermidis

LLLSYFRYTGALLQSLF
365

M. luteus

P. mirabilis

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

PF-043

M. luteus

MIKNETAYQMNELLVIRSAYAK
366

C. jejuni

PF-044

S. epidermidis

KLKKYIHKPD
367

M. luteus

MRSA

C. jeikeium

PF-045

S. epidermidis

LDINDYRSTY
368

E. coli

E. faecalis

C. jejuni

PF-046

E. coli

LDFYLTKHLTLML
369

E. faecalis

C. jeikeium

PF-047

S. mutans

NQEPSLQQDKEQKDNKG
370

PF-048

S. epidermidis

LYFAFKKYQERVNQAPNIEY
371

M. luteus

E. coli

MRSA

C. jeikeium

C. jejuni

PF-049

S. epidermidis

AYYLKRREEKGK
372

MRSA

C. jeikeium

C. jejuni

PF-050

S. epidermidis

SYYLKRREEKGK
373

M. luteus

E. coli

C. jeikeium

PF-051

S. epidermidis

RFFNFEIKKSTKVDYVFAHVDLSDV
374

M. luteus

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

PF-052

S. epidermidis

QELINEAVNLLVKSK
375

M. luteus

E. coli

MRSA

E. faecalis

C. jeikeium

C. jejuni

PF-053

S. epidermidis

KLFGQWGPELGSIYILPALIGSIILIAIVTL
376

M. luteus

ILRAMRK

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

PF-054

S. epidermidis

VSISRFIGGGHVFNGNNKRNL
377

E. coli

PF-055

S. mutans

GHVFNGNNKRNL
378

PF-056

S. epidermidis

AEQLFGKQKQRGVDLFLNRLTIILSILFF
379

M. luteus

VLMICISYLGM

P. mirabilis

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

PF-057

S. epidermidis

TMIVISIPRFEEYMKARHKKWM
380

M. luteus

P. mirabilis

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

C. jejuni

PF-058

S. epidermidis

FADQSQDNA
381

M. luteus

E. coli

C. albicans

MRSA

C. jeikeium

C. jejuni

PF-060

E. coli

HSSHL
382

C. albicans

C. jeikeium

PF-061

S. epidermidis

GYNSYKAVQDVKTHSEEQRVTAKK
383

S. pneumoniae

PF-062

S. epidermidis

MKKKRINNDILGRMIYSSSIDKRNLYNL
384

M. luteus

KYYE

E. coli

P. aeruginosa

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

PF-063

S. epidermidis

IAAIIVLVLFQKGLLQIFNWILIQLQ
385

M. luteus

E. coli

P. aeruginosa

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

C. jejuni

PF-064

E. coli

DYYGKE
386

PF-065

M. luteus

LEKNTRDNYFIHAIDRIYINTSKGLFPES
387

E. coli

ELVAWG

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

C. jeikeium

C. jejuni

PF-066

M. luteus

IKGTVKAVDETTVVITVNGHGTELTFEK
388

E. coli

PAIKQVDPS

C. jeikeium

PF-067

S. epidermidis

DLIVKVHICFVVKTASGYCYLNKREAQ
389

M. luteus

AAI

P. mirabilis

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

C. jejuni

PF-068

S. epidermidis

SHLINNFGLSVINPSTPICLNFSPVFNLLT
390

M. luteus

VYGITCN

P. mirabilis

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

PF-069

E. faecalis

FDPVPLKKDKSASKHSHKHNH
391

C. jejuni

PF-070

S. epidermidis

SMVKSEIVDLLNGEDNDD
392

C. jejuni

PF-071

S. epidermidis

HCVIGNVVDIANLLKRRAVYRDIADVIK
393

E. coli

MR

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

C. jejuni

PF-073

S. epidermidis

CPSVTMDACALLQKFDFCNNISHFRHFF
394

M. luteus

AIKQPIER

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

PF-074

S. epidermidis

RDIHPIYFMTKD
395

M. luteus

MRSA

PF-075

M. luteus

FVNSLIMKDLSDNDMRFKYEYYNREKDT
396

E. coli

P. aeruginosa

MRSA

C. jeikeium

PF-076

S. epidermidis

LYQYELLSKEEYLKCTLIINQRRNEQK
397

M. luteus

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

C. jejuni

PF-097

C. jeikeium

QPTQGEQGTRPRRPTPMRGLLI
398

PF-099

S. epidermidis

EIIAYLEGRFANA
399

M. luteus

E. coli

C. jeikeium

PF-101

S. mutans

DPVPERQEQACACHRTAKPGK
400

PF-104
MRSA
ERTAVNDLWI
401

C. jeikeium

PF-123

M. luteus

TTRPQVAEDRQLDDALKETFPASDPISP
402

E. coli

PF-124

S. epidermidis

MADGQIAAIAKLHGVPVATRNIRHFQSF
403

M. luteus

GVELINPWSG

P. mirabilis

E. coli

P. aeruginosa

C. albicans

MRSA

E. faecalis

C. jejuni

PF-125

S. epidermidis

YVVGALVILAVAGLIYSMLRKA
404

M. luteus

P. mirabilis

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jejuni

PF-126

S. epidermidis

FSPEAFGIGAAGVLGSFVTGLLIGWVAS
405

M. luteus

LLRKAK

P. mirabilis

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

C. jejuni

PF-127

S. epidermidis

MLRYLSLFAVGLATGYAWGWIDGLAA
406

M. luteus

SLAV

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

PF-128

M. luteus

GIKVVAARFEEIQFSENFDSIILA
407

P. aeruginosa

E. faecalis

PF-129

S. epidermidis

MKLLARDPWVCAWNDIW
408

MRSA

E. faecalis

C. jeikeium

C. jejuni

PF-130

E. faecalis

LQRSDEESMPRRHEKYS
409

C. jeikeium

C. jejuni

PF-131

S. epidermidis

RRAAARTKGNRR
410

E. coli

MRSA

C. jeikeium

PF-132

S. epidermidis

RPGDGAAEQGRSR
411

C. jeikeium

PF-133

S. epidermidis

GDPTAGQKPVECP
412

C. jeikeium

C. jejuni

M. smegmatis

PF-134

S. epidermidis

GKAMKRQDCSAL
413

C. jeikeium

PF-135

S. epidermidis

PPARPARIPQTPTLHGASLFRQRS
414

M. luteus

E. coli

P. aeruginosa

MRSA

C. jeikeium

M. smegmatis

PF-136

S. epidermidis

LRGRVGRITACGYPP
415

M. luteus

P. mirabilis

E. coli

MRSA

E. faecalis

C. jeikeium

C. jejuni

M. smegmatis

PF-137

S. epidermidis

VLGKGHDLLDVGKTALKSRVFAWLGGS
416

P. mirabilis

S. pneumoniae

C. jeikeium

C. jejuni

PF-138

S. epidermidis

AVHHSLLFR
417

M. luteus

P. mirabilis

E. coli

C. albicans

MRSA

C. jeikeium

C. jejuni

PF-139

S. epidermidis

ALSKPAIQARTLCRRQDPP
418

M. luteus

P. mirabilis

E. coli

P. aeruginosa

C. albicans

S. pneumoniae

E. faecalis

C. jeikeium

C. jejuni

PF-140

S. epidermidis

FHRRVIRASEWALTTRSFSTPLRSAAR
419

M. luteus

P. mirabilis

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

C. jejuni

M. smegmatis

PF-141

S. epidermidis

VVRRFQGM
420

M. luteus

C. albicans

MRSA

C. jeikeium

PF-142

S. mutans

GIDRGCQAAR
421

PF-143

S. epidermidis

LSPRPIIVSRRSRADNNNDWSR
422

MRSA

C. jeikeium

PF-144

S. epidermidis

RSGQPVGRPSRRAWLR
423

M. luteus

E. coli

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

PF-145

S. epidermidis

GIVLTGRAGLVSGACSMALGVGLG
424

M. luteus

P. mirabilis

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

C. jejuni

M. smegmatis

PF-146

S. epidermidis

GCGKRRIITKSASRDTR
425

M. luteus

P. aeruginosa

C. albicans

MRSA

C. jeikeium

PF-147

S. epidermidis

RRPRRRRSGHGQSASAA
426

M. luteus

MRSA

PF-148

S. epidermidis

RRGCTERLRRMARRNAWDLYAEHFY
427

M. luteus

P. mirabilis

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

C. jejuni

M. smegmatis

PF-149

S. epidermidis

GKVSVLTRVPRSLGGAPANQ
428

M. luteus

E. coli

MRSA

C. jeikeium

PF-150

S. epidermidis

EIQAKGTG
429

MRSA

PF-151

S. epidermidis

EEYPARVPLSGEDVTEARRH
430

MRSA

E. faecalis

C. jeikeium

PF-152

S. epidermidis

VGYFIWKDSHSRKG
431

C. albicans

MRSA

E. faecalis

C. jeikeium

PF-153

M. luteus

GILARADCSQIA
432

P. mirabilis

E. coli

MRSA

PF-154

S. mutans

GIKKSKHPSTDDYVVKTTIDSL
433

PF-155

C. jeikeium

GRYGDDSKERQGRAQ
434

PF-156

S. epidermidis

LITAEQPATAPIAGK
435

C. jeikeium

PF-157

S. epidermidis

HTAVVWLAGVSGCVALSHCEPA
436

M. luteus

P. mirabilis

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

C. jejuni

PF-158

S. epidermidis

VRLESRPADLPE
437

PF-159

S. epidermidis

TMAFVEKAQLRVPVGDDLPV
438

PF-160

S. epidermidis

SFHASLTKNEKPIKSTG
439

PF-161

S. epidermidis

RGRALASTATTRPARRRR
440

M. luteus

E. coli

C. jejuni

PF-162

S. epidermidis

GIRRLHSVENLNREISHRMAGLR
441

MRSA

PF-163

S. epidermidis

TSWLRAAERQEIGEPTKTFGEKTTSL
442

PF-164

S. epidermidis

EEVSRALAGIGLGLGCRIG
443

M. luteus

E. coli

C. jeikeium

PF-165
MRSA
GPVSVVASLRRGTTVQRHSQNNHNKG
444

C. jejuni

KP

PF-166

E. coli

SKAVSRKRSI
445

C. jeikeium

PF-167

S. epidermidis

AIEGVIKKGACFKLLRHEMF
446

E. coli

C. albicans

MRSA

C. jeikeium

C. jejuni

PF-168

S. epidermidis

VLPFPAIPLSRRRACVAAPRPRSRQRAS
447

M. luteus

E. coli

C. albicans

MRSA

C. jeikeium

C. jejuni

PF-169

S. epidermidis

APGSAADSPRSRADD
448

E. coli

C. albicans

E. faecalis

C. jeikeium

PF-170

S. epidermidis

RLARGRPTNLCGRRG
449

M. luteus

P. mirabilis

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jejuni

PF-171

S. epidermidis

TQVTLCRTW
450

E. coli

P. aeruginosa

S. pneumoniae

PF-172

S. epidermidis

LTGVRRPWRAPWAGTSGWALR
451

M. luteus

E. coli

P. aeruginosa

MRSA

E. faecalis

C. jejuni

PF-173

S. epidermidis

AGRTAIVQGGG
452

M. luteus

P. mirabilis

E. coli

P. aeruginosa

C. albicans

C. jeikeium

C. jejuni

PF-174

S. epidermidis

RGGDSPARRRPGLAGPGGPG
453

P. aeruginosa

C. jeikeium

PF-175

S. epidermidis

RRRPAGQRPEKASQAMIAA
454

E. faecalis

PF-176

S. epidermidis

RLTSNQFLTRITPFVFAQH
455

M. luteus

P. mirabilis

E. coli

C. albicans

MRSA

E. faecalis

C. jeikeium

PF-177

M. luteus

VTSEPGIAHDIRLLPRAAAFR
456

MRSA

E. faecalis

C. jeikeium

PF-178

S. epidermidis

EVYSSPTNNVAITVQNN
457

M. luteus

B. subtilis

P. mirabilis

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

PF-180

S. epidermidis

SGLGDLGFSSEAK
458

M. luteus

P. aeruginosa

C. albicans

MRSA

E. faecalis

C. jejuni

M. smegmatis

PF-181

S. epidermidis

GIAPRRNEWGAVGGR
459

M. luteus

E. coli

MRSA

E. faecalis

C. jeikeium

PF-182

S. epidermidis

LPATRDKTRVPASVAGAP
460

M. luteus

E. coli

E. faecalis

C. jeikeium

PF-183

S. epidermidis

KPGISVENRQ
461

M. luteus

E. coli

C. albicans

MRSA

E. faecalis

C. jeikeium

PF-184

S. epidermidis

LIADRHIRA
462

M. luteus

E. coli

P. aeruginosa

C. albicans

MRSA

C. jeikeium

PF-185

E. coli

RPAQARQGPGGLIADRHIRA
463

P. aeruginosa

PF-186

S. epidermidis

DADKNLSLERDRFAWRVAAP
464

M. luteus

E. coli

P. aeruginosa

MRSA

C. jeikeium

PF-187

S. epidermidis

EIQKIAKGVSGQVYGPSRQITISKKR
465

M. luteus

E. coli

MRSA

PF-188

S. epidermidis

ARTFAGRLGTRYFGGLMRSTKA
466

M. luteus

E. coli

C. albicans

MRSA

E. faecalis

PF-189

S. epidermidis

GNLTRSREAARATQ
467

M. luteus

C. albicans

MRSA

E. faecalis

C. jejuni

PF-190

S. epidermidis

HFILRKPLLFMIHSLKTGPLDRF
468

M. luteus

P. mirabilis

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

PF-191

E. coli

QFCNFAWLFLASNNAQVSALA
469

P. aeruginosa

C. jejuni

PF-192

S. epidermidis

VEEDEAPPPHY
470

M. luteus

P. aeruginosa

C. albicans

E. faecalis

C. jeikeium

PF-193

S. epidermidis

PPHCPPGHAKKGWC
471

M. luteus

E. coli

MRSA

E. faecalis

C. jejuni

PF-194

C. jeikeium

MKGNKLATAHEQPVKNSAPPL
472

PF-195

S. epidermidis

EMAEGSADDRLRKTPRDC
473

M. luteus

E. faecalis

C. jeikeium

PF-196

S. epidermidis

TTARYIRRQCHTSITPLSQG
474

M. luteus

P. mirabilis

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jejuni

PF-197

S. epidermidis

CNALLRRGHPPSAL
475

M. luteus

C. albicans

E. faecalis

C. jejuni

PF-200

S. epidermidis

GIELKSLIMAQIERWRQA
476

M. luteus

MRSA

E. faecalis

C. jeikeium

PF-201

S. epidermidis

GCRPASLSDADPDGR
477

M. luteus

E. coli

C. albicans

E. faecalis

C. jeikeium

C. jejuni

PF-202

S. epidermidis

ALNRASLRLALGE
478

M. luteus

E. coli

MRSA

E. faecalis

C. jeikeium

C. jejuni

PF-203

S. epidermidis

SWKCHHLAI
479

M. luteus

P. mirabilis

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jejuni

PF-204

S. epidermidis

ALQKQDMNLPSVKNQLVFLKSTG
480

P. mirabilis

E. coli

P. aeruginosa

C. albicans

C. jejuni

PF-205

S. epidermidis

AGVLETPRCRGEYGAN
481

M. luteus

E. coli

P. aeruginosa

C. albicans

MRSA

E. faecalis

C. jeikeium

C. jejuni

PF-206

M. luteus

KLRSASKKSLQEKSCGIMPEKPAG
482

C. albicans

C. jeikeium

C. jejuni

PF-207

M. luteus

AAGCRDLGSLSSLVTNPS
483

C. jeikeium

PF-208

S. epidermidis

DAYHCHLVRSPDAHDLSMRIGFV
484

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

C. jejuni

PF-209

C. albicans

NYAVVSHT
485

C. jeikeium

C. jejuni

PF-210

S. epidermidis

EREDGCDAMPLP
486

P. aeruginosa

C. albicans

MRSA

E. faecalis

C. jeikeium

C. jejuni

PF-211

S. epidermidis

DSFDSLSPFRERGGEREDGCDAMPLP
487

M. luteus

E. coli

P. aeruginosa

C. albicans

S. pneumoniae

E. faecalis

C. jeikeium

C. jejuni

M. smegmatis

PF-212

M. luteus

NDSKASN
488

P. aeruginosa

PF-213

S. epidermidis

MTTGVDFIIEKV
489

PF-214

S. mutans

GHLRVCWVFSASLLTPFRSATLI
490

S. epidermidis

M. luteus

E. coli

P. aeruginosa

A. baumannii

PF-215

S. epidermidis

ELKITNYNVNTVLYRYYKWGNDLCE
491

M. luteus

P. aeruginosa

A. baumannii

PF-216

S. mutans

ESVDKITEALEEDGFPAKVQ
492

E. coli

PF-217

S. mutans

DWEFTHKTIPQKK
493

PF-218

S. epidermidis

SETPEKPVGTFFYSIYYKIIL
494

M. luteus

P. aeruginosa

A. baumannii

PF-219

S. epidermidis

FLALAVIAGLFKVILIYAAPYLK
495

M. luteus

P. aeruginosa

A. baumannii

PF-221

S. epidermidis

VFDNIDINF
496

M. luteus

P. aeruginosa

PF-222

S. epidermidis

HIKETR
497

PF-223

S. epidermidis

VKFCIECQTKLERKRR
498

M. luteus

A. baumannii

PF-224

S. epidermidis

DYFYITLSQKNTF
499

P. aeruginosa

A. baumannii

PF-225

S. epidermidis

MNCASPEFKKLMELYK
500

PF-226

A. baumannii

LMFFSENMDKRDTLSGKFRYFAGSKVI
501

KLMNWLSENGK

PF-228

S. mutans

NQLGSQAFAQL
502

PF-229

S. epidermidis

DPILIQIGFTRFALRKAEAEKIEIQVEEGV
503

M. luteus

PA

P. aeruginosa

A. baumannii

PF-230

S. mutans

EDKPTNTIQEIKPVKWQ
504

PF-231

S. mutans

AVRDFKKSVREEDEAASLNSPRTIDAQ
505

VKTSESTSVKS

PF-232

S. epidermidis

FDQLYALEREGKLDELLA
506

M. luteus

PF-233

S. epidermidis

DANAMARTTIAIVYILALIALTISYSL
507

M. luteus

P. aeruginosa

A. baumannii

PF-234

S. epidermidis

RTPYILRS
508

M. luteus

PF-235

S. epidermidis

GIPFSKPHKRQVNYMKSDVLAYIEQNK
509

M. luteus

MAHTA

PF-236

S. mutans

KEIRTATVAELNAKRRLTSAEQALAEVS
510

S. epidermidis

E. coli

C. albicans

S. pneumoniae

E. faecalis

PF-237

S. epidermidis

YVKPKVGVHE
511

PF-238

S. mutans

RNAVVVTEATFPKYEEEITNYLNRRFGE
512

S. epidermidis

DWSLKLEKCSVA

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

PF-239

S. mutans

PKHNVVTGVSVDLDYKP
513

E. coli

PF-240

S. mutans

RITEVPPDEHSDR
514

E. coli

PF-242

S. mutans

KLFEDPLIKSKAVENFQTTWHEQCLAK
515

E. coli

ELAKNM

PF-244

S. epidermidis

HMRTISYLLAFAKFSLFIPPKQSLKRL
516

M. luteus

P. aeruginosa

A. baumannii

PF-245

S. epidermidis

MNDVKPVVQPKQTLKAFLVQLLSVRA
517

M. luteus

GVYIKQNNQLPKTKG

P. aeruginosa

A. baumannii

PF-246

S. mutans

QPDEKAEFFDPSLDKVYRHPTFYHIPDG
518

IEHM

PF-247

S. epidermidis

ETAASETH
519

PF-248

S. mutans

ILSKLWFWMINSLGVVLLVSYWLLAK
520

S. epidermidis

WGVA

M. luteus

E. coli

P. aeruginosa

A. baumannii

PF-249

S. epidermidis

INSRYKISF
521

M. luteus

PF-252

S. mutans

MKKLVAALAVIVILTGCVYDPVNYDKI
522

HDQEFQDHLRQNG

PF-253

S. epidermidis

VRDDDS
523

M. luteus

PF-254

S. epidermidis

FIYGVGFVPHFWLWKWLFSPWIAWPL
524

M. luteus

MLLGYYIWFLT

P. aeruginosa

A. baumannii

PF-255

P. aeruginosa

DHKINESQHNPFRSDSNKQNVDFF
525

PF-256

S. epidermidis

EYFKQVYVKNEKIYSFWICKDLSPKEA
526

AKRAEDILVKLK

PF-257

S. epidermidis

VWENRKKYLENEIERHNVFLKLGQEVI
527

KGLNALASRGR

PF-259

S. epidermidis

LPFSKIGRRVSYKKKDVLKYEQSKTVL
528

P. aeruginosa

NTAQLATV

A. baumannii

PF-262

S. mutans

DPHSEIDVTRYCQLHHFTCQTMQISERE
529

S. epidermidis

FHYLIETQ

M. luteus

E. coli

P. aeruginosa

A. baumannii

PF-263

S. epidermidis

NLKKCPC
530

M. luteus

A. baumannii

PF-265

S. epidermidis

MKTLFFPLFLIIFVLIIQALDQSYQKKIGI
531

M. luteus

SKPQKHPEFMQ

A. baumannii

PF-266

S. mutans

DQEKKNKTEESTEQ
532

PF-267

M. luteus

SDDKRTD
533

PF-268

S. mutans

EVLLSDLRPDIFSET
534

PF-270

S. epidermidis

MYLTPYAWIAVGSIFAFSVTTIKIGDQN
535

M. luteus

DEKQKSHKNDVHKR

P. aeruginosa

PF-271

S. epidermidis

AAQPQTTSP
536

M. luteus

P. aeruginosa

A. baumannii

PF-273

S. epidermidis

LVGALLIFVALIYMVLKGNADKN
537

M. luteus

P. aeruginosa

A. baumannii

PF-275

S. mutans

LVSGVANTVKNTAHTVGNTAKHAGHV
538

AADTTVKATKKQQVK

PF-276

S. epidermidis

LDLALSTNSLNLEGFSF
539

PF-278

M. luteus

LSLATFAKIFMTRSNWSLKRFNRL
540

A. baumannii

PF-279

S. mutans

SHIGFISISACLAVLLGIARLFVWTWVKF
541

S. epidermidis

FA

M. luteus

E. coli

P. aeruginosa

A. baumannii

PF-281

S. mutans

SYNTYYNKLIHGQRTPDGM
542

E. coli

PF-282

S. mutans

QNNDTSAWCGSAHKNGNS
543

PF-283

B. subtilis

MIRIRSPTKKKLNRNSISDWKSNTSGRF
544

B. fragilis

FY

C. difficile

PF-284

C. difficile

MRYITYSLIPRLLSKKVIHQQ
545

PF-285

S. mutans

VPAKLLRVIDEIPE
546

PF-288

S. mutans

IYQLLNIEYSEDD
547

E. coli

PF-289

C. difficile

MGRHLWNPSYFVATVSENTEEQIRKYR
548

KNK

PF-291

S. mutans

DVDGAIESEL
549

E. coli

PF-292

S. epidermidis

SFVSTTVRLIFEESKRYKF
550

B. subtilis

B. fragilis

PF-294

S. epidermidis

DFLVNFLWFKGELNWGKKRYK
551

C. difficile

PF-295

C. difficile

NIQVYESECGNYIFKKSDESFLIDIFDKN
552

GTH

PF-297

S. epidermidis

ISKGIDDIVYVINKILSIGNIFKIIKRK
553

B. subtilis

B. fragilis

PF-299

B. subtilis

LATKLKYEKEHKKM
554

PF-300

B. subtilis

VKDVLLELFNKIIGA
555

C. difficile

PF-301

C. difficile

GIVLIGLKLIPLLANVLN
556

PF-304

S. mutans

LVKDTSDIKNDLNNIEIVTSKNSNDIAKL
557

KSVK

PF-305

C. difficile

MREWICPSCNETHDRDINASINILKEGL
558

RLITIQNK

PF-306

C. difficile

GCILPHKKDNYNYIMSKFQDLVKITSKK
559

PF-307

S. epidermidis

MKRRRCNWCGKLFYLEEKSKEAYCCK
560

B. subtilis

ECRKKAKKVKK

B. fragilis

C. difficile

PF-308

C. difficile

QQYLILDRM
561

PF-309

S. mutans

GIPGMTAAPAEENEQEENADEE
562

E. coli

PF-311

C. difficile

IDAVTKKKTTCMIRAPTKIPIAHTDN
563

PF-313

S. epidermidis

YITSHKNARAIIKKFERDEILEEVITHYL
564

C. difficile

NRK

PF-314

S. mutans

ECLKKAIKSKALNKAFKIDVPDEVYDN
565

LLMELEEYEK

PF-317

S. mutans

LILVSDI
566

PF-319

S. epidermidis

SIGSMIGMYSFRHKTKHIKFTFGIPFILFL
567

B. subtilis

QFLLVYFYILK

C. difficile

PF-320

S. mutans

DSGYYALLENKEERVVWDGEVVANNI
568

E. coli

FNNLWIVVNKVKTG

PF-323

S. mutans

ARESIEKSHVPVDATIVGVVDSFEVFDE
569

PF-324

C. difficile

HFSLL
570

PF-325

S. mutans

LTIDEKLRNHR
571

E. coli

PF-326

S. mutans

VIVGNLGAQKEKRNDTPISAKKDIMGD
572

E. coli

KTVRVRADLHH

PF-328

S. mutans

NGNEKAFSEVENLVK
573

PF-329

S. epidermidis

IGILFDKSVRKY
574

PF-333

S. mutans

YMTKKLVEMAEQQMAGKSNR
575

PF-334

S. epidermidis

QQYLILDRM
576

C. difficile

PF-336

S. mutans

MLTSRKKRLKKIVEEQNKKDESI
577

E. coli

PF-337

S. epidermidis

YMTKKLVEMAERQMAGK
578

PF-338

S. mutans

KGTSCPDQLSKAIRQSI
579

PF-340

S. mutans

VKDVLLELFNKIIGA
580

E. coli

PF-344

B. subtilis

DERLPEAKAIRNFNGSVMVLGR
581

C. jejuni

PF-347

S. epidermidis

GIFTGVTVVVSLKHC
582

B. subtilis

B. fragilis

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

PF-348

B. subtilis

ESASAAEWYNPNMNVKKAICMG
583

E. coli

P. aeruginosa

C. albicans

E. faecalis

C. jejuni

PF-349

S. epidermidis

MPKSCHVPVLCDFFFLVIIKFLALFKTIQS
584

B. subtilis

B. fragilis

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

PF-350

S. epidermidis

LAVILRAIVY
585

E. coli

E. faecalis

C. jeikeium

C. jejuni

PF-351

S. mutans

YLFFKGKKVAEEEATKDEVKR
586

PF-352

C. jeikeium

RVKKIG
587

PF-353

S. epidermidis

EKTNFKGVKRNFYKKASFFV
588

M. luteus

B. subtilis

E. coli

C. albicans

S. pneumoniae

E. faecalis

C. jeikeium

C. jejuni

PF-354

S. epidermidis

FTFSKCRASNGRGFGTLWL
589

B. subtilis

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

C. jejuni

PF-355

S. epidermidis

WIAIGLLLYFSLKNQ
590

B. subtilis

B. fragilis

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

PF-356

S. epidermidis

VSIKIGAIVIGMIGLMELLTE
591

B. subtilis

B. fragilis

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

PF-357

S. epidermidis

MLTIIIGFIFWTMTLMLGYLIGEREGRK
592

M. luteus

HE

P. mirabilis

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

PF-358

S. epidermidis

RNTAHNIKWRSKN
593

B. subtilis

E. coli

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

C. jejuni

PF-359

S. epidermidis

MTVMEDPGSEQRNKIQSPMKGEDFSAL
594

B. fragilis

FGR

P. aeruginosa

C. albicans

MRSA

E. faecalis

C. jeikeium

PF-360

S. epidermidis

MEQKVKVIFVPRSKPDNQLKTFVSAVL
595

B. subtilis

FKA

E. coli

P. aeruginosa

C. albicans

E. faecalis

C. jeikeium

C. jejuni

PF-361

S. epidermidis

NQVTEGIRLLVE
596

E. coli

E. faecalis

C. jejuni

PF-362

S. epidermidis

NIERILKEKVWMIRCVE
597

E. coli

P. aeruginosa

C. albicans

E. faecalis

C. jejuni

PF-363

B. subtilis

SMLSVTVMCLMHASVAANQAMEKKV
598

E. coli

P. aeruginosa

C. albicans

S. pneumoniae

E. faecalis

PF-364

S. epidermidis

LVNGIKI
599

B. fragilis

P. aeruginosa

C. jeikeium

C. jejuni

PF-365

S. epidermidis

LYKQKIQLEEELEKLKDDRQ
600

B. subtilis

B. fragilis

P. aeruginosa

C. albicans

PF-366

S. epidermidis

ALCSVIKAIELGIINVHLQ
601

M. luteus

B. fragilis

P. mirabilis

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

C. jejuni

PF-367

B. subtilis

TKTPGTFTPGTGIQKTAVPL
602

PF-368

C. jeikeium

MLKQTA
603

C. jejuni

PF-369

B. subtilis

MSEAVNLLRGARYSQRYAKNQVPYEVI
604

B. fragilis

IEK

E. coli

P. aeruginosa

C. albicans

S. pneumoniae

C. jeikeium

C. jejuni

PF-370

S. epidermidis

VIFLHKESGNLKEIFY
605

E. coli

P. aeruginosa

E. faecalis

C. jejuni

PF-371

S. epidermidis

TFIYNEF
606

B. fragilis

C. jejuni

PF-372

C. jeikeium

KKQDKRIEDKYKRMKKGD
607

C. jejuni

PF-373

S. epidermidis

HFYLLFER
608

E. coli

P. aeruginosa

C. albicans

MRSA

E. faecalis

C. jejuni

PF-374

S. epidermidis

HLFFVKGMFILCQKNQINDE
609

B. subtilis

B. fragilis

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

C. jejuni

PF-375

S. epidermidis

MDSAKAQTMRTDWLAVSCLVASAYLR
610

B. subtilis

SMLA

B. fragilis

E. coli

P. aeruginosa

C. albicans

S. pneumoniae

E. faecalis

C. jeikeium

C. jejuni

PF-376

S. epidermidis

MTVFEALMLAIAFATLIVKISNKNDKK
611

B. subtilis

B. fragilis

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

C. jejuni

PF-378

B. subtilis

ESAKSNLNFLMQEEWALFLLL
612

B. fragilis

E. coli

P. aeruginosa

C. jeikeium

PF-379

S. epidermidis

VFVVLFIIYLASKLLTKLFPIKK
613

B. subtilis

B. fragilis

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

C. jejuni

PF-380

S. epidermidis

KKIIPLITLFVVTLVG
614

B. subtilis

B. fragilis

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

C. jejuni

PF-381

E. coli

QGANPCQQVGFTVNDPDCRLAKTV
615

P. aeruginosa

C. jejuni

PF-382

S. epidermidis

KYKCSWCKRVYTLRKDHKTAR
616

B. subtilis

B. fragilis

E. coli

P. aeruginosa

E. faecalis

C. jeikeium

C. jejuni

PF-383

S. epidermidis

WSEIEINTKQSN
617

B. subtilis

B. fragilis

E. coli

C. jejuni

PF-384

E. faecalis

HISKERFEAY
618

C. jeikeium

C. jejuni

PF-385

S. epidermidis

MIKKSILKIKYYVPVLISLTLILSA
619

E. coli

P. aeruginosa

C. albicans

E. faecalis

PF-386

S. epidermidis

FTLTLITTIVAILNYKDKKK
620

B. subtilis

B. fragilis

E. coli

P. aeruginosa

C. albicans

S. pneumoniae

E. faecalis

C. jeikeium

C. jejuni

PF-387

B. subtilis

GAVGIAFFAGNMKQDKRIADRQNKKSE
621

E. coli

KK

P. aeruginosa

E. faecalis

C. jeikeium

C. jejuni

PF-388

E. faecalis

ITPLLDEIGKVCIDKISK
622

C. jeikeium

C. jejuni

PF-389

S. epidermidis

GLQFKEIAEEFHITTTALQQWHKDNGY
623

C. albicans

PIYNKNNRK

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

PF-390

S. epidermidis

VVAYVITQVGAIRF
624

P. aeruginosa

C. albicans

MRSA

PF-392

S. epidermidis

DPAGCNDIVRKYCK
625

B. subtilis

S. pneumoniae

C. jeikeium

C. jejuni

PF-393

S. epidermidis

DLVQSILSEFKKSG
626

E. coli

C. albicans

MRSA

S. pneumoniae

C. jejuni

PF-394

S. epidermidis

VLKEECYQKN
627

MRSA

C. jejuni

PF-395

S. epidermidis

YCVPLGNMGNMNNKIW
628

E. coli

P. aeruginosa

S. pneumoniae

E. faecalis

C. jeikeium

C. jejuni

PF-396

S. epidermidis

LIYTILASLGVLTVLQAILGREPKAVKA
629

E. coli

P. aeruginosa

C. albicans

E. faecalis

C. jeikeium

PF-397

S. epidermidis

VEDLMEDLNA
630

MRSA

S. pneumoniae

E. faecalis

C. jejuni

PF-398

S. epidermidis

ILVVLAGILLVVLSYVGISKFKMNC
631

B. subtilis

B. fragilis

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

C. jejuni

PF-399

S. epidermidis

FPIISALLGAIICIAIYSFIVNRKA
632

M. luteus

P. mirabilis

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jejuni

PF-400

S. epidermidis

VIAWKFRNKFENSGV
633

E. coli

S. pneumoniae

E. faecalis

C. jeikeium

PF-401

S. epidermidis

YWLSRVTTGHSFAFEKPVPLSLTIK
634

E. coli

P. aeruginosa

MRSA

E. faecalis

C. jejuni

PF-402

S. epidermidis

FIDVLKSKINEFLN
635

P. aeruginosa

E. faecalis

C. jejuni

PF-403

E. coli

LLSTEQLLKYYDGETFDGFQLPSNE
636

P. aeruginosa

S. pneumoniae

E. faecalis

C. jeikeium

C. jejuni

PF-404

S. epidermidis

VLYFQATVV
637

E. coli

P. aeruginosa

E. faecalis

C. jeikeium

C. jejuni

PF-405

S. epidermidis

LVRIEVDDLEEWYERNFI
638

E. coli

E. faecalis

PF-406

E. coli

YLEMNADYLSNMDIFDELWEKYLENNK
639

C. jejuni

PF-407

S. epidermidis

KPKNKKEKTVISYEKLLSMY
640

B. subtilis

E. coli

P. aeruginosa

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

C. jejuni

PF-408

S. epidermidis

YCVPLGNMGNMNNKIW
641

E. coli

P. aeruginosa

MRSA

E. faecalis

C. jeikeium

C. jejuni

PF-409

S. epidermidis

DLVQSILSEFKKSG
642

MRSA

C. jeikeium

C. jejuni

PF-410

S. epidermidis

FALELIALCRNLFIVYFP
643

M. luteus

B. fragilis

P. mirabilis

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

PF-411

M. luteus

WVAVAILLNIALQTQLT
644

B. subtilis

B. fragilis

P. mirabilis

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

C. jejuni

PF-412

M. luteus

TSGWLGQLEQ
645

E. coli

C. albicans

C. jeikeium

C. jejuni

PF-413

P. aeruginosa

TFAGSIKIGVPDLVHVTFNCKR
646

C. albicans

C. jejuni

PF-414

E. coli

LLNKKLE
647

C. albicans

C. jeikeium

PF-416

S. pneumoniae

SKAGLYGKIERSDKRE
648

C. jeikeium

PF-417

S. epidermidis

DSYFRS
649

C. jeikeium

C. jejuni

PF-418

S. epidermidis

FFLVHFYIRKRKGKVSIFLNYF
650

M. luteus

P. mirabilis

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

C. jejuni

PF-421

C. jeikeium

KHCFEITDKTDVV
651

PF-422

C. albicans

MSRKKYENDEKSQKKLKIGRKSDVFYG
652

MRSA
IID

C. jeikeium

PF-423

S. epidermidis

AGKKERLLSFREQFLNKNKKK
653

M. luteus

E. coli

S. pneumoniae

E. faecalis

C. jeikeium

PF-424

S. epidermidis

IAAFVTSRAFSDTVSPI
654

C. albicans

MRSA

PF-425

S. epidermidis

MMELVLKTIIGPIVVGVVLRIVDKWLN
655

M. luteus

KDK

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

C. jeikeium

PF-426

S. epidermidis

MLQKYTQMISVTKCIITKNKKTQENVD
656

E. coli

AYN

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

PF-427

M. luteus

YVLEYHGLRATQDVDAFMAL
657

P. aeruginosa

C. albicans

C. jejuni

PF-428

S. epidermidis

ENEESIF
658

C. albicans

E. faecalis

C. jeikeium

PF-429

S. epidermidis

AATLICVGSGIMSSL
659

S. pneumoniae

C. jeikeium

PF-430

S. epidermidis

AVVCGYLAYTATS
660

M. luteus

E. coli

S. pneumoniae

E. faecalis

C. jeikeium

C. jejuni

PF-431

S. epidermidis

VAYAAICWW
661

M. luteus

E. coli

P. aeruginosa

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

C. jejuni

PF-432

S. epidermidis

FNGDSEFFLCIAF
662

M. luteus

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

C. jejuni

PF-433

S. epidermidis

MRKEFHNVLSSGQLLADKRPARDYNRK
663

E. coli

S. pneumoniae

C. jeikeium

PF-434

S. epidermidis

GQLLADKRPARDYNRK
664

M. luteus

S. pneumoniae

C. jeikeium

PF-435

C. jeikeium

MSRWDGHSDKGEAPAGKPPMHGFGLN
665

GENK

PF-436

C. jeikeium

KKHVLVGKQEKNG
666

PF-438

S. epidermidis

QPYFQNQFKKITGYTPLQYRKEKR
667

E. coli

S. pneumoniae

C. jeikeium

C. jejuni

PF-439

S. epidermidis

RVLVLKKFHGIMDGNRNVAVFFVGQ
668

M. luteus

B. fragilis

P. mirabilis

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

C. jejuni

PF-440

S. epidermidis

MFIISPDLFNIAVILYILFFIHDILLLILS
669

M. luteus

P. mirabilis

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

C. jejuni

PF-441

C. jeikeium

TQVHKMARGIDPGPANGIYR
670

PF-442

S. epidermidis

MQIFYIKTKIFLSFFLFLLIFSQCFYKIEE
671

E. coli

C. albicans

S. pneumoniae

E. faecalis

PF-443

S. epidermidis

KLLYFFNYFENLQQVHLLVQL
672

M. luteus

P. mirabilis

E. coli

P. aeruginosa

C. albicans

S. pneumoniae

E. faecalis

C. jeikeium

C. jejuni

PF-444

M. luteus

MAAKLWEEGKMVYASSASMTKRLKL
673

C. albicans

AMSKV

S. pneumoniae

C. jeikeium

PF-445

M. luteus

ASMTKRLKLAMSKV
674

S. pneumoniae

C. jeikeium

PF-446

M. luteus

SGNEKV
675

C. jeikeium

PF-447

S. epidermidis

IDKSRNKDQFSHIFGLYNICSG
676

M. luteus

E. coli

S. pneumoniae

PF-448

S. epidermidis

SLQSQLGPCLHDQRH
677

M. luteus

P. mirabilis

E. coli

S. pneumoniae

E. faecalis

C. jeikeium

C. jejuni

PF-450

S. epidermidis

HRNLIILQRTIFI
678

M. luteus

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

C. jejuni

PF-451

S. epidermidis

MVNYIIGSYMLYREQNNNEALRKFDIT
679

M. luteus

LAM

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

C. jejuni

M. smegmatis

PF-452

M. luteus

MNNWIKVAQISVTVINEVIDIMKEKQN
680

P. aeruginosa

GGK

C. albicans

S. pneumoniae

E. faecalis

C. jeikeium

M. smegmatis

PF-453

M. luteus

IIQDIAHAFGY
681

E. coli

P. aeruginosa

S. pneumoniae

E. faecalis

C. jeikeium

C. jejuni

PF-454

S. epidermidis

MSVFVPVTNIFMFIMSPIFNVNLLHFKV
682

M. luteus

YI

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

C. jejuni

M. smegmatis

PF-456

C. albicans

TCVKPRTIN
683

MRSA

E. faecalis

C. jeikeium

C. jejuni

PF-457

C. albicans

INKYHHIA
684

S. pneumoniae

E. faecalis

C. jeikeium

PF-458

S. epidermidis

ISLIIFIMLFVVALFKCITNYKHQS
685

M. luteus

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

C. jejuni

PF-459

P. aeruginosa

EKRMSFNENQSHRPLL
686

PF-460

S. epidermidis

MEHVLPFQNTPPNIVIIYKDFTHLKSITFS
687

M. luteus

P. mirabilis

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

C. jejuni

M. smegmatis

PF-461

E. coli

MTLAIKNCSVTKCLGFGDFVNDDSDSY
688

S. pneumoniae

FDA

PF-462

E. faecalis

KNKTDTL
689

C. jeikeium

PF-463

S. epidermidis

MVILVFSLIFIFTDNYLVYQSKSIKEDVMI
690

E. coli

P. aeruginosa

C. albicans

S. pneumoniae

E. faecalis

M. smegmatis

PF-464

S. epidermidis

VDMVNRFLGN
691

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

C. jejuni

PF-465

S. epidermidis

KPVGKALEEIADGKIEPVVPKEYLG
692

M. luteus

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

C. jejuni

PF-466
MRSA
VRKSDQ
693

C. jeikeium

C. jejuni

PF-467
MRSA
YYKDYFKEI
694

E. faecalis

C. jeikeium

C. jejuni

PF-469

S. epidermidis

YKVNYNNIDNHFNTLRH
695

M. luteus

P. mirabilis

E. coli

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

C. jejuni

PF-470

M. luteus

PYSDSYATRPHWEQHRAR
696

E. coli

MRSA

E. faecalis

C. jeikeium

C. jejuni

PF-471

S. epidermidis

MVGKIRGVTPRNDLLNANITGQLNLNY
697

M. luteus

RLI

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

C. jejuni

PF-472

S. epidermidis

MHISHLLDEVEQTEREKAVNVLENMNG
698

E. coli

NVI

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

PF-473

S. epidermidis

MAADIISTIGDLVKWIIDTVNKFKK
699

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

PF-474

S. epidermidis

MHRNLVLVKMEPIPHIMIIANQIGIIIEKA
700

M. luteus

P. mirabilis

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

C. jejuni

M. smegmatis

PF-475

S. epidermidis

MREKVRFTQAFKLFWTNYFNFKGRSRR
701

M. luteus

SEY

P. mirabilis

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

C. jejuni

PF-476

M. luteus

WADAQYKLCENCSE
702

P. mirabilis

C. albicans

S. pneumoniae

E. faecalis

C. jeikeium

C. jejuni

PF-477

S. epidermidis

HKNKLNIPHIKS
703

M. luteus

C. albicans

S. pneumoniae

C. jeikeium

C. jejuni

PF-478

S. epidermidis

HLFILKSHLKPFPPFRYTYD
704

M. luteus

P. mirabilis

E. coli

C. albicans

S. pneumoniae

E. faecalis

C. jeikeium

C. jejuni

PF-479

S. epidermidis

AYILKRREEKNK
705

M. luteus

P. mirabilis

E. coli

C. albicans

S. pneumoniae

E. faecalis

C. jeikeium

C. jejuni

PF-480

S. epidermidis

MVEILVNTAISVYIVALYTQWLSTRDNL
706

M. luteus

KA

P. mirabilis

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

C. jejuni

M. smegmatis

PF-481

C. jeikeium

DELYEIMDKVIEEFNKDIEQNNNNGNN
707

EDLTENKIN

PF-482

S. epidermidis

LVGYVRTSGTVRSYKIN
708

M. luteus

P. mirabilis

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

C. jejuni

PF-483

P. mirabilis

EDNKDKKDKKDK
709

C. jeikeium

C. jejuni

PF-484

S. epidermidis

HKKDIRKQVFKN
710

M. luteus

P. mirabilis

E. coli

E. faecalis

C. jeikeium

C. jejuni

PF-486

S. mutans

MQKEGEEDY
711

PF-487

S. mutans

MYKAIAVLAMTIMAFFIFVYPFFIVGLILG
712

E. coli

PF-488

S. mutans

YPNEQGHHKNNLKNIIIE
713

E. coli

PF-489

S. mutans

KVDRVSTTITEKIK
714

PF-490

S. mutans

RLILVSGNATVQK
715

E. coli

PF-491

S. mutans

IHQYSSKPDIVGQEAKTVQQINS
716

E. coli

PF-492

S. mutans

IQIDAASFYSISKSTIK
717

B. subtilis

E. coli

PF-493

S. mutans

PGAFFFCRGRGCWCGIGW
718

B. subtilis

E. coli

PF-494

S. mutans

FTEPLRPLQAKGQIISIKPSTSSS
719

PF-495

S. mutans

KGIYKKRTY
720

E. coli

PF-496

S. mutans

EVTKRLVALAQQQLRG
721

E. coli

PF-497

S. mutans

LVLRICTDLFTFIKWTIKQRKS
722

B. subtilis

E. coli

PF-498

S. mutans

MSEEEEVSEKVYNYLRRNEFFEVRKEE
723

E. coli

FSA

PF-499

S. mutans

VYSFLYVLVIVRKLLSMKKRIERL
724

E. coli

PF-500

S. mutans

MGIFKEEKIKFIDCKGEEVILKIKIKDIKK
725

E. coli

PF-501

S. mutans

GSTAHKSPIGSTNNQWGMKKTPTD
726

PF-502

S. mutans

NKGKQMQDQTGKQPIVDNG
727

PF-503

S. mutans

VVTLKDIVAVIEDQGYDVQ
728

PF-504

S. mutans

ILSVELSTKTSASGS
729

E. coli

PF-505

S. mutans

GYTKDPGTGI
730

PF-506

S. mutans

SGRGFALIVVLFILLIIVGAACIR
731

E. coli

PF-507

S. mutans

LALSIANLFKKKA
732

E. coli

PF-508

S. mutans

VSTFGKVVKVVDEK
733

PF-509

S. mutans

EAKVQAKGEQIACNNY
734

B. subtilis

E. coli

PF-510

S. mutans

WYLYKKQSNQNDRGIPK
735

E. coli

PF-511

E. coli

VMQSLYVKPPLILVTKLAQQN
736

P. aeruginosa

S. pneumoniae

C. jeikeium

PF-512

S. pneumoniae

SFMPEIQKNTIPTQMK
737

C. jeikeium

PF-513

C. albicans

SNGVGLGVGIGSGIRF-NH2
738

PF-514

S. epidermidis

QRFYKLFYHIDLTNEQALKLFQVK
739

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

PF-515

S. epidermidis

DKSTQDKDIKQAKLLAQELGL-NH2
740

C. albicans

S. pneumoniae

C. jeikeium

PF-517

C. jejuni

VKPTMTASLISTVC
741

PF-518

S. epidermidis

SFYSKYSRYIDNLAGAIFLFF
742

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

PF-519

M. luteus

YLVYSGVLATAAAF-NH2
743

E. faecalis

C. jeikeium

PF-520

S. epidermidis

LGLTAGVAYAAQPTNQPTNQPTNQPTN
744

M. luteus

QPTNQPTNQPRW-NH2

E. coli

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

C. jejuni

PF-521

S. epidermidis

CGKLLEQKNFFLKTR
745

E. coli

P. aeruginosa

S. pneumoniae

E. faecalis

PF-522

S. epidermidis

FELVDWLETNLGKILKSKSA-NH2
746

E. coli

P. aeruginosa

S. pneumoniae

E. faecalis

PF-523

S. epidermidis

ASKQASKQASKQASKQASKQASRSLKN
747

M. luteus

HLL

C. albicans

S. pneumoniae

C. jeikeium

C. jejuni

PF-524

S. epidermidis

PDAPRTCYHKPILAALSRIVVTDR
748

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

PF-526

S. epidermidis

VLLLFIFQPFQKQLL-NH2
749

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

C. jejuni

PF-527

S. epidermidis

GSVIKKRRKRMAKKKHRKLLKKTRIQR
750

M. luteus

RRAGK

P. mirabilis

E. coli

P. aeruginosa

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

C. jejuni

PF-528

S. epidermidis

LVDVVVLIRRHLPKSCS-NH2
751

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

PF-529

S. epidermidis

LSEMERRRLRKRA-NH2
752

E. coli

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

PF-537

S. epidermidis

LANDYYKKTKKSW
753

M. luteus

P. mirabilis

E. coli

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

PF-539

S. epidermidis

SIILTKKKRRKIPLSIDSQIYKYTFKQ
754

M. luteus

B. subtilis

P. mirabilis

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

PF-540

C. albicans

KSILILIKVIFIGQTTIIL
755

PF-542

C. jeikeium

KKDNPSLNDQDKNAVLNLLALAK
756

PF-543

S. epidermidis

NILFGIIGFVVAMTAAVIVTAISIAK
757

M. luteus

B. subtilis

P. mirabilis

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

PF-544

S. epidermidis

FGEKQMRSWWKVHWFHP
758

M. luteus

P. mirabilis

P. aeruginosa

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

C. jejuni

PF-545

S. epidermidis

RESKLIAMADMIRRRI-NH2
759

E. coli

P. aeruginosa

S. pneumoniae

E. faecalis

C. jeikeium

PF-546

S. epidermidis

PIIAPTIKTQIQ
760

E. coli

C. albicans

S. pneumoniae

E. faecalis

C. jeikeium

PF-547

S. epidermidis

WSRVPGHSDTGWKVWHRW-NH2
761

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

PF-548

M. luteus

ARPIADLIHFNSTTVTASGDVYYGPG
762

P. mirabilis

E. coli

P. aeruginosa

C. albicans

S. pneumoniae

E. faecalis

C. jeikeium

C. jejuni

PF-549

E. coli

TGIGPIARPIEHGLDS
763

C. albicans

S. pneumoniae

C. jeikeium

PF-550

S. pneumoniae

STENGWQEFESYADVGVDPRRYVPL
764

PF-551

S. pneumoniae

QVKEKRREIELQFRDAEKKLEASVQAE
765

PF-552

S. pneumoniae

ELDKADAALGPAKNLAPLDVINRS
766

PF-553

S. epidermidis

LTIVGNALQQKNQKLLLNQKKITSLG
767

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

C. jeikeium

PF-554

S. pneumoniae

AKNFLTRTAEEIGEQAVREGNINGP
768

PF-555
MRSA
EAYMRFLDREMEGLTAAYNVKLFTEAIS
769

S. pneumoniae

C. jeikeium

PF-556

S. epidermidis

SLQIRMNTLTAAKASIEAA
770

M. luteus

B. fragilis

P. mirabilis

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

PF-557

S. pneumoniae

AANKAREQAAAEAKRKAEEQAR
771

PF-558

S. epidermidis

ADAPPPLIVRYS
772

E. coli

C. albicans

C. jeikeium

C. jejuni

PF-559

S. epidermidis

SRPGKPGGVSIDVSRDRQDILSNYP
773

M. luteus

C. albicans

C. jeikeium

C. jejuni

PF-560

S. epidermidis

FGNPFRGFTLAMEADFKKRK
774

M. luteus

E. coli

S. pneumoniae

C. jeikeium

C. jejuni

PF-562

S. epidermidis

TPEQWLERSTVVVTGLLNRK
775

M. luteus

P. mirabilis

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

C. jejuni

PF-563

S. epidermidis

RPELDNELDVVQNSASLDKLQASYN
776

M. luteus

C. jeikeium

PF-564

S. epidermidis

TIILNDQINSLQERLNKLNAETDRR
777

C. albicans

S. pneumoniae

C. jeikeium

PF-566

P. mirabilis

EAQQVTQQLGADFNAITTPTATKV
778

S. pneumoniae

PF-567

S. epidermidis

QQRVKAVDASLSQVSTQVSGAVASA
779

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

C. jeikeium

PF-568

S. epidermidis

TQAVQVKTAQAQQQ
780

PF-569

M. luteus

KSKISEYTEKEFLEFVEDIYTNNK
781

P. mirabilis

S. pneumoniae

E. faecalis

C. jeikeium

PF-570

S. pneumoniae

KKFPTEESHIQAVLEFKKLTEHPSG
782

C. jeikeium

PF-572

S. epidermidis

WRASKGLPGFKAG
783

M. luteus

E. coli

S. pneumoniae

C. jeikeium

PF-573

S. epidermidis

EKKLIVKLIDSIGKSHEEIVGAG
784

S. pneumoniae

PF-575

M. luteus

LNFRAENKILEKIHISLIDTVEGSA
785

E. coli

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

PF-576

M. luteus

AYSGELPEPLVRKMSKEQVRSVMGK
786

P. mirabilis

E. coli

P. aeruginosa

C. albicans

S. pneumoniae

PF-577

S. epidermidis

PFETRESFRVPVIGILGGWDYFMHP
787

M. luteus

P. mirabilis

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

PF-578

S. epidermidis

QKANLRIGFTYTSDSNVCNLTFALLGSK
788

M. luteus

P. mirabilis

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

PF-579

S. epidermidis

MILVCAAVIWGRVLFILKFPIYFSIRLAFL
789

M. luteus

P. mirabilis

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

C. jejuni

PF-580

S. epidermidis

EILNNNQVIKELTMKYKTQFESNLGGW
790

M. luteus

TARARR

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

PF-581

S. epidermidis

WTARARR
791

M. luteus

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

PF-583

S. epidermidis

KFQGEFTNIGQSYIVSASHMSTSLNTGK
792

M. luteus

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

PF-584

S. epidermidis

SYIKNLSNQKFLIAF
793

M. luteus

P. mirabilis

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

PF-585

S. epidermidis

DYNHLLNVVQDWVNTN
794

E. coli

C. albicans

MRSA

S. pneumoniae

C. jeikeium

PF-586

S. epidermidis

FFNQANYFFKEF
795

M. luteus

E. coli

P. aeruginosa

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

C. jejuni

PF-587

S. epidermidis

ASGKYQSYLLNVYVDSKKDRLDIFDKL
796

M. luteus

KAKAKFVL

E. coli

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

PF-588

S. epidermidis

ESVEAIKAKAIK
797

E. coli

C. albicans

E. faecalis

C. jeikeium

C. jejuni

PF-589

S. epidermidis

APLRIDEIRNSNVIDEVLDCAPKKQEHFF
798

C. albicans

VVPKIIE

MRSA

S. pneumoniae

PF-590

S. epidermidis

YYQAKLFPLL
799

M. luteus

E. coli

E. faecalis

C. jeikeium

PF-592

S. epidermidis

IMKNYKYFKLFIVKYALF
800

M. luteus

P. mirabilis

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

C. jejuni

PF-593

C. jeikeium

MEISTLKKEKLHVKDELSQYLANYKK
801

PF-594

C. jeikeium

IVSAIV
802

PF-595

S. epidermidis

LQNKIYELLYIKERSKLCS
803

M. luteus

P. mirabilis

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

C. jejuni

PF-596

S. epidermidis

SKMWDKILTILILILELIRELIKL
804

M. luteus

P. mirabilis

E. coli

P. aeruginosa

MRSA

E. faecalis

C. jeikeium

C. jejuni

PF-597

P. mirabilis

DEIKVSDEEIEKFIKENNL
805

PF-598

S. epidermidis

MKFMLEVRNKAISAYKEITRTQI
806

M. luteus

P. mirabilis

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

C. jeikeium

PF-599

S. epidermidis

LFEIFKPKH
807

P. mirabilis

E. coli

C. albicans

MRSA

S. pneumoniae

C. jeikeium

PF-600

S. epidermidis

TKKIELKRFVDAFVKKSYENYILERELK
808

M. luteus

KLIKAINEELPTK

B. subtilis

P. mirabilis

E. coli

P. aeruginosa

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

PF-601

C. jeikeium

YRVTVKALE
809

PF-602

P. mirabilis

LEKEKKEYIEKLFKTK
810

C. jeikeium

PF-603

S. epidermidis

IDKLKKMNLQKLSYEVRISQDGKSIYAR
811

M. luteus

IK

B. subtilis

E. coli

P. aeruginosa

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

PF-604

S. epidermidis

LMEQVEV
812

C. albicans

C. jeikeium

PF-605

S. epidermidis

HYRWNTQWWKY
813

M. luteus

P. mirabilis

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

C. jejuni

PF-607

S. epidermidis

YIESDPRKFDYIFGAIRDH
814

P. mirabilis

E. coli

MRSA

S. pneumoniae

C. jeikeium

PF-609

P. mirabilis

TEIKLDNNEYLVLNLDDILGILK
815

E. coli

S. pneumoniae

PF-610

S. epidermidis

VFLKLKTSKIDLASIIFYP
816

M. luteus

P. mirabilis

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

C. jejuni

PF-612

S. epidermidis

GTTLKYGLERQLKIDIHPEITIINLNGGA
817

M. luteus

DEFAKL

P. mirabilis

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

PF-613

C. jeikeium

ADEFAKL
818

PF-614

S. epidermidis

GLDIYA
819

E. coli

C. jeikeium

PF-615

S. epidermidis

FLNRFIFYIFTVKTKSALIKNLFLD
820

M. luteus

P. mirabilis

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

C. jeikeium

C. jejuni

PF-616

C. jeikeium

IVFVVTKEKK
821

PF-617

P. aeruginosa

PMNAAEPE
822

C. albicans

PF-619

S. epidermidis

WSRVPGHSDTGWKVWHRW
823

M. luteus

B. subtilis

P. mirabilis

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

PF-621

S. epidermidis

PPSSFLV
824

C. albicans

PF-622

S. epidermidis

TREDVFSVRLINNIVNKQA
825

P. aeruginosa

C. albicans

S. pneumoniae

E. faecalis

C. jeikeium

PF-623

S. epidermidis

VLFAVYLGALDWLFSWLTQKM
826

P. aeruginosa

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

PF-625

S. epidermidis

SDSTNNARTRKKARDVTTKDIDK
827

M. luteus

S. pneumoniae

C. jeikeium

PF-626

S. epidermidis

KYDFDDFEPEEA
828

M. luteus

E. coli

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

PF-627

S. epidermidis

INDLLSYFTLHEK
829

P. aeruginosa

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

PF-629

S. epidermidis

GLAAIATVFALY
830

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

PF-630

S. epidermidis

IPATPIIHS
831

M. luteus

P. mirabilis

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

PF-631

S. epidermidis

LIIYFSKTGNTARATRQI
832

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

PF-632

S. epidermidis

TTIQGVASLEKHGFRYTIIYPTRI
833

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

PF-634

S. epidermidis

MPKARPVNHNKKKSKITIKSNFTLFYM
834

M. luteus

FNP

P. mirabilis

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

PF-635

S. epidermidis

MNAHGHSLIFQKMIVHAFAFFSKQKNY
835

P. aeruginosa

LYF

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

PF-636

S. epidermidis

LVRLA
836

C. albicans

MRSA

S. pneumoniae

E. faecalis

PF-637

S. epidermidis

SRIKQDARSVRKYDRIGIFFYSFKSA
837

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

PF-638

S. epidermidis

TFILPK
838

C. albicans

MRSA

C. jeikeium

PF-639

S. pneumoniae

QATQIKSWIDRLLVSED
839

C. jeikeium

PF-640

C. albicans

MGDINRNF
840

PF-641

S. epidermidis

SWKCHHLAIGGSWKCHHLAI
841

M. luteus

E. coli

C. albicans

MRSA

E. faecalis

C. jeikeium

C. jejuni

PF-642

M. luteus

FTTPMIGIPAGLLGGSYYLKRREEKGK
842

MRSA

C. jeikeium

PF-643

Mycobacteria spp
VRCRL
843

PF-644

Mycobacteria spp
TSGLIIGENGLNGL
844

PF-645

Mycobacteria spp
SNSVQQG
845

PF-646

Mycobacteria spp
APASPGRRPG
846

PF-647

Mycobacteria spp
GTFLGQKCAAATAS
847

PF-648

S. mutans

ARRYPAAGS
848

E. coli

PF-649

Mycobacteria spp
CPRYPFVDVGPAGPWRARWRVGS
849

PF-650

Mycobacteria spp
IRSDQPGRQSRSSPRWPTGAGRHR
850

PF-651

Mycobacteria spp
PRWPTGAGRHR
851

PF-652

Mycobacteria spp
FLAPARPDLQAQRQALAQ
852

PF-653

Mycobacteria spp
QSVHPLPAETPVADVI
853

PF-654

Mycobacteria spp
LSGRLAGRR
854

PF-655

M. smegmatis

DAPCFDDQFGDLKCQMC
855

PF-656

Mycobacteria spp
RGMFVPFHDVDCVQ
856

PF-657

Mycobacteria spp
YVANYTITQFGRDFDDRLAVAIHFA
857

PF-658

Mycobacteria spp
PTTPPPTTPPEIPTGGTVIST
858

PF-659

Mycobacteria spp
TVIST
859

PF-660

Mycobacteria spp
TDPQATAAPRRRTSPR
860

PF-661

Mycobacteria spp
PDEDIRRRAILPPAGPCRPMSPE
861

PF-662

Mycobacteria spp
GKQSRAHGPVASRREFRRKSG
862

PF-663

Mycobacteria spp
ATLIPRKA
863

PF-664

M. smegmatis

DQLCVEYPARVSTG
864

PF-665

Mycobacteria spp
VLRVATAVGEVPTGL
865

PF-666

Mycobacteria spp
PNRRSRPR
866

PF-667

Mycobacteria spp
PAHQRLRIDQRLVADRDMVQDYES
867

PF-668

Mycobacteria spp
TNAESMALAFRGRVHMSVNIAGLT
868

PF-669

Mycobacteria spp
RADRIESYPADGDRVITLWRNPYR
869

PF670

Mycobacteria spp
TVIVAPMHSGV
870

PF-671

S. mutans

TVSAFRTVH
871

E. coli

PF-673

S. mutans

VRRLRM
872

E. coli

PF-674

S. mutans

DGCDSEPALTYR
873

E. coli

PF-675

Mycobacteria spp
EIIPISPTRRCEMHTMSSAEYRGL
874

PF-676

S. mutans

AEYRGL
875

E. coli

PF-677

Mycobacteria spp
TCRGAGMH
876

PF-678

Mycobacteria spp
RDRRWTRRDMYDWLESARV
877

PF-679

S. mutans

CRARFIRR
878

E. coli

PF-680

Mycobacteria spp
ADPHPTTGI
879

PF-681

M. smegmatis

TALTTVGVSGARLITYCVGVEDI
880

PF-682

Mycobacteria spp
RRGKSEQGLSRR
881

PF-683

Mycobacteria spp
LWPVA
882

PF-684

Mycobacteria spp
RKLSLASGFALWRRSLV
883

PF-685

Mycobacteria spp
PTLWLACL
884

PF-686

M. smegmatis

LAVLMGYIGYRGWSGKRHINRQ
885

PF-687

Mycobacteria spp
AKRVLSLAVAPHRRQPVQGT
886

PF-688

Mycobacteria spp
ARNHAVIPAG
887

PF-689

S. mutans

SAPSG
888

E. coli

PF-690

Mycobacteria spp
MIPLAGDPVSSHRTVEFGVLGTYLVSG
889

GSL

PF-691

Mycobacteria spp
HRTVEFGVLGTYLVSGGSL
890

PF-692

Mycobacteria spp
GVAREDPLEPDPLAPIIDDSR
891

PF-693

Mycobacteria spp
PDPAR
892

PF-694

Mycobacteria spp
DLIRPLYSMSAPSVA
893

PF-695

Mycobacteria spp
ALSVMLGNIPLVVPNANQL
894

PF-696

Mycobacteria spp
IRSGISAAYARPLR
895

PF-697

Mycobacteria spp
RADARAK
896

PF-698

Mycobacteria spp
SSGRAGVKCRRPTGR
897

PF-699

Mycobacteria spp
GRAGVKCRRPTGR
898

PF-700

Mycobacteria spp
LNWPFTGR
899

PF-701

S. mutans

PRGAQSGHG
900

PF-702

Mycobacteria spp
LSGRLAGRR
901

PF-703

Mycobacteria spp
MTTVDNIVGLVIAVALMAFLFAALLFPE
902

KF

PF-704

Mycobacteria spp
APAARAAL
903

PF-705

S. mutans

GEEEGTVAD
904

E. coli

PF-706

L. pneumophila

LGYGAWIGCGLGLNGFHRID
905

PF-707

S. mutans

IDPESIVTTNNKQDNVDEQ
906

E. coli

PF-709

S. mutans

NKKHSPMD
907

PF-711

S. mutans

KTAGPTGTIYKTN
908

PF-712

S. mutans

QIYRHVHKVQAKSANLRLY
909

E. coli

PF-714

L. pneumophila

FVVTQRMLRMYKK
910

PF-716

S. mutans

HGENHHHKSDEKDNDSSEKKD
911

PF-717

E. coli

PQSEVTFENIYAPKANGGGLYGI
912

PF-720

S. mutans

SLDMGK
913

PF-724

L. pneumophila

CYRFLTPKRPTRIS
914

PF-727

S. mutans

AYARCRHDYPFTLGQMQTH
915

E. coli

PF-728

S. mutans

AIGQEQDRREYYYYSGYPYYY
916

E. coli

PF-731

L. pneumophila

RHKLIRLPLSESVFCFLNNPKI
917

PF-732

E. coli

DRPSQTTHHTLSSSRITGPS
918

PF-733

S. mutans

VISRQMGSEAVLELFIIM
919

E. coli

PF-735

S. mutans

YDPLFPNDKN
920

E. coli

PF-737

S. epidermidis

KSSGSSASASSTAGGSSSK
921

S. pneumoniae

PF-738

S. epidermidis

KSGATSAASGAKSGASS
922

C. albicans

C. jeikeium

PF-741

S. epidermidis

AKREDTVAAQIGANILNLIQ
923

M. luteus

P. mirabilis

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

PF-744

S. epidermidis

LGVGTFVGKVLIKNQQKQKSKKKAQ
924

M. luteus

E. coli

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

PF-745

S. epidermidis

ANSQNSLFSNRSSFKSIFDKKSNITTNAT
925

M. luteus

TPNSNIIIN

C. albicans

PF-746

S. epidermidis

FLGNSQYFTRK
926

M. luteus

E. coli

C. albicans

S. pneumoniae

E. faecalis

C. jeikeium

PF-748

S. epidermidis

FQGFFDVAVNKWWEEHNKAKLWKNV
927

M. luteus

KGKFLEGEGEEEDDE

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

PF-749

S. epidermidis

GVNKWWEEHNKAKLWKNVKGKFLEG
928

M. luteus

EGEEEDDE

E. coli

P. aeruginosa

C. albicans

S. pneumoniae

C. jeikeium

PF-750

M. luteus

AESSPAKTTA
929

C. jeikeium

PF-751

S. epidermidis

AESSPAQETT
930

E. coli

C. albicans

C. jeikeium

PF-752

S. epidermidis

LHVIRPRPELSELKFPITKILKVNKQGLKK
931

E. coli

MRSA

S. pneumoniae

E. faecalis

PF-756

S. epidermidis

DALLRLA
932

M. luteus

C. albicans

MRSA

C. jeikeium

PF-757

M. luteus

PQAISSVQQNA
933

C. albicans

MRSA

PF-758

S. epidermidis

PEIIKIVSGLL
934

M. luteus

E. coli

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

PF-760

S. epidermidis

DHITLDDYEIHDGFNFELYYG
935

M. luteus

PF-761

S. epidermidis

SKFELVNYASGCSCGADCKCASETECK
936

M. luteus

CASKK

P. mirabilis

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

PF-762

M. luteus

PAPAPSAPAPAPEQPEQPA
937

C. albicans

PF-763

S. epidermidis

GIWMARNYFHRSSIRKVYVESDKEYER
938

M. luteus

VHPMQKIQYEGNYKSQ

E. coli

C. albicans

MRSA

S. pneumoniae

E. faecalis

PF-764

S. epidermidis

GYFEPGKRD
939

M. luteus

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

PF-765

S. epidermidis

YLYWEVEHKPIIAKRDAYYAQLRKQKE
940

M. luteus

IEEGA

E. coli

MRSA

E. faecalis

C. jeikeium

PF-766

S. epidermidis

DAYYAQLRKQKEIEEGA
941

M. luteus

C. albicans

MRSA

E. faecalis

C. jeikeium

PF-767

S. epidermidis

DGKQGEPVALKPTDN
942

M. luteus

E. coli

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

PF-768

S. epidermidis

GFRGGKRGGARG
943

S. pneumoniae

E. faecalis

C. jeikeium

PF-770

S. epidermidis

GVGIGFIMMGVVGYAVKLVHIPIRYLIV
944

M. luteus

P. mirabilis

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

PF-772

S. epidermidis

TKESSS
945

C. albicans

MRSA

S. pneumoniae

C. jeikeium

PF-773

S. epidermidis

TLKESK
946

C. albicans

C. jeikeium

PF-776

S. epidermidis

VSILLYLSATIILPNVLRLLVARAIIVRV
947

M. luteus

P. mirabilis

C. albicans

MRSA

S. pneumoniae

E. faecalis

PF-777

Mycobacteria spp.
PGADGKLAEASAAIARLVRS
948

PF-778

Mycobacteria spp.
MNLILTAHGT
949

PF-779

Mycobacteria spp.
IYGDFFNFYLCDISLKVNGLQPGGPVRT
950

VKLFGQPTGRCTPQ

PF-780

Mycobacteria spp.
AVYDALVALAAAEHRAELATRDARAK
951

DTYEKIGVHVVVAA

PF-781

Mycobacteria spp.
PLVVVNHRRAERSRG
952

PF-782

Mycobacteria spp.
TGPRRGIDLTSNRALSEVLDEGLELNSRK
953

PF-783

Mycobacteria spp.
FTSEVRGVFTYRVNKAGLITNMRGYW
954

NLDMMTFGNQE

PF-784

Mycobacteria spp.
MAMTTVDNIVGLVIAVALMAFLFAALL
955

FPEKF

PF-785

Mycobacteria spp.
MRPQHSPAGKAFVVKKITHEQS
956

PF-786

Mycobacteria spp.
LSERERRRLKRGII
957

PF-787

Mycobacteria spp.
MTERQRRALLKQHPEVVSWSDYLEKR
958

KRRTGTAG

PF-788

Mycobacteria spp.
GLITVFAGTARILQLRRAAKKTHAAALR
959

PF-789

Mycobacteria spp.
PRGAQSGHG
960

PF-790

Mycobacteria spp.
PAGPDHLDQRDHR
961

PF-791

S. mutans

IFLTTQNTDYSEHNAA
962

PF-792

S. mutans

ALHASGIQAI
963

PF-793

S. mutans

YTQUNNASAYAMLLTNKDTVP
964

PF-794

S. mutans

NLYFENQGN
965

PF-795

S. mutans

ALHKSGIQVIADWVPDQIYN
966

PF-796

S. mutans

YTQSNIPTAYALMLSNKDSI
967

PF-797

S. mutans

WYYFDNNGYM
968

PF-798

S. mutans

ALHSKGIKVMADWVPDQMYA
969

PF-799

S. mutans

YTHYNTALSYALLLTNKSSVP
970

PF-800

S. mutans

WYYFDNNGYM
971

PF-C003

A. naeslundii

FCSVDHDVITIAADHVKQGAEA
972

P. gingivalis

S. mutans

PF-C008

A. naeslundii

AQPRRTWLVNFGEVPSPGLTNDGMPDH
973

PF-C034

S. mutans

HPMPITVRSRKPGPLTAPSEH
974

E. coli

PF-C045

A. naeslundii

FREGMGWPLSNEGSPTAPLPKHRNQV
975

T. denticola

PF-C050

A. naeslundii

QGLARPVLRRIPL
976

S. mutans

PF-C052

A. naeslundii

SRFRNGV
977

F. nucleatum

S. mutans

PF-C055

A. naeslundii

YNLSIYIYFLHTITIAGLITLPFII
978

F. nucleatum

P. gingivalis

S. mutans

PF-C057

A. naeslundii

YFWWYWVQDCIPYKNNEVWLELSNN
979

F. nucleatum

MK

P. gingivalis

S. mutans

PF-C058

A. naeslundii

FETGFGDGYYMSLWGLNEKDEVCKVV
980

F. nucleatum

IPFINPELID

P. gingivalis

S. mutans

PF-C061

A. naeslundii

TLNYKKMFFSVIFLLGLNYLICNSPLFFK
981

F. nucleatum

QIEF

P. gingivalis

S. mutans

T. denticola

PF-C062

A. naeslundii

PLARATEVVATLFIICSLLLYLTR
982

F. nucleatum

P. gingivalis

S. mutans

T. denticola

PF-C063

A. naeslundii

SHFRKGD
983

F. nucleatum

S. mutans

PF-C064

A. naeslundii

DEEALEMGANLYAQFAIDFLNSKK
984

F. nucleatum

P. gingivalis

S. mutans

T. denticola

PF-C065

A. naeslundii

DEERYSDSYFLKEKVFYLILALFLILFHQ
985

F. nucleatum

KYLYFLEIITI

P. gingivalis

S. mutans

PF-C068

A. naeslundii

LNLFASI
986

F. nucleatum

S. mutans

PF-C069

A. naeslundii

NALMLREMQLAKNIKVEVTDVLSNKK
987

F. nucleatum

YC

P. gingivalis

S. mutans

T. denticola

PF-C071

A. naeslundii

QVIVKIL
988

F. nucleatum

S. mutans

PF-C072

A. naeslundii

KKMFSLIRKVNWIFFILFIVLDLTNVFPLI
989

F. nucleatum

RTILFAILSRQ

P. gingivalis

S. mutans

T. denticola

PF-C075

A. naeslundii

KALVISVFAIVFSIIFVKFFYWRDKK
990

F. nucleatum

P. gingivalis

S. mutans

T. denticola

PF-C080

A. naeslundii

INIPGLF
991

F. nucleatum

S. mutans

PF-C084

A. naeslundii

FFSVIFLFGLNYLICNSPLFNILR
992

F. nucleatum

P. gingivalis

S. mutans

PF-C085

A. naeslundii

KKFKIFVIINWFYHKYIILNFEENF
993

F. nucleatum

P. gingivalis

S. mutans

T. denticola

PF-C086

A. naeslundii

ELFFTILSDCNELFLLHLLQQPLFYIKKGK
994

F. nucleatum

P. gingivalis

S. mutans

T. denticola

PF-C088

A. naeslundii

DIANNILNSVSERLIIA
995

F. nucleatum

P. gingivalis

S. mutans

T. denticola

PF-C091

A. naeslundii

ASNTPRFVRLTLFNFYSKIWNVTHLFLF
996

F. nucleatum

NNL

P. gingivalis

S. mutans

T. denticola

PF-C093

A. naeslundii

EKLGTMV
997

F. nucleatum

S. mutans

PF-C095

A. naeslundii

LLALNMNEDTYYFELFFIFDNQNKKWL
998

F. nucleatum

IFDLKERG

P. gingivalis

S. mutans

PF-C098

A. naeslundii

PETKGKVSAFVFGIVVANVIAVVYILYM
999

F. nucleatum

LREIGIIQ

P. gingivalis

S. mutans

T. denticola

PF-C120

A. naeslundii

ASLSTMTFKVMELKELIILLCGLTMLMI
1000

F. nucleatum

QTEFV

P. gingivalis

S. mutans

T. denticola

PF-C131

A. naeslundii

QWIVAKREIRMHIYCHISVIHVIIFFG
1001

F. nucleatum

P. gingivalis

S. mutans

PF-C134

A. naeslundii

NELMKYPATLTATATTPGIKYSHLCSVCL
1002

F. nucleatum

P. gingivalis

S. mutans

T. denticola

PF-C135

A. naeslundii

KNTHAYLRVLRLSSLILSYQASVYPLFA
1003

F. nucleatum

YLCQQKDY

P. gingivalis

S. mutans

PF-C136

A. naeslundii

LILSYQASVYPLFAYLCQQKDY
1004

F. nucleatum

P. gingivalis

S. mutans

T. denticola

PF-C137

A. naeslundii

QRMYWFKRGFETGDFSAGDTFAELK
1005

F. nucleatum

P. gingivalis

S. mutans

PF-C139

A. naeslundii

LLASHPERLSLGVFFVYRVLHLLLENT
1006

F. nucleatum

P. gingivalis

S. mutans

T. denticola

PF-C142

A. naeslundii

DFPPLSFFRRRFHAYTAPIDNFFGANPF
1007

F. nucleatum

P. gingivalis

S. mutans

T. denticola

PF-C143

A. naeslundii

VVFGGGDRLV
1008

F. nucleatum

P. gingivalis

S. mutans

T. denticola

PF-C145

A. naeslundii

YGKESDP
1009

F. nucleatum

P. gingivalis

S. mutans

T. denticola

PF-C160

F. nucleatum

AASGFTYCASNGVWHPY
1010

PF-C180

F. nucleatum

TVEELDKAFTWGAAAALAIGVIAINVG
1011

P. gingivalis

LAAGYCYNNNDVF

S. mutans

T. denticola

PF-C181

P. gingivalis

KMRAGQVVFIYKLILVLLFYVLQKLFD
1012

LKKGCF

PF-C194

A. naeslundii

NTNDLLQAFELMGLGMAGVFIVLGILYI
1013

F. nucleatum

VAELLIKIFPVNN

P. gingivalis

S. mutans

T. denticola

PF-C259

F. nucleatum

AEIQPHCLSVL
1014

S. mutans

PF-C271

A. naeslundii

FFPSYYSIIITYF
1015

F. nucleatum

P. gingivalis

S. mutans

T. denticola

PF-C273

A. naeslundii

KNMLKRRMKQKRLFDEEDRLRVLSKY
1016

P. gingivalis

TKSYY

S. mutans

T. denticola

PF-C281

A. naeslundii

KKEKLLTAIRLQHRAEIRGYFTIFFLFFRI
1017

F. nucleatum

P. gingivalis

S. mutans

T. denticola

PF-C285

A. naeslundii

FTIIELKKQKIKHGENNKKTAHPLNEPF
1018

F. nucleatum

CARA

P. gingivalis

S. mutans

T. denticola

PF-C290

A. naeslundii

GNVHPESDFHNLIQFIKTFLYFTIFFKYFL
1019

F. nucleatum

P. gingivalis

S. mutans

T. denticola

PF-C291

A. naeslundii

HPFLTGTGCPLFLIFRLFFVKAYFSFTVF
1020

F. nucleatum

P. gingivalis

S. mutans

PF-S003

S. epidermidis

ALALLKQDLLNFEGRGRIITSTYLQFNE
1021

M. luteus

GCVP

P. mirabilis

E. coli

P. aeruginosa

C. albicans

MRSA

S. pneumoniae

E. faecalis

C. jeikeium

C. jejuni

M. smegmatis

PF-S004

S. epidermidis

VLLNIFRTLLEFFSPSNAPGAEDVPLPDT
1022

MRSA
QA

C. jeikeium

PF-S007

S. epidermidis

VVAGVVLLTALAVGSKRKEKKQIKEIQ
1023

MRSA
RLLAATR

PF-S015

S. epidermidis

IENLERGARRPP
1024

MRSA

C. jeikeium

PF-S018

S. epidermidis

GMPQIPRLRI
1025

M. luteus

C. albicans

MRSA

E. faecalis

C. jeikeium

C. jejuni

PF-S023

S. epidermidis

MAEDERRALKRRTNRGRTRTRKRITV
1026

MRSA

PF-S026

S. epidermidis

TELKYNGEEYLLLTQRDILAVIEK
1027

MRSA

C. jeikeium

PF-S029

M. luteus

TSDTQSQSPWLFDNADIVNIYPVQLMHS
1028

P. mirabilis

SDND

E. coli

C. albicans

C. jeikeium

C. jejuni

*Peptide binding was conducted in aqueous buffers that varied depending on peptide solubility. For example: Brain Heart Infusion (BHI) Media; 1× Phosphate-buffered saline (PBS); 0.05% v/v Tween-20; 0.05% v/v Tween-80; 1% v/v Glycerol; 50 μM Guanidine hydrochloride; 0.05% v/v Acetic acid; 50 μM Urea; 1% v/v Polyethylene glycol 400 (PEG 400); 20 mM Sodium glutamate; 50 mM Piperazine-1,4-bis(2-ethanesulfonic acid) (PIPES); 50 mM Sodium acetate; 1% v/v Pluronic 17R4; 1% w/v Pluronic F108; 1% w/v Pluronic P123; 0.2% v/v Cetyl trimethylammonium bromide (CTAB); 0.8% v/v β-D-Octyl glucoside (BOG); 0.2% CTAB and 0.05% Tween-20; 0.2% CTAB and 0.05% Tween-80; 0.2% CTAB and 1% glycerol; and 20 mM HEPES (4-(2-hydroxyethyl)-1- piperazineethanesulfonic acid), 150 mM sodium chloride, 1 mM magnesium chloride and 0.1% CTAB. Preferably, binding was evaluated in 1× PBS.

**Three-amino acid code: Dab: Diaminobutyric acid; Orn: Ornithine; cDOrn, cOrn: side-chain cyclical Ornithine; Abreviations: c(X . . . Y) indicates amino acids are cyclic, connected X to Y; DX indicates D-isoform amino acids.

In certain embodiments, the amino acid sequence of the targeting peptides comprises or consists of a single amino acid sequence, e.g., as listed above in Table 3. In certain embodiments the amino acid sequence of the targeting peptides comprises two copies, three copies, four copies, five copies six copies or more of one or more of the amino acid sequences listed in Table 3, and/or Table 10, and/or Table 12. Thus, compound targeting constructs are contemplated where the construct comprises multiple domains each having targeting activity. The targeting domains comprising such a construct can be the same or different. In certain embodiments the construct comprises at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, or at least 8 different targeting domains each domain comprising a different targeting sequence.

Various targeting domains comprising such a construct can be joined directly to each other or two or more of such domains can be attached to each other via a linker. An illustrative, but non-limiting, list of suitable linkers is provided in Table 16. Thus, in certain embodiments, two or more targeting domains comprising a compound/multiple targeting construct are chemically conjugated together.

In certain embodiments the two or more targeting domains comprising the construct are joined by a peptide linker. Where all the targeting domains are attached directly to each other or are joined by peptide linkers, the entire construct can be provided as a single-chain peptide (fusion protein).

In various embodiments, the targeting peptides described herein comprise one or more of the amino acid sequences shown in Table 3, and/or Table 10, and/or Table 12 (and/or the retro, inverso, retroinverso, etc. forms of such sequences). In certain embodiments the peptides range in length up to about 100 amino acids in length, preferably up to about 80, about 70, about 60, or about 51 amino acids in length. In certain embodiments the peptides range in length from about 8 amino acids up to about 100 amino acids 80 amino acids, 60 amino acids or about 51 amino acids in length. In certain embodiments the peptides range in length from about 8 up to about 50, 40, 30, 20, 15, 15, 13, or 12 amino acids in length.

As shown in Tables 3, 10, and 12 the various amino acid sequences described herein target particular microorganisms. The range of activity of the peptides or compositions comprising such peptides can be increased by including amino acid sequences that target different microorganisms either as separate components and/or as multiple domains within a single construct.

In some embodiments greater specificity and/or avidity can be obtained by including multiple different amino acid sequences that target the same microorganism.

II. Antimicrobial Peptides.

A) Uses of Antimicrobial Peptides.

The antimicrobial peptides described herein also have a wide variety of uses. For example, the peptides can be formulated individually, in combination, in combination with other antimicrobial peptides, and/or in combination with various antibacterial agents to provide antimicrobial pharmaceuticals.

In various embodiments, the antimicrobial peptides described herein can be formulated individually, in combination, in combination with other antimicrobial peptides, and/or in combination with various antibiotic (e.g., antibacterial) agents in “home healthcare” formulations. Such formulations include, but are not limited to toothpaste, mouthwash, tooth whitening strips or solutions, contact lens storage, wetting, or cleaning solutions, dental floss, toothpicks, toothbrush bristles, oral sprays, oral lozenges, nasal sprays, aerosolizers for oral and/or nasal application, wound dressings (e.g., bandages), and the like.

In various embodiments the antimicrobial peptides described herein can be formulated individually, in combination, in combination with other antimicrobial peptides, and/or in combination with various antibiotic (e.g., antibacterial) agents in various cleaning and/or sterilization formulations for use in agriculture, in fool preparation and transport, in the home, workplace, clinic, or hospital.

In certain embodiments the antimicrobial peptides described herein are attached to one or more targeting moieties to specifically and/or to preferentially deliver the peptide(s) to a target (e.g. a target microorganism, biofilm, bacterial film, particular tissue, etc.).

Other possible uses of the targeting and/or antimicrobial peptides disclosed herein include, but are not limited to biofilm dispersal, biofilm retention, biofilm formation, anti-biofilm formation, cell agglutination, induction of motility or change in motility type, chemoattractant or chemorepellent, extracellular signal for sporogenesis or other morphological change, induction or inhibition of virulence gene expression, utilized as extracellular scaffold, adhesin or binding site, induction or suppression of host immune response, induction or suppression of bacterial/fungal antimicrobial molecule production, quorum-sensing, induction of swarming behavior, apoptosis or necrosis inducing in eukaryotic cells, affecting control of or inducing the initiation of cell cycle in eukaryotes, in archaea or prokaryotes, induces autolysis or programmed cell death, inhibition of phage/virus attachment or replication, evasion of innate immunity, induction or inhibition of genetic transformation or transduction competence, induction or inhibition of pilus-mediated conjugation, induction or inhibition of mating behavior in bacteria and fungi, induction or inhibition of nodule formation or metabolic compartmentalization, metal, ion, or nutrient binding, acquisition or inhibition of metal, ion, or nutrient binding and acquisition, and the like.

In certain embodiments, compositions and methods are provided for decreasing the infectivity, morbidity, and rate of mortality associated with a variety of pathogens. The present invention also relates to methods and compositions for decontaminating areas, samples, solutions, and foodstuffs colonized or otherwise infected by pathogens and microorganisms. Certain embodiments of the present compositions are nontoxic and may be safely ingested by humans and other animals. Additionally, certain embodiments of the present invention are chemically stable and non-staining.

In some embodiments, the present invention provides compositions and methods suitable for treating animals, including humans, exposed to pathogens or the threat of pathogens. In some embodiments, the animal is contacted with effective amounts of the compositions prior to exposure to pathogenic organisms. In other embodiments, the animal or human is contacted with effective amounts of the compositions after exposure to pathogenic organisms. Thus, the present invention contemplates both the prevention and treatment of microbiological and other infections.

In certain embodiments compositions and methods are provided for decontaminating solutions and surfaces, including organic and inorganic samples that are exposed to pathogens or suspected of containing pathogens. In still other embodiments of the present invention, the compositions are used as additives to prevent the growth of harmful or undesired microorganisms in biological and environmental samples.

These applications of the peptides described herein are intended to be illustrative and not limiting. Using the teaching provided herein, other uses will be recognized by one of skill in the art.

B Illustrative Novel Antimicrobial Peptides.

Antimicrobial peptides (also called host defense peptides) are an evolutionarily conserved component of the innate immune response and are found among all classes of life. Unmodified, these peptides are potent, broad spectrum antibiotics which demonstrate potential as novel therapeutic agents. Antimicrobial peptides have been demonstrated to kill Gram-negative and Gram-positive bacteria (including strains that are resistant to conventional antibiotics), mycobacteria (including Mycobacterium tuberculosis), enveloped viruses, and fungi.

Naturally-occurring antimicrobial peptides are typically short peptides, generally between 12 and 50 amino acids. These peptides often include two or more positively charged residues provided by arginine, lysine or, in acidic environments, histidine, and frequently a large proportion (generally >50%) of hydrophobic residues (see, e.g., Papagianni et al. (2003) Biotechnol Adv 21: 465; Sitaram and Nagaraj (2002) Curr Pharm Des 8: 727; Dürr et al. (2006) Biochim. Biophys. Acta 1758: 1408-1425).

Frequently the secondary structures of these molecules follow 4 themes, including i) α-helical, ii) β-stranded due to the presence of 2 or more disulfide bonds, iii) β-hairpin or loop due to the presence of a single disulfide bond and/or cyclization of the peptide chain, and iv) extended. Many of these peptides are unstructured in free solution, and fold into their final configuration upon partitioning into biological membranes. The ability to associate with membranes is a definitive feature of antimicrobial peptides although membrane permeabilisation is not necessary. These peptides have a variety of antimicrobial activities ranging from membrane permeabilization to action on a range of cytoplasmic targets.

The modes of action by which antimicrobial peptides kill bacteria is varied and includes, but is not limited to disrupting membranes, interfering with metabolism, and targeting cytoplasmic components. In many cases the exact mechanism of killing is not known.

In certain embodiments the antimicrobial peptides include peptides comprising or consisting of one or more of the amino acid sequences shown in Tables 4 (SEQ ID NOs:1029-1078), and/or Table 5 (SEQ ID NOs:1079-1566). In various embodiments the peptides include peptides comprising or consisting of the retro, inverso, retro-inverso, and/or beta form of one or more of the amino acid sequences shown in Tables 4 (SEQ ID NOs:1029-1078), and/or Table 5 (SEQ ID NOs:1079-1566). The peptides can comprise all “L” amino acids, all “D” amino acids, or combinations of “L” and “D” amino acids. Also contemplated are circular permutations of these sequences as well as peptides comprising or consisting of the retro, inverso, retro-inverso, and/or beta form of such circular permutations.

It will also be recognized, that in certain embodiments, any peptide or compound AMP described herein can be circularized.

In various embodiments the peptides can optionally bear one or more protecting groups, e.g., and the amino and/or carboxyl termini, and/or on side chains.

Also contemplated are peptides comprising one, two, three four, or five conservative substitutions of these amino acid sequences.

TABLE 4

Novel antimicrobial peptides, target microorganisms

and MIC values.

Organism MIC

SEQ

ID
(μM)
Structure/sequence
ID NO

K-1

S. mutans, 25
GLGRVIGRLIKQIIWRR
1029

K-2

S. mutans, 12.5
VYRKRKSILKIYAKLKGWH
1030

K-7

S. mutans, 12.5
NYRLVNAIFSKIFKKKFIKF
1031

K-8

S. mutans, 4
KILKFLFKKVF
1032

K-9

S. mutans, 4
FIRKFLKKWLL
1033

K-10

S. mutans, 4
KLFKFLRKHLL
1034

K-11

S. mutans, 4
KILKFLFKQVF
1035

K-12

S. mutans, 8
KILKKLFKFVF
1036

K-13

S. mutans, 16
GILKKLFTKVF
1037

K-14

S. mutans, 8
LRKFLHKLF
1038

K-15

S. mutans, 4
LRKNLRWLF
1039

K-16

S. mutans, 8
FIRKFLQKLHL
1040

P. aeruginosa, 12.5

MRSA, 25

K-17

S. mutans, 8
FTRKFLKFLHL
1041

K-18

S. mutans, 16
KKFKKFKVLKIL
1042

K-19

S. mutans, 16
LLKLLKLKKLKF
1043

K-20

S. mutans, 8
FLKFLKKFFKKLKY
1044

K-21

S. mutans, 8
GWLKMFKKIIGKFGKF
1045

K-22

S. mutans, 8
GIFKKFVKILYKVQKL
1046

1T-88

GRLVLEITADEVKALGEALANAKI
1047

PF-531

A. baumannii, 25
YIQFHLNQQPRPKVKKIKIFL-NH2
1048

P. aeruginosa, 50

T. rubrum, 50

A. niger, 25

B. subtilis, 25

C. difficile, 12.5

C. jeikeium, 6.25

S. epidermidis, 50

S. mutans, 12.5

PF-527

P. aeruginosa, 50
GSVIKKRRKRMAKKKHRKLLKKTRIQR
1049

T. rubrum, 25
RRAGK

A. niger, 50

B. subtilis, 12.5

C. jeikeium, 6.25

MRSA, 50

S. epidermidis, 25

PF-672

C. albicans, 1.56
MRFGSLALVAYDSAIKHSWPRPSSVRR
1050

T. rubrum, 0.78
LRM

A. niger, 3

B. subtilis, 0.78

E. faecalis, 3.13

MRSA, 1.56

S. epidermidis, 0.39

PF-606

E. coli, 50
FESKILNASKELDKEKKVNTALSFNSHQ
1051

MRSA, 50
DFAKAYQNGKI

S. epidermidis, 50

S. mutans, 50

S. pneumoniae, 50

PF-547

T. rubrum, 25
WSRVPGHSDTGWKVWHRW-NH2
1052

B. subtilis, 25

S. mutans, 12.5

PF-006

A. baumannii, 50
MGIIAGIIKFIKGLIEKFTGK
1053

B. subtilis, 25

MRSA, 50

PF-545

A. niger, 50
RESKLIAMADMIRRRI-NH2
1054

B. subtilis, 25

MRSA, 50

PF-278

C. albicans, 50
LSLATFAKIFMTRSNWSLKRFNRL
1055

T. rubrum, 50

S. epidermidis, 50

PF-283

T. rubrum, 50
MIRIRSPTKKKLNRNSISDWKSNTSGRF
1056

B. subtilis, 50
FY

S. epidermidis, 50

PF-307

C. albicans, 50
MKRRRCNWCGKLFYLEEKSKEAYCCK
1057

T. rubrum, 50
ECRKKAKKVKK

B. subtilis, 50

PF-168

T. rubrum, 50
VLPFPAIPLSRRRACVAAPRPRSRQRAS
1058

A. niger, 50

MRSA, 50

PF-538

A. baumannii, 25
KNKKQTDILEKVKEILDKKKKTKSVGQ
1059

C. difficile, 25
KLY

PF-448

A. niger, 25
SLQSQLGPCLHDQRH
1060

S. pneumoniae, 50

PF-583
MRSA, 50
KFQGEFTNIGQSYIVSASHMSTSLNTGK
1061

S. epidermidis, 50

PF-600

E. coli, 50
TKKIELKRFVDAFVKKSYENYILERELK
1062

S. pneumoniae, 50
KLIKAINEELPTK

PF-525

A. niger, 50
KFSDQIDKGQDALKDKLGDL
1063

S. pneumoniae, 50

PF-529

A. niger, 50
LSEMERRRLRKRA-NH2
1064

S. pneumoniae, 50

PF-148

A. niger, 50
RRGCTERLRRMARRNAWDLYAEHFY
1065

B. subtilis, 50

PF-530

A. baumannii, 25
SKFKVLRKIIIKEYKGELMLSIQKQR
1066

PF-522

C. difficile, 25
FELVDWLETNLGKILKSKSA-NH2
1067

PF-497

B. subtilis, 50
LVLRICTDLFTFIKWTIKQRKS
1068

PF-499

B. subtilis, 50
VYSFLYVLVIVRKLLSMKKRIERL
1069

PF-322

B. subtilis, 50
GIVLIGLKLIPLLANVLR
1070

PF-511

S. pneumoniae, 50
VMQSLYVKPPLILVTKLAQQN
1071

PF-512

S. pneumoniae, 50
SFMPEIQKNTIPTQMK
1072

PF-520

S. pneumoniae, 50
LGLTAGVAYAAQPTNQPTNQPTNQPTN
1073

QPTNQPTNQPRW-NH2

PF-521

S. pneumoniae, 50
CGKLLEQKNFFLKTR
1074

PF-523

S. pneumoniae, 50
ASKQASKQASKQASKQASKQASRSLKN
1075

HLL

PF-524

S. pneumoniae, 50
PDAPRTCYHKPILAALSRIVVTDR
1076

PF-209
MRSA, 50
NYAVVSHT
1077

PF-437

S. pneumoniae, 50
FQKPFTGEEVEDFQDDDEIPTII
1078

Where protecting groups are shown (e.g., —NH₂) they are optional. Conversely any peptide shown without protecting groups can bear one or more such groups.

In certain embodiments peptides that induce alterations in phenotype or other biological activities can also be used as antimicrobial effector moieties. Illustrative alternative peptides are shown in Table 5.

TABLE 5

Illustrative list of novel morphology, biofilm and growth

disrupting peptides.

SEQ ID

ID
Organism, effect
Structure/sequence
NO

G-1

S. mutans: Ca2+
DSSQSDSDSDSNSSNTNSNSSITNG
1079

binding

G-2

S. mutans: biofilm
LPGTLHIQAEFPVQLEAGSLIQIFD
1080

structure

G-4

S. mutans:
EIPIQLANDLANYYDISLDSIFFW
1081

Biofilm structure

G-5

M. xanthus:
RDMTVAGKRPNFLIITTDEE
1082

Altered cell

morphology

G-6

M. xanthus:
NTSIVCAVTFAPIKEVPLLWRAGLTLRS
1083

Altered cell
RQS

morphology

G-7

M. xanthus:
QAKVEREVERDLVYTLRRLCDPSGSER
1084

Altered cell
TK

morphology

G-8

S. mutans:
PRMIDIISFHGCHGDHQVWTDPQATAL
1085

Altered biofilm
PR

structure

PF-001

S. epidermidis (C)
MNNWIIVAQLSVTVINEIIDIMKEKQKG
1086

M. luteus (C)
GK

MRSA (R)

C. jeikeium (D)

PF-002

B. subtilis (R)
NDDAQ
1087

S. pneumoniae (H)

PF-003

S. epidermidis (D)
MNNWIKVAQISVTVINEVIDIMKEKQN
1088

M. luteus (A)
GGK

MRSA (R)

C. jeikeium (A)

PF-004

S. epidermidis (A)
ARLSKAIIIAVIVVYHLDVRGLF
1089

M. luteus (A)

MRSA (R)

C. jeikeium (A)

PF-005

B. subtilis (C)
MESIFKIKLMNGICRSENMNMKKKNK
1090

S. pneumoniae (H)
GEKI

PF-006

S. epidermidis (D)
MGIIAGIIKFIKGLIEKFTGK
1091

M. luteus (A)

B. subtilis (I)

MRSA (I)

S. pneumoniae (R)

C. jejuni (D)

PF-007

S. epidermidis (A)
MGIIAGIIKVIKSLIEQFTGK
1092

M. luteus (A)

E. coli (A)

MRSA (R)

E. faecalis (A)

PF-008

B. subtilis (D)
MIEIGSIAYLNGGSKKYNHILNQENR
1093

C. jejuni (R)

PF-009

S. epidermidis (S)
SKKYNHILNQENR
1094

PF-010

S. epidermidis (S)
MDIDVNKLLQAFVYFKSFEKLRHNNS
1095

M. luteus (A)

MRSA (R)

C. jeikeium (A)

PF-011
MRSA (R)
MFCYYKQHKGDNFSIEEVKNIIADNEM
1096

C. jeikeium (C)
KVN

PF-012

S. epidermidis (S)
WRGPNTEAGGKSANNIVQVGGAPT
1097

M. luteus (C)

MRSA (R)

C. jeikeium (A)

PF-013

S. epidermidis (C)
LIQKGLNQTFIVVIRLNNFIKKS
1098

M. luteus (D)

MRSA (R)

C. jeikeium (D)

PF-015
MRSA (W)
SIDKRNLYNLKYYE
1099

PF-017
MRSA (M)
ESIIE
1100

PF-019
MRSA (M)
NDTNK
1101

PF-020

S. mutans (F)
MKIILLLFLIFGFIVVVTLKSEHQLTLFSI
1102

S. epidermidis (C)

M. luteus (C)

MRSA (C)

S. pneumoniae (D)

PF-021

S. epidermidis (A)
FSLNFSKQKYVTVN
1103

M. luteus (A)

MRSA (R)

C. jeikeium (R)

PF-022

S. epidermidis (D)
MINELKNKNSGIMNNYVVTKESKL
1104

M. luteus (A)

MRSA (R)

C. jeikeium (A)

PF-023
MRSA (S)
MTKNTIISLENEKTQINDSENESSDLRK
1105

AK

PF-024

S. epidermidis (D)
DLRKAK
1106

MRSA (M)

PF-025

S. epidermidis (S)
LLIIFRLWLELKWKNKK
1107

M. luteus (A)

MRSA (R)

C. jeikeium (A)

PF-026
MRSA (M)
SIHFIN
1108

PF-027

S. epidermidis (D)
HNARKYLEFISQKIDGDKLTKEDSL
1109

MRSA (M)

PF-028

S. epidermidis (M)
ALDCSEQSVILWYETILDKIVGVIK
1110

MRSA (R)

C. jeikeium (M)

PF-029
MRSA (M)
NSTNE
1111

PF-030

S. epidermidis (D)
MTCHQAPTTTHQSNMA
1112

M. luteus (C)

MRSA (R)

C. jeikeium (C)

PF-031
MRSA (M)
MPHHSTTSSRIVVPAHQSNMASTPNLSI
1113

TP

PF-032

S. epidermidis (S)
RIVVPAHQSNMASTPNLSITP
1114

C. jeikeium (C)

PF-033

S. epidermidis (M)
MFIFKTTSKSHFHNNVKSLECIKIPINK
1115

B. subtilis (C)
NR

MRSA (M)

S. pneumoniae (R)

C. jeikeium (D)

C. jejuni (R)

PF-034

S. epidermidis (A)
EPKKKHFPKMESASSEP
1116

PF-035
MRSA (M)
SFYESY
1117

PF-036

S. epidermidis (S)
ILNRLSRIVSNEVTSLIYSLK
1118

M. luteus (A)

MRSA (R)

C. jeikeium (A)

PF-037

S. epidermidis (D)
MTKKRRYDTTEFGLAHSMTAKITLHQ
1119

M. luteus (C)
ALYK

MRSA (R)

C. jeikeium (D)

PF-040

S. mutans (F)
MIHLTKQNTMEALHFIKQFYDMFFILN
1120

S. epidermidis (D) FNV

M. luteus (D)

B. subtilis (D)

P. mirabilis (C)

E. coli (C)

MRSA (D)

S. pneumoniae (D)

C. jeikeium (D)

C. jejuni (D)

PF-041

S. epidermidis (R)
ELLVILPGFI
1121

MRSA (M)

PF-042

S. epidermidis (D)
LLLSYFRYTGALLQSLF
1122

M. luteus (C)

MRSA (R)

C. jeikeium (S)

PF-043

S. epidermidis (D)
MIKNETAYQMNELLVIRSAYAK
1123

M. luteus (C)

MRSA (R)

C. jeikeium (A)

PF-045
MRSA (S)
LDINDYRSTY
1124

PF-046

S. epidermidis (C)
LDFYLTKHLTLML
1125

MRSA (R)

C. jeikeium (R)

PF-048

S. epidermidis (D)
LYFAFKKYQERVNQAPNIEY
1126

MRSA (W)

C. jeikeium (S)

PF-049
MRSA (S)
AYYLKRREEKGK
1127

PF-051

S. mutans (D)
RFFNFEIKKSTKVDYVFAHVDLSDV
1128

S. epidermidis (D)

M. luteus (C)

MRSA (D)

S. pneumoniae (D)

PF-052

S. epidermidis (S)
QELINEAVNLLVKSK
1129

M. luteus (A)

MRSA (R)

C. jeikeium (D)

PF-053

S. epidermidis (C)
KLFGQWGPELGSIYILPALIGSIILIAIVT
1130

M. luteus (D)
LILRAMRK

B. subtilis (H)

E. coli (A)

P. aeruginosa (A)

C. albicans (A)

MRSA (D)

S. pneumoniae (S)

E. faecalis (A)

C. jeikeium (D)

C. jejuni (D)

PF-056

S. epidermidis (D)
AEQLFGKQKQRGVDLFLNRLTIILSILF
1131

M. luteus (D)
FVLMICISYLGM

B. subtilis (C)

C. albicans (B)

MRSA (M)

S. pneumoniae (D)

C. jeikeium (S)

C. jejuni (D)

PF-057

S. epidermidis (D)
TMIVISIPRFEEYMKARHKKWM
1132

M. luteus (C)

E. coli (M)

C. albicans (A)

MRSA (M)

S. pneumoniae (R)

E. faecalis (A)

C. jeikeium (A)

C. jejuni (D)

PF-058
MRSA (M)
FADQSQDNA
1133

PF-059

C. jejuni (C)
TITLKAGIERALHEEVPGVIEVEQVF
1134

PF-061

S. epidermidis (R)
GYNSYKAVQDVKTHSEEQRVTAKK
1135

B. subtilis (R)

S. pneumoniae (R)

C. jejuni (R)

PF-063

S. epidermidis (R)
IAAIIVLVLFQKGLLQIFNWILIQLQ
1136

M. luteus (R)

B. subtilis (C)

P. aeruginosa (A)

MRSA (M)

S. pneumoniae (D)

C. jeikeium (D)

C. jejuni (D)

PF-064

S. epidermidis (D)
DYYGKE
1137

MRSA (M)

PF-065

S. epidermidis (D)
LEKNTRDNYFIHAIDRIYINTSKGLFPES
1138

MRSA (R)
ELVAWG

C. jeikeium (A)

PF-066
MRSA (S)
IKGTVKAVDETTVVITVNGHGTELTFE
1139

KPAIKQVDPS

PF-067

S. epidermidis (D)
DLIVKVHICFVVKTASGYCYLNKREAQ
1140

M. luteus (R)
AAI

B. subtilis (C)

P. aeruginosa (A)

MRSA (M)

S. pneumoniae (D)

C. jeikeium (D)

C. jejuni (D)

PF-068

S. epidermidis (M)
SHLINNFGLSVINPSTPICLNFSPVFNLL
1141

M. luteus (D)
TVYGITCN

B. subtilis (A)

E. coli (A)

MRSA (M)

S. pneumoniae (D)

E. faecalis (A)

C. jeikeium (R)

C. jejuni (D)

PF-069

B. subtilis (D)
FDPVPLKKDKSASKHSHKHNH
1142

C. jejuni (R)

PF-070

B. subtilis (D)
SMVKSEIVDLLNGEDNDD
1143

PF-071

S. epidermidis (R)
HCVIGNVVDIANLLKRRAVYRDIADVI
1144

M. luteus (R)
KMR

B. subtilis (D)

C. albicans (B)

MRSA (C)

S. pneumoniae (A)

C. jejuni (A)

PF-073

S. epidermidis (R)
CPSVTMDACALLQKFDFCNNISHFRHF
1145

M. luteus (R)
FAIKQPIER

MRSA (M)

S. pneumoniae (D)

C. jeikeium (D)

C. jejuni (D)

PF-074

S. epidermidis (D)
RDIHPIYFMTKD
1146

MRSA (M)

PF-075

S. epidermidis (D)
FVNSLIMKDLSDNDMRFKYEYYNREK
1147

M. luteus (A)
DT

MRSA (R)

C. jeikeium (D)

PF-076

S. epidermidis (S)
LYQYELLSKEEYLKCTLIINQRRNEQK
1148

M. luteus (A)

MRSA (R)

C. jeikeium (A)

PF-099

S. epidermidis (D)
EIIAYLEGRFANA
1149

C. jeikeium (C)

PF-123

S. epidermidis (M)
TTRPQVAEDRQLDDALKETFPASDPISP
1150

PF-124

S. epidermidis (C)
MADGQIAAIAKLHGVPVATRNIRHFQS
1151

C. jeikeium (R)
FGVELINPWSG

PF-125

S. epidermidis (D)
YVVGALVILAVAGLIYSMLRKA
1152

M. luteus (C)

PF-127

S. epidermidis (M)
MLRYLSLFAVGLATGYAWGWIDGLA
1153

M. luteus (A)
ASLAV

C. jeikeium (A)

PF-128

S. epidermidis (D)
GIKVVAARFEEIQFSENFDSIILA
1154

P. aeruginosa (C)

PF-129

S. epidermidis (M)
MKLLARDPWVCAWNDIW
1155

C. jeikeium (R)

PF-133

C. jeikeium (R)
GDPTAGQKPVECP
1156

PF-135

C. jeikeium (R)
PPARPARIPQTPTLHGASLFRQRS
1157

PF-137

S. epidermidis (D)
VLGKGHDLLDVGKTALKSRVFAWLG
1158

M. luteus (D)
GS

C. jeikeium (A)

PF-139

S. epidermidis (M)
ALSKPAIQARTLCRRQDPP
1159

M. luteus (C)

C. jeikeium (R)

PF-140

S. epidermidis (D)
FHRRVIRASEWALTTRSFSTPLRSAAR
1160

M. luteus (R)

P. aeruginosa (A)

C. albicans (B)

MRSA (M)

S. pneumoniae (D)

C. jeikeium (D)

C. jejuni (D)

PF-143

P. aeruginosa (C)
LSPRPIIVSRRSRADNNNDWSR
1161

PF-144

S. pneumoniae (H)
RSGQPVGRPSRRAWLR
1162

PF-145

S. epidermidis (D)
GIVLTGRAGLVSGACSMALGVGLG
1163

M. luteus (A)

B. subtilis (C)

MRSA (M)

S. pneumoniae (R)

C. jeikeium (R)

C. jejuni (R)

PF-148

S. epidermidis (D)
RRGCTERLRRMARRNAWDLYAEHFY
1164

M. luteus (A)

B. subtilis (I)

C. albicans (B)

MRSA (C)

S. pneumoniae (R)

C. jeikeium (H)

C. jejuni (H)

PF-149
MRSA (H)
GKVSVLTRVPRSLGGAPANQ
1165

PF-153

S. epidermidis (M)
GILARADCSQIA
1166

C. jeikeium (C)

PF-156
MRSA (H)
LITAEQPATAPIAGK
1167

PF-157

S. epidermidis (M)
HTAVVWLAGVSGCVALSHCEPA
1168

PF-164

C. jeikeium (R)
EEVSRALAGIGLGLGCRIG
1169

PF-168

P. aeruginosa (H)
VLPFPAIPLSRRRACVAAPRPRSRQRAS
1170

MRSA (I)

PF-171

S. epidermidis (R)
TQVTLCRTW
1171

M. luteus (R)

B. subtilis (D)

MRSA (M)

S. pneumoniae (D)

C. jejuni (R)

PF-173

S. epidermidis (A)
AGRTAIVQGGG
1172

C. jeikeium (D)

PF-175

M. luteus (S)
RRRPAGQRPEKASQAMIAA
1173

B. subtilis (D)

C. albicans (B)

S. pneumoniae (A)

C. jejuni (M)

PF-176

S. epidermidis (C)
RLTSNQFLTRITPFVFAQH
1174

M. luteus (C)

C. jeikeium (D)

PF-178

S. epidermidis (D)
EVYSSPTNNVAITVQNN
1175

E. coli (C)

MRSA (M)

S. pneumoniae (D)

PF-180

S. epidermidis (C)
SGLGDLGFSSEAK
1176

PF-186

S. epidermidis (C)
DADKNLSLERDRFAWRVAAP
1177

C. jeikeium (A)

PF-188

C. jeikeium (H)
ARTFAGRLGTRYFGGLMRSTKA
1178

PF-190

S. epidermidis (C)
HFILRKPLLFMIHSLKTGPLDRF
1179

C. jeikeium (R)

PF-191

S. epidermidis (A)
QFCNFAWLFLASNNAQVSALA
1180

MRSA (H)

C. jeikeium (R)

PF-192

S. epidermidis (D)
VEEDEAPPPHY
1181

PF-196

S. epidermidis (C)
TTARYIRRQCHTSITPLSQG
1182

C. jeikeium (R)

PF-199

S. epidermidis (C)
FPAFSFGAIAGSVSVAR
1183

M. luteus (A)

C. jeikeium (R)

PF-203

S. epidermidis (A)
SWKCHHLAI
1184

C. jeikeium (R)

PF-204

S. epidermidis (C)
ALQKQDMNLPSVKNQLVFLKSTG
1185

M. luteus (C)

P. aeruginosa (H)

C. jeikeium (D)

PF-208

S. epidermidis (D)
DAYHCHLVRSPDAHDLSMRIGFV
1186

C. jeikeium (A)

PF-209

S. epidermidis (C)
NYAVVSHT
1187

P. aeruginosa (H)

MRSA (I)

PF-212

M. luteus (M)
NDSKASN
1188

PF-215

M. luteus (T)
ELKITNYNVNTVLYRYYKWGNDLCE
1189

PF-220

S. pneumoniae (H)
VDPADDGTRHIRPEDGDPIEIDE
1190

PF-224

M. luteus (T)
DYFYITLSQKNTF
1191

PF-226

S. epidermidis (C)
LMFFSENMDKRDTLSGKFRYFAGSKVI
1192

M. luteus (T)
KLMNWLSENGK

PF-233

S. epidermidis (C)
DANAMARTTIAIVYILALIALTISYSL
1193

PF-234

M. luteus (T)
RTPYILRS
1194

PF-235

M. luteus (T)
GIPFSKPHKRQVNYMKSDVLAYIEQNK
1195

MAHTA

PF-249

M. luteus (R)
INSRYKISF
1196

PF-250

M. luteus (T)
SEDIFGRLANEKANGLEELRKIRLKQ
1197

PF-255

M. luteus (M)
DHKINESQHNPFRSDSNKQNVDFF
1198

PF-257

M. luteus (R)
VWENRKKYLENEIERHNVFLKLGQEVI
1199

KGLNALASRGR

PF-264

M. luteus (H)
MQSLSNRQSLIASYILMGIFLSFGYPPA
1200

SLSKFFCRLSHL

PF-270

M. luteus (H)
MYLTPYAWIAVGSIFAFSVTTIKIGDQN
1201

DEKQKSHKNDVHKR

PF-271

M. luteus (T)
AAQPQTT SP
1202

PF-273

S. epidermidis (C)
LVGALLIFVALIYMVLKGNADKN
1203

PF-274

M. luteus (M)
SIQEAEKIIKNDPFYIHDVADYDFMWF
1204

EPSKSLEEIKEFV

PF-276

M. luteus (M)
LDLALSTNSLNLEGFSF
1205

PF-278

S. epidermidis (I)
LSLATFAKIFMTRSNWSLKRFNRL
1206

M. luteus (R)

C. albicans (B)

PF-283

S. epidermidis (H)
MIRIRSPTKKKLNRNSISDWKSNTSGRF
1207

B. subtilis (H)
FY

PF-289

B. subtilis (C)
MGRHLWNPSYFVATVSENTEEQIRKY
1208

RKNK

PF-290

S. epidermidis (C)
MVHDMTNGTLIIVKH
1209

PF-292

S. epidermidis (C)
SFVSTTVRLIFEESKRYKF
1210

B. subtilis (C)

PF-293

S. epidermidis (C)
YDPLK
1211

PF-294

S. epidermidis (C)
DFLVNFLWFKGELNWGKKRYK
1212

PF-296

S. epidermidis (C)
GAFGMPSIKTNTICGEKGKFISACDAW
1213

B. subtilis (C)
LSNLK

PF-297

S. epidermidis (C)
ISKGIDDIVYVINKILSIGNIFKIIKRK
1214

B. subtilis (C)

PF-301

S. epidermidis (C)
GIVLIGLKLIPLLANVLN
1215

B. subtilis (C)

PF-303

B. subtilis (C)
EYPWSWISEPWPWDKSFYK
1216

PF-305

B. subtilis (C)
MREWICPSCNETHDRDINASINILKEGL
1217

RLITIQNK

PF-306

B. subtilis (C)
GCILPHKKDNYNYIMSKFQDLVKITSKK
1218

PF-307

S. epidermidis (T)
MKRRRCNWCGKLFYLEEKSKEAYCC
1219

B. subtilis (H)
KECRKKAKKVKK

C. albicans (B)

PF-310

S. epidermidis (C)
GVALIGTILVPLLSGLFG
1220

PF-313

S. epidermidis (C)
YITSHKNARAIIKKFERDEILEEVITHYL
1221

NRK

PF-318

S. epidermidis (C)
MGRHLWNPSYFVATVSENTEEQIRKYI
1222

B. subtilis (C)
NNQKKQVK

PF-319

S. epidermidis (C)
SIGSMIGMYSFRHKTKHIKFTFGIPFILF
1223

B. subtilis (C)
LQFLLVYFYILK

PF-322

S. epidermidis (C)
GIVLIGLKLIPLLANVLR
1224

B. subtilis (H)

PF-335

S. epidermidis (C)
AAYPIEDWSDWYEDFFIMLSNI
1225

B. subtilis (C)

PF-339

S. epidermidis (C)
KKIDILINKYMYLSK
1226

B. subtilis (C)

PF-342

S. epidermidis (C)
AFSGVYKTLIVYTRRK
1227

B. subtilis (C)

PF-344

E. coli (A)
DERLPEAKAIRNFNGSVMVLGR
1228

PF-347

S. epidermidis (C)
GIFTGVTVVVSLKHC
1229

E. coli (C)

MRSA (C)

E. faecalis (C)

PF-349

S. epidermidis (C)
MPKSCHVPVLCDFFFLVIIKFLALFKTI
1230

E. coli (C)
QS

MRSA (C)

E. faecalis (C)

PF-350

S. epidermidis (C)
LAVILRAIVY
1231

E. coli (C)

MRSA (C)

PF-354
MRSA (H)
FTFSKCRASNGRGFGTLWL
1232

PF-355

S. epidermidis (C)
WIAIGLLLYFSLKNQ
1233

E. coli (C)

P. aeruginosa (A)

MRSA (A)

S. pneumoniae (D)

E. faecalis (D)

C. jejuni (D)

PF-356

S. epidermidis (S)
VSIKIGAIVIGMIGLMELLTE
1234

P. aeruginosa (A)

MRSA (C)

S. pneumoniae (R)

E. faecalis (R)

C. jejuni (D)

PF-357

S. epidermidis (M)
MLTIIIGFIFWTMTLMLGYLIGEREGRK
1235

M. luteus (C)
HE

MRSA (M)

S. pneumoniae (M)

PF-360

S. epidermidis (S)
MEQKVKVIFVPRSKPDNQLKTFVSAVL
1236

E. coli (C)
FKA

MRSA (H)

PF-362

E. coli (C)
NIERILKEKVWMIRCVE
1237

MRSA (C)

PF-363

S. epidermidis (S)
SMLSVTVMCLMHASVAANQAMEKKV
1238

E. coli (C)

MRSA (H)

S. pneumoniae (R)

E. faecalis (D)

C. jejuni (D)

PF-366

S. epidermidis (R)
ALCSVIKAIELGIINVHLQ
1239

E. coli (C)

P. aeruginosa (A)

MRSA (D)

S. pneumoniae (C)

E. faecalis (C)

C. jejuni (D)

PF-369

S. epidermidis (S)
MSEAVNLLRGARYSQRYAKNQVPYEV
1240

E. coli (R)
IIEK

MRSA (H)

E. faecalis (C)

PF-370

S. epidermidis (C)
VIFLHKESGNLKEIFY
1241

E. coli (R)

MRSA (C)

PF-373

S. epidermidis (M)
HFYLLFER
1242

MRSA (M)

PF-374

S. epidermidis (C)
HLFFVKGMFILCQKNQINDE
1243

E. coli (C)

MRSA (M)

E. faecalis (C)

PF-375

S. epidermidis (C)
MDSAKAQTMRTDWLAVSCLVASAYL
1244

E. coli (C)
RSMLA

MRSA (C)

E. faecalis (C)

PF-376

S. epidermidis (C)
MTVFEALMLAIAFATLIVKISNKNDKK
1245

E. coli (C)

MRSA (C)

E. faecalis (C)

PF-378

S. epidermidis (M)
ESAKSNLNFLMQEEWALFLLL
1246

MRSA (M)

PF-379

S. epidermidis (C)
VFVVLFIIYLASKLLTKLFPIKK
1247

E. coli (C)

MRSA (C)

E. faecalis (C)

PF-380

S. epidermidis (C)
KKIIPLITLFVVTLVG
1248

E. coli (C)

P. aeruginosa (A)

MRSA (D)

S. pneumoniae (D)

E. faecalis (C)

C. jejuni (D)

PF-381

S. epidermidis (C)
QGANPCQQVGFTVNDPDCRLAKTV
1249

E. coli (R)

MRSA (C)

E. faecalis (C)

PF-382
MRSA (M)
KYKCSWCKRVYTLRKDHKTAR
1250

PF-383

S. epidermidis (C)
WSEIEINTKQSN
1251

E. coli (R)

PF-385

E. coli (A)
MIKKSILKIKYYVPVLISLTLILSA
1252

PF-386

S. epidermidis (C)
FTLTLITTIVAILNYKDKKK
1253

E. coli (C)

MRSA (C)

E. faecalis (C)

PF-387

S. epidermidis (C)
GAVGIAFFAGNMKQDKRIADRQNKKS
1254

E. coli (M)
EKK

MRSA (C)

E. faecalis (C)

PF-389

S. epidermidis (R)
GLQFKEIAEEFHITTTALQQWHKDNGY
1255

MRSA (C)
PIYNKNNRK

S. pneumoniae (D)

E. faecalis (R)

C. jejuni (R)

PF-390

S. epidermidis (D)
VVAYVITQVGAIRF
1256

E. coli (C)

MRSA (D)

S. pneumoniae (D)

E. faecalis (D)

C. jejuni (D)

PF-392
MRSA (S)
DPAGCNDIVRKYCK
1257

E. faecalis (A)

C. jejuni (A)

PF-393

S. epidermidis (R)
DLVQSILSEFKKSG
1258

MRSA (C)

S. pneumoniae (R)

E. faecalis (A)

C. jejuni (R)

PF-394
MRSA (C)
VLKEECYQKN
1259

E. faecalis (A)

PF-395

S. epidermidis (C)
YCVPLGNMGNMNNKIW
1260

E. coli (R)

MRSA (C)

PF-396

S. epidermidis (S)
LIYTILASLGVLTVLQAILGREPKAVKA
1261

E. coli (C)

MRSA (C)

E. faecalis (C)

PF-397

S. epidermidis (C)
VEDLMEDLNA
1262

PF-398

S. epidermidis (C)
ILVVLAGILLVVLSYVGISKFKMNC
1263

E. coli (C)

MRSA (C)

E. faecalis (C)

PF-399

S. epidermidis (C)
FPIISALLGAIICIAIYSFIVNRKA
1264

E. coli (C)

MRSA (C)

E. faecalis (C)

PF-401

S. epidermidis (C)
YWLSRVTTGHSFAFEKPVPLSLTIK
1265

E. coli (R)

MRSA (C)

E. faecalis (C)

PF-403

S. epidermidis (M)
LLSTEQLLKYYDGETFDGFQLPSNE
1266

E. coli (R)

MRSA (M)

PF-404

S. epidermidis (M)
VLYFQATVV
1267

MRSA (M)

PF-405
MRSA (M)
LVRIEVDDLEEWYERNFI
1268

PF-406

S. epidermidis (C)
YLEMNADYLSNMDIFDELWEKYLENNK
1269

MRSA (M)

PF-407

S. epidermidis (M)
KPKNKKEKTVISYEKLLSMY
1270

MRSA (C)

S. pneumoniae (R)

E. faecalis (R)

PF-408

S. epidermidis (M)
YCVPLGNMGNMNNKIW
1271

MRSA (M)

PF-410

S. epidermidis (C)
FALELIALCRNLFIVYFP
1272

E. coli (S)

MRSA (M)

E. faecalis (C)

PF-411

S. epidermidis (C)
WVAVAILLNIALQTQLT
1273

E. coli (C)

P. aeruginosa (A)

MRSA (D)

S. pneumoniae (D)

E. faecalis (D)

C. jejuni (D)

PF-413

S. epidermidis (C)
TFAGSIKIGVPDLVHVTFNCKR
1274

E. coli (S)

MRSA (C)

PF-414

S. pneumoniae (H)
LLNKKLE
1275

PF-415

S. pneumoniae (D)
MIDVTIGQKSKTGAFNASYSICFSGENF
1276

SF

PF-416

S. pneumoniae (H)
SKAGLYGKIERSDKRE
1277

PF-417

S. epidermidis (M)
DSYFRS
1278

MRSA (M)

S. pneumoniae (M)

PF-418

S. epidermidis (M)
FFLVHFYIRKRKGKVSIFLNYF
1279

E. coli (C)

MRSA (D)

S. pneumoniae (D)

E. faecalis (D)

C. jejuni (D)

PF-419

S. pneumoniae (H)
VVTGKVGSLPQIK
1280

PF-421

S. pneumoniae (H)
KHCFEITDKTDVV
1281

PF-422

S. epidermidis (R)
MSRKKYENDEKSQKKLKIGRKSDVFY
1282

MRSA (C)
GIID

S. pneumoniae (C)

E. faecalis (R)

C. jejuni (R)

PF-423

S. pneumoniae (H)
AGKKERLLSFREQFLNKNKKK
1283

PF-424

S. pneumoniae (H)
IAAFVTSRAFSDTVSPI
1284

PF-425

S. epidermidis (D)
MMELVLKTIIGPIVVGVVLRIVDKWLN
1285

E. coli (C)
KDK

P. aeruginosa (A)

C. albicans (A)

MRSA (D)

S. pneumoniae (D)

E. faecalis (D)

C. jejuni (D)

PF-426

S. epidermidis (D)
MLQKYTQMISVTKCIITKNKKTQENVD
1286

E. coli (C)
AYN

C. albicans (A)

MRSA (D)

S. pneumoniae (D)

E. faecalis (D)

C. jejuni (D)

PF-427

E. coli (C)
YVLEYHGLRATQDVDAFMAL
1287

MRSA (C)

S. pneumoniae (R)

E. faecalis (C)

PF-428

S. pneumoniae (H)
ENEESIF
1288

PF-429

S. epidermidis (C)
AATLICVGSGIMSSL
1289

MRSA (C)

S. pneumoniae (M)

E. faecalis (C)

PF-430

S. epidermidis (M)
AVVCGYLAYTATS
1290

MRSA (M)

S. pneumoniae (M)

PF-431

S. epidermidis (M)
VAYAAICWW
1291

MRSA (C)

S. pneumoniae (R)

E. faecalis (R)

C. jejuni (R)

PF-432

S. epidermidis (M)
FNGDSEFFLCIAF
1292

E. coli (R)

P. aeruginosa (A)

MRSA (M)

S. pneumoniae (D)

E. faecalis (D)

C. jejuni (D)

PF-433

S. pneumoniae (H)
MRKEFHNVLSSGQLLADKRPARDYNRK
1293

PF-434

S. pneumoniae (S)
GQLLADKRPARDYNRK
1294

PF-437

S. pneumoniae (I)
FQKPFTGEEVEDFQDDDEIPTII
1295

PF-439

S. epidermidis (C)
RVLVLKKFHGIMDGNRNVAVFFVGQ
1296

E. coli (R)

MRSA (M)

S. pneumoniae (R)

E. faecalis (C)

PF-440

S. epidermidis (C)
MFIISPDLFNIAVILYILFFIHDILLLILS
1297

E. coli (R)

MRSA (C)

S. pneumoniae (R)

E. faecalis (C)

PF-442
MRSA (M)
MQIFYIKTKIFLSFFLFLLIFSQCFYKIEE
1298

S. pneumoniae (C)

PF-443

E. coli (R)
KLLYFFNYFENLQQVHLLVQL
1299

MRSA (C)

S. pneumoniae (C)

PF-444

S. epidermidis (C)
MAAKLWEEGKMVYASSASMTKRLKL
1300

E. coli (R)
AMSKV

MRSA (C)

S. pneumoniae (R)

E. faecalis (C)

PF-445

S. pneumoniae (M)
ASMTKRLKLAMSKV
1301

PF-446

S. pneumoniae (H)
SGNEKV
1302

PF-447

S. epidermidis (C)
IDKSRNKDQFSHIFGLYNICSG
1303

MRSA (C)

S. pneumoniae (C)

E. faecalis (C)

PF-448

S. pneumoniae (I)
SLQSQLGPCLHDQRH
1304

PF-449

S. pneumoniae (H)
MPTTKSKQKGWTNTKKASNTQ
1305

PF-450
MRSA (C)
HRNLIILQRTIFI
1306

S. pneumoniae (C)

E. faecalis (C)

PF-451

S. epidermidis (C)
MVNYIIGSYMLYREQNNNEALRKFDIT
1307

E. coli (R)
LAM

MRSA (C)

S. pneumoniae (C)

E. faecalis (C)

PF-452

S. epidermidis (C)
MNNWIKVAQISVTVINEVIDIMKEKQN
1308

E. coli (C)
GGK

MRSA (C)

S. pneumoniae (R)

E. faecalis (C)

PF-453

S. epidermidis (C)
IIQDIAHAFGY
1309

E. coli (C)

MRSA (C)

S. pneumoniae (C)

PF-454

S. epidermidis (C)
MSVFVPVTNIFMFIMSPIFNVNLLHFKV
1310

E. coli (R)
YI

P. aeruginosa (H)

MRSA (C)

S. pneumoniae (R)

E. faecalis (C)

PF-455

S. pneumoniae (A)
MARNDDDIKKIKGTLGQSPEVYGERK
1311

LPYT

PF-456

E. faecalis (A)
TCVKPRTIN
1312

C. jejuni (A)

PF-457

S. pneumoniae (M)
INKYHHIA
1313

PF-458

P. aeruginosa (H)
ISLIIFIMLFVVALFKCITNYKHQS
1314

MRSA (M)

S. pneumoniae (M)

PF-459

S. pneumoniae (H)
EKRMSFNENQSHRPLL
1315

PF-460

S. epidermidis (C)
MEHVLPFQNTPPNIVIIYKDFTHLKSITFS
1316

E. coli (H)

MRSA (C)

S. pneumoniae (R)

E. faecalis (C)

PF-461
MRSA (R)
MTLAIKNCSVTKCLGFGDFVNDDSDS
1317

S. pneumoniae (R)
YFDA

E. faecalis (A)

PF-462

S. pneumoniae (H)
KNKTDTL
1318

PF-464

S. pneumoniae (S)
VDMVNRFLGN
1319

PF-465

S. pneumoniae (H)
KPVGKALEEIADGKIEPVVPKEYLG
1320

PF-466

S. pneumoniae (H)
VRKSDQ
1321

PF-467

S. pneumoniae (H)
YYKDYFKEI
1322

PF-468

S. pneumoniae (H)
EDNKDKKDKKDK
1323

PF-469

S. epidermidis (D)
YKVNYNNIDNHFNTLRH
1324

E. coli (C)

MRSA (D)

S. pneumoniae (D)

E. faecalis (D)

C. jejuni (D)

PF-470

E. faecalis (A)
PYSDSYATRPHWEQHRAR
1325

C. jejuni (A)

PF-471

S. epidermidis (C)
MVGKIRGVTPRNDLLNANITGQLNLN
1326

E. coli (C)
YRLI

P. aeruginosa (A)

MRSA (D)

S. pneumoniae (D)

E. faecalis (C)

C. jejuni (D)

PF-472
MRSA (C)
MHISHLLDEVEQTEREKAVNVLENMN
1327

S. pneumoniae (R)
GNVI

E. faecalis (A)

C. jejuni (R)

PF-473

S. epidermidis (R)
MAADIISTIGDLVKWIIDTVNKFKK
1328

E. coli (C)

MRSA (C)

S. pneumoniae (H)

E. faecalis (R)

C. jejuni (R)

PF-474

S. epidermidis (C)
MHRNLVLVKMEPIPHIMIIANQIGIIIEKA
1329

E. coli (C)

P. aeruginosa (A)

C. albicans (B)

MRSA (D)

S. pneumoniae (D)

E. faecalis (C)

C. jejuni (D)

PF-475

S. epidermidis (M)
MREKVRFTQAFKLFWTNYFNFKGRSR
1330

C. albicans (B)
RSEY

MRSA (S)

S. pneumoniae (R)

E. faecalis (R)

C. jejuni (R)

PF-476

S. pneumoniae (H)
WADAQYKLCENCSE
1331

PF-477

S. pneumoniae (H)
HKNKLNIPHIKS
1332

PF-478

S. epidermidis (C)
HLFILKSHLKPFPPFRYTYD
1333

E. coli (C)

MRSA (H)

S. pneumoniae (C)

PF-479

S. pneumoniae (C)
AYILKRREEKNK
1334

PF-480

S. epidermidis (C)
MVEILVNTAISVYIVALYTQWLSTRDN
1335

E. coli (R)
LKA

MRSA (C)

S. pneumoniae (R)

E. faecalis (C)

PF-482

S. pneumoniae (S)
LVGYVRTSGTVRSYKIN
1336

PF-484

E. faecalis (A)
HKKDIRKQVFKN
1337

PF-485

S. pneumoniae (A)
KNSMSRSIALID
1338

PF-511

S. pneumoniae (H)
VMQSLYVKPPLILVTKLAQQN
1339

PF-512

S. pneumoniae (H)
SFMPEIQKNTIPTQMK
1340

PF-513

S. pneumoniae (M)
SNGVGLGVGIGSGIRF-NH2
1341

PF-514

S. epidermidis (C)
QRFYKLFYHIDLTNEQALKLFQVK
1342

E. coli (R)

S. pneumoniae (M)

E. faecalis (C)

PF-515

S. pneumoniae (H)
DKSTQDKDIKQAKLLAQELGL-NH2
1343

PF-516

S. pneumoniae (H)
ASKQASKQASKQASKQ
1344

PF-517

S. pneumoniae (M)
VKPTMTASLISTVC
1345

PF-518

S. epidermidis (C)
SFYSKYSRYIDNLAGAIFLFF
1346

E. coli (R)

MRSA (C)

S. pneumoniae (M)

E. faecalis (C)

PF-519

E. coli (R)
YLVYSGVLATAAAF-NH2
1347

MRSA (C)

S. pneumoniae (S)

E. faecalis (C)

PF-520

S. pneumoniae (M)
LGLTAGVAYAAQPTNQPTNQPTNQPT
1348

NQPTNQPTNQPRW-NH2

PF-521

S. pneumoniae (H)
CGKLLEQKNFFLKTR
1349

PF-522

S. pneumoniae (H)
FELVDWLETNLGKILKSKSA-NH2
1350

PF-524

E. coli (M)
PDAPRTCYHKPILAALSRIVVTDR
1351

MRSA (C)

S. pneumoniae (M)

E. faecalis (C)

PF-525

S. pneumoniae (H)
KFSDQIDKGQDALKDKLGDL
1352

PF-526

S. epidermidis (C)
VLLLFIFQPFQKQLL-NH2
1353

E. coli (R)

C. albicans (C)

MRSA (C)

S. pneumoniae (R)

PF-527

S. epidermidis (M)
GSVIKKRRKRMAKKKHRKLLKKTRIQ
1354

M. luteus (S)
RRRAGK

B. subtilis (I)

P. aeruginosa (I)

C. albicans (B)

MRSA (I)

S. pneumoniae (H)

C. jeikeium (I)

C. jejuni (M)

PF-528

S. epidermidis (H)
LVDVVVLIRRHLPKSCS-NH2
1355

E. coli (H)

C. albicans (C)

MRSA (H)

S. pneumoniae (R)

PF-529

S. pneumoniae (H)
LSEMERRRLRKRA-NH2
1356

PF-530

S. epidermidis (H)
SKFKVLRKIIIKEYKGELMLSIQKQR
1357

E. coli (R)

MRSA (C)

S. pneumoniae (R)

E. faecalis (C)

PF-531

S. epidermidis (I)
YIQFHLNQQPRPKVKKIKIFL-NH2
1358

E. coli (M)

P. aeruginosa (I)

S. pneumoniae (C)

PF-532

E. coli (C)
KFIYKYKLSFIIYKILIQTLTMELNK
1359

MRSA (C)

S. pneumoniae (C)

E. faecalis (C)

PF-533

S. epidermidis (H)
KTPNDKIHKTIIIKHIIL
1360

E. coli (R)

MRSA (H)

S. pneumoniae (C)

E. faecalis (C)

PF-534

S. epidermidis (C)
KYFHLFYHNIIHYSKQHLSLKVDFKN-
1361

E. coli (R)
NH2

MRSA (C)

S. pneumoniae (R)

E. faecalis (C)

PF-535

P. aeruginosa (H)
NIKTRKRALKIIKQHQRSK
1362

S. pneumoniae (H)

PF-536

S. epidermidis (C)
MEPIPHIMIIANQIGIIIEKA
1363

E. coli (R)

P. aeruginosa (H)

MRSA (C)

S. pneumoniae (M)

E. faecalis (C)

PF-537

S. pneumoniae (C)
LANDYYKKTKKSW
1364

PF-538

S. pneumoniae (H)
KNKKQTDILEKVKEILDKKKKTKSVG
1365

QKLY

PF-539
MRSA (H)
SIILTKKKRRKIPLSIDSQIYKYTFKQ
1366

S. pneumoniae (A)

PF-540

S. epidermidis (H)
KSILILIKVIFIGQTTIIL
1367

E. coli (R)

MRSA (H)

S. pneumoniae (R)

PF-541

E. coli (H)
RRNLNSPNIKTRKRALKIIKQHQRSK
1368

S. pneumoniae (H)

PF-542

S. pneumoniae (H)
KKDNPSLNDQDKNAVLNLLALAK
1369

PF-543

S. mutans (S)
NILFGIIGFVVAMTAAVIVTAISIAK
1370

S. epidermidis (D)

M. luteus (C)

E. coli (C)

MRSA (D)

S. pneumoniae (D)

PF-544

S. epidermidis (D)
FGEKQMRSWWKVHWFHP
1371

MRSA (D)

S. pneumoniae (M)

E. faecalis (R)

PF-545

B. subtilis (I)
RESKLIAMADMIRRRI-NH2
1372

C. albicans (B)

E. faecalis (H)

C. jeikeium (H)

PF-546

S. epidermidis (D)
PIIAPTIKTQIQ
1373

E. coli (R)

MRSA (D)

S. pneumoniae (D)

E. faecalis (D)

C. jeikeium (D)

PF-547

S. epidermidis (R)
WSRVPGHSDTGWKVWHRW-NH2
1374

B. subtilis (I)

MRSA (M)

E. faecalis (R)

PF-548

S. epidermidis (M)
ARPIADLIHFNSTTVTASGDVYYGPG
1375

M. luteus (A)

B. subtilis (C)

MRSA (M)

S. pneumoniae (D)

C. jeikeium (R)

C. jejuni (D)

PF-549

B. subtilis (D)
TGIGPIARPIEHGLDS
1376

MRSA (C)

PF-550

B. subtilis (D)
STENGWQEFESYADVGVDPRRYVPL
1377

PF-551
MRSA (C)
QVKEKRREIELQFRDAEKKLEASVQAE
1378

PF-552

B. subtilis (D)
ELDKADAALGPAKNLAPLDVINRS
1379

PF-553

B. subtilis (D)
LTIVGNALQQKNQKLLLNQKKITSLG
1380

MRSA (M)

S. pneumoniae (R)

C. jeikeium (R)

PF-554

B. subtilis (D)
AKNFLTRTAEEIGEQAVREGNINGP
1381

PF-555
MRSA (M)
EAYMRFLDREMEGLTAAYNVKLFTEA
1382

S. pneumoniae (R)
IS

C. jejuni (R)

PF-556

S. epidermidis (A)
SLQIRMNTLTAAKASIEAA
1383

M. luteus (A)

B. subtilis (C)

MRSA (M)

S. pneumoniae (D)

E. faecalis (A)

C. jeikeium (D)

C. jejuni (R)

PF-557

B. subtilis (D)
AANKAREQAAAEAKRKAEEQAR
1384

PF-558

S. epidermidis (M)
ADAPPPLIVRYS
1385

B. subtilis (D)

MRSA (C)

S. pneumoniae (R)

C. jejuni (H)

PF-559

B. subtilis (C)
SRPGKPGGVSIDVSRDRQDILSNYP
1386

C. jejuni (A)

PF-560

B. subtilis (D)
FGNPFRGFTLAMEADFKKRK
1387

MRSA (C)

S. pneumoniae (R)

C. jejuni (A)

PF-561

B. subtilis (D)
ESLEADVQAELDTEAAKYPALPASF
1388

MRSA (M)

PF-562

S. epidermidis (A)
TPEQWLERSTVVVTGLLNRK
1389

M. luteus (R)

MRSA (M)

S. pneumoniae (D)

C. jejuni (R)

PF-563

B. subtilis (D)
RPELDNELDVVQNSASLDKLQASYN
1390

S. pneumoniae (H)

C. jejuni (H)

PF-564

B. subtilis (D)
TIILNDQINSLQERLNKLNAETDRR
1391

MRSA (C)

C. jeikeium (R)

C. jejuni (R)

PF-565

B. subtilis (D)
RAEAEAQRQAEADAKRKAEEAARL
1392

MRSA (C)

PF-566

M. luteus (D)
EAQQVTQQLGADFNAITTPTATKV
1393

B. subtilis (C)

MRSA (M)

S. pneumoniae (D)

C. jeikeium (C)

C. jejuni (D)

PF-567

M. luteus (C)
QQRVKAVDASLSQVSTQVSGAVASA
1394

MRSA (D)

S. pneumoniae (D)

C. jeikeium (C)

C. jejuni (D)

PF-569

B. subtilis (D)
KSKISEYTEKEFLEFVEDIYTNNK
1395

PF-571

B. subtilis (D)
SDLLYYPNENREDSPAGVVKEVKE
1396

PF-572

B. subtilis (D)
WRASKGLPGFKAG
1397

S. pneumoniae (R)

PF-573

S. pneumoniae (C)
EKKLIVKLIDSIGKSHEEIVGAG
1398

PF-574

B. subtilis (D)
LVKSGKLESPYEHSEHLTLSQEKGLE
1399

PF-575

P. aeruginosa (A)
LNFRAENKILEKIHISLIDTVEGSA
1400

S. pneumoniae (A)

C. jeikeium (A)

C. jejuni (R)

PF-576

S. epidermidis (A)
AYSGELPEPLVRKMSKEQVRSVMGK
1401

E. coli (A)

MRSA (R)

S. pneumoniae (C)

C. jejuni (C)

PF-577

S. epidermidis (A)
PFETRESFRVPVIGILGGWDYFMHP
1402

E. coli (A)

P. aeruginosa (A)

MRSA (M)

S. pneumoniae (R)

E. faecalis (A)

C. jejuni (R)

PF-578

S. mutans (D)
QKANLRIGFTYTSDSNVCNLTFALLGSK
1403

S. epidermidis (D)

M. luteus (C)

P. mirabilis (C)

E. coli (C)

MRSA (C)

S. pneumoniae (D)

PF-580

S. epidermidis (M)
EILNNNQVIKELTMKYKTQFESNLGG
1404

M. luteus (C)
WTARARR

MRSA (M)

S. pneumoniae (C)

PF-581
MRSA (A)
WTARARR
1405

S. pneumoniae (A)

E. faecalis (A)

C. jejuni (A)

PF-582

E. faecalis (A)
NLKTIEKECPFCNNKMDIKLKD
1406

PF-583

S. mutans (F)
KFQGEFTNIGQSYIVSASHMSTSLNTGK
1407

S. epidermidis (I)

MRSA (I)

S. pneumoniae (D)

PF-584

S. epidermidis (C)
SYIKNLSNQKFLIAF
1408

E. coli (C)

MRSA (D)

S. pneumoniae (D)

E. faecalis (D)

C. jejuni (D)

PF-585

S. epidermidis (S)
DYNHLLNVVQDWVNTN
1409

MRSA (S)

S. pneumoniae (R)

E. faecalis (A)

C. jejuni (R)

PF-586

S. epidermidis (C)
FFNQANYFFKEF
1410

E. coli (C)

MRSA (D)

S. pneumoniae (D)

E. faecalis (D)

C. jejuni (D)

PF-587

S. pneumoniae (C)
ASGKYQSYLLNVYVDSKKDRLDIFDK
1411

LKAKAKFVL

PF-588

E. faecalis (A)
ESVEAIKAKAIK
1412

PF-589
MRSA (M)
APLRIDEIRNSNVIDEVLDCAPKKQEHF
1413

S. pneumoniae (C)
FVVPKIIE

PF-590

C. jejuni (R)
YYQAKLFPLL
1414

PF-591

S. pneumoniae (R)
DLLKSLLGQDGAKNDEIIEFIKIIMEK
1415

E. faecalis (A)

C. jejuni (C)

PF-592

S. epidermidis (M)
IMKNYKYFKLFIVKYALF
1416

E. coli (C)

MRSA (D)

S. pneumoniae (D)

E. faecalis (D)

C. jejuni (S)

PF-593

E. faecalis (A)
MEISTLKKEKLHVKDELSQYLANYKK
1417

PF-594

E. faecalis (C)
IVSAIV
1418

PF-595

S. epidermidis (C)
LQNKIYELLYIKERSKLCS
1419

E. coli (C)

MRSA (D)

S. pneumoniae (R)

E. faecalis (D)

C. jejuni (D)

PF-596

S. epidermidis (D)
SKMWDKILTILILILELIRELIKL
1420

E. coli (C)

MRSA (D)

S. pneumoniae (D)

E. faecalis (D)

C. jejuni (D)

PF-597

E. faecalis (A)
DEIKVSDEEIEKFIKENNL
1421

PF-598

S. epidermidis (R)
MKFMLEVRNKAISAYKEITRTQI
1422

E. coli (C)

MRSA (D)

S. pneumoniae (R)

E. faecalis (R)

C. jejuni (R)

PF-599

S. epidermidis (M)
LFEIFKPKH
1423

MRSA (C)

S. pneumoniae (R)

E. faecalis (A)

C. jejuni (R)

PF-600

S. mutans (S)
TKKIELKRFVDAFVKKSYENYILEREL
1424

S. epidermidis (C)
KKLIKAINEELPTK

M. luteus (C)

E. coli (H)

MRSA (M)

S. pneumoniae (R)

PF-601

E. faecalis (A)
YRVTVKALE
1425

C. jejuni (A)

PF-602

E. faecalis (A)
LEKEKKEYIEKLFKTK
1426

PF-603

S. epidermidis (D)
IDKLKKMNLQKLSYEVRISQDGKSIYA
1427

M. luteus (A)
RIK

E. coli (M)

MRSA (M)

S. pneumoniae (C)

PF-604

E. faecalis (A)
LMEQVEV
1428

PF-605

S. epidermidis (R)
HYRWNTQWWKY
1429

E. coli (C)

P. aeruginosa (A)

C. albicans (B)

MRSA (C)

S. pneumoniae (D)

E. faecalis (R)

C. jejuni (R)

PF-606

S. mutans (I)
FESKILNASKELDKEKKVNTALSFNSH
1430

S. epidermidis (I)
QDFAKAYQNGKI

C. albicans (B)

MRSA (I)

S. pneumoniae (H)

PF-607

S. epidermidis (M)
YIESDPRKFDYIFGAIRDH
1431

MRSA (S)

S. pneumoniae (R)

E. faecalis (A)

C. jejuni (R)

PF-609
MRSA (C)
TEIKLDNNEYLVLNLDDILGILK
1432

S. pneumoniae (R)

E. faecalis (A)

C. jejuni (R)

PF-610

S. epidermidis (C)
VFLKLKTSKIDLASIIFYP
1433

E. coli (C)

MRSA (D)

S. pneumoniae (D)

E. faecalis (D)

C. jejuni (D)

PF-612

S. mutans (F)
GTTLKYGLERQLKIDIHPEITIINLNGGA
1434

S. epidermidis (C)
DEFAKL

M. luteus (A)

P. mirabilis (C)

E. coli (C)

MRSA (C)

S. pneumoniae (C)

PF-613

S. epidermidis (R)
ADEFAKL
1435

MRSA (C)

E. faecalis (A)

PF-614

S. epidermidis (M)
GLDIYA
1436

S. pneumoniae (R)

E. faecalis (A)

C. jejuni (R)

PF-615

S. epidermidis (D)
FLNRFIFYIFTVKTKSALIKNLFLD
1437

E. coli (C)

MRSA (D)

S. pneumoniae (D)

E. faecalis (D)

C. jejuni (D)

PF-616

S. epidermidis (R)
IVFVVTKEKK
1438

E. faecalis (A)

PF-617

C. albicans (H)
PMNAAEPE
1439

S. pneumoniae (I)

E. faecalis (H)

PF-618

S. pneumoniae (I)
KLNTLNKKDNPSLNDQDKNAVLNLLA
1440

E. faecalis (H)
LAK

PF-619

S. epidermidis (M)
WSRVPGHSDTGWKVWHRW
1441

E. coli (C)

MRSA (M)

S. pneumoniae (C)

PF-621

S. pneumoniae (I)
PPSSFLV
1442

E. faecalis (H)

PF-622

S. epidermidis (D)
TREDVFSVRLINNIVNKQA
1443

MRSA (D)

S. pneumoniae (M)

E. faecalis (D)

C. jeikeium (D)

PF-623

S. epidermidis (M)
VLFAVYLGALDWLFSWLTQKM
1444

MRSA (D)

S. pneumoniae (D)

E. faecalis (D)

C. jeikeium (R)

PF-624

S. mutans (D)
VFLLDSYCFVKINL
1445

S. epidermidis (D)

M. luteus (C)

P. mirabilis (C)

E. coli (C)

MRSA (C)

S. pneumoniae (D)

PF-625

S. pneumoniae (H)
SDSTNNARTRKKARDVTTKDIDK
1446

PF-626

S. pneumoniae (H)
KYDFDDFEPEEA
1447

PF-627

S. epidermidis (H)
INDLLSYFTLHEK
1448

C. albicans (B)

MRSA (R)

S. pneumoniae (I)

E. faecalis (H)

PF-629

S. epidermidis (C)
GLAAIATVFALY
1449

MRSA (D)

S. pneumoniae (M)

E. faecalis (R)

C. jeikeium (R)

PF-630
MRSA (M)
IPATPIIHS
1450

PF-631

S. pneumoniae (I)
LIIYFSKTGNTARATRQI
1451

E. faecalis (H)

PF-632

S. epidermidis (D)
TTIQGVASLEKHGFRYTIIYPTRI
1452

B. subtilis (H)

C. albicans (B)

MRSA (D)

S. pneumoniae (M)

E. faecalis (D)

C. jeikeium (D)

PF-634

S. mutans (D)
MPKARPVNHNKKKSKITIKSNFTLFYM
1453

S. epidermidis (D)
FNP

M. luteus (C)

P. mirabilis (C)

E. coli (C)

MRSA (D)

S. pneumoniae (D)

PF-635

S. epidermidis (M)
MNAHGHSLIFQKMIVHAFAFFSKQKN
1454

C. albicans (B)
YLYF

MRSA (D)

S. pneumoniae (D)

E. faecalis (D)

C. jeikeium (D)

PF-636

B. subtilis (H)
LVRLA
1455

C. albicans (B)

S. pneumoniae (H)

E. faecalis (H)

PF-637

S. epidermidis (M)
SRIKQDARSVRKYDRIGIFFYSFKSA
1456

MRSA (M)

S. pneumoniae (M)

E. faecalis (D)

C. jeikeium (D)

PF-638

S. epidermidis (R)
TFILPK
1457

MRSA (M)

S. pneumoniae (I)

E. faecalis (H)

PF-639

C. albicans (B)
QATQIKSWIDRLLVSED
1458

MRSA (R)

S. pneumoniae (I)

E. faecalis (H)

PF-640

C. albicans (B)
MGDINRNF
1459

S. pneumoniae (I)

E. faecalis (H)

PF-642
MRSA (M)
FTTPMIGIPAGLLGGSYYLKRREEKGK
1460

PF-643
MRSA (C)
VRCRL
1461

S. pneumoniae (R)

E. faecalis (R)

PF-644

S. pneumoniae (H)
TSGLIIGENGLNGL
1462

PF-645

C. albicans (B)
SNSVQQG
1463

S. pneumoniae (I)

PF-646

C. albicans (B)
APASPGRRPG
1464

S. pneumoniae (H)

PF-647

C. albicans (B)
GTFLGQKCAAATAS
1465

S. pneumoniae (R)

PF-649

E. faecalis (R)
CPRYPFVDVGPAGPWRARWRVGS
1466

PF-651

S. pneumoniae (H)
PRWPTGAGRHR
1467

PF-652

S. pneumoniae (A)
FLAPARPDLQAQRQALAQ
1468

PF-653

S. pneumoniae (H)
QSVHPLPAETPVADVI
1469

PF-654

C. albicans (B)
LSGRLAGRR
1470

MRSA (R)

S. pneumoniae (A)

PF-655

S. epidermidis (R)
DAPCFDDQFGDLKCQMC
1471

B. subtilis (H)

MRSA (M)

S. pneumoniae (H)

PF-656
MRSA (R)
RGMFVPFHDVDCVQ
1472

PF-657

S. epidermidis (C)
YVANYTITQFGRDFDDRLAVAIHFA
1473

MRSA (D)

S. pneumoniae (H)

E. faecalis (D)

C. jeikeium (D)

PF-658
MRSA (R)
PTTPPPTTPPEIPTGGTVIST
1474

S. pneumoniae (H)

PF-659

S. epidermidis (M)
TVIST
1475

B. subtilis (H)

MRSA (R)

S. pneumoniae (C)

PF-660

S. pneumoniae (H)
TDPQATAAPRRRTSPR
1476

PF-661
MRSA (R)
PDEDIRRRAILPPAGPCRPMSPE
1477

PF-662

S. pneumoniae (A)
GKQSRAHGPVASRREFRRKSG
1478

PF-663

S. pneumoniae (A)
ATLIPRKA
1479

PF-664

S. epidermidis (M)
DQLCVEYPARVSTG
1480

MRSA (R)

S. pneumoniae (M)

E. faecalis (R)

PF-665

S. pneumoniae (H)
VLRVATAVGEVPTGL
1481

PF-666

S. pneumoniae (A)
PNRRSRPR
1482

PF-667

S. epidermidis (R)
PAHQRLRIDQRLVADRDMVQDYES
1483

MRSA (R)

S. pneumoniae (R)

E. faecalis (R)

PF-668

S. epidermidis (M)
TNAESMALAFRGRVHMSVNIAGLT
1484

B. subtilis (A)

C. albicans (A)

MRSA (R)

S. pneumoniae (M)

E. faecalis (D)

C. jeikeium (D)

PF-670

B. subtilis (H)
TVIVAPMHSGV
1485

S. pneumoniae (H)

PF-672

S. epidermidis (I)
MRFGSLALVAYDSAIKHSWPRPSSVRR
1486

B. subtilis (I)
LRM

C. albicans (I)

MRSA (I)

S. pneumoniae (I)

E. faecalis (I)

C. jeikeium (R)

PF-675

S. pneumoniae (C)
EIIPISPTRRCEMHTMSSAEYRGL
1487

E. faecalis (R)

PF-677

S. epidermidis (R)
TCRGAGMH
1488

MRSA (D)

S. pneumoniae (D)

E. faecalis (R)

PF-680
MRSA (R)
ADPHPTTGI
1489

PF-681

S. epidermidis (M)
TALTTVGVSGARLITYCVGVEDI
1490

MRSA (M)

S. pneumoniae (M)

E. faecalis (R)

C. jeikeium (R)

PF-682

S. pneumoniae (A)
RRGKSEQGLSRR
1491

PF-683

S. epidermidis (R)
LWPVA
1492

MRSA (R)

S. pneumoniae (H)

PF-684

C. albicans (B)
RKLSLASGFALWRRSLV
1493

S. pneumoniae (C)

E. faecalis (A)

PF-685

S. epidermidis (M)
PTLWLACL
1494

MRSA (M)

S. pneumoniae (M)

E. faecalis (R)

C. jeikeium (R)

PF-686

S. epidermidis (H)
LAVLMGYIGYRGWSGKRHINRQ
1495

B. subtilis (I)

C. albicans (B)

MRSA (M)

S. pneumoniae (A)

E. faecalis (R)

PF-687

S. pneumoniae (A)
AKRVLSLAVAPHRRQPVQGT
1496

PF-688

S. pneumoniae (A)
ARNHAVIPAG
1497

PF-690

S. epidermidis (R)
MIPLAGDPVSSHRTVEFGVLGTYLVSG
1498

MRSA (R)
GSL

S. pneumoniae (M)

E. faecalis (R)

PF-691

S. pneumoniae (R)
HRTVEFGVLGTYLVSGGSL
1499

PF-692
MRSA (R)
GVAREDPLEPDPLAPIIDDSR
1500

PF-693

S. pneumoniae (A)
PDPAR
1501

PF-694
MRSA (R)
DLIRPLYSMSAPSVA
1502

S. pneumoniae (A)

PF-695
MRSA (R)
ALSVMLGNIPLVVPNANQL
1503

S. pneumoniae (C)

E. faecalis (R)

PF-696

S. pneumoniae (H)
IRSGISAAYARPLR
1504

PF-697

C. albicans (H)
RADARAK
1505

S. pneumoniae (H)

PF-698

C. albicans (H)
SSGRAGVKCRRPTGR
1506

S. pneumoniae (A)

E. faecalis (A)

PF-699

S. pneumoniae (A)
GRAGVKCRRPTGR
1507

PF-700

S. pneumoniae (C)
LNWPFTGR
1508

PF-702

S. pneumoniae (H)
LSGRLAGRR
1509

PF-704

S. pneumoniae (C)
APAARAAL
1510

PF-737

S. pneumoniae (D)
KSSGSSASASSTAGGSSSK
1511

PF-738
MRSA (M)
KSGATSAASGAKSGASS
1512

PF-741

S. mutans (D)
AKREDTVAAQIGANILNLIQ
1513

S. epidermidis (C)

M. luteus (C)

P. mirabilis (C)

E. coli (C)

MRSA (C)

S. pneumoniae (D)

PF-744

S. pneumoniae (H)
LGVGTFVGKVLIKNQQKQKSKKKAQ
1514

PF-745

S. mutans (D)
ANSQNSLFSNRSSFKSIFDKKSNITTNA
1515

M. luteus (C)
TTPNSNIIIN

MRSA (C)

S. pneumoniae (C)

PF-746

S. mutans (D)
FLGNSQYFTRK
1516

S. epidermidis (C)

M. luteus (C)

E. coli (C)

P. aeruginosa (A)

MRSA (C)

S. pneumoniae (C)

PF-748

S. pneumoniae (H)
FQGFFDVAVNKWWEEHNKAKLWKN
1517

VKGKFLEGEGEEEDDE

PF-749

S. pneumoniae (H)
GVNKWWEEHNKAKLWKNVKGKFLE
1518

GEGEEEDDE

PF-752

S. pneumoniae (C)
LHVIRPRPELSELKFPITKILKVNKQGL
1519

KK

PF-756

S. pneumoniae (A)
DALLRLA
1520

PF-757

S. pneumoniae (H)
PQAISSVQQNA
1521

PF-760

S. epidermidis (M)
DHITLDDYEIHDGFNFELYYG
1522

MRSA (M)

S. pneumoniae (C)

PF-761

S. mutans (D)
SKFELVNYASGCSCGADCKCASETECK
1523

S. epidermidis (C)
CASKK

M. luteus (C)

E. coli (C)

P. aeruginosa (C)

MRSA (D)

S. pneumoniae (C)

PF-762

S. pneumoniae (H)
PAPAPSAPAPAPEQPEQPA
1524

PF-763

S. epidermidis (M)
GIWMARNYFHRSSIRKVYVESDKEYE
1525

M. luteus (C)
RVHPMQKIQYEGNYKSQ

MRSA (D)

S. pneumoniae (C)

PF-764
MRSA (D)
GYFEPGKRD
1526

S. pneumoniae (H)

PF-770

S. mutans (D)
GVGIGFIMMGVVGYAVKLVHIPIRYLIV
1527

S. epidermidis (D)

M. luteus (C)

P. mirabilis (C)

E. coli (C)

MRSA (D)

S. pneumoniae (C)

PF-776

S. mutans (D)
VSILLYLSATIILPNVLRLLVARAIIVRV
1528

S. epidermidis (D)

M. luteus (C)

E. coli (C)

MRSA (D)

S. pneumoniae (C)

PF-C052

P. gingivalis (H)
SRFRNGV
1529

PF-C055

F. nucleatum (T)
YNLSIYIYFLHTITIAGLITLPFII
1530

S. mutans (I)

PF-C057

S. mutans (I)
YFWWYWVQDCIPYKNNEVWLELSNN
1531

MK

PF-C058

S. mutans (F)
FETGFGDGYYMSLWGLNEKDEVCKV
1532

VIPFINPELID

PF-C061

F. nucleatum (T)
TLNYKKMFFSVIFLLGLNYLICNSPLFF
1533

S. mutans (F)
KQIEF

PF-C062

F. nucleatum (T)
PLARATEVVATLFIICSLLLYLTR
1534

S. mutans (I)

PF-C064

F. nucleatum (T)
DEEALEMGANLYAQFAIDFLNSKK
1535

PF-C065

F. nucleatum (T)
DEERYSDSYFLKEKVFYLILALFLILFH
1536

QKYLYFLEIITI

PF-C069

F. nucleatum (T)
NALMLREMQLAKNIKVEVTDVLSNKK
1537

YC

PF-C071

F. nucleatum (T)
QVIVKIL
1538

PF-C072

F. nucleatum (T)
KKMFSLIRKVNWIFFILFIVLDLTNVFP
1539

P. gingivalis (T)
LIRTILFAILSRQ

S. mutans (F)

PF-C075

F. nucleatum (T)
KALVISVFAIVFSIIFVKFFYWRDKK
1540

P. gingivalis (R)

S. mutans (F)

PF-C084

F. nucleatum (T)
FFSVIFLFGLNYLICNSPLFNILR
1541

P. gingivalis (R)

S. mutans (F)

PF-C085

S. mutans (F)
KKFKIFVIINWFYHKYIILNFEENF
1542

PF-C086

F. nucleatum (T)
ELFFTILSDCNELFLLHLLQQPLFYIKK
1543

GK

PF-C088

F. nucleatum (H)
DIANNILNSVSERLIIA
1544

P. gingivalis (R)

S. mutans (I)

PF-C089

P. gingivalis (R)
MPKRHYYKLEAKALQFGLPFAYSPIQL
1545

LK

PF-C091

F. nucleatum (T)
ASNTPRFVRLTLFNFYSKIWNVTHLFLF
1546

NNL

PF-C095

F. nucleatum (T)
LLALNMNEDTYYFELFFIFDNQNKKW
1547

LIFDLKERG

PF-C098

F. nucleatum (T)
PETKGKVSAFVFGIVVANVIAVVYILY
1548

S. mutans (F)
MLREIGIIQ

PF-C120

F. nucleatum (T)
ASLSTMTFKVMELKELIILLCGLTMLMI
1549

QTEFV

PF-C131

F. nucleatum (T)
QWIVAKREIRMHIYCHISVIHVIIFFG
1550

S. mutans (F)

PF-C135

F. nucleatum (C)
KNTHAYLRVLRLSSLILSYQASVYPLF
1551

S. mutans (F)
AYLCQQKDY

PF-C136

F. nucleatum (C)
LILSYQASVYPLFAYLCQQKDY
1552

P. gingivalis (R)

PF-C137

F. nucleatum (T)
QRMYWFKRGFETGDFSAGDTFAELK
1553

PF-C139

S. mutans (F)
LLASHPERLSLGVFFVYRVLHLLLENT
1554

PF-C142

S. mutans (I)
DFPPLSFFRRRFHAYTAPIDNFFGANPF
1555

PF-C143

F. nucleatum (C)
VVFGGGDRLV
1556

PF-C145

F. nucleatum (C)
YGKESDP
1557

S. mutans (I)

PF-C180

P. gingivalis (R)
TVEELDKAFTWGAAAALAIGVIAINVG
1558

S. mutans (S)
LAAGYCYNNNDVF

PF-C181

F. nucleatum (T)
KMRAGQVVFIYKLILVLLFYVLQKLFD
1559

LKKGCF

PF-C194

F. nucleatum (T)
NTNDLLQAFELMGLGMAGVFIVLGILY
1560

P. gingivalis (T)
IVAELLIKIFPVNN

S. mutans (F)

PF-C214

F. nucleatum (T)
GGHKQLVIEPLVSQ
1561

PF-C281

S. mutans (F)
KKEKLLTAIRLQHRAEIRGYFTIFFLFFRI
1562

PF-C290

S. mutans (F)
GNVHPESDFHNLIQFIKTFLYFTIFFKYFL
1563

PF-C291

F. nucleatum (T)
HPFLTGTGCPLFLIFRLFFVKAYFSFTVF
1564

S. mutans (F)

PF-C293

F. nucleatum (T)
IIIILPKIYLVCKTV
1565

P. gingivalis (R)

S. mutans (F)

PF-S003

S. epidermidis (R)
ALALLKQDLLNFEGRGRIITSTYLQFNE
1566

M. luteus (R)
GCVP

B. subtilis (A)

P. aeruginosa (A)

C. albicans (A)

MRSA (M)

S. pneumoniae (D)

C. jeikeium (D)

C. jejuni (D)

Key to Abbreviations:

(A) Peptide aggregates;

(B) Less hyphal formation;

(C) Clumps;

(D) Diffuse clumps and small polyps;

(F) Diffuse growth;

(H) Thin;

(I) Growth inhibition;

(M) Microcolony formation;

(R) Rippled;

(S) Small polyps;

(T) Thick;

(W) Halo formation on top, microlonies on bottom. These data thus indicate peptide-mediated interruption of bacterial biofilm formation processes, cellular metabolism, cellular import/export, nutrient acquisition, quorum sensing and communication, motility, chemotaxis, replication, translation, and/or transcription. Accordingly, without being bound to a particular theory, it is believed that the alteration of one or more of these basic pathways is important to pathogenesis, or the stopping thereof.

In certain embodiments, the amino acid sequence of the antimicrobial peptides comprises or consists of a single amino acid sequence, e.g., as listed above in Tables 4 and/or 5, and/or Table 15, and/or below in Table 14. In certain embodiments the amino acid sequence of the antimicrobial peptides comprises two copies, three copies, four copies, five copies six copies or more of one or more of the amino acid sequences listed in Tables 4, and/or 5, and/or Table 15, and/or Table 14. Thus, compound antimicrobial constructs are contemplated where the construct comprises multiple domains each having antimicrobial activity. The AMP domains comprising such a construct can be the same or different. In certain embodiments the construct comprises at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, or at least 8 different AMP domains each domain comprising a different AMP sequence.

Various AMP domains comprising such a construct can be joined directly to each other or two or more of such domains can be attached to each other via a linker. An illustrative, but non-limiting, list of suitable linkers is provided in Table 16. Thus, in certain embodiments, two or more AMP domains comprising a compound AMP construct are chemically conjugated together.

In certain embodiments the two or more AMP domains comprising the AMP construct are joined by a peptide linker. Where all the AMP domains are attached directly to each other or are joined by peptide linkers, the entire construct can be provided as a single-chain peptide (fusion protein).

In various embodiments, the antimicrobial peptides described herein comprise one or more of the amino acid sequences shown in Tables 4, and/or 5, and/or 15 and/or 14 (and/or the retro, inverso, retroinverso, etc. forms of such sequences). In certain embodiments the peptides range in length up to about 100 amino acids in length, preferably up to about 80, about 70, about 60, or about 51 amino acids in length. In certain embodiments the peptides range in length from about 8 amino acids up to about 100 amino acids 80 amino acids, 60 amino acids or about 51 amino acids in length. In certain embodiments the peptides range in length from about 8 up to about 50, 40, 30, 20, 15, 15, 13, or 12 amino acids in length.

As shown in Tables 4, and/or 5, and/or 15 and/or 14, the various amino acid sequences described herein are effective against particular microorganisms. The range of activity of the peptides or compositions comprising such peptides can be increased by including amino acid sequences effective against different microorganisms either as separate components and/or as multiple domains within a single construct.

TABLE 6

Illustrative target microorganisms and peptides effective against that target.

Gram Positive Bacteria:

A. naeslundii

PF-531, PF-527, PF-672, PF-545, PF-168, PF-448, PF-525, PF-529, PF-

148

B. subtilis

PF-002, PF-005, PF-006, PF-040, PF-053, PF-056, PF-061, PF-063, PF-

067, PF-068, PF-069, PF-070, PF-071, PF-145, PF-148, PF-171, PF-175,

PF-283, PF-289, PF-292, PF-296, PF-297, PF-301, PF-303, PF-305, PF-

306, PF-307, PF-318, PF-319, PF-322, PF-335, PF-339, PF-342, PF-497,

PF-499, PF-527, PF-531, PF-545, PF-547, PF-548, PF-549, PF-550, PF-

552, PF-553, PF-554, PF-556, PF-557, PF-558, PF-559, PF-560, PF-561,

PF-563, PF-564, PF-565, PF-566, PF-569, PF-571, PF-572, PF-574, PF-

632, PF-636, PF-655, PF-659, PF-668, PF-670, PF-672, PF-686, PF-998,

PF-2003

C. difficile

PF-522, PF-531, PF-538

C. jeikeium

PF-001, PF-003, PF-004, PF-101, PF-011, PF-012, PF-013, PF-021, PF-

022, PF-025, PF-028, PF-030, PF-032, PF-033, PF-036, PF-037, PF-040,

PF-042, PF-043, PF-046, PF-048, PF-052, PF-053, PF-056, PF-057, PF-

063, PF-065, PF-067, PF-068, PF-073, PF-075, PF-076, PF-099, PF-124,

PF-127, PF-129, PF-133, PF-135, PF-137, PF-139, PF-140, PF-145, PF-

148, PF-164, PF-173, PF-176, PF-186, PF-188, PF-190, PF-191, PF-196,

PF-199, PF-203, PF-204, PF-208, PF-527, PF-531, PF-545, PF-546, PF-

548, PF-553, PF-556, PF-564, PF-566, PF-567, PF-575, PF-622, PF-523,

PF-629, PF-632, PF-635, PF-637, PF-657, PF-668, PF-672, PF-681, PF-

685, PF-S003

E. faecalis

PF-007, PF-053, PF-057, PF-068, PF-347, PF-349, PF-355, PF-356, PF-

363, PF-366, PF-369, PF-374, PF-375, PF-376, PF-379, PF-380, PF-381,

PF-386, PF-387, PF-389, PF-390, PF-392, PF-393, PF-394, PF-396, PF-

398, PF-399, PF-401, PF-407, PF-410, PF-411, PF-418, PF-422, PF-425,

PF-426, PF-427, PF-429, PF-431, PF-432, PF-439, PF-440, PF-444, PF-

447, PF-450, PF-451, PF-452, PF-454, PF-456, PF-460, PF-461, PF-469,

PF-470, PF-471, PF-472, PF-473, PF-474, PF-475, PF-480, PF-484, PF-

514, PF-518, PF-519, PF-524, PF-530, PF-532, PF-533, PF-534, PF-536,

PF-544, PF-545, PF-546, PF-547, PF-556, PF-577, PF-581, PF-582, PF-

584, PF-585, PF-586, PF-588, PF-591, PF-592, PF-593, PF-594, PF-595,

PF-596, PF-597, PF-598, PF-599, PF-601, PF-602, PF-604, PF-605, PF-

607, PF-609, PF-610, PF-613, PF-614, PF-615, PF-616, PF-617, PF-618,

PF-621, PF-622, PF-623, PF-627, PF-629, PF-631, PF-632, PF-635, PF-

636, PF-637, PF-638, PF-639, PF-640, PF-643, PF-649, PF-657, PF-664,

PF-667, PF-668, PF-672, PF-675, PF-677, PF-681, PF-684, PF-685, PF-

686, PF-690, PF-695, PF-698

M. luteus

PF-001, PF-003, PF-004, PF-006, PF-007, PF-010, PF-012, PF-013, PF-

020, PF-021, PF-022, PF-025, PF-030, PF-036, PF-037, PF-040, PF-042,

PF-043, PF-051, PF-052, PF-053, PF-056, PF-057, PF-063, PF-067, PF-

068, PF-071, PF-073, PF-075, PF-076, PF-125, PF-127, PF-137, PF-139,

PF-140, PF-145, PF-148, PF-171, PF-175, PF-176, PF-199, PF-204, PF-

212, PF-215, PF-224, PF-226, PF-234, PF-235, PF-249, PF-250, PF-255,

PF-257, PF-264, PF-270, PF-271, PF-274, PF-276, PF-278, PF-357, PF-

527, PF-543, PF-548, PF-556, PF-562, PF-566, PF-567, PF-578, PF-580,

PF-600, PF-603, PF-612, PF-624, PF-634, PF-741, PF-745, PF-746, PF-

761, PF-763, PF-770, PF-776, PF-S003

MRSA
PF-001, PF-003, PF-004, PF-006, PF-007, PF-010, PF-011, PF-012, PF-

013, PF-015, PF-017, PF-019, PF-020, PF-021, PF-022, PF-023, PF-024,

PF-025, PF-026, PF-027, PF-028, PF-029, PF-030, PF-031, PF-033, PF-

035, PF-036, PF-037, PF-040, PF-041, PF-042, PF-043, PF-045, PF-046,

PF-048, PF-049, PF-051, PF-052, PF-053, PF-056, PF-057, PF-058, PF-

063, PF-064, PF-065, PF-066, PF-067, PF-068, PF-071, PF-073, PF-074,

PF-075, PF-076, PF-140, PF-145, PF-148, PF-149, PF-156, PF-168, PF-

171, PF-178, PF-191, PF-209, PF-347, PF-349, PF-350, PF-354, PF-355,

PF-356, PF-357, PF-360, PF-362, PF-366, PF-369, PF-370, PF-373, PF-

374, PF-375, PF-376, PF-378, PF-379, PF-380, PF-381, PF-382, PF-386,

PF-387, PF-389, PF-390, PF-392, PF-393, PF-394, PF-395, PF-396, PF-

398, PF-399, PF-401, PF-403, PF-404, PF-405, PF-406, PF-407, PF-408,

PF-410, PF-411, PF-413, PF-417, PF-418, PF-422, PF-425, PF-426, PF-

427, PF-429, PF-430, PF-431, PF-432, PF-439, PF-440, PF-442, PF-443,

PF-444, PF-447, PF-450, PF-451, PF-452, PF-453, PF-454, PF-458, PF-

460, PF-461, PF-469, PF-471, PF-472, PF-473, PF-474, PF-475, PF-478,

PF-480, PF-518, PF-519, PF-524, PF-526, PF-527, PF-528, PF-530, PF-

532, PF-533, PF-534, PF-536, PF-539, PF-540, PF-543, PF-544, PF-545,

PF-546, PF-547, PF-548, PF-549, PF-551, PF-553, PF-555, PF-556, PF-

558, PF-560, PF-561, PF-562, PF-564, PF-565, PF-566, PF-567, PF-576,

PF-577, PF-578, PF-580, PF-581, PF-583, PF-584, PF-585, PF-586, PF-

589, PF-592, PF-595, PF-596, PF-598, PF-599, PF-600, PF-603, PF-605,

PF-606, PF-607, PF-609, PF-610, PF-612, PF-613, PF-615, PF-619, PF-

622, PF-623, PF-624, PF-627, PF-629, PF-630, PF-632, PF-634, PF-635,

PF-637, PF-638, PF-639, PF-652, PF-643, PF-654, PF-655, PF-656, PF-

657, PF-658, PF-659, PF-661, PF-664, PF-667, PF-778, PF-672, PF-677,

PF-680, PF-683, PF-685, PF-686, PF-690, PF-692, PF-694, PF-695, PF-

738, PF-741, PF-745, PF-746, PF-760, PF-761, PF-763, PF-764, PF-770,

PF-776, PF-S003

S. epidermidis

PF-001, PF-003, PF-004, PF-006, PF-007, PF-009, PF-010, PF-012, PF-

013, PF-020, PF-021, PF-022, PF-024, PF-025, PF-027, PF-028, PF-030,

PF-032, PF-033, PF-034, PF-036, PF-037, PF-040, PF-041, PF-042, PF-

043, PF-046, PF-048, PF-051, PF-052, PF-953, PF-956, PF-957, PF-961,

PF-963, PF-964, PF-965, PF-967, PF-968, PF-971, PF-073, PF-074, PF-

075, PF-076, PF-099, PF-123, PF-124, PF-125, PF-127, PF-128, PF-129,

PF-137, PF-139, PF-140, PF-145, PF-148, PF-153, PF-157, PF-171, PF-

173, PF-176, PF-178, PF-180, PF-186, PF-190, PF-191, PF-192, PF-196,

PF-199, PF-203, PF-204, PF-208, PF-209, PF-226, PF-233, PF-273, PF-

278, PF-283, PF-290, PF-292, PF-293, PF-294, PF-296, PF-297, PF-301,

PF-307, PF-310, PF-313, PF-318, PF-319, PF-322, PF-335, PF-339, PF-

342, PF-347, PF-349, PF-350, PF-355, PF-356, PF-357, PF-360, PF-363,

PF-366, PF-369, PF-370, PF-373, PF-374, PF-375, PF-376, PF-378, PF-

379, PF-380, PF-381, PF-383, PF-386, PF-387, PF-389, PF-390, PF-393,

PF-395, PF-396, PF-397, PF-398, PF-399, PF-401, PF-403, PF-404, PF-

406, PF-407, PF-408, PF-410, PF-411, PF-413, PF-417, PF-418, PF-422,

PF-425, PF-246, PF-249, PF-430, PF-431, PF-432, PF-439, PF-440, PF-

444, PF-447, PF-451, PF-452, PF-453, PF-454, PF-460, PF-469, PF-471,

PF-473, PF-474, PF-475, PF-478, PF-480, PF-514, PF-518, PF-526, PF-

527, PF-528, PF-530, PF-531, PF-533, PF-534, PF-536, PF-540, PF-543,

PF-544, PF-546, PF-547, PF-548, PF-556, PF-558, PF-562, PF-576, PF-

577, PF-578, PF-580, PF-583, PF-584, PF-585, PF-586, PF-592, PF-595,

PF-596, PF-598, PF-599, PF-600, PF-603, PF-605, PF-606, PF-607, PF-

610, PF-612, PF-613, PF-614, PF-615, PF-616, PF-619, PF-622, PF-623,

PF-624, PF-627, PF-632, PF-634, PF-635, PF-637, PF-638, PF-655, PF-

657, PF-659, PF-664, PF-667, PF-778, PF-672, PF-677, PF-681, PF-683,

PF-685, PF-686, PF-690, PF-741, PF-746, PF-760, PF-761, PF-763, PF-

770, PF-776, PF-S003

S. mutans

G-1, G-2, G-4, G-8, PF-020, PF-040, PF-051, PF-531, PF-543, PF-547,

PF-578, PF-583, PF-600, PF-606, PF-612, PF-624, PF-634, PF-741, PF-

745, PF-746, PF-761, PF-770, PF-776, PF-C055, PF-C057, PF-C058, PF-

C061, PF-C062, PF-C072, PF-C075, PF-C084, PF-C085, PF-C088, PF-

C098, PF-C131, PF-C135, PF-C139, PF-C142, PF-C146, PF-C180, PF-

C194, PF-C281, PF-C290, PF-C291, PF-C293

S. pneumoniae

PF-002, PF-005, PF-006, PF-020, PF-033, PF-040, PF-051, PF-053, PF-

056, PF-057, PF-061, PF-063, PF-068, PF-071, PF-073, PF-140, PF-144,

PF-145, PF-148, PF-171, PF-175, PF-178, PF-220, PF-355, PF-356, PF-

357, PF-363, PF-366, PF-380, PF-389, PF-390, PF-393, PF-407, PF-411,

PF-414, PF-415, PF-416, PF-417, PF-418, PF-419, PF-421, PF-422, PF-

423, PF-424, PF-425, PF-426, PF-427, PF-428, PF-429, PF-430, PF-431,

PF-432, PF-433, PF-434, PF-437, PF-439, PF-440, PF-442, PF-443, PF-

444, PF-445, PF-446, PF-447, PF-448, PF-449, PF-450, PF-451, PF-452,

PF-453, PF-454, PF-455, PF-457, PF-458, PF-469, PF-460, PF-461, PF-

462, PF-464, PF-465, PF-466, PF-467, PF-468, PF-469, PF-471, PF-472,

PF-473, PF-474, PF-475, PF-476, PF-477, PF-478, PF-479, PF-480, PF-

482, PF-485, PF-511, PF-512, PF-513, PF-514, PF-515, PF-516, PF-517,

PF-518, PF-519, PF-520, PF-521, PF-522, PF-523, PF-524, PF-525, PF-

526, PF-527, PF-528, PF-529, PF-530, PF-531, PF-532, PF-533, PF-534,

PF-535, PF-536, PF-537, PF-538, PF-539, PF-540, PF-541, PF-542, PF-

543, PF-544, PF-546, PF-548, PF-553, PF-555, PF-556, PF-558, PF-560,

PF-562, PF-563, PF-566, PF-567, PF-572, PF-573, PF-575, PF-576, PF-

577, PF-578, PF-580, PF-581, PF-583, PF-585, PF-585, PF-586, PF-587,

PF-589, PF-591, PF-592, PF-595, PF-596, PF-598, PF-599, PF-600, PF-

603, PF-605, PF-606, PF-607, PF-609, PF-610, PF-612, PF-614, PF-615,

PF-617, PF-618, PF-619, PF-621, PF-622, PF-623, PF-624, PF-625, PF-

626, PF-627, PF-629, PF-631, PF-632, PF-634, PF-635, PF-636, PF-637,

PF-638, PF-639, PF-640, PF-643, PF-644, PF-645, PF-646, PF-647, PF-

651, PF-652, PF-653, PF-654, PF-655, PF-657, PF-658, PF-659, PF-660,

PF-662, PF-663, PF-664, PF-665, PF-666, PF-667, PF-668, PF-670, PF-

672, PF-675, PF-677, PF-681, PF-682, PF-683, PF-684, PF-685, PF-686,

PF-687, PF-688, PF-690, PF-691, PF-693, PF-694, PF-695, PF-696, PF-

697, PF-698, PF-699, PF-700, PF-702, PF-704, PF-737, PF-741, PF-744,

PF-745, PF-746, PF-748, PF-749, PF-752, PF-756, PF-757, PF-760, PF-

761, PF-762, PF-763, PF-764, PF-770, PF-776, PF-S003

Gram Negative Bacteria:

A. baumannii

PF-531, PF-006, PF-538, PF-530

C. jejuni

PF-006, PF-008, PF-033, PF-040, PF-053, PF-056, PF-057, PF-059, PF-

061, PF-063, PF-067, PF-068, PF-069, PF-071, PF-073, PF-140, PF-145,

PF-148, PF-171, PF-175, PF-355, PF-356, PF-363, PF-366, PF-380, PF-

389, PF-390, PF-392, PF-393, PF-411, PF-418, PF-422, PF-425, PF-426,

PF-431, PF-432, PF-456, PF-469, PF-470, PF-471, PF-472, PF-473, PF-

474, PF-475, PF-527, PF-548, PF-555, PF-556, PF-558, PF-559, PF-560,

PF-562, PF-563, PF-564, PF-566, PF-567, PF-575, PF-576, PF-577, PF-

581, PF-584, PF-585, PF-586, PF-590, PF-591, PF-592, PF-595, PF-596,

PF-598, PF-599, PF-601, PF-605, PF-607, PF-609, PF-610, PF-614, PF-

615, PF-S003

E. coli

PF-007, PF-040, PF-053, PF-057, PF-068, PF-178, PF-344, PF-347, PF-

349, PF-350, PF-355, PF-360, PF-362, PF-363, PF-366, PF-369, PF-370,

PF-374, PF-375, PF-376, PF-379, PF-380, PF-381, PF-383, PF-385, PF-

386, PF-387, PF-390, PF-395, PF-396, PF-398, PF-399, PF-401, PF-403,

PF-410, PF-411, PF-413, PF-418, PF-425, PF-426, PF-427, PF-432, PF-

439, PF-440, PF-443, PF-444, PF-451, PF-452, PF-453, PF-454, PF-460,

PF-469, PF-471, PF-473, PF-474, PF-478, PF-480, PF-514, PF-518, PF-

519, PF-524, PF-526, PF-528, PF-530, PF-531, PF-532, PF-533, PF-534,

PF-536, PF-540, PF-541, PF-543, PF-546, PF-576, PF-577, PF-578, PF-

584, PF-586, PF-592, PF-595, PF-596, PF-598, PF-600, PF-603, PF-605,

PF-606, PF-610, PF-612, PF-615, PF-619, PF-624, PF-634, PF-741, PF-

746, PF-761, PF-770, PF-776

F. nucleatum

PF-C055, PF-C061, PF-C062, PF-C064, PF-C065, PF-C069, PF-C071,

PF-C072, PF-C075, PF-C084, PF-C086, PF-C088, PF-C091, PF-C095,

PF-C098, PF-C120, PF-C131, PF-C135, PF-C136, PF-C137, PF-C143,

PF-C145, PF-C181, PF-C194, PF-C214, PF-C291, PF-C293

M. xanthus

G-5, G-6, G-7

P. aeruginosa

PF-053, PF-063, PF-067, PF-128, PF-140, PF-143, PF-168, PF-204, PF-

209, PF-355, PF-356, PF-366, PF-380, PF-411, PF-425, PF-432, PF-454,

PF-458, PF-471, PF-474, PF-527, PF-531, PF-535, PF-536, PF-575, PF-

577, PF-605, PF-746, PF-761, PF-S003

P. gingivalis

PF-C052, PF-C072, PF-C075, PF-C084, PF-C088, PF-C089, PF-C136,

PF-C180, PF-C194, C293

P. mirabilis

PF-040, PF-578, PF-612, PF-624, PF-634, PF-741, PF-770

Yeast Fungi:

A. niger

PF-531, PF-527, PF-672, PF-545, PF-168, PF-448, PF-525, PF-529, PF-

148

C. albicans

PF-053, PF-056, PF-057, PF-071, PF-140, PF-148, PF-175, PF-278, PF-

307, PF-425, PF-426, PF-474, PF-475, PF-526, PF-527, PF-528, PF-545,

PF-605, PF-606, PF-617, PF-627, PF-632, PF-635, PF-636, PF-639, PF-

640, PF-645, PF-646, PF-647, PF-654, PF-668, PF-672, PF-684, PF-686,

PF-697, PF-698, PF-S003

T. rubrum

PF-283, PF-307, PF-527, PF-531, PF-547, PF-672

In certain embodiments the activity against a particular microorganism or group of microorganisms can be increased by increasing the number of peptides or peptide domains with activity against that microorganism or group of microorganisms.

Thus, for example, in certain embodiments, a peptide or composition effective to kill or inhibit the growth and/or proliferation of a yeast or fungus can comprise or more peptides and/or one or more peptide domains having sequences selected from the sequences shown in Tables 4, 5, or 6 (e.g., PF-S003, PF-053, PF-056, PF-057, PF-071, PF-140, PF-148, PF-168, PF-175, PF-278, PF-283, PF-307, PF-425, PF-426, PF-448, PF-474, PF-475, PF-525, PF-526, PF-527, PF-528, PF-529, PF-531, PF-545, PF-547, PF-606, PF-617, PF-627, PF-632, PF-635, PF-636, PF-639, PF-640, PF-645, PF-646, PF-647, PF-654, PF-668, PF-672, PF-684, PF-686, PF-697, and PF-69)8. A peptide or composition effective to kill or inhibit the growth and/or proliferation of Aspergillus niger can comprise one or more peptides and/or one or more peptide domains having sequences selected from the group consisting of PF-531, PF-527, PF-672, PF-545, PF-168, PF-448, PF-525, PF-529, and PF-148. A peptide or composition effective to kill or inhibit the growth and/or proliferation of Candida albicans can comprise one or more peptides and/or one or more peptide domains having sequences selected from the group consisting of PF-053, PF-056, PF-057, PF-071, PF-140, PF-148, PF-175, PF-278, PF-307, PF-425, PF-426, PF-474, PF-475, PF-526, PF-527, PF-528, PF-545, PF-605, PF-606, PF-617, PF-627, PF-632, PF-635, PF-636, PF-639, PF-640, PF-645, PF-646, PF-647, PF-654, PF-668, PF-672, PF-684, PF-686, PF-697, PF-698, and PF-S003. A peptide or composition effective to kill or inhibit the growth and/or proliferation of Trichophyton rubrum can comprise one or more peptides and/or one or more peptide domains having sequences selected from the group consisting of PF-283, PF-307, PF-527, PF-531, PF-547, and PF-672.

In certain embodiments a peptide or composition effective to kill or inhibit the growth and/or proliferation of a bacterium can comprise one or more peptides and/or one or more peptide domains comprising or consisting of sequences identified as having activity against a bacterium in Tables 4, 5, or 6.

In certain embodiments a peptide or composition effective to kill or inhibit the growth and/or proliferation of a gram positive bacterium can comprise one or more peptides and/or one or more peptide domains comprising or consisting of sequences identified as having activity against a gram positive bacterium in Tables 4, 5, or 6. In certain embodiments a peptide or composition effective to kill or inhibit the growth and/or proliferation of a gram negative bacterium can comprise one or more peptides and/or one or more peptide domains comprising or consisting of sequences identified as having activity against a gram negative bacterium in Tables 4, 5, or 6.

In certain embodiments a peptide or composition effective to kill or inhibit the growth and/or proliferation of A. naeslundii can comprise one or more peptides and/or one or more peptide domains comprising or consisting of sequences identified as having activity against A. Naeslundii in Tables 4, 5, or 6 (e.g., from the group consisting of PF-531, PF-527, PF-672, PF-545, PF-168, PF-448, PF-525, PF-529, and PF-148).

In certain embodiments a peptide or composition effective to kill or inhibit the growth and/or proliferation of B. subtilis can comprise one or more peptides and/or one or more peptide domains comprising or consisting of sequences identified as having activity against B. subtilis in Tables 4, 5, or 6 (e.g., from the group consisting of PF-002, PF-005, PF-006, PF-040, PF-053, PF-056, PF-061, PF-063, PF-067, PF-068, PF-069, PF-070, PF-071, PF-145, PF-148, PF-171, PF-175, PF-283, PF-289, PF-292, PF-296, PF-297, PF-301, PF-303, PF-305, PF-306, PF-307, PF-318, PF-319, PF-322, PF-335, PF-339, PF-342, PF-497, PF-499, PF-527, PF-531, PF-545, PF-547, PF-548, PF-549, PF-550, PF-552, PF-553, PF-554, PF-556, PF-557, PF-558, PF-559, PF-560, PF-561, PF-563, PF-564, PF-565, PF-566, PF-569, PF-571, PF-572, PF-574, PF-632, PF-636, PF-655, PF-659, PF-668, PF-670, PF-672, PF-686, PF-998, and PF-2003).

In certain embodiments a peptide or composition effective to kill or inhibit the growth and/or proliferation of C. difficile can comprise one or more peptides and/or one or more peptide domains comprising or consisting of sequences identified as having activity against C. difficile in Tables 4, 5, or 6 (e.g., from the group consisting of PF-522, PF-531, and PF-538).

In certain embodiments a peptide or composition effective to kill or inhibit the growth and/or proliferation of C. jeikeium can comprise one or more peptides and/or one or more peptide domains comprising or consisting of sequences identified as having activity against C. jeikeium in Tables 4, 5, or 6 (e.g., from the group consisting of PF-001, PF-003, PF-004, PF-101, PF-011, PF-012, PF-013, PF-021, PF-022, PF-025, PF-028, PF-030, PF-032, PF-033, PF-036, PF-037, PF-040, PF-042, PF-043, PF-046, PF-048, PF-052, PF-053, PF-056, PF-057, PF-063, PF-065, PF-067, PF-068, PF-073, PF-075, PF-076, PF-099, PF-124, PF-127, PF-129, PF-133, PF-135, PF-137, PF-139, PF-140, PF-145, PF-148, PF-164, PF-173, PF-176, PF-186, PF-188, PF-190, PF-191, PF-196, PF-199, PF-203, PF-204, PF-208, PF-527, PF-531, PF-545, PF-546, PF-548, PF-553, PF-556, PF-564, PF-566, PF-567, PF-575, PF-622, PF-523, PF-629, PF-632, PF-635, PF-637, PF-657, PF-668, PF-672, PF-681, PF-685, and PF-S003).

In certain embodiments a peptide or composition effective to kill or inhibit the growth and/or proliferation of E. faecalis can comprise one or more peptides and/or one or more peptide domains comprising or consisting of sequences identified as having activity against E. faecalis in Tables 4, 5, or 6 (e.g., from the group consisting of PF-007, PF-053, PF-057, PF-068, PF-347, PF-349, PF-355, PF-356, PF-363, PF-366, PF-369, PF-374, PF-375, PF-376, PF-379, PF-380, PF-381, PF-386, PF-387, PF-389, PF-390, PF-392, PF-393, PF-394, PF-396, PF-398, PF-399, PF-401, PF-407, PF-410, PF-411, PF-418, PF-422, PF-425, PF-426, PF-427, PF-429, PF-431, PF-432, PF-439, PF-440, PF-444, PF-447, PF-450, PF-451, PF-452, PF-454, PF-456, PF-460, PF-461, PF-469, PF-470, PF-471, PF-472, PF-473, PF-474, PF-475, PF-480, PF-484, PF-514, PF-518, PF-519, PF-524, PF-530, PF-532, PF-533, PF-534, PF-536, PF-544, PF-545, PF-546, PF-547, PF-556, PF-577, PF-581, PF-582, PF-584, PF-585, PF-586, PF-588, PF-591, PF-592, PF-593, PF-594, PF-595, PF-596, PF-597, PF-598, PF-599, PF-601, PF-602, PF-604, PF-605, PF-607, PF-609, PF-610, PF-613, PF-614, PF-615, PF-616, PF-617, PF-618, PF-621, PF-622, PF-623, PF-627, PF-629, PF-631, PF-632, PF-635, PF-636, PF-637, PF-638, PF-639, PF-640, PF-643, PF-649, PF-657, PF-664, PF-667, PF-668, PF-672, PF-675, PF-677, PF-681, PF-684, PF-685, PF-686, PF-690, PF-695, and PF-698).

In certain embodiments a peptide or composition effective to kill or inhibit the growth and/or proliferation of M. luteus can comprise one or more peptides and/or one or more peptide domains comprising or consisting of sequences identified as having activity against M. luteus in Tables 4, 5, or 6 (e.g., from the group consisting of PF-001, PF-003, PF-004, PF-006, PF-007, PF-010, PF-012, PF-013, PF-020, PF-021, PF-022, PF-025, PF-030, PF-036, PF-037, PF-040, PF-042, PF-043, PF-051, PF-052, PF-053, PF-056, PF-057, PF-063, PF-067, PF-068, PF-071, PF-073, PF-075, PF-076, PF-125, PF-127, PF-137, PF-139, PF-140, PF-145, PF-148, PF-171, PF-175, PF-176, PF-199, PF-204, PF-212, PF-215, PF-224, PF-226, PF-234, PF-235, PF-249, PF-250, PF-255, PF-257, PF-264, PF-270, PF-271, PF-274, PF-276, PF-278, PF-357, PF-527, PF-543, PF-548, PF-556, PF-562, PF-566, PF-567, PF-578, PF-580, PF-600, PF-603, PF-612, PF-624, PF-634, PF-741, PF-745, PF-746, PF-761, PF-763, PF-770, PF-776, and PF-S003).

In certain embodiments a peptide or composition effective to kill or inhibit the growth and/or proliferation of MRSA can comprise one or more peptides and/or one or more peptide domains comprising or consisting of sequences identified as having activity against MRSA in Tables 4, 5, or 6 (e.g., from the group consisting of PF-001, PF-003, PF-004, PF-006, PF-007, PF-010, PF-011, PF-012, PF-013, PF-015, PF-017, PF-019, PF-020, PF-021, PF-022, PF-023, PF-024, PF-025, PF-026, PF-027, PF-028, PF-029, PF-030, PF-031, PF-033, PF-035, PF-036, PF-037, PF-040, PF-041, PF-042, PF-043, PF-045, PF-046, PF-048, PF-049, PF-051, PF-052, PF-053, PF-056, PF-057, PF-058, PF-063, PF-064, PF-065, PF-066, PF-067, PF-068, PF-071, PF-073, PF-074, PF-075, PF-076, PF-140, PF-145, PF-148, PF-149, PF-156, PF-168, PF-171, PF-178, PF-191, PF-209, PF-347, PF-349, PF-350, PF-354, PF-355, PF-356, PF-357, PF-360, PF-362, PF-366, PF-369, PF-370, PF-373, PF-374, PF-375, PF-376, PF-378, PF-379, PF-380, PF-381, PF-382, PF-386, PF-387, PF-389, PF-390, PF-392, PF-393, PF-394, PF-395, PF-396, PF-398, PF-399, PF-401, PF-403, PF-404, PF-405, PF-406, PF-407, PF-408, PF-410, PF-411, PF-413, PF-417, PF-418, PF-422, PF-425, PF-426, PF-427, PF-429, PF-430, PF-431, PF-432, PF-439, PF-440, PF-442, PF-443, PF-444, PF-447, PF-450, PF-451, PF-452, PF-453, PF-454, PF-458, PF-460, PF-461, PF-469, PF-471, PF-472, PF-473, PF-474, PF-475, PF-478, PF-480, PF-518, PF-519, PF-524, PF-526, PF-527, PF-528, PF-530, PF-532, PF-533, PF-534, PF-536, PF-539, PF-540, PF-543, PF-544, PF-545, PF-546, PF-547, PF-548, PF-549, PF-551, PF-553, PF-555, PF-556, PF-558, PF-560, PF-561, PF-562, PF-564, PF-565, PF-566, PF-567, PF-576, PF-577, PF-578, PF-580, PF-581, PF-583, PF-584, PF-585, PF-586, PF-589, PF-592, PF-595, PF-596, PF-598, PF-599, PF-600, PF-603, PF-605, PF-606, PF-607, PF-609, PF-610, PF-612, PF-613, PF-615, PF-619, PF-622, PF-623, PF-624, PF-627, PF-629, PF-630, PF-632, PF-634, PF-635, PF-637, PF-638, PF-639, PF-652, PF-643, PF-654, PF-655, PF-656, PF-657, PF-658, PF-659, PF-661, PF-664, PF-667, PF-778, PF-672, PF-677, PF-680, PF-683, PF-685, PF-686, PF-690, PF-692, PF-694, PF-695, PF-738, PF-741, PF-745, PF-746, PF-760, PF-761, PF-763, PF-764, PF-770, PF-776, and PF-S003).

In certain embodiments a peptide or composition effective to kill or inhibit the growth and/or proliferation of S. epidermidis can comprise one or more peptides and/or one or more peptide domains comprising or consisting of sequences identified as having activity against of S. epidermidis in Tables 4, 5, or 6 (e.g., from the group consisting of PF-001, PF-003, PF-004, PF-006, PF-007, PF-009, PF-010, PF-012, PF-013, PF-020, PF-021, PF-022, PF-024, PF-025, PF-027, PF-028, PF-030, PF-032, PF-033, PF-034, PF-036, PF-037, PF-040, PF-041, PF-042, PF-043, PF-046, PF-048, PF-051, PF-052, PF-953, PF-956, PF-957, PF-961, PF-963, PF-964, PF-965, PF-967, PF-968, PF-971, PF-073, PF-074, PF-075, PF-076, PF-099, PF-123, PF-124, PF-125, PF-127, PF-128, PF-129, PF-137, PF-139, PF-140, PF-145, PF-148, PF-153, PF-157, PF-171, PF-173, PF-176, PF-178, PF-180, PF-186, PF-190, PF-191, PF-192, PF-196, PF-199, PF-203, PF-204, PF-208, PF-209, PF-226, PF-233, PF-273, PF-278, PF-283, PF-290, PF-292, PF-293, PF-294, PF-296, PF-297, PF-301, PF-307, PF-310, PF-313, PF-318, PF-319, PF-322, PF-335, PF-339, PF-342, PF-347, PF-349, PF-350, PF-355, PF-356, PF-357, PF-360, PF-363, PF-366, PF-369, PF-370, PF-373, PF-374, PF-375, PF-376, PF-378, PF-379, PF-380, PF-381, PF-383, PF-386, PF-387, PF-389, PF-390, PF-393, PF-395, PF-396, PF-397, PF-398, PF-399, PF-401, PF-403, PF-404, PF-406, PF-407, PF-408, PF-410, PF-411, PF-413, PF-417, PF-418, PF-422, PF-425, PF-246, PF-249, PF-430, PF-431, PF-432, PF-439, PF-440, PF-444, PF-447, PF-451, PF-452, PF-453, PF-454, PF-460, PF-469, PF-471, PF-473, PF-474, PF-475, PF-478, PF-480, PF-514, PF-518, PF-526, PF-527, PF-528, PF-530, PF-531, PF-533, PF-534, PF-536, PF-540, PF-543, PF-544, PF-546, PF-547, PF-548, PF-556, PF-558, PF-562, PF-576, PF-577, PF-578, PF-580, PF-583, PF-584, PF-585, PF-586, PF-592, PF-595, PF-596, PF-598, PF-599, PF-600, PF-603, PF-605, PF-606, PF-607, PF-610, PF-612, PF-613, PF-614, PF-615, PF-616, PF-619, PF-622, PF-623, PF-624, PF-627, PF-632, PF-634, PF-635, PF-637, PF-638, PF-655, PF-657, PF-659, PF-664, PF-667, PF-778, PF-672, PF-677, PF-681, PF-683, PF-685, PF-686, PF-690, PF-741, PF-746, PF-760, PF-761, PF-763, PF-770, PF-776, and PF-S003).

In certain embodiments a peptide or composition effective to kill or inhibit the growth and/or proliferation of S. mutans can comprise one or more peptides and/or one or more peptide domains comprising or consisting of sequences identified as having activity against S. mutans in Tables 4, 5, or 6 (e.g., from the group consisting of G-1, G-2, G-4, G-8, PF-020, PF-040, PF-051, PF-531, PF-543, PF-547, PF-578, PF-583, PF-600, PF-606, PF-612, PF-624, PF-634, PF-741, PF-745, PF-746, PF-761, PF-770, PF-776, PF-0055, PF-0057, PF-0058, PF-0061, PF-0062, PF-0072, PF-0075, PF-0084, PF-0085, PF-0088, PF-0098, PF-C131, PF-C135, PF-C139, PF-C142, PF-C146, PF-C180, PF-C194, PF-C281, PF-C290, PF-C291, PF-C293

In certain embodiments a peptide or composition effective to kill or inhibit the growth and/or proliferation of S. pneumoniae can comprise one or more peptides and/or one or more peptide domains comprising or consisting of sequences identified as having activity against S. pneumoniae in Tables 4, 5, or 6 (e.g., from the group consisting of PF-002, PF-005, PF-006, PF-020, PF-033, PF-040, PF-051, PF-053, PF-056, PF-057, PF-061, PF-063, PF-068, PF-071, PF-073, PF-140, PF-144, PF-145, PF-148, PF-171, PF-175, PF-178, PF-220, PF-355, PF-356, PF-357, PF-363, PF-366, PF-380, PF-389, PF-390, PF-393, PF-407, PF-411, PF-414, PF-415, PF-416, PF-417, PF-418, PF-419, PF-421, PF-422, PF-423, PF-424, PF-425, PF-426, PF-427, PF-428, PF-429, PF-430, PF-431, PF-432, PF-433, PF-434, PF-437, PF-439, PF-440, PF-442, PF-443, PF-444, PF-445, PF-446, PF-447, PF-448, PF-449, PF-450, PF-451, PF-452, PF-453, PF-454, PF-455, PF-457, PF-458, PF-469, PF-460, PF-461, PF-462, PF-464, PF-465, PF-466, PF-467, PF-468, PF-469, PF-471, PF-472, PF-473, PF-474, PF-475, PF-476, PF-477, PF-478, PF-479, PF-480, PF-482, PF-485, PF-511, PF-512, PF-513, PF-514, PF-515, PF-516, PF-517, PF-518, PF-519, PF-520, PF-521, PF-522, PF-523, PF-524, PF-525, PF-526, PF-527, PF-528, PF-529, PF-530, PF-531, PF-532, PF-533, PF-534, PF-535, PF-536, PF-537, PF-538, PF-539, PF-540, PF-541, PF-542, PF-543, PF-544, PF-546, PF-548, PF-553, PF-555, PF-556, PF-558, PF-560, PF-562, PF-563, PF-566, PF-567, PF-572, PF-573, PF-575, PF-576, PF-577, PF-578, PF-580, PF-581, PF-583, PF-585, PF-585, PF-586, PF-587, PF-589, PF-591, PF-592, PF-595, PF-596, PF-598, PF-599, PF-600, PF-603, PF-605, PF-606, PF-607, PF-609, PF-610, PF-612, PF-614, PF-615, PF-617, PF-618, PF-619, PF-621, PF-622, PF-623, PF-624, PF-625, PF-626, PF-627, PF-629, PF-631, PF-632, PF-634, PF-635, PF-636, PF-637, PF-638, PF-639, PF-640, PF-643, PF-644, PF-645, PF-646, PF-647, PF-651, PF-652, PF-653, PF-654, PF-655, PF-657, PF-658, PF-659, PF-660, PF-662, PF-663, PF-664, PF-665, PF-666, PF-667, PF-668, PF-670, PF-672, PF-675, PF-677, PF-681, PF-682, PF-683, PF-684, PF-685, PF-686, PF-687, PF-688, PF-690, PF-691, PF-693, PF-694, PF-695, PF-696, PF-697, PF-698, PF-699, PF-700, PF-702, PF-704, PF-737, PF-741, PF-744, PF-745, PF-746, PF-748, PF-749, PF-752, PF-756, PF-757, PF-760, PF-761, PF-762, PF-763, PF-764, PF-770, PF-776, and PF-S003).

In certain embodiments a peptide or composition effective to kill or inhibit the growth and/or proliferation of A. baumannii can comprise one or more peptides and/or one or more peptide domains comprising or consisting of sequences identified as having activity against A. baumannii in Tables 4, 5, or 6 (e.g., from the group consisting of PF-531, PF-006, PF-538, and PF-530).

In certain embodiments a peptide or composition effective to kill or inhibit the growth and/or proliferation of C. jejuni can comprise one or more peptides and/or one or more peptide domains comprising or consisting of sequences identified as having activity against C. jejuni in Tables 4, 5, or 6 (e.g., from the group consisting of PF-006, PF-008, PF-033, PF-040, PF-053, PF-056, PF-057, PF-059, PF-061, PF-063, PF-067, PF-068, PF-069, PF-071, PF-073, PF-140, PF-145, PF-148, PF-171, PF-175, PF-355, PF-356, PF-363, PF-366, PF-380, PF-389, PF-390, PF-392, PF-393, PF-411, PF-418, PF-422, PF-425, PF-426, PF-431, PF-432, PF-456, PF-469, PF-470, PF-471, PF-472, PF-473, PF-474, PF-475, PF-527, PF-548, PF-555, PF-556, PF-558, PF-559, PF-560, PF-562, PF-563, PF-564, PF-566, PF-567, PF-575, PF-576, PF-577, PF-581, PF-584, PF-585, PF-586, PF-590, PF-591, PF-592, PF-595, PF-596, PF-598, PF-599, PF-601, PF-605, PF-607, PF-609, PF-610, PF-614, PF-615, and PF-S003).

In certain embodiments a peptide or composition effective to kill or inhibit the growth and/or proliferation of E. coli can comprise one or more peptides and/or one or more peptide domains comprising or consisting of sequences identified as having activity against E. coli in Tables 4, 5, or 6 (e.g., from the group consisting of PF-007, PF-040, PF-053, PF-057, PF-068, PF-178, PF-344, PF-347, PF-349, PF-350, PF-355, PF-360, PF-362, PF-363, PF-366, PF-369, PF-370, PF-374, PF-375, PF-376, PF-379, PF-380, PF-381, PF-383, PF-385, PF-386, PF-387, PF-390, PF-395, PF-396, PF-398, PF-399, PF-401, PF-403, PF-410, PF-411, PF-413, PF-418, PF-425, PF-426, PF-427, PF-432, PF-439, PF-440, PF-443, PF-444, PF-451, PF-452, PF-453, PF-454, PF-460, PF-469, PF-471, PF-473, PF-474, PF-478, PF-480, PF-514, PF-518, PF-519, PF-524, PF-526, PF-528, PF-530, PF-531, PF-532, PF-533, PF-534, PF-536, PF-540, PF-541, PF-543, PF-546, PF-576, PF-577, PF-578, PF-584, PF-586, PF-592, PF-595, PF-596, PF-598, PF-600, PF-603, PF-605, PF-606, PF-610, PF-612, PF-615, PF-619, PF-624, PF-634, PF-741, PF-746, PF-761, PF-770, and PF-776).

In certain embodiments a peptide or composition effective to kill or inhibit the growth and/or proliferation of F. nucleatum can comprise one or more peptides and/or one or more peptide domains comprising or consisting of sequences identified as having activity against F. nucleatum in Tables 4, 5, or 6 (e.g., from the group consisting of PF-C055, PF-0061, PF-0062, PF-0064, PF-0065, PF-0069, PF-0071, PF-0072, PF-0075, PF-C084, PF-0086, PF-0088, PF-0091, PF-0095, PF-0098, PF-C120, PF-C131, PF-C135, PF-C136, PF-C137, PF-C143, PF-C145, PF-C181, PF-C194, PF-C214, PF-C291, and PF-C293).

In certain embodiments a peptide or composition effective to kill or inhibit the growth and/or proliferation of M. Xanthus can comprise one or more peptides and/or one or more peptide domains comprising or consisting of sequences identified as having activity against M. Xanthus in Tables 4, 5, or 6 (e.g., from the group consisting of G-5, G-6, and G-7).

In certain embodiments a peptide or composition effective to kill or inhibit the growth and/or proliferation of P. aeruginosa can comprise one or more peptides and/or one or more peptide domains comprising or consisting of sequences identified as having activity against P. aeruginosa in Tables 4, 5, or 6 (e.g., from the group consisting of PF-053, PF-063, PF-067, PF-128, PF-140, PF-143, PF-168, PF-204, PF-209, PF-355, PF-356, PF-366, PF-380, PF-411, PF-425, PF-432, PF-454, PF-458, PF-471, PF-474, PF-527, PF-531, PF-535, PF-536, PF-575, PF-577, PF-605, PF-746, PF-761, and PF-S003).

In certain embodiments a peptide or composition effective to kill or inhibit the growth and/or proliferation of P. gingivalis can comprise one or more peptides and/or one or more peptide domains comprising or consisting of sequences identified as having activity against P. gingivalis in Tables 4, 5, or 6 (e.g., from the group consisting of PF-C052, PF-0072, PF-0075, PF-0084, PF-0088, PF-0089, PF-C136, PF-C180, PF-C194, and C293).

In certain embodiments a peptide or composition effective to kill or inhibit the growth and/or proliferation of P. mirabilis can comprise one or more peptides and/or one or more peptide domains comprising or consisting of sequences identified as having activity against P. mirabilis in Tables 4, 5, or 6 (e.g., from the group consisting of PF-040, PF-578, PF-612, PF-624, PF-634, PF-741, and PF-770).

It was also a surprising discovery that a number of novel antimicrobial peptides are characterized by the presence of particular amino acid motifs. Such motifs include KIF, FIK, KIH, HIK, and KIV, as illustrated in Table 7.

TABLE 7

Antimicrobial peptides characterized

by particular motifs.

SEQ ID

Motif
Omnibus #
Sequence
NO

KIF
PF-278
LSLATFAKIFMTRSNWSLKRFNRL
1567

PF-C059
QKIIDMSKFLFSLILFIMIVVIYIGKSIGGYSAIVSS
1568

IMLELDTVLYNKKIFFIYK

PF-C073
FESLLPQATKKIVNNKGSKINKIF
1569

PF-C085
KKFKIFVIINWFYHKYIILNFEENF
1570

PF-531
YIQFHLNQQPRPKVKKIKIFL
1571

PF-C194
NTNDLLQAFELMGLGMAGVFIVLGILYIVAELLI
1572

KIF
PVNN

PF-C201
IFKLFEEHLLYLLDAFYYSKIFRRLKQGLYRRKE
1573

QPYTQDLFRM

PF-442
MQIFYIKTKIFLSFFLFLLIFSQCFYKIEE
1574

PF-C252
NYRLVNAIFSKIFKKKFIKF
1575

FIK
PF-251
MAWKFIKLDKVVSQKECNNFLEKEENKKLLKL
1576

LRIQKNMR

PF-261
MDIWKFIKSFNTVNTYLLLSCVLLIILVLYFYVI
1577

NPA

PF-497
LVLRICTDLFTFIKWTIKQRKS
1578

PF-775
DLCGQEFIKFKTCVTNQLAKK
1579

PF-591
DLLKSLLGQDGAKNDEIIEFIKIIMEK
1580

PF-597
DEIKVSDEEIEKFIKENNL
1581

PF-608
LICEVVKPEEDFIKVKLNEDNVTAKISREFIAKKI
1582

DA

IT-133
YFIKDDNEALSKDWEVIGNDLKGTIDKYGKEFK
1583

VR

PF-C252
NYRLVNAIFSKIFKKKFIKF
1584

PF-C278
DMKIIKLYIKILSFLFIKYCNKKLNSVKLKA
1585

PF-C290
GNVHPESDFHNLIQFIKTFLYFTIFFKYFL
1586

PF-006
MGIIAGIIKFIKGLIEKFTGK
1587

PF-013
LIQKGLNQTFIVVIRLNNFIKKS
1588

PF-040
MIHLTKQNTMEALHFIKQFYDMFFILNFNV
1589

KIH
PF-252
MKKLVAALAVIVILTGCVYDPVNYDKIHDQEF
1590

QDHLRQNG

PF-575
LNFRAENKILEKIHISLIDTVEGSA
1591

PF-533
KTPNDKIHKTIIIKHIIL
1592

HIK
PF-222

HIK
ETR
1593

PF-319
SIGSMIGMYSFRHKTKHIKFTFGIPFILFLQFLLV
1594

YFYILK

PF-477
HKNKLNIPHIKS
1595

KIV
PF-272
MTLTIKIKHRSKIVPLNLISLVYAFFTYNFVANRI
1596

MFLTND

PF-758
PEIIKIVSGLL
1597

PF-336
MLTSRKKRLKKIVEEQNKKDESI
1598

PF-C073
FESLLPQATKKIVNNKGSKINKIF
1599

PF-721
TEQAKKIVDILNNWLE
1600

PF-730
FEDIEQIIKYHLIDGKIVAPLLLDR
1601

PF-095
KRGSKIVIAIAVVLIVLAGVWVW
1602

PF-028
ALDCSEQSVILWYETILDKIVGVIK
1603

VIK
PF-257
VWENRKKYLENEIERHNVFLKLGQEVIKGLNA
1604

LASRGR

PF-226
LMFFSENMDKRDTLSGKFRYFAGSKVIKLMNW
1605

LSENGK

PF-580
EILNNNQVIKELTMKYKTQFESNLGGWTARARR
1606

PF-366
ALCSVIKAIELGIINVHLQ
1607

PF-C092
NGDKKAKEELDKWDEVIKELNIQF
1608

PF-S028
GSVIKKRRKRMSKKKHRKMLRRTRVQRRKLGK
1609

PF-103

VIK
ISVPGQVQMLIP
1610

PF-527
GSVIKKRRKRMAKKKHRKLLKKTRIQRRRAGK
1611

PF-167
AIEGVIKKGACFKLLRHEMF
1612

PF-C166
KRKHENVIVAEEMRVIKN
1613

PF-007
MGIIAGIIKVIKSLIEQFTGK
1614

PF-071
HCVIGNVVDIANLLKRRAVYRDIADVIKMR
1615

PF-028
ALDCSEQSVILWYETILDKIVGVIK
1616

PRP
PF-C031
WSESQPPTATPRPHAEVARAGLVTPPTL
1617

PF-752
LHVIRPRPELSELKFPITKILKVNKQGLKK
1618

PF-672
MRFGSLALVAYDSAIKHSWPRPSSVRRLRM
1619

PF-088
VMFVLTRGRSPRPMIPAY
1620

PF-143
LSPRPIIVSRRSRADNNNDWSR
1621

PF-168
VLPFPAIPLSRRRACVAAPRPRSRQRAS
1622

PF-531
YIQFHLNQQPRPKVKKIKIFL
1623

All groups are associated with antimicrobial activity

In certain embodiments, peptides described herein can have multiple activities. Thus for example, a peptide can have both binding/targeting activity and antimicrobial activity. Illustrative peptides having multiple activities are shown in Table 8. Such peptides can be used, e.g., in a chimeric construct, for any or all of these properties. Thus, for example, a peptide designated “B” in Table 8 can be used as a targeting peptide. If it is also designated G or M it can also be used for antimicrobial activity.

TABLE 8

Peptides having multiple activities.

Peptide
Activities
Peptide
Activities
Peptide
Activities
Peptide
Activities

PF-001
G B
PF-224
G B
PF-448
G B M
PF-592
G B

PF-002
G B
PF-226
G B
PF-450
G B
PF-593
G B

PF-003
G B
PF-233
G B
PF-451
G B
PF-594
G B

PF-004
G B
PF-234
G B
PF-452
G B
PF-595
G B

PF-005
G B
PF-235
G B
PF-453
G B
PF-596
G B

PF-006
G B M
PF-249
G B
PF-454
G B
PF-597
G B

PF-007
G B
PF-255
G B
PF-456
G B
PF-598
G B

PF-008
G B
PF-257
G B
PF-457
G B
PF-599
G B

PF-009
G B
PF-270
G B
PF-458
G B
PF-600
G B M

PF-010
G B
PF-271
G B
PF-459
G B
PF-601
G B

PF-011
G B
PF-273
G B
PF-460
G B
PF-602
G B

PF-012
G B
PF-276
G B
PF-461
G B
PF-603
G B

PF-013
G B
PF-278
G B M
PF-462
G B
PF-604
G B

PF-015
G B
PF-283
G B M
PF-464
G B
PF-605
G B

PF-017
G B
PF-289
G B
PF-465
G B
PF-606
G M

PF-020
G B
PF-292
G B
PF-466
G B
PF-607
G B

PF-021
G B
PF-294
G B
PF-467
G B
PF-609
G B

PF-022
G B
PF-297
G B
PF-469
G B
PF-610
G B

PF-023
G B
PF-301
G B
PF-470
G B
PF-612
G B

PF-024
G B
PF-305
G B
PF-471
G B
PF-613
G B

PF-025
G B
PF-306
G B
PF-472
G B
PF-614
G B

PF-026
G B
PF-307
G B M
PF-473
G B
PF-615
G B

PF-027
G B
PF-313
G B
PF-474
G B
PF-616
G B

PF-028
G B
PF-319
G B
PF-475
G B
PF-617
G B

PF-029
G B
PF-322
G M
PF-476
G B
PF-619
G B

PF-030
G B
PF-344
G B
PF-477
G B
PF-621
G B

PF-031
G B
PF-347
G B
PF-478
G B
PF-622
G B

PF-033
G B
PF-349
G B
PF-479
G B
PF-623
G B

PF-034
G B
PF-350
G B
PF-480
G B
PF-625
G B

PF-035
G B
PF-354
G B
PF-482
G B
PF-626
G B

PF-036
G B
PF-355
G B
PF-484
G B
PF-627
G B

PF-037
G B
PF-356
G B
PF-497
B M
PF-629
G B

PF-040
G B
PF-357
G B
PF-499
B M
PF-630
G B

PF-041
G B
PF-360
G B
PF-511
G B M
PF-631
G B

PF-042
G B
PF-362
G B
PF-512
G B M
PF-632
G B

PF-043
G B
PF-363
G B
PF-513
G B
PF-634
G B

PF-045
G B
PF-366
G B
PF-514
G B
PF-635
G B

PF-046
G B
PF-369
G B
PF-515
G B
PF-636
G B

PF-048
G B
PF-370
G B
PF-516
G
PF-637
G B

PF-049
G B
PF-373
G B
PF-517
G B
PF-638
G B

PF-051
G B
PF-374
G B
PF-518
G B
PF-639
G B

PF-052
G B
PF-375
G B
PF-519
G B
PF-640
G B

PF-053
G B
PF-376
G B
PF-520
G B M
PF-642
G B

PF-056
G B
PF-378
G B
PF-521
G B M
PF-655
G B

PF-057
G B
PF-379
G B
PF-522
G B M
PF-664
G B

PF-058
G B
PF-380
G B
PF-523
B M
PF-672
G B M

PF-061
G B
PF-381
G B
PF-524
G B M
PF-681
G B

PF-063
G B
PF-382
G B
PF-525
G M
PF-686
G B

PF-064
G B
PF-383
G B
PF-526
G B
PF-737
G B

PF-065
G B
PF-385
G B
PF-527
G B M
PF-738
G B

PF-066
G B
PF-386
G B
PF-528
G B
PF-741
G B

PF-067
G B
PF-387
G B
PF-529
G B M
PF-744
G B

PF-068
G B
PF-389
G B
PF-530
G M
PF-745
G B

PF-069
G B
PF-390
G B
PF-531
G M
PF-746
G B

PF-070
G B
PF-392
G B
PF-537
G B
PF-748
G B

PF-071
G B
PF-393
G B
PF-538
G M
PF-749
G B

PF-073
G B
PF-394
G B
PF-539
G B
PF-752
G B

PF-074
G B
PF-395
G B
PF-540
G B
PF-756
G B

PF-075
G B
PF-396
G B
PF-542
G B
PF-757
G B

PF-076
G B
PF-397
G B
PF-543
G B
PF-760
G B

PF-099
G B
PF-398
G B
PF-544
G B
PF-761
G B

PF-123
G B
PF-399
G B
PF-545
G B M
PF-762
G B

PF-124
G B
PF-401
G B
PF-546
G B
PF-763
G B

PF-125
G B
PF-403
G B
PF-547
G B M
PF-764
G B

PF-127
G B
PF-404
G B
PF-548
G B
PF-770
G B

PF-128
G B
PF-405
G B
PF-549
G B
PF-776
G B

PF-129
G B
PF-406
G B
PF-550
G B
PF-C052
G B

PF-133
G B
PF-407
G B
PF-551
G B
PF-C055
G B

PF-135
G B
PF-408
G B
PF-552
G B
PF-C057
G B

PF-137
G B
PF-410
G B
PF-553
G B
PF-C058
G B

PF-139
G B
PF-411
G B
PF-554
G B
PF-C061
G B

PF-140
G B
PF-413
G B
PF-555
G B
PF-C062
G B

PF-143
G B
PF-414
G B
PF-556
G B
PF-C064
G B

PF-144
G B
PF-416
G B
PF-557
G B
PF-C065
G B

PF-145
G B
PF-417
G B
PF-558
G B
PF-C069
G B

PF-148
G B M
PF-418
G B
PF-559
G B
PF-C071
G B

PF-149
G B
PF-421
G B
PF-560
G B
PF-C072
G B

PF-153
G B
PF-422
G B
PF-562
G B
PF-C075
G B

PF-156
G B
PF-423
G B
PF-563
G B
PF-C084
G B

PF-157
G B
PF-424
G B
PF-564
G B
PF-C085
G B

PF-164
G B
PF-425
G B
PF-566
G B
PF-C086
G B

PF-168
G B M
PF-426
G B
PF-567
G B
PF-C088
G B

PF-171
G B
PF-427
G B
PF-569
G B
PF-C091
G B

PF-173
G B
PF-428
G B
PF-572
G B
PF-C095
G B

PF-175
G B
PF-429
G B
PF-573
G B
PF-C098
G B

PF-176
G B
PF-430
G B
PF-575
G B
PF-C120
G B

PF-178
G B
PF-431
G B
PF-576
G B
PF-C131
G B

PF-180
G B
PF-432
G B
PF-577
G B
PF-C135
G B

PF-186
G B
PF-433
G B
PF-578
G B
PF-C136
G B

PF-188
G B
PF-434
G B
PF-580
G B
PF-C137
G B

PF-190
G B
PF-437
G M
PF-581
G B
PF-C139
G B

PF-191
G B
PF-439
G B
PF-583
G B M
PF-C142
G B

PF-192
G B
PF-440
G B
PF-584
G B
PF-C143
G B

PF-196
G B
PF-442
G B
PF-585
G B
PF-C145
G B

PF-203
G B
PF-443
G B
PF-586
G B
PF-C180
G B

PF-204
G B
PF-444
G B
PF-587
G B
PF-C181
G B

PF-208
G B
PF-445
G B
PF-588
G B
PF-C194
G B

PF-209
G B M
PF-446
G B
PF-589
G B
PF-C281
G B

PF-212
G B
PF-447
G B
PF-590
G B
PF-C290
G B

PF-215
G B
PF-S003
G B

PF-C291
G B

B: targeting/binding activity;

M: antimicrobial activity;

G: Growth or phenotype altering.

Other peptides believed to show binding, growth altering, and/or antimicrobial activity are shown in Table 9.

TABLE 9

Additional peptides believed to have binding,

growth altering, and/or antimicrobial activity.

ID
Sequence
SEQ ID No.

PF-198
RRLASRRSLVVST
1624

PF-227
RLLGLYGENSAAGFIASVIGAVIILFIYNLIARKS
1625

PF-260
GHLRVCWILWLQSANPLSFRHHYLAVMW
1626

PF-261
MDIWKFIKSFNTVNTYLLLSCVLLIILVLYFYVINPA
1627

PF-277
MIIQNKKIEKIYKYQTKEIFLNKTSLRAGFVFRMVRVLI
1628

PF-280
MLIDWQEPDIEKSFCAAFLKISVSVLVYRTPLGYGNQLRE
1629

PF-286
FFDGEVGCGC
1630

PF-287
ILEQNIEEVFFIQS
1631

PF-312
MDKIRIWNNFHISNEYIKQRYGIISIPLFYVYLF
1632

PF-321
FAKKNPCRMRVPNTGTWYLVVNQDGNSGIVNFSINTIQN
1633

PF-327
MLVFQMRYQMRYVDKTSTVLKQTKNSDYADK
1634

PF-330
MLMNFEVYQQRILIIYNKCYHLKAVGKNLQLFIIVD
1635

PF-331
MGRHLWNPSYFVATVSENTEEQIRKYINNQKKQVK
1636

PF-341
DDKNEGKIAQGEY
1637

PF-391
EASVYRE
1638

PF-420
MVKHNFDVTDKTGKISSKHCFEITDKTDVV
1639

PF-708
DRPSQTTHHTLSSSRITGPS
1640

PF-710
EALLPPDPPDEDSQRIIPQ
1641

PF-713
DRPSQTTHHTLSSSRITGPS
1642

PF-715
LEDTKALFPCFVPI
1643

PF-718
KKYSSFKSMIDDLEYDA
1644

PF-719
FKSMIDDLEYDA
1645

PF-721
TEQAKKIVDILNNWLE
1646

PF-722
STSPSVTSVYAEALGLK
1647

PF-723
VGAMAIFLNVVAMLAGV
1648

PF-725
ARTIQNNGCLIHNSRYP
1649

PF-726
CDDLYALEAQGTLNELLKK
1650

PF-729
TPEPVVIVKP
1651

PF-730
FEDIEQIIKYHLIDGKIVAPLLLDR
1652

PF-734
SDIIAEMFQQGELEPMLRDAVAA
1653

PF-736
KGSASGSASGSGSAK
1654

PF-739
KSGASSVASAAKSG
1655

PF-742
AAATTATTAK
1656

PF-743
TKGTTTGTAKTTGVTTGTAK
1657

PF-769
GSRGGAKRGGARG
1658

PF-
WSESQPPTATPRPHAEVARAGLVTPPTL
1659

C031

PF-
QPIGFPTDSVHGTDLVHRLRGTTSSR
1660

C038

PF-
LENLDIEGLTEMKEHIEDLIAEKSAAESIEEVIVEAE
1661

C077

PF-
AYSLTFQNPNDNLTDEEVAKYMEKITKALTEKIGAEVR
1662

C205

PF-S016
PLTRETFAERGIRKARVARTFSEEEPPF
1663

III. Design and Construction of STAMPs and Other Chimeric Constructs.

In various embodiments this invention provides chimeric moieties comprising one or more targeting moieties attached to one or more effectors. The targeting moieties can be selected to preferentially bind to a target microorganism (e.g., bacteria, virus, fungi, yeast, alga, protozoan, etc.) or group of microorganisms (e.g., gram-negative or gram-positive bacteria, particular genus, species, etc.) In certain embodiments the targeting moiety comprises one or more novel microorganism-binding peptides as described herein (see, e.g., Table 3, and/or Table 10, and/or Table 12). In certain embodiments the targeting moiety comprises non-peptide moieties (e.g., antibodies, receptor, receptor ligand, lectin, and the like).

In various embodiments the effector comprises a moiety whose activity is to be delivered to the target microorganism(s), to a biofilm comprising the target microorganism(s), to a cell or tissue comprising the target microorganism(s), and the like. In certain embodiments the targeting moiety comprises one or more antimicrobial peptide(s) as described herein (see, e.g., Tables 4, 5 and/or 14), an antibiotic (including, but not limited to a steroid antibiotic), a detectable label, a porphyrin, a photosensitizing agent, an epitope tag, a lipid or liposome, a nanoparticle, a dendrimer, and the like.

In certain embodiments one or more targeting moieties are attached to a single effector. In certain embodiments one or more effectors are attached to a single targeting moiety. In certain embodiments multiple targeting moieties are attached to multiple effectors. The targeting moieties(s) can be attached directly to the effector(s) or through a linker. Where the targeting moiety and the effector comprise peptides the chimeric moiety can be a fusion protein.

A) Targeting Moieties.

In various embodiments this invention provides targeting moieties that preferentially and/or specifically bind to a microorganism (e.g., a bacterium, a fungus, a yeast, etc.). One or more such targeting moieties can be attached to one or more effectors to provide chimeric moieties that are capable of delivering the effector(s) to a target (e.g., a bacterium, a fungus, a yeast, a biofilm comprising the bacterium or fungus or yeast, etc.).

In various embodiments, targeting moieties include, but are not limited to peptides that preferentially bind particular microorganisms (e.g., bacteria, fungi, yeasts, protozoa, algae, viruses, etc.) or groups of such microorganisms, e.g., as described above, antibodies that bind particular microorganisms or groups of microorganisms, receptor ligands that bind particular microorganisms or groups of microorganisms, porphyrins (e.g., metalloporphyrins), lectins that bind particular microorganisms or groups of microorganisms, and the like. As indicated it will be appreciated that references to microorganisms or groups of microorganism include bacteria or groups of bacteria, viruses or groups of viruses, yeasts or groups of yeasts, protozoa or groups of protozoa, viruses or groups of viruses, and the like.

i. Targeting Peptides.

In certain embodiments the targeting peptide can comprise one or more domains capable of binding, specifically binding, or preferentially binding to a microorganism, e.g., a target microbial organism (see, e.g., Table 3). In certain embodiment, the targeting peptide be identified via screening peptide libraries. For example, a phage display peptide library can be screened against a target microbial organism or a desired antigen or epitope thereof. Any peptide identified through such screening can be used as a targeting peptide for the target microbial organism. Illustrative additional targeting peptides are shown in Table 10.

TABLE 10

Additional illustrative targeting moieties.

SEQ

Targeting Moiety/

ID

Organism
Structure/sequence
NO

LPSB-1
RGLRRLGRRGLRRLGR
1664

Phob-1
KPVLPVLPVLPVL
1665

LPSB-2
VLRIIRIAVLRIIRIA
1666

LPTG-1
LPETGGSGGSLPETG
1667

α-1
RAHIRRAHIRR
1668

ANION-1
DEDEDDEEDDDEEE
1669

PHILIC-1
STMCGSTMCGSTMCG
1670

SA5.1/S. aureus
VRLPLWLPSLNE
1671

SA5.3/S. aureus
ANYFLPPVLSSS
1672

SA5.4/S. aureus
SHPWNAQRELSV
1673

SA5.5/S. aureus
SVSVGMRPMPRP
1674

SA5.6/S. aureus
WTPLHPSTNRPP
1675

SA5.7/S. aureus
SVSVGMKPSPRP
1676

SA5.8/S. aureus
SVSVGMKPSPRP
1677

SA5.9/S. aureus
SVPVGPYNESQP
1678

SA5.10/S. aureus
WAPPLFRSSLFY
1679

SA2.2/S. aureus
WAPPXPXSSLFY
1680

SA2.4/S. aureus
HHGWTHHWPPPP
1681

SA2.5/S. aureus
SYYSLPPIFHIP
1682

SA2.6/S. aureus
HFQENPLSRGGEL
1683

SA2.7/S. aureus
FSYSPTRAPLNM
1684

SA2.8/S. aureus
SXPXXMKXSXXX
1685

SA2.9/S. aureus
VSRHQSWHPHDL
1686

SA2.10/S. aureus
DYXYRGLPRXET
1687

SA2.11/S. aureus
SVSVGMKPSPRP
1688

S. aureus/Consensus
V/Q/H-P/H-H-E-F/Y-K/H-H/A-L/H-X-X-K/R-P/L
1689

DH5.1/E coli.
KHLQNRSTGYET
1690

DH5.2/E coli.
HIHSLSPSKTWP
1691

DH5.3/E coli.
TITPTDAEMPFL
1692

DH5.4/E coli.
HLLESGVLERGM
1693

DH5.5/E coli.
HDRYHIPPLQLH
1694

DH5.6/E coli.
VNTLQNVRHMAA
1695

DH5.7/E coli.
SNYMKLRAVSPF
1696

DH5.8/E coli.
NLQMPYAWRTEF
1697

DH5.9/E coli.
QKPLTGPHFSLI
1698

CSP/S. mutans
SGSLSTFFRLFNRSFTQALGK
1699

CSPC18/S. mutans
LSTFFRLFNRSFTQALGK
1700

CSPC16/S. mutans
TFFRLFNRSFTQALGK
1701

CSPM8/S. mutans
TFFRLFNR
1702

KH/Pseudomonas spp
KKHRKHRKHRKH
1703

(US 2004/0137482)

cCF10
LVTLVFV
1704

AgrD1
YSTCDFIM
1705

AgrD2
GVNACSSLF
1706

AgrD3
YINCDFLL
1707

NisinA
ITSISLCTPGCKTGALMGCNMRTATCIICSIIIVSK
1708

PlnA
KSSAYSLQMGATAIKQVKKLFKKWGW
1709

S3L1-5
WWYNWWQDW
1710

Penetratin
RQIKIWFWNRRMKWKK*
1711

Tat
EHWSYCDLRPG
1712

Pep-1N
KETWWETWWTEW
1713

Pep27
MRKEFHNVLSSGQLLADKRPARDYNRK
1714

HABP35
LKQKIKHVVKLKVVVKLRSQLVKRKQN
1715

HABP42 (all D)
STMMSRSHKTRSHHV
1716

HABP52
GAHWQFNALTVRGGGS
1717

Hi3/17
KQRTSIRATEGCLPS
1718

α-E. coli peptide
QEKIRVRLSA
1719

Salivary Receptor
QLKTADLPAGRDETTSFVLV*
1720

Adhesion Fragment

S1 (Sushi frag.)
GFKLKGMARISCLPNGQWSNFPPKCIRECAMVSS
1721

(LPS binding)

S3 (Sushi frag.)
HAEHKVKIGVEQKYGQFPQGTEVTYTCSGNYFLM
1722

(LPS binding)

MArg.1
AMDMYSIEDRYFGGYAPEVG
1723

(Mycoplasma infected

cell line binding

peptide

BPI fragment 1
ASQQGTAALQKELKRIKPDYSDSFKIKH
1724

(LPS binding)

6,376,462

BPI fragment 2
SSQISMVPNVGLKFSISNANIKISGKWKAQKRFLK
1725

(LPS binding)

6,376,462

BPI fragment 3
VHVHISKSKVGWLIQLFHKKIESALRNK
1726

(LPS binding)

6,376,462

LBP fragment 1
AAQEGLLALQSELLRITLPDFTGDLRIPH
1727

(LPS binding)

6,376,462

LBP fragment 2
HSALRPVPGQGLSLSISDSSIRVQGRWKVRKSFFK
1728

(LPS binding)

6,376,462

LBP fragment 3
VEVDMSGDLGWLLNLFHNQIESKFQKV
1729

(LPS binding)

6,376,462

B. anthracis spore
ATYPLPIR
1730

binding

(WO/1999/036081)

Bacillus spore binding
peptides of 5-12 amino acids containing the sequence
1731

(WO/1999/036081)
Asn-His-Phe-Leu

peptides of 5-12 amino acids containing the sequence
1732

Asn-His-Phe-Leu-Pro

Thr-Ser-Glu-Asn-Val-Arg-Thr (TSQNVRT)
1733

A peptide of formula Thr-Tyr-Pro-X-Pro-X-Arg
1734

(TYPXPXR) where X is a Ile, Val or Leu.

A peptide having the sequence TSQNVRT.
1735

A peptide having the sequence TYPLPIR
1736

LPS binding peptide 1
TFRRLKWK
1737

(6,384,188)

LPS BP 2 (6,384,188)
RWKVRKSFFKLQ
1738

LPS BP 3 (6,384,188)
KWKAQKRFLKMS
1739

Pseudomonas pilin
KCTSDQDEQFIPKGCSK
1740

binding peptide

(5,494,672)

RNAII inhibiting
YSPWTNF
1741

peptide (S. Aureus)

Patents and patent publications disclosing the referenced antibodies are identified in the table.

In certain embodiments the targeting moieties can comprise other entities, particularly when utilized with an antimicrobial peptide as described, for example, in Table 4. Illustrative targeting moieties can include a polypeptide, a peptide, a small molecule, a ligand, a receptor, an antibody, a protein, or portions thereof that specifically interact with a target microbial organism, e.g., the cell surface appendages such as flagella and pili, and surface exposed proteins, lipids and polysaccharides of a target microbial organism.

ii. Targeting Antibodies.

In certain embodiments the targeting moieties can comprise one or more antibodies that bind specifically or preferentially a microorganism or group of microorganisms (e.g., bacteria, fungi, yeasts, protozoa, viruses, algae, etc.). The antibodies are selected to bind an epitope characteristic or the particular target microorganism(s). In various embodiments such epitopes or antigens are typically is gram-positive or gram-negative specific, or genus-specific, or species-specific, or strain specific and located on the surface of a target microbial organism. The antibody that binds the epitope or antigen can direct an anti-microbial peptide moiety or other effector to the site. Furthermore, in certain embodiments the antibody itself can provide anti-microbial activity in addition to the activity provided by effector moiety since the antibody may engage an immune system effector (e.g., a T-cell) and thereby elicit an antibody-associated immune response, e.g., a humoral immune response.

Antibodies that bind particular target microorganisms can be made using any methods readily available to one skilled in the art. For example, as described in U.S. Pat. No. 6,231,857 (incorporated herein by reference) three monoclonal antibodies, i.e., SWLA1, SWLA2, and SWLA3 have been made against S. mutans. Monoclonal antibodies obtained from non-human animals to be used in a targeting moiety can also be humanized by any means available in the art to decrease their immunogenicity and increase their ability to elicit anti-microbial immune response of a human. Illustrative microorganisms and/or targets to which antibodies may be directed are shown, for example, in Tables 3 and 11.

Various forms of antibody include, without limitation, whole antibodies, antibody fragments (e.g., (Fab′)₂Fab′, etc.), single chain antibodies (e.g., scFv), minibodies, Di-miniantibody, Tetra-miniantibody, (scFv)₂, Diabody, scDiabody, Triabody, Tetrabody, Tandem diabody, VHH, nanobodies, affibodies, unibodies, and the like.

Methods of making such antibodies are well known to those of skill in the art. In various embodiments, such methods typically involve providing the microorganism, or a component thereof for use as an antigen to raise an immune response in an organism or for use in a screening protocol (e.g., phage or yeast display).

For example, polyclonal antibodies are typically raised by one or more injections (e.g. subcutaneous or intramuscular injections) of the target microorganism(s) or components thereof into a suitable non-human mammal (e.g., mouse, rabbit, rat, etc.).

If desired, the immunizing microorganism or antigen derived therefrom can be administered with or coupled to a carrier protein by conjugation using techniques that are well-known in the art. Such commonly used carriers which are chemically coupled to the peptide include keyhole limpet hemocyanin (KLH), thyroglobulin, bovine serum albumin (BSA), and tetanus toxoid. The coupled peptide is then used to immunize the animal (e.g. a mouse or a rabbit).

The antibodies are then obtained from blood samples taken from the mammal. The techniques used to develop polyclonal antibodies are known in the art (see, e.g., Methods of Enzymology, “Production of Antisera With Small Doses of Immunogen: Multiple Intradermal Injections”, Langone, et al. eds. (Acad. Press, 1981)). Polyclonal antibodies produced by the animals can be further purified, for example, by binding to and elution from a matrix to which the peptide to which the antibodies were raised is bound. Those of skill in the art will know of various techniques common in the immunology arts for purification and/or concentration of polyclonal antibodies, as well as monoclonal antibodies see, for example, Coligan, et al. (1991) Unit 9, Current Protocols in Immunology, Wiley Interscience).

In certain embodiments the antibodies produced will be monoclonal antibodies (“mAb's”). The general method used for production of hybridomas secreting mAbs is well known (Kohler and Milstein (1975) Nature, 256:495

Antibody fragments, e.g. single chain antibodies (scFv or others), can also be produced/selected using phage display and/or yeast display technology. The ability to express antibody fragments on the surface of viruses that infect bacteria (bacteriophage or phage) or yeasts makes it possible to isolate a single binding antibody fragment, e.g., from a library of greater than 10¹⁰nonbinding clones. To express antibody fragments on the surface of phage (phage display) or yeast, an antibody fragment gene is inserted into the gene encoding a phage surface protein (e.g., pIII) and the antibody fragment-pIII fusion protein is displayed on the phage surface (McCafferty et al. (1990) Nature, 348: 552-554; Hoogenboom et al. (1991) Nucleic Acids Res. 19: 4133-4137).

Since the antibody fragments on the surface of the phage or yeast are functional, phage bearing antigen binding antibody fragments can be separated from non-binding phage by antigen affinity chromatography (McCafferty et al. (1990) Nature, 348: 552-554). Depending on the affinity of the antibody fragment, enrichment factors of 20 fold—1,000,000 fold are obtained for a single round of affinity selection.

Human antibodies can be produced without prior immunization by displaying very large and diverse V-gene repertoires on phage (Marks et al. (1991) J. Mol. Biol. 222: 581-597.

In certain embodiments, nanobodies can be used as targeting moieties. Methods of making V_hH (nanobodies) are also well known to those of skill in the art. The Camelidae heavy chain antibodies are found as homodimers of a single heavy chain, dimerized via their constant regions. The variable domains of these camelidae heavy chain antibodies are referred to as V_HHdomains or V_HH, and can be either used per se as nanobodies and/or as a starting point for obtaining nanobodies. Isolated V_HHretain the ability to bind antigen with high specificity (see, e.g., Hamers-Casterman et al. (1993) Nature 363: 446-448). In certain embodiments such V_HHdomains, or nucleotide sequences encoding them, can be derived from antibodies raised in Camelidae species, for example in camel, dromedary, llama, alpaca and guanaco. Other species besides Camelidae (e.g. shark, pufferfish) can produce functional antigen-binding heavy chain antibodies, from which (nucleotide sequences encoding) such naturally occurring V_HHcan be obtained, e.g. using the methods described in U.S. Patent Publication US 2006/0211088.

In various embodiments, for use in therapy, human proteins are preferred, primarily because they are not as likely to provoke an immune response when administered to a patient. Comparisons of camelid V_HHwith the V_Hdomains of human antibodies reveals several key differences in the framework regions of the camelid V_HHdomain corresponding to the V_H/V_Linterface of the human V_Hdomains. Mutation of these human residues to V_HHresembling residues has been performed to produce “camelized” human V_Hdomains that retain antigen binding activity, yet have improved expression and solubility.

Libraries of single V_Hdomains have also been derived for example from V_Hgenes amplified from genomic DNA or from mRNA from the spleens of immunized mice and expressed in E. coli (Ward et al. (1989) Nature 341: 544-546) and similar approaches can be performed using the V_Hdomains and/or the V_Ldomains described herein. The isolated single VH domains are called “dAbs” or domain antibodies. A “dAb” is an antibody single variable domain (V_Hor V_L) polypeptide that specifically binds antigen. A “dAb” binds antigen independently of other V domains; however, as the term is used herein, a “dAb” can be present in a homo- or heteromultimer with other V_Hor V_Ldomains where the other domains are not required for antigen binding by the dAb, i.e., where the dAb binds antigen independently of the additional V_Hor V_Ldomains.

As described in U.S. Patent Publication US 2006/0211088 methods are known for the cloning and direct screening of immunoglobulin sequences (including but not limited to multivalent polypeptides comprising: two or more variable domains—or antigen binding domains—and in particular V_Hdomains or V_HHdomains; fragments of V_L, V_Hor V_HHdomains, such as CDR regions, for example CDR3 regions; antigen-binding fragments of conventional 4-chain antibodies such as Fab fragments and scFv's, heavy chain antibodies and domain antibodies; and in particular of V_Hsequences, and more in particular of V_HHsequences) that can be used as part of and/or to construct such nanobodies.

Methods and procedures for the production of VHH/nanobodies can also be found for example in WO 94/04678, WO 96/34103, WO 97/49805, WO 97/49805 WO 94/25591, WO 00/43507 WO 01/90190, WO 03/025020, WO 04/062551, WO 04/041863, WO 04/041865, WO 04/041862, WO 04/041867, PCT/BE2004/000159, Hamers-Casterman et al. (1993) Nature 363: 446; Riechmann and Muyldermans (1999) J. Immunological Meth., 231: 25-38; Vu et al. (1997) Molecular Immunology, 34(16-17): 1121-1131; Nguyen et al. (2000) EMBO J., 19(5): 921-930; Arbabi Ghahroudi et al. (19997) FEBS Letters 414: 521-526; van der Linden et al. (2000) J. Immunological Meth., 240: 185-195; Muyldermans (2001) Rev. Molecular Biotechnology 74: 277-302; Nguyen et al. (2001) Adv. Immunol. 79: 261, and the like.

In certain embodiments the antibody targeting moiety is a unibody. Unibodies provide an antibody technology that produces a stable, smaller antibody format with an anticipated longer therapeutic window than certain small antibody formats. In certain embodiments unibodies are produced from IgG4 antibodies by eliminating the hinge region of the antibody. Unlike the full size IgG4 antibody, the half molecule fragment is very stable and is termed a uniBody. Halving the IgG4 molecule left only one area on the UniBody that can bind to a target. Methods of producing unibodies are described in detail in PCT Publication WO2007/059782, which is incorporated herein by reference in its entirety (see, also, Kolfschoten et al. (2007) Science 317: 1554-1557).

Affibody molecules are class of affinity proteins based on a 58-amino acid residue protein domain, derived from one of the IgG-binding domains of staphylococcal protein A. This three helix bundle domain has been used as a scaffold for the construction of combinatorial phagemid libraries, from which Affibody variants that target the desired molecules can be selected using phage display technology (see, e.g., Nord et al. (1997) Nat. Biotechnol. 15: 772-777; Ronmark et al. (2002) Eur. J. Biochem., 269: 2647-2655.). Details of Affibodies and methods of production are known to those of skill (see, e.g., U.S. Pat. No. 5,831,012 which is incorporated herein by reference in its entirety).

It will also be recognized that antibodies can be prepared by any of a number of commercial services (e.g., Berkeley antibody laboratories, Bethyl Laboratories, Anawa, Eurogenetec, etc.).

Illustrative antibodies that bind various microorganisms are shown in Table 11.

TABLE 11

Illustrative antibodies that bind target microorganisms.

Source
Antibody

U.S. Pat. No. 7,195,763
Polyclonal/monoclonal binds specific Gram(+) cell

wall repeats

U.S. Pat. No. 6,939,543
Antibodies against G(+) LTA

U.S. Pat. No. 7,169,903
Antibodies against G(+) peptidoglycan

U.S. Pat. No. 6,231,857
Antibody against S. mutans (Shi)

U.S. Pat. No. 5,484,591
Gram(−) binding antibodies

US 2007/0231321
Diabody binding to Streptococcus surface antigen I/II

US 2003/0124635
Antibody against S. mutans

US 2006/0127372
Antibodies to Actinomyces naeslundii, Lactobacillus

casei

US 2003/0092086
Antibody to S. sobrinus

U.S. Pat. No. 7,364,738
Monoclonal antibodies to the ClfA protein in S. aureus

U.S. Pat. No. 7,632,502
Antibodies against C. albicans

U.S. Pat. No. 7,608,265
Monoclonal against C. difficile

U.S. Pat. No. 4,777,136
Monoclonal Antibodies against Pseudomonas aeruginosa

see, e.g., ab20429, ab20560,
Antibody against S. pneumoniae

ab79522, ab35165, ab65602

from AbCAMm Cambridge

Science Park, U.K.

In addition, antibodies (targeting moieties) that bind other microorganisms can readily be produced using, for example, the methods described above.

iii. Porphyrins.

In certain embodiments porphyrins, or other photosensitizing agents, can be used as targeting moieties in the constructs described herein. In particular, metalloporphyrins, particularly a number of non-iron metalloporphyrins mimic heme in their molecular structure and are actively accumulated by bacteria via high affinity heme-uptake systems. The same uptake systems can be used to deliver antibiotic-porphyrin and antibacterial-porphyrin conjugates. Illustrative targeting porphyrins suitable for this purpose are described in U.S. Pat. No. 6,066,628 and shown herein, for example, in FIGS. 1 and 2.

For example, certain artificial (non-iron) metalloporphyrins (MPs) (Ga—IX, Mn—IX,) are active against Gram-negative and Gram-positive bacteria and acid-fast bacilli (e.g., Y. enterocolitica, N. meningitides, S. marcescens, E. coli, P. mirabills, K. pneumoniae, K. oxytoca, Ps. aeruginosa, C. freundii, E. aerogenes, F. menigosepticum, S. aureus, B. subtilis, S. pyogenes A, E. faecalis, M. smegmatis, M. bovis, M. tuber., S. crevisiae) as described in Tables 1-5 of U.S. Pat. No. 6,066,628. These MPs can be used as targeting moieties against these microorganisms.

Similarly, some MPs are also growth-inhibitory against yeasts, indicating their usefulness targeting moieties to target Candida species (e.g., Candida albicans, C. krusei, C. pillosus, C. glabrata, etc.) and other mycoses including but not limited to those caused by as Trichophyton, Epidermophyton, Histoplasma, Aspergillus, Cryptococcus, and the like.

Porphyrins, and other photosensitizers, also have antimicrobial activity. Accordingly, in certain embodiments, the porphyrins, or other photosensitizers, can be used as effectors (e.g., attached to targeting peptides as described herein). In various embodiments the porphyrins or other photosensitizers can provide a dual functionality, e.g., as a targeting moiety and an antimicrobial and can be attached to a targeting peptide and/or to an antimicrobial peptide as described herein.

Illustrative porphyrins and other photosensitizers are shown in FIGS. 1-11 and described in more detail in the discussion of effectors below.

iv. Pheromones.

In certain embodiments, pheromones from microorganisms can be used as targeting moieties. Illustrative pheromones from bacteria and fungi are shown in Table 12.

TABLE 12

Illustrative bacterial and fungal pheromones utilizable as targeting moieties.

Locus tag
Product
Sequence
SEQ ID

Bacterial Pheromones

gi|1041118|dbj|BAA11198.1|
iPD1 [Enterococcus
MKQQKKHIAALLF
1742

faecalis]
ALILTLVS

gi|1113947|gb|AAB35253.1|
iAM373sex pheromone
SIFTLVA
1743

inhibito [Enterococcus

faecalis, Peptide, 7 aa]

gi|115412|sp|P13268.1|CAD1_ENTFA
Sex pheromone CAD1
LFSLVLAG
1744

gi|116406|sp|P11932.1|CIA_ENTFA
Sex pheromone cAM373
AIFILAS
1745

(Clumping-inducing

agent) (CIA)

gi|117240|sp|P13269.1|CPD1_ENTFA
Sex pheromone cPD1
FLVMFLSG
1746

gi|12056953|gb|AAG48144.1|AF322594_1
putative peptide
DSIRDVSPTFNKIRR
1747

pheromone PrcA
WFDGLFK

[Lactobacillus paracasei]

gi|123988|sp|P24803.1|IAD1_ENTFA
Sex pheromone inhibitor
MSKRAMKKIIPLIT
1748

determinant precursor
LFVVTLVG

(iAD1)

gi|126362994|emb|CAM35812.1|
precursor of pheromone
KDEIYWKPS
1749

peptide ComX [Bacillus

amyloliquefaciens FZB42]

gi|1587088|prf||2205353A
pheromone
YSTCDFIM
1750

gi|15900442|ref|NP_345046.1|
peptide pheromone BlpC
GLWEDLLYNINRY
1751

[Streptococcus
AHYIT

pneumoniae TIGR4]

gi|1617436|emb|CAA66791.1|
competence pheromone
DIRHRINNSIWRDIF
1752

[Streptococcus gordonii]
LKRK

gi|1617440|emb|CAA66786.1|
competence pheromone
DVRSNKIRLWWEN
1753

[Streptococcus gordonii]
IFFNKK

gi|18307870|gb|AAL67728.1|AF456134_2
ComX pheromone
PTTREWDG
1754

precursor [Bacillus

mojavensis]

gi|18307874|gb|AAL67731.1|AF456135_2
ComX pheromone
LQIYTNGNWVPS
1755

precursor [Bacillus

mojavensis]

gi|29377808|ref|NP_816936.1|
sex pheromone inhibitor
MSKRAMKKIIPLIT
1756

determinant [Enterococcus
LFVVTLVG

faecalis V583]

gi|3342125|gb|AAC27522.1|
putative pheromone
GAGKNLIYGMGYG
1757

[Enterococcus faecium]
YLRSCNRL

gi|41018893|sp|P60242.1|CSP1_STRPN
Competence-stimulating
EMRLSKFFRDFILQ
1758

peptide type 1 precursor
RKK

(CSP-1)

gi|57489126|gb|AAW51333.1|
PcfP [Enterococcus
WSEIEINTKQSN
1759

faecalis]

gi|57489152|gb|AAW51349.1|
PrgT [Enterococcus
HISKERFEAY
1760

faecalis]

gi|58616083|ref|YP_195761.1|
UvaF [Enterococcus
KYKCSWCKRVYTL
1761

faecalis]
RKDHRTAR

gi|58616111|ref|YP_195802.1|
PcfP [Enterococcus
WSEIEINTKQSN
1762

faecalis]

gi|58616132|ref|YP_195769.1|
PrgQ [Enterococcus
MKTTLKKLSRYIA
1763

faecalis]
VVIAITLIFI

gi|58616137|ref|YP_195772.1|
PrgT [Enterococcus
HISKERFEAY
1764

faecalis]

gi|6919848|sp|O33689.1|CSP_STROR
Competence-stimulating
DKRLPYFFKHLFSN
1765

peptide precursor (CSP)
RTK

gi|6919849|sp|O33666.1|CSP2_STRMT
Competence-stimulating
EMRKPDGALFNLF
1766

peptide precursor (CSP)
RRR

gi|6919850|sp|O33668.1|CSP3_STRMT
Competence-stimulating
EMRKSNNNFFHFL
1767

peptide precursor (CSP)
RRI

gi|6919851|sp|O33672.1|CSP1_STRMT
Competence-stimulating
ESRLPKIRFDFIFPR
1768

peptide precursor (CSP)
KK

gi|6919852|sp|O33675.1|CSP4_STRMT
Competence-stimulating
EIRQTHNIFFNFFKRR
1769

peptide precursor (CSP)

gi|6919853|sp|O33690.1|CSP2_STROR
Competence-stimulating
DWRISETIRNLIFPR
1770

peptide precursor (CSP)
RK

gi|999344|gb|AAB34501.1|
cOB1bacterial sex
VAVLVLGA
1771

pheromone [Enterococcus

faecalis, Peptide, 8 aa]

gi|18307878|gb|AAL67734.1|AF456136_2
ComX pheromone
FFEDDKRKSFI
1772

precursor [Bacillus

subtilis]

gi|18307882|gb|AAL67737.1|AF456137_2
ComX pheromone
FFEDDKRKSFI
1773

precursor [Bacillus

subtilis]

gi|28272731|emb|CAD65660.1|
accessory gene regulator
MKQKMYEAIAHLF
1774

protein D, peptide
KYVGAKQLVMCC

pheromone precursor
VGIWFETKIPDELRK

[Lactobacillus plantarum

WCFS1]

gi|28379890|ref|NP_786782.1|
accessory gene regulator
MKQKMYEAIAHLF
1775

protein D, peptide
KYVGAKQLVMCC

pheromone precursor
VGIWFETKIPDELRK

[Lactobacillus plantarum

WCFS1]

gi|57489105|gb|AAW51312.1|
PrgF [Enterococcus
VVAYVITQVGAIRF
1776

faecalis]

gi|58616090|ref|YP_195779.1|
PrgF [Enterococcus
VVAYVITQVGAIRF
1777

faecalis]

gi|58616138|ref|YP_195762.1|
PrgN [Enterococcus
LLKLQDDYLLHLE
1778

faecalis]
RHRRTKKIIDEN

gi|57489117|gb|AAW51324.1|
PcfF [Enterococcus
EDIKDLTDKVQSLN
1779

faecalis]
ALVQSELNKLIKRK

DQS

gi|57489119|gb|AAW51326.1|
PcfH [Enterococcus
WFLDFSDWLSKVP
1780

faecalis]
SKLWAE

gi|58616102|ref|YP_195792.1|
PcfF [Enterococcus
EDIKDLTDKVQSLN
1781

faecalis]
ALVQSELNKLIKRK

DQS

gi|58616104|ref|YP_195794.1|
PcfH [Enterococcus
WFLDFSDWLSKVP
1782

faecalis]
SKLWAE

Fungi

gi|1127585|gb|AAA99765.1|
mfa1 gene product
MLSIFAQTTQTSAS
1783

EPQQSPTAPQGRDN

GSPIGYSSCVVA

gi|1127592|gb|AAA99771.1|
mfa2 gene product
MLSIFETVAAAAPV
1784

TVAETQQASNNEN

RGQPGYYCLIA

gi|11907715|gb|AAG41298.1|
pheromone precursor
PSLPSSPPSLLPPLPL
1785

MFalpha1D
LKLLATRRPTLVG

[Cryptococcus neoformans
MTLCV

var. neoformans]

gi|13810235|emb|CAC37424.1|
M-factor precursor Mfm1
MDSMANSVSSSSV
1786

[Schizosaccharomyces
VNAGNKPAETLNK

pombe]
TVKNYTPKVPYMC

VIA

gi|14269436|gb|AAK58071.1|AF378295_1
peptide mating pheromone
MDTFTYVDLAAVA
1787

precursor Bbp2-3
AAAVADEVPRDFE

[Schizophyllum
DQITDYQSYCIIC

commune]

gi|14269440|gb|AAK58073.1|AF378297_1
peptide mating pheromone
SNVHGWCVVA
1788

precursor Bbp2-1

[Schizophyllum

commune]

gi|1813600|gb|AAB41859.1|
pheromone precursor
NTTAHGWCVVA
1789

Bbp1(1) [Schizophyllum

commune]

gi|24940428|emb|CAD56313.1|
a-pheromone
MQPSTVTAAPKDK
1790

[Saccharomyces
TSAEKKDNYIIKGV

paradoxus]
FWDPACVIA

gi|27549492|gb|AAO17258.1|
pheromone phb3.1
GPTWWCVNA
1791

[Coprinopsis cinerea]

gi|27549494|gb|AAO17259.1|
pheromone phb3.2
SGPTWFCIIQ
1792

[Coprinopsis cinerea]

gi|27752314|gb|AAO19469.1|
pheromone protein a
FTAIFSTLSSSVASK
1793

pecursor [Cryptococcus
TDAPRNEEAYSSG

neoformans var. grubii]
NSP

gi|2865510|gb|AAC02682.1|
MAT-1 pheromone
MFSIFAQPAQTSVS
1794

[Ustilago hordei]
ETQESPANHGANP

GKSGSGLGYSTCV

VA

gi|3023372|sp|P78742.1|BB11_SCHCO
RecName: Full = Mating-
NTTAHGWCVVA
1795

type pheromone BBP1(1);

Flags: Precursor

gi|3025079|sp|P56508.1|SNA2_YEAST
RecName: Full = Protein
SDDNYGSLA
1796

SNA2

gi|37626077|gb|AAQ96360.1|
pheromone precursor Phb3
NGLTFWCVIA
1797

B5 [Coprinopsis cinerea]

gi|37626081|gb|AAQ96362.1|
pheromone precursor
PSWFCVIA
1798

Phb3.2 B45 [Coprinopsis

cinerea]

gi|37626083|gb|AAQ96363.1|
pheromone precursor
ASWFCTIA
1799

Phb3.1 B47 [Coprinopsis

cinerea]

gi|37961432|gb|AAP57503.1|
Ste3-like pheromone
PHHKIANASDKRR
1800

receptor [Thanatephorus
RMYFEIFMCAVL

cucumeris]

gi|400250|sp|P31962.1|MFA1_USTMA
RecName: Full = A1-
MLSIFAQTTQTSAS
1801

specific pheromone;
EPQQSPTAPQGRDN

AltName: Full = Mating
GSPIGYSSCVVA

factor A1

gi|400251|sp|P31963.1|MFA2_USTMA
RecName: Full = A2-
MLSIFETVAAAAPV
1802

specific pheromone;
TVAETQQASNNEN

AltName: Full = Mating
RGQPGYYCLIA

factor A2

gi|41209131|gb|AAR99617.1|
lipopeptide mating
SLTYAWCVVA
1803

pheromone precursor

Bap2(3) [Schizophyllum

commune]

gi|41209146|gb|AAR99650.1|
lipopeptide mating
TSMAHAWCVVA
1804

pheromone precursor

Bap3(2) [Schizophyllum

commune]

gi|41209149|gb|AAR99653.1|
lipopeptide mating
GYCVVA
1805

pheromone precursor

Bbp2(8) [Schizophyllum

commune]

gi|46098187|gb|EAK83420.1|
MFA1_USTMA A1-
MLSIFAQTTQTSAS
1806

SPECIFIC PHEROMONE
EPQQSPTAPQGRDN

(MATING FACTOR A1)
GSPIGYSSCVVA

[Ustilago maydis 521]

gi|546861|gb|AAB30833.1|
M-factor mating
MDSMANTVSSSVV
1807

pheromone
NTGNKPSETLNKT

[Schizosaccharomyces
VKNYTPKVPYMCV

pombe]
IA

gi|5917793|gb|AAD56043.1|AF184069_1
pheromone Mfa2
MFSLFETVAAAVK
1808

[Ustilago hordei]
VVSAAEPEHAPTNE

GKGEPAPYCIIA

gi|6014618|gb|AAF01424.1|AF186389_1
Phb3.2.42 [Coprinus
LTWFCVIA
1809

cinereus]

gi|68266363|gb|AAY88882.1|
putative pheromone
LREKRRRRWFEAF
1810

receptor STE3.4
MGFGL

[Coprinellus disseminatus]

gi|71012805|ref|XP_758529.1|
A1-specific pheromone
MLSIFAQTTQTSAS
1811

[Ustilago maydis 521]
EPQQSPTAPQGRDN

GSPIGYSSCVVA

gi|72414834|emb|CAI59748.1|
mating factor a1.3
MDALTLFAPVSLG
1812

[Sporisorium reilianum]
AVATEQAPVDEER

PNRQTFPWIGCVVA

gi|72414854|emb|CAI59758.1|
mating factor a2.1
MFIFESVVASVQAV
1813

[Sporisorium reilianum]
SVAEQDQTPVSEG

RGKPAVYCTIA

gi|1127587|gb|AAA99767.1|
rba1 gene product
PWMSLLFSFLALLA
1814

LILPKLSKDDPLGL

TRQPR

gi|151941959|gb|EDN60315.1|
pheromone-regulated
ASISLIMEGSANIEA
1815

membrane protein
VGKLVWLAAALPL

[Saccharomyces cerevisiae
AFI

YJM789]

gi|3025095|sp|Q07549.1|SNA4_YEAST
Protein SNA4
ARNVYPSVETPLLQ
1816

GAAPHDNKQSLVE

SPPPYVP

gi|73921293|sp|Q08245.3|ZEO1_YEAST
RecName: Full = Protein
FLKKLNRKIASIFN
1817

ZEO1; AltName:

Full = Zeocin resistance

protein 1

gi|74644573|sp|Q9P305.3|IGO2_YEAST
RecName: Full = Protein
DSISRQGSISSGPPP
1818

EDF (E. coli)
IGO2
RSPNK

NNWNN
1819

v. Targeting Enhancers/Opsonins

In certain embodiments compositions are contemplated that incorporate a targeting enhancer (e.g., an opsonin) along with one or more targeting moieties (e.g., targeting peptides). Targeting enhancers include moieties that increase binding affinity, and/or binding specificity, and/or internalization of a moiety by the target cell/microorganism.

Accordingly, in certain embodiments, a targeting moiety and/or a targeted antimicrobial molecule comprise a peptide, with the desired level of binding specificity and/or avidity, attached (e.g., conjugated) to an opsonin. When bound to a target cell through the targeting peptide, the opsonin component encourages phagocytosis and destruction by resident macrophages, dendritic cells, monocytes, or PMNs. Opsonins contemplated for conjugation can be of a direct or indirect type.

Direct opsonins include, fore example, any bacterial surface antigen, PAMP (pathogen-associated molecular pattern), or other molecule recognized by host PRRs (pathogen recognizing receptors). Opsonins can include, but are not limited to, bacterial protein, lipid, nucleic acid, charbohydrate and/or oligosaccharide moieties.

In certain embodiments opsonins include, but are not limited to, N-acetyl-D-glucosamine (GlcNAc), N-acetyl-D-galactosamine (GlaNAc), N-acetylglucosamine-containing muramyl peptides, NAG-muramyl peptides, NAG-NAM, peptidoglycan, teichoic acid, lipoteichoic acid, LPS, o-antigen, mannose, fucose, ManNAc, galactose, maltose, glucose, glucosamine, sucrose, mannosamine, galactose-alpha-1,3-galactosyl-beta-1,4-N-acetyl glucosamine, or alpha-1,3-gal-gal, or other sugars.

In certain embodiments, opsonins include indirect opsonins Indirect opsonins function through binding to a direct opsonin already present. For example an Fc portion of an antibody, a sugar-binding lectin protein (example MBL), or host complement factors (example C3b, C4b, iC3b).

In certain embodiments the opsonin is to galactose-alpha-1,3-galactosyl-beta-1,4-N-acetyl glucosamine, or alpha-1,3-gal-gal.

Other examples of opsonin molecules include, but are not limited to antibodies (e.g., IgG and IgA), components of the complement system (e.g., C3b, C4b, and iC3b), mannose-binding lectin (MBL) (initiates the formation of C3b), and the like.

Methods of coupling an opsonin to a targeting moiety are well known to those of skill in the art (see, e.g., discussion below regarding attachment of effectors to targeting moieties).

B) Effectors.

Any of a wide number of effectors can be coupled to targeting moieties as described herein to preferentially deliver the effector to a target organism and/or tissue. Illustrative effectors include, but are not limited to detectable labels, small molecule antibiotics, antimicrobial peptides, porphyrins or other photosensitizers, epitope tags/antibodies for use in a pretargeting protocol, agents that physically disrupt the extracellular matrix within a community of microorganisms, microparticles and/or microcapsules, nanoparticles and/or nanocapsules, “carrier” vehicles including, but not limited to lipids, liposomes, dendrimers, cholic acid-based peptide mimics or other peptide mimics, steroid antibiotics, and the like.

i. Detectable Labels.

In certain embodiments chimeric moieties are provided comprising a targeting moiety (e.g., as described in Table 3) attached directly or through a linker to a detectable label. Such chimeric moieties are effective for detecting the presence and/or quantity, and/or location of the microorganism(s) to which the targeting moiety is directed. Similarly these chimeric moieties are useful to identify cells and/or tissues and/or food stuffs and/or other compositions that are infected with the targeted microorganism(s).

Detectable labels suitable for use in such chimeric moieties include any composition detectable by spectroscopic, photochemical, biochemical, immunochemical, electrical, optical, or chemical means. Illustrative useful labels include, but are not limited to, biotin for staining with labeled streptavidin conjugates, avidin or streptavidin for labeling with biotin conjugates fluorescent dyes (e.g., fluorescein, texas red, rhodamine, green fluorescent protein, and the like, see, e.g., Molecular Probes, Eugene, Oreg., USA), radiolabels (e.g., ³H, ¹²⁵I, ³⁵S, ¹⁴C, ³²P, ⁹⁹Tc, ²⁰³Pb, ⁶⁷Ga, ⁶⁸Ga, ⁷²As, ¹¹¹In, ^113mIn, ⁹⁷Ru, ⁶²Cu, 641Cu, ⁵²Fe, ^52mMn, ⁵¹Cr, ¹⁸⁶Re, ¹⁸⁸Re, ⁷⁷As, ⁹⁰Y, ⁶⁷Cu, ¹⁶⁹Er, ¹²¹Sn, ¹²⁷Te, ¹⁴²Pr, ¹⁴³Pr, ¹⁹⁸Au, ¹⁹⁹Au, ¹⁶¹Tb, ¹⁰⁹Pd, ¹⁶⁵Dy, ¹⁴⁹Pm, ¹⁵¹Pm, ¹⁵³Sm, ¹⁵⁷Gd, ¹⁵⁹Gd, ¹⁶⁶Ho, ¹⁷²Tm, ¹⁶⁹Yb, ¹⁷⁵Yb, ¹⁷⁷Lu, ¹⁰⁵Rh, ¹¹¹Ag, and the like), enzymes (e.g., horse radish peroxidase, alkaline phosphatase and others commonly used in an ELISA), various colorimetric labels, magnetic or paramagnetic labels (e.g., magnetic and/or paramagnetic nanoparticles), spin labels, radio-opaque labels, and the like. Patents teaching the use of such labels include, for example, U.S. Pat. Nos. 3,817,837; 3,850,752; 3,939,350; 3,996,345; 4,277,437; 4,275,149; and 4,366,241.

It will be recognized that fluorescent labels are not to be limited to single species organic molecules, but include inorganic molecules, multi-molecular mixtures of organic and/or inorganic molecules, crystals, heteropolymers, and the like. Thus, for example, CdSe-CdS core-shell nanocrystals enclosed in a silica shell can be easily derivatized for coupling to a biological molecule (Bruchez et al. (1998) Science, 281: 2013-2016). Similarly, highly fluorescent quantum dots (zinc sulfide-capped cadmium selenide) have been covalently coupled to biomolecules for use in ultrasensitive biological detection (Warren and Nie (1998) Science, 281: 2016-2018).

In various embodiments spin labels are provided by reporter molecules with an unpaired electron spin which can be detected by electron spin resonance (ESR) spectroscopy. Illustrative spin labels include organic free radicals, transitional metal complexes, particularly vanadium, copper, iron, and manganese, and the like. Exemplary spin labels include, for example, nitroxide free radicals.

Means of detecting such labels are well known to those of skill in the art. Thus, for example, where the label is a radioactive label, means for detection include a scintillation counter or photographic film as in autoradiography. Where the label is a fluorescent label, it may be detected by exciting the fluorochrome with the appropriate wavelength of light and detecting the resulting fluorescence, e.g., by microscopy, visual inspection, via photographic film, by the use of electronic detectors such as charge coupled devices (CCDs) or photomultipliers and the like. Similarly, enzymatic labels may be detected by providing appropriate substrates for the enzyme and detecting the resulting reaction product. Finally, simple colorimetric labels may be detected simply by observing the color associated with the label.

ii. Antibiotics.

In certain embodiments chimeric moieties are provided comprising a targeting moiety (e.g. as described in Table 3) attached directly or through a linker to a small molecule antibiotic and/or to a carrier (e.g., a lipid or liposome, a polymer, etc.) comprising a small molecule antibiotic. Illustrative antibiotics are shown in Table 13.

TABLE 13

Illustrative antibiotics for use in the chimeric moieties described herein.

Class
Generic Name
BRAND NAME

Aminoglycosides
Amikacin
AMIKIN ®

Gentamicin
GARAMYCIN ®

Kanamycin
KANTREX ®

Neomycin

Netilmicin
NETROMYCIN ®

Streptomycin

Tobramycin
NEBCIN ®

Paromomycin
HUMATIN ®

Carbacephem
Loracarbef
LORABID ®

Carbapenems
Ertapenem
INVANZ ®

Doripenem
FINIBAX ®

Imipenem/Cilastatin
PRIMAXIN ®

Meropenem
MERREM ®

Cephalosporins
Cefadroxil
DURICEF ®

(First generation)
Cefazolin
ANCEF ®

Cefalotin or Cefalothin
KEFLIN ®

Cefalexin
KEFLEX ®

Cephalosporins
Cefaclor
CECLOR ®

(Second
Cefamandole
MANDOLE ®

generation)
Cefoxitin
MEFOXIN ®

Cefprozil
CEFZIL ®

Cefuroxime
CEFTIN, ZINNAT ®

Cephalosporins
Cefixime
SUPRAX ®

(Third
Cefdinir
OMNICEF ®

generation)
Cefditoren
SPECTRACEF ®

Cefoperazone
CEFOBID ®

Cefotaxime
CLAFORAN ®

Cefpodoxime

Ceftazidime
FORTAZ ®

Ceftibuten
CEDAX ®

Ceftizoxime

Ceftriaxone
ROCEPHIN ®

Cephalosporins
Cefepime
MAXIPIME ®

(Fourth

generation)

Cephalosporins
Ceftobiprole

(Fifth generation)

Glycopeptides
Teicoplanin

Vancomycin
VANCOCIN ®

Macrolides

Azithromycin
Zithromax

Clarithromycin
Biaxin

Dirithromycin

Erythromycin
Erythocin, Erythroped

Roxithromycin

Troleandomycin

Telithromycin
Ketek

Monobactams
Aztreonam

Penicillins
Amoxicillin
NOVAMOX ®,

AMOXIL ®

Ampicillin

Azlocillin

Carbenicillin

Cloxacillin

Dicloxacillin

Flucloxacillin
FLOXAPEN ®

Mezlocillin

Meticillin

Nafcillin

Oxacillin

Penicillin

Piperacillin

Ticarcillin

Polypeptides
Bacitracin

Colistin

Polymyxin B

Quinolones
Mafenide

Prontosil (archaic)

Sulfacetamide

Sulfamethizole

Sulfanilimide (archaic)

Sulfasalazine

Sulfisoxazole

Trimethoprim
BACTRIM ®

Trimethoprim-

Sulfamethoxazole (Co-

trimoxazole) (TMP-SMX)

Tetracyclines
Demeclocycline

Doxycycline
VIBRAMYCIN ®

Minocycline
MINOCIN ®

Oxytetracycline
TERRACIN ®

Tetracycline
SUMYCIN ®

Natural products
Antimicrobial herbal

extracts

Essential oils

Farnesol

Licorice root extracts

Glycyrrhizol A

Glycyrrhizol B

6,8-diisoprenyl-5,7,4′-

trihydroxyisoflavone

Others
Arsphenamine
SALVARSAN ®

Chloramphenicol
CHLOROMYCETIN ®

Clindamycin
CLEOCIN ®

Lincomycin

Ethambutol

Fosfomycin

Fusidic acid
FUCIDIN ®

Furazolidone

Isoniazid

Linezolid
ZYVOX ®

Metronidazole
FLAGYL ®

Mupirocin
BACTROBAN ®

Nitrofurantoin
MACRODANTIN ®,

MACROBID ®

Platensimycin

Pyrazinamide

Quinupristin/Dalfopristin
SYNCERCID ®

Rifampin or Rifampicin

Tinidazole

Artemisinin

Antifungals
Amphotericin B

Anidulafungin

Caspofungin acetate

Clotrimazole

Fluconazole

Flucytosine

Griseofulvin

Itraconazole

Ketoconazole

Micafungin

Miconazole

Nystatin

Pentamidine

Posaconazole

Terbinafine

Voriconazole

Antimycobiotics
Aminosalicylic Acid

Capreomycin

Clofazimine

Cycloserine

Ethionamide

Rifabutin

Rifapentine

Antivirals
Abacavir

Acyclovir

Adefovir

Amantadine

Atazanavir

Cidofovir

Darunavir

Didanosine

Docosanol

Efavirenz

Emtricitabine

Enfuvirtide

Entecavir

Etravirine

Famciclovir

Fomivirsen

Fosamprenavir

Foscarnet

Ganciclovir

Idoxuridine

Indinavir

Interferon alpha

Lamivudine

Lopinavir/ritonavir

Maraviroc

Nelfinavir

Nevirapine

Oseltamivir

Penciclovir

Peramivir

Raltegravir

Ribavirin

Rimantadine

Ritonavir

Saquinavir

Stavudine

Telbivudine

Tenofovir

Tipranavir

Trifluridine

Valacyclovir

Valganciclovir

Zanamivir

Zidovudine

Anti-parasitics
Albendazole

Artesunate

Atovaquone

Bephenium

hydroxynaphthoate

Chloroquine

Dapsone

Diethyl-carbamazine

Diloxanide furoate

Eflornithine

Emetine HCl

Furazolidone

Ivermectin

Lindane

Mebendazole

Mefloquine

Melarsoprol

Miltefosine

Niclosamide

Nifurtimox

Nitazoxanide

Oxamniquine

Paromomycin

Permethrin

Piperazine

Praziquantel

Primaquine

Pyrantel pamoate

Pyrimethamine

Proguanil

Quinacrine HCl

Quinidine

Quinine

Sodium Stibogluconate

Spiramycin

Thiabendazole

Tinidazole

iii. Porphyrins and Non-Porphyrin Photosensitizers.

In certain embodiments, porphyrins and other photosensitizers can be used as targeting moieties and/or as effectors in the methods and compositions of this invention. A photosensitizer is a drug or other chemical that increases photosensitivity of the organism (e.g., bacterium, yeast, fungus, etc.). As targeting moieties the photosensitizers (e.g., porphyrins) are preferentially uptaken by the target microorganisms and thereby facilitate delivery of the chimeric moiety to the target microorganism.

As effectors, photosensitizers can be useful in photodynamic antimicrobial chemotherapy (PACT). In various embodiments PACT utilizes photosensitizers and light (e.g., visible, ultraviolet, infrared, etc.) in order to give a phototoxic response in the target organism(s), often via oxidative damage.

Currently, the major use of PACT is in the disinfection of blood products, particularly for viral inactivation, although more clinically-based protocols are used, e.g. in the treatment of oral infection or topical infection. The technique has been shown to be effective in vitro against bacteria (including drug-resistant strains), yeasts, viruses, parasites, and the like.

Attaching a targeting moiety (e.g., a targeting peptide) to the photosensitizer, e.g., as described herein, provides a means of specifically or preferentially targeting the photosensitizer(s) to particular species or strains(s) of microorganism.

A wide range of photosensitizers, both natural and synthetic are known to those of skill in the art (see, e.g., Wainwright (1998) J. Antimicrob. Chemotherap. 42: 13-28). Photosensitizers are available with differing physicochemical make-up and light-absorption properties. In various embodiments photosensitizers are usually aromatic molecules that are efficient in the formation of long-lived triplet excited states. In terms of the energy absorbed by the aromatic-system, this again depends on the molecular structure involved. For example: furocoumarin photosensitizers (psoralens) absorb relatively high energy ultraviolet (UV) light (c. 300-350 nm), whereas macrocyclic, heteroaromatic molecules such as the phthalocyanines absorb lower energy, near-infrared light.

Illustrative photosensitizers include, but are not limited to porphyrinic macrocyles (especially porphyrins, chlorines, etc., see, e.g., FIGS. 1 and 2). In particular, metalloporphyrins, particularly a number of non-iron metalloporphyrins mimic haem in their molecular structure and are actively accumulated by bacteria via high affinity haem-uptake systems. The same uptake systems can be used to deliver antibiotic-porphyrin and antibacterial-porphyrin conjugates. Illustrative targeting porphyrins suitable for this purpose are described in U.S. Pat. No. 6,066,628 and shown herein in FIGS. 1 and 2.

Illustrative examples of targeted porphyrins are described in Example 5 and associated figures and in FIG. 13.

For example, certain artificial (non-iron) metalloporphyrins (MPs) (Ga—IX, Mn—IX,) are active against Gram-negative and Gram-positive bacteria and acid-fast bacilli (e.g., Y. enterocolitica, N. meningitides, S. marcescens, E. coli, P. mirabills, K. pneumoniae, K. oxytoca, Ps. aeruginosa, C. freundii, E. aerogenes, F. menigosepticum, S. aureus, B. subtilis, S. pyogenes A, E. faecalis, M. smegmatis, M. bovis, M tuber., S. crevisiae) as described in Tables 1-5 of U.S. Pat. No. 6,066,628. These MPs can be used as targeting moieties against these microorganisms.

Other photosensitizers include, but are not limited to cyanines (see, e.g., FIG. 6) and phthalocyanines (see, e.g., FIG. 4), azines (see, e.g., FIG. 5) including especially methylene blue and touidine blue, hypericin (see, e.g., FIG. 8), acridines (see, e.g., FIG. 9) including especially Rose Bengal (see, e.g., FIG. 10), crown ethers (see, e.g., FIG. 11), and the like. In certain embodiments, the photosensitizers include tin chlorin 6 and related compounds (e.g., other chlorines and tin porphyrins).

Another light-activated compound is cucumin (see, FIG. 12).

In certain embodiments the photosensitizers are toxic or growth inhibitors without light activation. For example, some non-iron metalloporphyrins (MPs) (see, e.g., FIGS. 1 and 2 herein) possess a powerful light-independent antimicrobial activity. In addition, haemin, the most well known natural porphyrin, possesses a significant antibacterial activity that can augmented by the presence of physiological concentrations of hydrogen peroxide or a reducing agent.

Typically, when activated by light, the toxicity or growth inhibition effect is substantially increased. Typically, they generate radical species that affect anything within proximity. In certain embodiments to get the best selectivity from targeted photosensitizers, anti-oxidants can be used to quench un-bound photosensitizers, limiting the damage only to cells where the conjugates have accumulated due to the targeting peptide. The membrane structures of the target cell act as the proton donors in this case.

In typical photodynamic antimicrobial chemotherapy (PACT) the targeted photosensitizer is “activated by the application of a light source (e.g., a visible light source, an ultraviolate light source, an infrared light source, etc.). PACT applications however need not be limited to topical use. Regions of the mouth, throat, nose, sinuses are readily illuminated. Similarly regions of the gut can readily be illuminated using endoscopic techniques. Other internal regions can be illumined using laparoscopic methods or during other surgical procedures. For example, in certain embodiments involving the insertion or repair or replacement of an implantable device (e.g., a prosthetic device) it contemplated that the device can be coated or otherwise contacted with a chimeric moiety comprising a targeting moiety attached to a photosensitizer as described herein. During the surgical procedure and/or just before closing, the device can be illuminated with an appropriate light source to activate the photosensitizer.

The targeted photosensitizers and uses thereof described herein are illustrative and not to be limiting. Using the teachings provided herein, other targeted photosensitizers and uses thereof will be available to one of skill in the art.

iv. Antimicrobial Peptides.

In certain embodiments, the effector can comprise one or more antimicrobial peptides or compound antimicrobial peptides, e.g., as described above. Numerous antimicrobial peptides are well known to those of skill in the art.

In certain embodiments the antimicrobial peptides comprise one or more amino acid sequences described above (e.g., one or more domains comprising amino acid sequences in Tables 4 and/or 5) and/or one or more of the amino acid sequences shown in Table 14. In certain embodiments the antimicrobial peptides comprise one or more amino acid sequences described in the “Collection of Anti-Microbial Peptides” (CAMP) an online database developed for advancement the understanding of antimicrobial peptides (see, e.g., Thomas et al. (2009) Nucleic Acids Research, 2009, 1-7.doi:10.1093/nar/gkp1021) available at www.bicnirrh.res.in/antimicrobial.

TABLE 14

Other illustrative antimicrobial peptides. AP numbers

refer to ID in antimicrobial peptide database

(http://aps.unmc.edu/AP/main.php).

SEQ

ID

Effector
Structure/Sequence
No

AP00274
1BH4, Circulin A
GIPCGESCVWIPCISAALGCSCKNK
1820

(CirA, plant
VCYRN

cyclotides, XXC,

ZZHp)

AP00036
1BNB, Beta-
DFASCHTNGGICLPNRCPGHMIQIG
1821

defensin 1 (cow)
ICFRPRVKCCRSW

AP00047
1BNB, Bovine
GPLSCGRNGGVCIPIRCPVPMRQIG
1822

neutrophil beta-
TCFGRPVKCCRSW

defensin 12

(BNBD-12, cow)

AP00428
1C01, MiAMP1
SAFTVWSGPGCNNRAERYSKCGCS
1823

(Macadamia
AIHQKGGYDFSYTGQTAALYNQA

integrifolia

GCSGVAHTRFGSSARACNPFGWKS

antimicrobial
IFIQC

peptide 1, plant)

AP00154
1CIX, Tachystatin
YSRCQLQGFNCVVRSYGLPTIPCC
1824

A2 (Horseshoe
RGLTCRSYFPGSTYGRCQRY

crabs, Crustacea,

BBS)

AP00145
1CW5,
VNYGNGVSCSKTKCSVNWGQAFQ
1825

Carnobacteriocin
ERYTAGINSFVSGVASGAGSIGRRP

B2 (CnbB2, class

IIA

bacteriocin, bacteria)

AP00153
1CZ6, Androctonin
RSVCRQIKICRRRGGCYYKCTNRPY
1826

(scorpions)

AP00152
1D6X, Tritrpticin
VRRFPWWWPFLRR
1827

(synthetic)

AP00201
1D7N, Mastoparan
INLKALAALAKKIL
1828

(insect)

AP00140
1D9J, CecropinA-
KWKLFKKIGIGKFLHSAKKF
1829

Magainin2 hybrid

(synthetic)

AP00178
1DFN, human
DCYCRIPACIAGERRYGTCIYQGRL
1830

alpha Defensin
WAFCC

HNP-3 (human

neutrophil peptide-

3, HNP3, human

defensin, ZZHh)

AP01153
1DQC, Tachycitin
YLAFRCGRYSPCLDDGPNVNLYSC
1831

(horseshoe crabs,
CSFYNCHKCLARLENCPKGLHYN

Crustacea, BBS)
AYLKVCDWPSKAGCT

AP00437
1DUM, Magainin 2
GIGKYLHSAKKFGKAWVGEIMNS
1832

analog (synthetic)

AP00451
1E4S, Human beta
DHYNCVSSGGQCLYSACPIFTKIQG
1833

defensin 1 (HBD-1,
TCYRGKAKCCK

human defensin)

AP00149
1EWS, Rabbit
MPCSCKKYCDPWEVIDGSCGLFNS
1834

kidney defensin 1
KYICCREK

(RK-1)

AP00141
1F0E, CecropinA-
KWKLFKKIPKFLHSAKKF
1835

Magainin2 Hybrid

(P18, synthetic)

AP00142
1F0G, CecropinA-
KLKLFKKIGIGKFLHSAKKF
1836

Magainin2 Hybrid

(synthetic)

AP00143
1F0H, CecropinA-
KAKLFKKIGIGKFLHSAKKF
1837

Magainin2 Hybrid

(synthetic)

AP00524
1FD4, Human beta
GIGDPVTCLKSGAICHPVFCPRRYK
1838

defensin 2 (HBD-2,
QIGTCGLPGTKCCKKP

human defensin,

ZZHh)

AP00438
1FJN, Mussel
GFGCPNNYQCHRHCKSIPGRCGGY
1839

Defensin MGD-1
CGGWHRLPCTCYRCG

AP00155
1FRY, SMAP-29
RGLRRLGRKIAHGVKKYGPTVLRII
1840

(SMAP29, sheep
RIAG

cathelicidin)

AP00150
1G89, Indolicidin
ILPWKWPWWPWRR
1841

(cow cathelicidin,

BBN, ZZHa)

AP00156
1GR4, Microcin
VGIGTPISFYGGGAGHVPEYF
1842

J25, linear

(MccJ25,

bacteriocin,

bacteria)

AP00151
1HR1, Indolicidin
ILAWKWAWWAWRR
1843

P to A mutant

(synthetic)

AP00196
1HU5, Ovispirin-1
KNLRRIIRKIIHIIKKYG
1844

(synthetic)

AP00197
1HU6, Novispirin
KNLRRIIRKGIHIIKKYG
1845

G10 (synthetic)

AP00198
1HU7, Novispirin
KNLRRITRKIIHIIKKYG
1846

T7 (synthetic)

AP00445
1HVZ, Monkey
GFCRCLCRRGVCRCICTR
1847

RTD-1 (rhesus

theta-defensin-1,

minidefensin-1,

animal defensin,

XXC, BBS, lectin,

ZZHa)

AP00103
1i2v, Heliomicin
DKLIGSCVWGAVNYTSDCNGECL
1848

variant (Hel-LL,
LRGYKGGHCGSFANVNCWCET

synthetic)

AP00216
1ICA, Phormia
ATCDLLSGTGINHSACAAHCLLRG
1849

defensin A (insect
NRGGYCNGKGVCVCRN

defensin A)

AP01224
1Jo3, Gramicidin B
VGALAVVVWLFLWLW
1850

(bacteria)

AP01225
1jo4, Gramicidin C
VGALAVVVWLYLWLW
1851

(bacteria)

AP00191
1KFP, Gomesin
ECRRLCYKQRCVTYCRGR
1852

(Gm, Spider, XXA)

AP00283
1KJ6, Huamn beta
GIINTLQKYYCRVRGGRCAVLSCL
1853

defensin 3 (HBD-3,
PKEEQIGKCSTRGRKCCRRKK

human defensin,

ZZHh)

AP00147
1KV4, Moricin
AKIPIKAIKTVGKAVGKGLRAINIA
1854

(insect, silk moth)
STANDVFNFLKPKKRKA

AP00227
1L4V, Sapecin
ATCDLLSGTGINHSACAAHCLLRG
1855

(insect, flesh fly)
NRGGYCNGKAVCVCRN

AP01161
1L9L, Human
GRDYRTCLTIVQKLKKMVDKPTQ
1856

granulysin
RSVSNAATRVCTRGRSRWRDVCR

(huGran)
NFMRRYQSRVIQGLVAGETAQQIC

EDLRLCIPSTGPL

AP00026
1LFC,
FKCRRWQWRMKKLGAPSITCVRR
1857

Lactoferricin B
AF

(LfcinB, cow,

ZZHa)

AP00193
1M4F, human
DTHFPICIFCCGCCHRSKCGMCCKT
1858

LEAP-1 (Hepcidin

25)

AP00499
1MAG, Gramicidin
VGALAVVVWLWLWLW
1859

A (gA, bacteria)

AP00403
1MM0, Termicin
ACNFQSCWATCQAQHSIYFRRAFC
1860

(termite defensin,
DRSQCKCVFVRG

insect defensin)

AP00194
1MMC, Ac-AMP2
VGECVRGRCPSGMCCSQFGYCGK
1861

(plant defensin,
GPKYCGR

BBS)

AP01206
1MQZ, Mersacidin
CTFTLPGGGGVCTLTSECIC
1862

(bacteria)

AP00429
1NKL, Porcine
GYFCESCRKIIQKLEDMVGPQPNE
1863

NK-Lysin (pig)
DTVTQAASQVCDKLKILRGLCKKI

MRSFLRRISWDILTGKKPQAICVDI

KICKE

AP00633
1og7, Sakacin P/
KYYGNGVHCGKHSCTVDWGTAIG
1864

Sakacin 674 (SakP,
NIGNNAAANWATGGNAGWNK

class IIA

bacteriocin,

bacteria)

AP00195
1PG1, Protegrin 1
RGGRLCYCRRRFCVCVGR
1865

(Protegrin-1, PG-1,

pig cathelicidin,

XXA, ZZHa,

BBBm)

AP00928
1PXQ, Subtilosin
NKGCATCSIGAACLVDGPIPDFEIA
1866

A (XXC, class I
GATGLFGLWG

bacteriocin, Gram-

positive bacteria)

AP00480
1Q71, Microcin
VGIGTPIFSYGGGAGHVPEYF
1867

J25 (cyclic

MccJ25, class I

microcins,

bacteriocins, Gram-

negative bacteria,

XXC; BBP)

AP00211
1RKK,
RRWCFRVCYRGFCYRKCR
1868

Polyphemusin I

(crabs, Crustacea)

AP00430
1T51, IsCT
ILGKIWEGIKSLF
1869

(Scorpion)

AP00731
1ut3, Spheniscin-2
SFGLCRLRRGFCARGRCRFPSIPIGR
1870

(Sphe-2, penguin
CSRFVQCCRRVW

defensin, avian

defensin)

AP00013
1VM5, Aurein 1.2
GLFDIIKKIAESF
1871

(frog)

AP00214
1WO1,
KWCFRVCYRGICYRRCR
1872

Tachyplesin I

(crabs, Crustacea,

XXA, ZZHa)

AP00644
1xc0, Pardaxin 4
GFFALIPKIISSPLFKTLLSAVGSALS
1873

(Pardaxin P-4,
SSGGQE

Pardaxin P4, Pa4,

flat fish)

AP00493
1XKM, Distinctin
NLVSGLIEARKYLEQLHRKLKNCKV
1874

(two chains for

stability and

transport? frog)

AP00420
1XV3, Penaeidin-
HSSGYTRPLRKPSRPIFIRPIGCDVC
1875

4d (penaeidin 4,
YGIPSSTARLCCFRYGDCCHL

shrimp, Crustacea)

AP00035
1YTR, Plantaricin
KSSAYSLQMGATAIKQVKKLFKK
1876

A (PlnA,
WGW

bacteriocin,

bacteria)

AP00166
1Z64, Pleurocidin
GWGSFFKKAAHVGKHVGKAALT
1877

(fish)
HYL

AP00780
1Z6V, Human
GRRRRSVQWCAVSQPEATKCFQW
1878

lactoferricin
QRNMRKVRGPPVSCIKRDSPIQCIQA

AP00549
1ZFU, Plectasin
GFGCNGPWDEDDMQCHNHCKSIK
1879

(fungi, fungal
GYKGGYCAKGGFVCKCY

defensin)

AP00177
1ZMH, human
CYCRIPACIAGERRYGTCIYQGRL
1880

alpha Defensin
WAFCC

HNP-2 (human

neutrophil peptide-

2, HNP2, human

defensin, ZZHh)

AP00179
1ZMM, human
VCSCRLVFCRRTELRVGNCLIGGV
1881

alpha Defensin
SFTYCCTRVD

HNP-4 (human

neutrophil peptide-

4, HNP4, human

defensin)

AP00180
1ZMP, human
QARATCYCRTGRCATRESLSGVCE
1882

alpha Defensin
ISGRLYRLCCR

HD-5 (HD5,

human defensin)

AP00181
1ZMQ, human
STRAFTCHCRRSCYSTEYSYGTCT
1883

alpha Defensin
VMGINHRFCCL

HD-6 (HD6,

human defensin)

AP00399
1ZRW, Spinigerin
HVDKKVADKVLLLKQLRIMRLLT
1884

(insect, termite)
RL

AP01157
1ZRX, Stomoxyn
RGFRKHFNKLVKKVKHTISETAHV
1885

(insect)
AKDTAVIAGSGAAVVAAT

AP00637
2A2B, Curvacin A/
ARSYGNGVYCNNKKCWVNRGEA
1886

sakacin A (CurA,
TQSIIGGMISGWASGLAGM

SakA, class IIA

bacteriocin,

bacteria)

AP00558
2B68, Cg-Def
GFGCPGNQLKCNNHCKSISCRAGY
1887

(Crassostrea gigas
CDAATLWLRCTCTDCNGKK

defensin, oyster

defensin, animal

defensin)

AP01154
2B9K, LCI
AIKLVQSPNGNFAASFVLDGTKWI
1888

(bacteria)
FKSKYYDSSKGYWVGIYEVWDRK

AP01005
2DCV, Tachystatin
YVSCLFRGARCRVYSGRSCCFGYY
1889

B1 (BBS,
CRRDFPGSIFGTCSRRNF

horseshoe crabs)

AP01006
2DCW,
YITCLFRGARCRVYSGRSCCFGYY
1890

Tachystatin B1
CRRDFPGSIFGTCSRRNF

(BBS, horseshoe

crabs)

AP00275
2ERI, Circulin B
CGESCVFIPCISTLLGCSCKNKVCY
1891

(CirB, plant
RNGVIP

cyclotides, XXC,

ZZHp)

AP00707
2f3a, LLAA (LL-
RLFDKIRQVIRKF
1892

37-derived aurein

1.2 analog, retro-

FK13, synthetic)

AP00708
2fbs, FK-13 (FK13,
FKRIVQRIKDFLR
1893

NMR-discovered

LL-37 core peptide,

XXA, ZZHs,

synthetic)

AP00088
2G9L, Gaegurin-4
GILDTLKQFAKGVGKDLVKGAAQ
1894

(Gaegurin 4, frog)
GVLSTVSCKLAKTC

AP01011
2G9P, Latarcin 2a
GLFGKLIKKFGRKAISYAVKKARG
1895

(Ltc2a, BBM,
KH

spider)

AP00612
2GDL, Fowlicidin-
LVQRGRFGRFLRKIRRFRPKVTITI
1896

2 (chCATH-2, bird
QGSARFG

cathelicidin,

chicken

cathelicidin, BBL)

AP00402
2GL1, VrD2
KTCENLANTYRGPCFTTGSCDDHC
1897

(Vigna radiata
KNKEHLRSGRCRDDFRCWCTRNC

defensin 2, plant

defensin, mung

bean)

AP00285
2GW9, Cryptdin-4
GLLCYCRKGHCKRGERVRGTCGIR
1898

(Crp4, animal
FLYCCPRR

defensin, alpha,

mouse)

AP00613
2hfr, Fowlicidin-3
RVKRFWPLVPVAINTVAAGINLYK
1899

(chCATH-3, bird
AIRRK

cathelicidin,

chicken

cathelicidin)

AP01007
2JMY, CM15
KWKLFKKIGAVLKVL
1900

(Synthetic)

AP00728
2jni, Arenicin-2
RWCVYAYVRIRGVLVRYRRCW
1901

(marine polychaeta,

BBBm)

AP00473
2jos, Piscidin 1
FFHHIFRGIVHVGKTIHRLVTG
1902

(fish)

AP01151
2JPJ, Lactococcin
GTWDDIGQGIGRVAYWVGKALGN
1903

G-a (chain a, class
LSDVNQASRINRKKKH

IIb bacteriocin,

bacteria. For chain

b, see info)

AP00757
2jpy, Phylloseptin-
FLSLIPHAINAVSTLVHHF
1904

H2 (PLS-H2,

Phylloseptin-2, PS-

2) (XXA, frog)

AP00546
2jq0, Phylloseptin-
FLSLIPHAINAVSAIAKHN
1905

1 (Phylloseptin-H1,

PLS-H1, PS-1,

XXA, frog)

AP00758
2jq1, Phylloseptin-
FLSLIPHAINAVSALANHG
1906

3 (Phylloseptin-H3,

PLS-H3, PS-3)

(XXA, frog)

AP00727
2jsb, Arenicin-1
RWCVYAYVRVRGVLVRYRRCW
1907

(marine polychaeta,

BBBm)

AP00592
2k10, Ranatuerin-
GILSSFKGVAKGVAKDLAGKLLET
1908

2CSa (frog)
LKCKITGC

AP00485
2K38, Cupiennin
GFGALFKFLAKKVAKTVAKQAAK
1909

1a (spider)
QGAKYVVNKQME

AP00310
2K6O, Human LL-
LLGDFFRKSKEKIGKEFKRIVQRIK
1910

37 (LL37, human
DFLRNLVPRTES

cathelicidin;

released by

proteinase 3 from

its precursor in

neutrophils; FALL-

39; BBB, BBM,

BBP, BBW, BBD,

BBL, ZZHh)

AP00199
2LEU, Leucocin A
KYYGNGVHCTKSGCSVNWGEAFS
1911

(LeuA, class IIa
AGVHRLANGGNGFW

bacteriocin,

bacteria)

AP00144
2MAG, Magainin 2
GIGKFLHSAKKFGKAFVGEIMNS
1912

(frog)

AP00146
2MLT, Melittin
GIGAVLKVLTTGLPALISWIKRKRQQ
1913

(insect, ZZHa)

AP01010
2PCO, Latarcin 1
SMWSGMWRRKLKKLRNALKKKL
1914

(Ltc1, BBM,
KGEK

spider)

AP00176
2PM1, human
ACYCRIPACIAGERRYGTCIYQGRL
1915

alpha Defensin
WAFCC

HNP-1 (human

neutrophil peptide-

1, HNP1, human

defensin, ZZHh)

AP01158
2RLG, RP-1
ALYKKFKKKLLKSLKRL
1916

(synthetic)

AP00102
8TFV, Thanatin
GSKKPVPIIYCNRRTGKCQRM
1917

(insect)

AP00995
A58718, Carnocin
GSEIQPR
1918

UI49 (bacteria)

AP01002
AAC18827,
KSWSLCTPGCARTGSFNSYCC
1919

Mutacin III

(mutacin 1140,

bacteria)

AP00987
ABI74601, Arasin
SRWPSPGRPRPFPGRPKPIFRPRPCN
1920

1 (Crustacea)
CYAPPCPCDRW

AP01000
CAA63706,
GSGVIPTISHECHMNSFQFVFTCCS
1921

variacin

(lantibiotic, class I

bacteriocin,

bacteria)

AP00361
O15946, Lebocin 4
DLRFWNPREKLPLPTLPPFNPKPIYI
1922

(insect, silk moth)
DMGNRY

AP00343
O16825, Andropin
VFIDILDKMENAIHKAAQAGIGIAK
1923

(insect, fruit fly)
PIEKMILPK

AP00417
O17513,
SIGTAVKKAVPIAKKVGKVAIPIAK
1924

Ceratotoxin D
AVLSVVGQLVG

(insect, fly)

AP00435
O18494, Styelin C
GWFGKAFRSVSNFYKKHKTYIHA
1925

(sea squirt,
GLSAATLL

tunicate, XXA)

AP00330
O18495, Styelin D
GWLRKAAKSVGKFYYKHKYYIKA
1926

(Sea squirt,
AWQIGKHAL

tunicate, XXA)

AP00331
O18495, Styelin E
GWLRKAAKSVGKFYYKHKYYIKA
1927

(Sea squirt,
AWKIGRHAL

tunicate, XXA)

AP01001
O54329, Mutacin II
NRWWQGVVPTVSYECRMNSWQH
1928

(lantibiotic,
VFTCC

mutacin H-29B, J-

T8, class I

bacteriocin,

bacteria)

AP00342
O81338,
AKCIKNGKGCREDQGPPFCCSGFC
1929

Antimicrobial
YRQVGWARGYCKNR

peptide 1 (plant)

AP00373
O96059, Moricin 2
AKIPIKAIKTVGKAVGKGLRAINIA
1930

(insect)
STANDVFNFLKPKKRKH

AP00449
P01190,
SYSMEHFRWGKPV
1931

Melanotropin alpha

(Alpha-MSH)

AP00187
P01376,
VVCACRRALCLPRERRAGFCRIRG
1932

CORTICOSTATIN
RIHPLCCRR

III (MCP-1, rabbit

neutrophil peptide

1, NP-1) (animal

defensin, alpha-

defensin, rabbit)

AP00188
P01377,
VVCACRRALCLPLERRAGFCRIRG
1933

CORTICOSTATIN
RIHPLCCRR

IV (MCP-2, rabbit

neutrophil defensin

2, NP-2, animal

defensin, rabbit)

AP00049
P01505, Bombinin
GIGALSAKGALKGLAKGLAEHFAN
1934

(toad)

AP00139
P01507, Cecropin
KWKLFKKIEKVGQNIRDGIIKAGP
1935

A (insect, ZZHa)
AVAVVGQATQIAK

AP00128
P01509, Cecropin
KWKIFKKIEKVGRNIRNGIIKAGPA
1936

B (insect, silk
VAVLGEAKAL

moth)

AP00131
P01511, Cecropin
WNPFKELERAGQRVRDAIISAGPA
1937

D (insect, moth)
VATVAQATALAK

AP00136
P01518, Crabrolin
FLPLILRKIVTAL
1938

(insect, XXA)

AP00183
P04142, Cecropin
RWKIFKKIEKMGRNIRDGIVKAGP
1939

B (insect)
AIEVLGSAKAI

AP00448
P04205,
INLKAIAALAKKLL
1940

Mastoparan M

(MP-M, insect,

XXA)

AP00234
P06833,
SDEKASPDKHHRFSLSRYAKLANR
1941

Seminalplasmin
LANPKLLETFLSKWIGDRGNRSV

(SPLN, calcium

transporter

inhibitor, caltrin,

cow)

AP00314
P07466, Rabbit
VFCTCRGFLCGSGERASGSCTINGV
1942

neutrophil peptide
RHTLCCRR

5 (NP-5, animal

defensin, alpha-

defensin)

AP00189
P07467, Rabbit
VSCTCRRFSCGFGERASGSCTVNG
1943

neutrophil peptide
VRHTLCCRR

4 (NP-4)

AP00186
P07468,
GRCVCRKQLLCSYRERRIGDCKIR
1944

CORTICOSTATIN
GVRFPFCCPR

II (Rabbit

neutrophil peptide

3b (NP-3b, rabbit)

AP00185
P07469,
ICACRRRFCPNSERFSGYCRVNGA
1945

CORTICOSTATIN
RYVRCCSRR

I (rabbit)

AP00217
P07469, Rabbit
GICACRRRFCPNSERFSGYCRVNG
1946

neutrophil defensin
ARYVRCCSRR

3a (NP-3a, animal

defensin, alpha-

defensin)

AP00067
P07493,
SKITDILAKLGKVLAHV
1947

Bombolitin II

(insect, bee)

AP00068
P07494,
IKIMDILAKLGKVLAHV
1948

Bombolitin III

(insect, bee)

AP00069
P07495,
INIKDILAKLVKVLGHV
1949

Bombolitin IV

(insect, bee)

AP00070
P07496,
INVLGILGLLGKALSHL
1950

Bombolitin V

(insect, bee)

AP00236
P07504, Pyrularia
KSCCRNTWARNCYNVCRLPGTISR
1951

thionin (Pp-TH,
EICAKKCDCKIISGTTCPSDYPK

plant)

AP00230
P08375, Sarcotoxin
GWLKKIGKKIERVGQHTRDATIQG
1952

IA (insect, flesh
LGIAQQAANVAATAR

AP00231
P08376, Sarcotoxin
GWLKKIGKKIERVGQHTRDATIQV
1953

IB (insect, flesh
IGVAQQAANVAATAR

AP00232
P08377, Sarcotoxin
GWLRKIGKKIERVGQHTRDATIQV
1954

IC (insect, flesh
LGIAQQAANVAATAR

AP00066
P10521,
IKITTMLAKLGKVLAHV
1955

Bombolitin I

(insect, bee)

AP00206
P10946, Lantibiotic
WKSESLCTPGCVTGALQTCFLQTL
1956

subtilin (class I
TCNCKISK

bacteriocin,

bacteria)

AP00312
P11477, Cryptdin-2
LRDLVCYCRARGCKGRERMNGTC
1957

(Crp2, animal
RKGHLLYMLCCR

defensin, alpha,

mouse)

AP00205
P13068, Nisin A
ITSISLCTPGCKTGALMGCNMKTA
1958

(lantibiotic, class I
TCHCSIHVSK

bacteriocin,

bacteria)

AP00215
P14214,
RWCFRVCYRGICYRKCR
1959

Tachyplesin II

(crabs, Crustacea)

AP00212
P14216,
RRWCFRVCYKGFCYRKCR
1960

Polyphemusin II

(crabs, Crustacea,

XXA, ZZHa.

Derivatives: T22)

AP00134
P14661, Cecropin
SWLSKTAKKLENSAKKRISEGIAIA
1961

P1 (pig)
IQGGPR

AP00011
P14662,
WNPFKELERAGQRVRDAVISAAPA
1962

Bactericidin B2
VATVGQAAAIARG

(insect)

AP00032
P14663,
WNPFKELERAGQRVRDAIISAGPA
1963

Bactericidin B-3
VATVGQAAAIARG

(insect)

AP00033
P14664,
WNPFKELERAGQRVRDAIISAAPA
1964

Bactericidin B-4
VATVGQAAAIARG

(insect)

AP00034
P14665,
WNPFKELERAGQRVRDAVISAAA
1965

Bactericidin B-5P
VATVGQAAAIARG

(insect)

AP00125
P14666, Cecropin
RWKIFKKIEKVGQNIRDGIVKAGP
1966

(insect, silk moth)
AVAVVGQAATI

AP00002
P15450,
YVPLPNVPQPGRRPFPTFPGQGPFN
1967

ABAECIN (insect,
PKIKWPQGY

honeybee)

AP00505
P15516, human
DSHAKRHHGYKRKFHEKHHSHRGY
1968

Histatin 5 (ZZHs;

derivatives Dh-5)

AP00520
P15516, human
DSHAKRHHGYKRKFHEKHHSHRG
1969

Histatin 3
YRSNYLYDN

AP00523
P15516, human
KFHEKHHSHRGY
1970

Histatin 8

AP00226
P17722, Royalisin
VTCDLLSFKGQVNDSACAANCLSL
1971

(insect, honeybee)
GKAGGHCEKVGCICRKTSFKDLW

DKRF

AP00213
P18252,
KWCFRVCYRGICYRKCR
1972

Tachyplesin III

(horseshoe crabs,

Crustacea)

AP00233
P18312, Sarcotoxin
GWIRDFGKRIERVGQHTRDATIQTI
1973

ID (insect, flesh
AVAQQAANVAATLKG

AP00207
P19578, Lantibiotic
TAGPAIRASVKQCQKTLKATRLFT
1974

PEP5 (class I
VSCKGKNGCK

bacteriocin,

bacteria)

AP00009
P19660,
RFRPPIRRPPIRPPFYPPFRPPIRPPIF
1975

BACTENECIN 5
PPIRPPFRPPLGPFP

(bac5, cow

cathelicidin)

AP00010
P19661,
RRIRPRPPRLPRPRPRPLPFPRPGPR
1976

BACTENECIN 7
PIPRPLPFPRPGPRPIPRPLPFPRPGP

(bac7, cow
RPIPRPL

cathelicidin)

AP00200
P21564,
LKLKSIVSWAKKVL
1977

Mastoparan B

(MP-B, insect,

XXA)

AP00005
P21663, Andropin
VFIDILDKVENAIHNAAQVGIGFAK
1978

(insect, fly)
PFEKLINPK

AP00008
P22226, Cyclic
RLCRIVVIRVCR
1979

dodecapeptide

(cow cathelicidin)

AP01205
P23826, Lactocin S
STPVLASVAVSMELLPTASVLYSD
1980

(XXD3, bacteria)
VAGCFKYSAKHHC

AP00239
P24335, XPF (the
GWASKIGQTLGKIAKVGLKELIQPK
1981

xenopsin precursor

fragment, African

clawed frog)

AP00235
P25068, Bovine
NPVSCVRNKGICVPIRCPGSMKQIG
1982

tracheal
TCVGRAVKCCRKK

antimicrobial

peptide (TAP, cow)

AP00418
P25230, CAP18
GLRKRLRKFRNKIKEKLKKIGQKIQ
1983

(rabbit cathelicidin,
GFVPKLAPRTDY

BBL)

AP00203
P25403, Mj-AMP1
QCIGNGGRCNENVGPPYCCSGFCL
1984

(MjAMP1, plant
RQPGQGYGYCKNR

defensin)

AP00202
P25404, Mj-AMP2
CIGNGGRCNENVGPPYCCSGFCLR
1985

(MjAMP2, plant
QPNQGYGVCRNR

defensin)

AP00138
P28310, Cryptdin-3
LRDLVCYCRKRGCKRRERMNGTC
1986

(Crp3, animal
RKGHLMYTLCCR

defensin, alpha,

mouse)

AP00184
P28794, MBP-1
RSGRGECRRQCLRRHEGQPWETQ
1987

(plant)
ECMRRCRRRG

AP00050
P29002, Bombinin-
GIGASILSAGKSALKGLAKGLAEHF
1988

like peptide 1
AN

(BLP-1, toad)

AP00051
P29003, Bombinin-
GIGSAILSAGKSALKGLAKGLAEHF
1989

like peptide 2
AN

(BLP-2, toad)

AP00052
P29004, Bombinin-
GIGAAILSAGKSALKGLAKGLAEHF
1990

like peptide 3

(BLP-3, XXA,

toad)

AP00053
P29005, Bombinin-
GIGAAILSAGKSIIKGLANGLAEHF
1991

like peptide 4

(BLP-4, toad)

AP00634
P29430, Pediocin
KYYGNGVTCGKHSCSVDWGKATT
1992

PA-1/AcH
CIINNGAMAWATGGHQGNHKC

(PedPA1, class IIA

bacteriocin, bacteria)

AP00204
P29559, Nisin Z
ITSISLCTPGCKTGALMGCNMKTA
1993

(lantibiotic, class I
TCNCSIHVSK

bacteriocin,

bacteria)

AP00130
P29561, Cecropin
GWLKKLGKRIERIGQHTRDATIQG
1994

C (insect, fly)
LGIAQQAANVAATAR

AP00001
P31107,
GLWSKIKEVGKEAAKAAAKAAGK
1995

ADENOREGULIN
AALGAVSEAV

(Dermaseptin B2,

Dermaseptin-B2,

DRS-B2, DRS B2,

frog)

AP00228
P31529, Sapecin B
LTCEIDRSLCLLHCRLKGYLRAYCS
1996

(insect, flesh fly)
QQKVCRCVQ

AP00229
P31530, Sapecin C
ATCDLLSGIGVQHSACALHCVFRG
1997

(insect, flesh fly)
NRGGYCTGKGICVCRN

AP00218
P32195, Protegrin
RGGRLCYCRRRFCICV
1998

2 (PG-2, pig

cathelicidin)

AP00219
P32196, Protegrin
RGGGLCYCRRRFCVCVGR
1999

3 (PG-3, pig

cathelicidin)

AP00073
P32412, Brevinin-
FLPLLAGLAANFLPKIFCKITRKC
2000

1E (frog)

AP00080
P32414,
GIFSKLGRKKIKNLLISGLKNVGKE
2001

Esculentin-1 (frog)
VGMDVVRTGIDIAGCKIKGEC

AP00074
P32423, Brevinin-1
FLPVLAGIAAKVVPALFCKITKKC
2002

(frog)

AP00075
P32424, Brevinin-2
GLLDSLKGFAATAGKGVLQSLLST
2003

(frog)
ASCKLAKTC

AP00175
P34084, Macaque
DSHEERHHGRHGHHKYGRKFHEK
2004

histatin (M-Histatin
HHSHRGYRSNYLYDN

1, primate,

monkey)

AP00006
P35581, Apidaecin
GNNRPVYIPQPRPPHPRI
2005

IA (insect,

honeybee)

AP00007
P35581, Apidaecin
GNNRPVYIPQPRPPHPRL
2006

IB (insect,

honeybee)

AP00414
P36190,
SIGSALKKALPVAKKIGKIALPIAK
2007

Ceratotoxin A
AALP

(insect, fly)

AP00415
P36191,
SIGSAFKKALPVAKKIGKAALPIAK
2008

Ceratotoxin B
AALP

(insect, fly)

AP00172
P36193, Drosocin
GKPRPYSPRPTSHPRPIRV
2009

(insect)

AP00170
P37362,
VDKGSYLPRPTPPRPIYNRN
2010

Pyrrhocoricin

(insect)

AP00635
P38577,
KYYGNGVHCTKSGCSVNWGEAAS
2011

Mesentericin Y105
AGIHRLANGGNGFW

(MesY105, class

IIA bacteriocin,

bacteria)

AP00636
P38579,
AISYGNGVYCNKEKCWVNKAENK
2012

Carnobacteriocin
QAITGIVIGGWASSLAGMGH

BM1 (CnbBM1,

PiscV1b, class IIA

bacteriocin,

bacteria)

AP00209
P39080, Peptide
GVLSNVIGYLKKLGTGALNAVLKQ
2013

PGQ (frog)

AP00513
P39084, Ranalexin
FLGGLIKIVPAMICAVTKKC
2014

(frog)

AP00071
P40835, Brevinin-
FLPAIFRMAAKVVPTIICSITKKC
2015

1EA (frog)

AP00072
P40836, Brevinin-
VIPFVASVAAEMQHVYCAASRKC
2016

1EB (frog)

AP00076
P40837, Brevinin-
GILDTLKNLAISAAKGAAQGLVNK
2017

2EA (frog)
ASCKLSGQC

AP00077
P40838, Brevinin-
GILDTLKNLAKTAGKGALQGLVK
2018

2EB (frog)
MASCKLSGQC

AP00078
P40839, Brevinin-
GILLDKLKNFAKTAGKGVLQSLLN
2019

2EC (frog)
TASCKLSGQC

AP00079
P40840, Brevinin-
GILDSLKNLAKNAGQILLNKASCK
2020

2ED (frog)
LSGQC

AP00081
P40843,
GIFSKLAGKKIKNLLISGLKNVGKE
2021

Esculentin-1A
VGMDVVRTGIDIAGCKIKGEC

(frog)

AP00082
P40844,
GIFSKLAGKKLKNLLISGLKNVGK
2022

Esculentin-1B
EVGMDVVRTGIDIAGCKIKGEC

(frog)

AP00083
P40845,
GILSLVKGVAKLAGKGLAKEGGKF
2023

Esculentin-2A
GLELIACKIAKQC

(frog)

AP00084
P40846,
GIFSLVKGAAKLAGKGLAKEGGKF
2024

Esculentin-2B
GLELIACKIAKQC

(ES2B_RANES,

frog)

AP00299
P46156, Chicken
GRKSDCFRKSGFCAFLKCPSLTLIS
2025

gallinacin 1 (Gal 1,
GKCSRFYLCCKRIW

avian beta-

defensin, bird)

AP00300
P46157, Gallinacin
GRKSDCFRKNGFCAFLKCPYLTLIS
2026

1 alpha (avian beta-
GKCSRFHLCCKRIW

defensin, Bird),

AP00298
P46158, Chicken
LFCKGGSCHFGGCPSHLIKVGSCFG
2027

gallinacin 2 (Gal 2,
FRSCCKWPWNA

avian beta-

defensin, bird)

AP00037
P46160, Beta-
VRNHVTCRINRGFCVPIRCPGRTRQ
2028

defensin 2 (cow)
IGTCFGPRIKCCRSW

AP00038
P46161, Beta-
QGVRNHVTCRINRGFCVPIRCPGR
2029

defensin 3 (cow)
TRQIGTCFGPRIKCCRSW

AP00039
P46162, Beta-
QRVRNPQSCRWNMGVCIPFLCRV
2030

defensin 4 (cow)
GMRQIGTCFGPRVPCCRR

AP00040
P46163, Beta-
QVVRNPQSCRWNMGVCIPISCPGN
2031

defensin 5 (cow)
MRQIGTCFGPRVPCCRRW

AP00041
P46164, Beta-
QGVRNHVTCRIYGGFCVPIRCPGR
2032

defensin 6 (cow)
TRQIGTCFGRPVKCCRRW

AP00042
P46165, Beta-
QGVRNFVTCRINRGFCVPIRCPGHR
2033

defensin 7 (cow)
RQIGTCLGPRIKCCR

AP00043
P46166, Beta-
VRNFVTCRINRGFCVPIRCPGHRRQ
2034

defensin 8 (cow)
IGTCLGPQIKCCR

AP00044
P46167, Beta-
QGVRNFVTCRINRGFCVPIRCPGHR
2035

defensin 9 (cow)
RQIGTCLAPQIKCCR

AP00045
P46168, Beta-
QGVRSYLSCWGNRGICLLNRCPGR
2036

defensin 10 (cow)
MRQIGTCLAPRVKCCR

AP00046
P46169, Beta-
GPLSCRRNGGVCIPIRCPGPMRQIG
2037

defensin 11 (cow)
TCFGRPVKCCRSW

AP00048
P46171, Bovine
SGISGPLSCGRNGGVCIPIRCPVPM
2038

beta-defensin 13
RQIGTCFGRPVKCCRSW

(cow)

AP00350
P48821, Enbocin
PWNIFKEIERAVARTRDAVISAGPA
2039

(insect, moth)
VRTVAAATSVAS

AP00173
P49112, GNCP-2
RCICTTRTCRFPYRRLGTCLFQNRV
2040

(Guinea pig
YTFCC

neutrophil cationic

peptide 2)

AP00369
P49930, PMAP-23
RIIDLLWRVRRPQKPKFVTVWVR
2041

(PMAP23, pig

cathelicidin)

AP00370
P49931, PMAP-36
VGRFRRLRKKTRKRLKKIGKVLK
2042

(PMAP36, pig
WIPPIVGSIPLGCG

cathelicidin)

AP00371
P49932, PMAP-37
GLLSRLRDFLSDRGRRLGEKIERIG
2043

(PMAP37, pig
QKIKDLSEFFQS

cathelicidin)

AP00220
P49933, Protegrin
RGGRLCYCRGWICFCVGR
2044

4 (PG-4, pig

cathelicidin)

AP00221
P49934, Protegrin
RGGRLCYCRPRFCVCVGR
2045

5 (PG-5, pig

cathelicidin)

AP00346
P50720, Hyphancin
RWKIFKKIERVGQNVRDGIIKAGP
2046

IIID (Fall
AIQVLGTAKAL

webworm, insect)

AP00347
P50721, Hyphancin
RWKFFKKIERVGQNVRDGLIKAGP
2047

IIIE (Fall
AIQVLGAAKAL

webworm, insect)

AP00348
P50722, Hyphancin
RWKVFKKIEKVGRNIRDGVIKAGP
2048

IIIF (Fall
AIAVVGQAKAL

webworm, insect)

AP00349
P50723, Hyphancin
RWKVFKKIEKVGRHIRDGVIKAGP
2049

IIIG (Fall
AITVVGQATAL

webworm, insect)

AP00281
P51473, mCRAMP
GLLRKGGEKIGEKLKKIGQKIKNFF
2050

(mouse
QKLVPQPEQ

cathelicidin;

derivatives:

CRAMP 18)

AP00366
P54228, BMAP-27
GRFKRFRKKFKKLFKKLSPVIPLLH
2051

(BMAP27, cow
LG

cathelicidin, ZZHs,

derivatives BMAP-

18 and BMAP-15)

AP00367
P54229, BMAP-28
GGLRSLGRKILRAWKKYGPIIVPIIR
2052

(BMAP28, cow
IG

cathelicidin)

AP00450
P54230, Cyclic
RICRIIFLRVCR
2053

dodecapeptide

(sheep cathelicidin)

AP00359
P54684, Lebocin
DLRFLYPRGKLPVPTPPPFNPKPIYI
2054

½ (insect, silk
DMGNRY

moth)

AP00360
P55796, Lebocin 3
DLRFLYPRGKLPVPTLPPFNPKPIYI
2055

(insect, silk moth)
DMGNRY

AP00307
P55897, Buforin I
AGRGKQGGKVRAKAKTRSSRAGL
2056

(toad)
QFPVGRVHRLLRKGNY

AP00308
P55897, Buforin II
TRSSRAGLQFPVGRVHRLLRK
2057

(toad)

AP00240
P56226, Caerin 1.1
GLLSVLGSVAKHVLPHVVPVIAEHL
2058

(frog, ZZHa)

AP00241
P56227, Caerin 1.2
GLLGVLGSVAKHVLPHVVPVIAEHL
2059

(frog)

AP00242
P56228, Caerin 1.3
GLLSVLGSVAQHVLPHVVPVIAEHL
2060

(frog)

AP00243
P56229, Caerin 1.4
GLLSSLSSVAKHVLPHVVPVIAEHL
2061

(frog)

AP00244
P56230, Caerin 1.5
GLLSVLGSVVKHVIPHVVPVIAEHL
2062

(frog)

AP00245
P56231, Caerin 1.6
GLFSVLGAVAKHVLPHVVPVIAEK
2063

(frog)

AP00246
P56232, Caerin 1.7
GLFKVLGSVAKHLLPHVAPVIAEK
2064

(frog)

AP00249
P56233, Caerin 2.1
GLVSSIGRALGGLLADVVKSKGQPA
2065

(frog)

AP00250
P56234, Caerin 2.2
GLVSSIGRALGGLLADVVKSKEQPA
2066

(frog)

AP00251
P56236, Caerin 2.4
GLVSSIGKALGGLLADVVKTKEQPA
2067

(frog)

AP00252
P56236, Caerin 2.5
GLVSSIGRALGGLLADVVKSKEQPA
2068

(frog)

AP00253
P56238, Caerin 3.1
GLWQKIKDKASELVSGIVEGVK
2069

(frog)

AP00254
P56238, Caerin 3.2
GLWEKIKEKASELVSGIVEGVK
2070

(frog)

AP00255
P56240, Caerin 3.3
GLWEKIKEKANELVSGIVEGVK
2071

(frog)

AP00256
P56241, Caerin 3.4
GLWEKIREKANELVSGIVEGVK
2072

(frog)

AP00257
P56242, Caerin 4.1
GLWQKIKSAAGDLASGIVEGIKS
2073

(frog)

AP00258
P56243, Caerin 4.2
GLWQKIKSAAGDLASGIVEGIKS
2074

(frog)

AP00259
P56244, Caerin 4.3
GLWQKIKNAAGDLASGIVEGIKS
2075

(frog)

AP00434
P56249, Frenatin 3
GLMSVLGHAVGNVLGGLFKS
2076

(frog)

AP00272
P56386, Murine
DQYKCLQHGGFCLRSSCPSNTKLQ
2077

beta-defensin 1
GTCKPDKPNCCKS

(mBD-1, mouse)

AP00368
P56425, BMAP-34
GLFRRLRDSIRRGQQKILEKARRIG
2078

(BMAP34, cow
ERIKDIFRG

cathelicidin)

AP00273
P56685, Buthinin
SIVPIRCRSNRDCRRFCGFRGGRCT
2079

(Sahara scorpion)
YARQCLCGY

AP00282
P56872,
SIPCGESCVFIPCTVTALLGCSCKSK
2080

Cyclopsychotride
VCYKN

A (CPT, plant

cyclotides, XXC)

AP00094
P56917, Temporin
FLPLIGRVLSGIL
2081

A (XXA, frog)

AP00096
P56918, Temporin
LLPILGNLLNGLL
2082

C (XXA, frog)

AP00097
P56920, Temporin
VLPIIGNLLNSLL
2083

E (XXA, frog)

AP00098
P56921, Temporin
FLPLIGKVLSGIL
2084

F (XXA, frog)

AP00100
P56923, Temporin
LLPNLLKSLL
2085

K (XXA, frog)

AP00295
P56928, eNAP-2
EVERKHPLGGSRPGRCPTVPPGTF
2086

(horse)
GHCACLCTGDASEPKGQKCCSN

AP00101
P57104, Temporin
FVQWFSKFLGRIL
2087

L (XXA, frog)

AP00095
P79874, Temporin
LLPIVGNLLKSLL
2088

B (XXA, frog)

AP00099
P79875, Temporin
FFPVIGRILNGIL
2089

G (XXA, frog)

AP00413
P80032,
SLQGGAPNFPQPSQQNGGWQVSP
2090

Coleoptericin
DLGRDDKGNTRGQIEIQNKGKDH

(insect)
DFNAGWGKVIRGPNKAKPTWHVG

GTYRR

AP00396
P80054, PR-39
RRRPRPPYLPRPRPPPFFPPRLPPRIP
2091

(PR39, pig
PGFPPRFPPRFP

cathelicidin)

AP00182
P80154, Insect
GFGCPLDQMQCHRHCQTITGRSGG
2092

defensin
YCSGPLKLTCTCYR

AP00444
P80223,
GICACRRRFCLNFEQFSGYCRVNG
2093

Corticostatin VI
ARYVRCCSRR

(CS-VI) (animal

defensin, rabbit)

AP00208
P80230, Peptide
RADTQTYQPYNKDWIKEKIYVLLR
2094

3910 (pig)
RQAQQAGK

AP00157
P80277,
ALWKTMLKKLGTMALHAGKAAL
2095

Dermaseptin-S1
GAAADTISQGTQ

(Dermaseptin S1,

DRS S1, DRS-S1,

frog)

AP00158
P80278,
ALWFTMLKKLGTMALHAGKAAL
2096

Dermaseptin-S2
GAAANTISQGTQ

(Dermaseptin S2,

DRS S2, DRS-S2,

frog)

AP00159
P80279,
ALWKNMLKGIGKLAGKAALGAV
2097

Dermaseptin-S3
KKLVGAES

(Dermaseptin S3,

DRS S3, DRS-S3,

frog)

AP00160
P80280,
ALWMTLLKKVLKAAAKALNAVL
2098

Dermaseptin-S4
VGANA

(Dermaseptin S4,

DRS S4, DRS-S4,

frog)

AP00161
P80281,
GLWSKIKTAGKSVAKAAAKAAVK
2099

Dermaseptin-S5
AVTNAV

(Dermaseptin S5,

DRS S5, DRS-S5,

frog)

AP00293
P80282,
AMWKDVLKKIGTVALHAGKAAL
2100

Dermaseptin-B1
GAVADTISQ

(DRS-B1, DRS B1,

frog)

AP00264
P80389, Chicken
GRKSDCFRKSGFCAFLKCPSLTLIS
2101

Heterophil Peptide
GKCSRFYLCCKRIR

1 (CHP1, bird,

animal)

AP00265
P80390, Chicken
GRKSDCFRKNGFCAFLKCPYLTLIS
2102

Heterophil Peptide
GLCSFHLC

2 (CHP2, bird,

animal)

AP00266
P80391, Turkey
GKREKCLRRNGFCAFLKCPTLSVIS
2103

Heterophil Peptide
GTCSRFQVCC

1 (THP1, turkey)

AP00267
P80392, Turkey
LFCKRGTCHFGRCPSHLIKVGSCFG
2104

Heterophil Peptide
FRSCCKWPWDA

2 (THP2, bird,

anaimal)

AP00269
P80393, Turkey
LSCKRGTCHFGRCPSHLIKGSCSGG
2105

Heterophil Peptide

3 (THP3, bird,

animal)

AP00085
P80395, Gaegurin-
SLFSLIKAGAKFLGKNLLKQGACY
2106

1 (Gaegurin 1,
AACKASKQC

frog)

AP00086
P80396, Gaegurin-
GIMSIVKDVAKNAAKEAAKGALST
2107

2 (Gaegurin 2,
LSCKLAKTC

frog)

AP00087
P80397, Gaegurin-
GIMSIVKDVAKTAAKEAAKGALST
2108

3 (Gaegurin 3,
LSCKLAKTC

frog)

AP00089
P80399, Gaegurin-
FLGALFKVASKVLPSVFCAITKKC
2109

5 (Gaegurin 5,

frog)

AP00090
P80400, Gaegurin-
FLPLLAGLAANFLPTIICKISYKC
2110

6 (Gaegurin 6,

frog)

AP00362
P80408,
VDKPDYRPRPRPPNM
2111

Metalnikowin I

(insect)

AP00363
P80409,
VDKPDYRPRPWPRPN
2112

Metalnikowin IIA

(insect)

AP00364
P80410,
VDKPDYRPRPWPRNMI
2113

Metalnikowin IIB

(insect)

AP00365
P80411,
VDKPDYRPRPWPRPNM
2114

Metalnikowin III

(insect)

AP00632
P80569, Piscicolin
KYYGNGVSCNKNGCTVDWSKAIG
2115

126/Piscicocin
IIGNNAAANLTTGGAAGWNKG

Via (PiscV1a,

Pisc126, class IIA

bacteriocin,

bacteria)

AP01003
P80666, Mutacin
FKSWSFCTPGCAKTGSFNSYCC
2116

B-Ny266 (bacteria)

AP00276
P80710, Clavanin
VFQFLGKIIHHVGNFVHGFSHVF
2117

A (urochordates,

sea squirts, and sea

pork, tunicate)

AP00277
P80711, Clavanin
VFQFLGRIIHHVGNFVHGFSHVF
2118

B (Sea squirt,

tunicate)

AP00278
P80712, Clavanin
VFHLLGKIIHHVGNFVYGFSHVF
2119

C (Sea squirt,

tunicate)

AP00279
P80713, Clavanin
AFKLLGRIIHHVGNFVYGFSHVF
2120

D (Sea squirt,

tunicate)

AP00280
P80713, Clavanin
LFKLLGKIIHHVGNFVHGFSHVF
2121

D (Sea squirt,

tunicate)

AP00294
P80930, eNAP-1
DVQCGEGHFCHDQTCCRASQGGA
2122

(horse)
CCPYSQGVCCADQRHCCPVGF

AP00400
P80952, Skin
YPPKPESPGEDASPEEMNKYLTAL
2123

peptide tyrosine-
RHYINLVTRQRY

tyrosine (skin-

PYY, SPYY, frog)

AP00091
P80954, Rugosin A
GLLNTFKDWAISIAKGAGKGVLTT
2124

(frog)
LSCKLDKSC

AP00092
P80955, Rugosin B
SLFSLIKAGAKFLGKNLLKQGAQY
2125

(frog)
AACKVSKEC

AP00093
P80956, Rugosin C
GILDSFKQFAKGVGKDLIKGAAQG
2126

(frog)
VLSTMSCKLAKTC

AP00392
P81056, Penaeidin-
YRGGYTGPIPRPPPIGRPPLRLVVC
2127

1 (shrimp,
ACYRLSVSDARNCCIKFGSCCHLVK

Crustacea)

AP00393
P81057, Penaeidin-
YRGGYTGPIPRPPPIGRPPFRPVCN
2128

2a (shrimp,
ACYRLSVSDARNCCIKFGSCCHLVK

Crustacea)

AP00394
P81058, Penaeidin-
QVYKGGYTRPIPRPPPFVRPLPGGP
2129

3a (shrimp,
IGPYNGCPVSCRGISFSQARSCCSR

Crustacea)
LGRCCHVGKGYS

AP00247
P81251, Caerin 1.8
GLFKVLGSVAKHLLPHVVPVIAEK
2130

(frog)

AP00248
P81252, Caerin 1.9
GLFGVLGSIAKHVLPHVVPVIAEK
2131

(frog, ZZHa)

AP00126
P81417, Cecropin
GGLKKLGKKLEGVGKRVFKASEK
2132

A (insect,
ALPVAVGIKALG

mosquito)

AP00169
P81437, Formaecin
GRPNPVNTKPTPYPRL
2133

2 (insect, ants)

AP00168
P81438, Formaecin
GRPNPVNNKPTPHPRL
2134

1 (insect, ants)

AP00296
P81456, Fabatin-1
LLGRCKVKSNRFHGPCLTDTHCST
2135

(plant defensin)
VCRGEGYKGGDCHGLRRRCMCLC

AP00297
P81457, Fabatin-2
LLGRCKVKSNRFNGPCLTDTHCST
2136

(plant defensin)
VCRGEGYKGGDCHGLRRRCMCLC

AP01215
P81463, European
FVPYNPPRPYQSKPFPSFPGHGPFN
2137

bumblebee abaecin
PKIQWPYPLPNPGH

(insect)

AP01214
P81464, Apidaecin
GNRPVYIPPPRPPHPRL
2138

(insect)

AP00440
P81465, defensin
VTCFCRRRGCASRERHIGYCRFGN
2139

HANP-1 (hamster)
TIYRLCCRR

AP00441
P81466, defensin
CFCKRPVCDSGETQIGYCRLGNTF
2140

HANP-2 (hamster)
YRLCCRQ

AP00442
P81467, defensin
VTCFCRRRGCASRERLIGYCRFGN
2141

HANP-3 (hamster)
TIYGLCCRR

AP00439
P81468, defensin
VTCFCKRPVCDSGETQIGYCRLGN
2142

HANP-4 (hamster)
TFYRLCCRQ

AP00328
P81469, Styelin A
GFGKAFHSVSNFAKKHKTA
2143

(Sea squirt,

tunicate, XXA)

AP00329
P81470, Styelin B
GFGPAFHSVSNFAKKHKTA
2144

(Sea squirt,

tunicate, XXA)

AP00492
P81474, Misgurin
RQRVEELSKFSKKGAAARRRK
2145

(fish)

AP00165
P81485,
ALWKNMLKGIGKLAGQAALGAV
2146

Dermaseptin-B3
KTLVGAE

(Dermaseptin B3,

DRS-B3, DRS B3,

frog)

AP00163
P81486,
ALWKDILKNVGKAAGKAVLNTVT
2147

Dermaseptin-B4
DMVNQ

(Dermaseptin B4,

DRS-B4, DRS B4,

DRS-TR1, IRP,

frog)

AP00162
P81487,
GLWNKIKEAASKAAGKAALGFVN
2148

Dermaseptin-B5
EMV

(Dermaseptin B5,

DRS-B5, DRS B5,

frog)

AP00164
P81488,
ALWKTIIKGAGKMIGSLAKNLLGS
2149

Dermaseptin-B9
QAQPES

(Dermaseptin B9,

DRS-B9, DRS

DRG3, frog)

AP00167
P81565, Phylloxin
GWMSKIASGIGTFLSGMQQ
2150

(phylloxin-B1,

PLX-B1, XXA,

frog)

AP00291
P81568, Defensin
MFFSSKKCKTVSKTFRGPCVRNAN
2151

D5 (So-D5) (plant

defensin)

AP00290
P81569, Defensin
MFFSSKKCKTVSKTFRGPCVRNA
2152

D4 (So-D4) (plant

defensin)

AP00289
P81570, Defensin
GIFSSRKCKTVSKTFRGICTRNANC
2153

D3 (So-D3) (plant

defensin)

AP00288
P81572, Defensin
TCESPSHKFKGPCATNRNCES
2154

D1 (So-D1) (plant

defensin)

AP00292
P81573, Defensin
GIFSSRKCKTPSKTFKGYCTRDSNC
2155

D7 (So-D7) (plant
DTSCRYEGYPAGD

defensin)

AP00270
P81591, Pn-AMP
QQCGRQASGRLCGNRLCCSQWGY
2156

(PnAMP, plant
CGSTASYCGAGCQSQCRS

defensin)

AP00412
P81592,
SLQPGAPNVNNKDQPWQVSPHISR
2157

Acaloleptin A1
DDSGNTRTDINVQRHGENNDFEAG

(insect)
WSKVVRGPNKAKPTWHIGGTHRW

AP00433
P81605, human
SSLLEKGLDGAKKAVGGLGKLGK
2158

Dermcidin (DCD-
DAVEDLESVGKGAVHDVKDVLDSV

1)

AP00332
P81612, Mytilin A
GCASRCKAKCAGRRCKGWASASF
2159

(Blue mussel)
RGRCYCKCFRC

AP00333
P81613, Mytilin B
SCASRCKGHCRARRCGYYVSVLY
2160

(Blue mussel)
RGRCYCKCLRC

AP00334
P81613,
FFHHIFRGIVHVGKTIHKLVTG
2161

Moronecidin (fish)

AP00351
P81835, Citropin
GLFDVIKKVASVIGGL
2162

1.1 (amphibian,

frog)

AP00352
P81840, Citropin
GLFDIIKKVASVVGGL
2163

1.2 (amphibian,

frog)

AP00353
P81846, Citropin
GLFDIIKKVASVIGGL
2164

1.3 (amphibian,

frog)

AP00338
P81903, Histone
PDPAKTAPKKGSKKAVTKA
2165

H2B-1(HLP-1)

(fish)

AP00271
P82018, ChBac5
RFRPPIRRPPIRPPFNPPFRPPVRPPF
2166

(Goat cathelicidin)
RPPFRPPFRPPIGPFP

AP00316
P82027, Uperin 2.1
GIVDFAKKVVGGIRNALGI
2167

(amphibian, toad)

AP00317
P82028, Uperin 2.2
GFVDLAKKVVGGIRNALGI
2168

(amphibian, toad)

AP00318
P82029, Uperin 2.3
GFFDLAKKVVGGIRNALGI
2169

(amphibian, toad)

AP00319
P82030, Uperin 2.4
GILDFAKTVVGGIRNALGI
2170

(amphibian, toad)

AP00320
P82031, Uperin 2.5
GIVDFAKGVLGKIKNVLGI
2171

(amphibian, toad)

AP00323
P82032, Uperin 3.1
GVLDAFRKIATVVKNVV
2172

(amphibian, toad)

AP00326
P82035, Uperin 4.1
GVGSFIHKVVSAIKNVA
2173

(amphibian, toad)

AP00321
P82039, Uperin 2.7
GIIDIAKKLVGGIRNVLGI
2174

(amphibian, toad)

AP00322
P82040, Uperin 2.8
GILDVAKTLVGKLRNVLGI
2175

(amphibian, toad)

AP00324
P82042, Uperin 3.5
GVGDLIRKAVSVIKNIV
2176

(amphibian, toad)

AP00325
P82042, Uperin 3.6
GVIDAAKKVVNVLKNLP
2177

(amphibian, toad)

AP00327
P82050, Uperin 7.1
GWFDVVKHIASAV
2178

(amphibian, frog)

AP00260
P82066, Maculatin
GLFVGVLAKVAAHVVPAIAEHF
2179

1.1 (XXA, frog,

ZZHa)

AP00261
P82067, Maculatin
GLFVGLAKVAAHNNPAIAEHFQA
2180

1.2 (XXA, frog)

AP00262
P82068, Maculatin
GFVDFLKKVAGTIANVVT
2181

2.1 (frog)

AP00263
P82069, Maculatin
GLLQTIKEKLESLESLAKGIVSGIQA
2182

3.1 (frog)

AP00345
P82104, Caerin
GLLSVLGSVAKHVLPHVVPVIAEKL
2183

1.10 (frog)

AP00456
P82232, Brevinin-
VNPIILGVLPKFVCLITKKC
2184

1T (frog)

AP00459
P82233, Brevinin-
FITLLLRKFICSITKKC
2185

1TA (frog)

AP00457
P82234, Brevinin-
GLWETIKNFGKKFTLNILHKLKCKI
2186

2TC (frog)
GGGC

AP00458
P82235, Brevinin-
GLWETIKNFGKKFTLNILHNLKCKI
2187

2TD (frog)
GGGC

AP00397
P82238,
SGFVLKGYTKTSQ
2188

Salmocidin 2A

(fish, trout)

AP00398
P82239,
AGFVLKGYTKTSQ
2189

Salmocidin 2B

(fish, trout)

AP00055
P82282, Bombinin
IIGPVLGMVGSALGGLLKKI
2190

H1 (frog)

AP00056
P82284, Bombinin
LIGPVLGLVGSALGGLLKKI
2191

H4 (frog, XXA,

XXD)

AP00057
P82285, Bombinin
IIGPVLGLVGSALGGLLKKI
2192

H5 (frog, XXD)

AP00419
P82286, Bombinin-
GIGASILSAGKSALKGFAKGLAEHF
2193

like peptides 2
AN

(amphibian, toad)

AP00137
P82293, Cryptdin-1
LRDLVCYCRTRGCKRRERMNGTC
2194

(Crp1, animal
RKGHLMYTLCCR

defensin, alpha,

mouse)

AP00443
P82317, defensin
ACYCRIPACLAGERRYGTCFYMGR
2195

RMAD-2 (monkey)
VWAFCC

AP00012
P82386, Aurein 1.1
GLFDIIKKIAESI
2196

(amphibian, frog)

AP00014
P82388, Aurein 2.1
GLLDIVKKVVGAFGSL
2197

(amphibian, frog)

AP00015
P82389, Aurein 2.2
GLFDIVKKVVGALGSL
2198

(amphibian, frog)

AP00016
P82390, Aurein 2.3
GLFDIVKKVVGAIGSL
2199

(XXA,

amphibian, frog)

AP00017
P82391, Aurein 2.4
GLFDIVKKVVGTIAGL
2200

(XXA,

amphibian, frog)

AP00018
P82392, Aurein 2.5
GLFDIVKKVVGAFGSL
2201

(XXA,

amphibian, frog)

AP00019
P82393, Aurein 2.6
GLFDIAKKVIGVIGSL
2202

(XXA,

amphibian, frog)

AP00020
P82394, Aurein 3.1
GLFDIVKKIAGHIAGSI
2203

(XXA,

amphibian, frog)

AP00021
P82395, Aurein 3.2
GLFDIVKKIAGHIASSI
2204

(XXA,

amphibian, frog)

AP00022
P82396, Aurein 3.3
GLFDIVKKIAGHIVSSI
2205

(XXA,

amphibian, frog)

AP00376
P82414, Ponericin
GWKDWAKKAGGWLKKKGPGMA
2206

G1 (ants)
KAALKAAMQ

AP00377
P82415, Ponericin
GWKDWLKKGKEWLKAKGPGIVK
2207

G2 (ants)
AALQAATQ

AP00378
P82416, Ponericin
GWKDWLNKGKEWLKKKGPGIMK
2208

G3 (ants)
AALKAATQ

AP00379
P82417, Ponericin
DFKDWMKTAGEWLKKKGPGILKA
2209

G4 (ants)
AMAAAT

AP00380
P82418, Ponericin
GLKDWVKIAGGWLKKKGPGILKA
2210

G5 (ants)
AMAAATQ

AP00381
P82419, Ponericin
GLVDVLGKVGGLIKKLLP
2211

G6 (ants)

AP00382
P82420, Ponericin
GLVDVLGKVGGLIKKLLPG
2212

G7 (ants)

AP00383
P82421, Ponericin
LLKELWTKMKGAGKAVLGKIKGLL
2213

L1 (ants)

AP00384
P82422, Ponericin
LLKELWTKIKGAGKAVLGKIKGLL
2214

L2 (ants)

AP00386
P82423, Ponericin
WLGSALKIGAKLLPSVVGLFKKKKQ
2215

W1 (ants)

AP00387
P82424, Ponericin
WLGSALKIGAKLLPSVVGLFQKKKK
2216

W2 (ants)

AP00388
P82425, Ponericin
GIWGTLAKIGIKAVPRVISMLKKK
2217

W3 (ants)
KQ

AP00389
P82426, Ponericin
GIWGTALKWGVKLLPKLVGMAQT
2218

W4 (ants)
KKQ

AP00390
P82427, Ponericin
FWGALIKGAAKLIPSVVGLFKKKQ
2219

W5 (ants)

AP00391
P82428, Ponericin
FIGTALGIASAIPAIVKLFK
2220

W6 (ants)

AP00303
P82651, Tigerinin-
FCTMIPIPRCY
2221

1 (frog)

AP00304
P82652, Tigerinin-
RVCFAIPLPICH
2222

2 (frog)

AP00305
P82653, Tigerinin-
RVCYAIPLPICY
2223

3 (frog)

AP00301
P82656, Hadrurin
GILDTIKSIASKVWNSKTVQDLKR
2224

(scorpion)
KGINWVANKLGVSPQAA

AP00113
P82740,
GLLSGLKKVGKHVAKNVAVSLMD
2225

RANATUERIN 1T
SLKCKISGDC

(frog)

AP00114
P82741,
SMLSVLKNLGKVGLGFVACKINK
2226

RANATUERIN 1
QC

(Ranatuerin-1,

frog)

AP00115
P82742,
GLFLDTLKGAAKDVAGKLEGLKC
2227

RANATUERIN 2
KITGCKLP

(Ranatuerin-2,

frog)

AP00116
P82780,
GFLDIINKLGKTFAGHMLDKIKCTI
2228

RANATUERIN 3
GTCPPSP

(Ranatuerin-3,

frog)

AP00117
P82819,
FLPFIARLAAKVFPSIICSVTKKC
2229

RANATUERIN 4

(Ranatuerin-4,

frog)

AP00405
P82821,
FISAIASMLGKFL
2230

RANATUERIN 6

(frog)

AP00406
P82822,
FLSAIASMLGKFL
2231

RANATUERIN 7

(frog)

AP00407
P82823,
FISAIASFLGKFL
2232

RANATUERIN 8

(frog)

AP00408
P82824,
FLFPLITSFLSKVL
2233

RANATUERIN 9

(frog)

AP00461
P82825, Brevinin-
FLPMLAGLAASMVPKLVCLITKKC
2234

1LA (frog)

AP00462
P82826, Brevinin-
FLPMLAGLAASMVPKFVCLITKKC
2235

1LB (frog)

AP00118
P82828,
GILDSFKGVAKGVAKDLAGKLLD
2236

RANATUERIN
KLKCKITGC

2La (Ranatuerin-

2La, frog)

AP00119
P82829,
GILSSIKGVAKGVAKNVAAQLLDT
2237

RANATUERIN
LKCKITGC

2Lb (Ranatuerin-

2Lb, frog)

AP00109
P82830, Temporin-
VLPLISMALGKLL
2238

1La (Temporin

1La, frog)

AP00110
P82831, Temporin-
NFLGTLINLAKKIM
2239

1Lb (Temporin

1Lb, frog)

AP00111
P82832, Temporin-
FLPILINLIHKGLL
2240

1Lc (Temporin

1Lc, frog)

AP00463
P82833, Brevinin-
FLPFIAGMAAKFLPKIFCAISKKC
2241

1BA (frog)

AP00464
P82834, Brevinin-
FLPAIAGMAAKFLPKIFCAISKKC
2242

1BB (frog)

AP00465
P82835, Brevinin-
FLPFIAGVAAKFLPKIFCAISKKC
2243

1BC (frog)

AP00466
P82836, Brevinin-
FLPAIAGVAAKFLPKIFCAISKKC
2244

1BD (frog)

AP00467
P82837, Brevinin-
FLPAIVGAAAKFLPKIFCVISKKC
2245

1BE (frog)

AP00468
P82838, Brevinin-
FLPFIAGMAANFLPKIFCAISKKC
2246

1BF (frog)

AP00120
P82840,
GLLDTIKGVAKTVAASMLDKLKC
2247

RANATUERIN 2B
KISGC

(Ranatuerin-2B,

frog)

AP00469
P82841, Brevinin-
FLPIIAGVAAKVFPKIFCAISKKC
2248

1PA (frog)

AP00460
P82842, Brevinin-
FLPIIAGIAAKVFPKIFCAISKKC
2249

1PB (frog)

AP00470
P82843, Brevinin-
FLPIIASVAAKVFSKIFCAISKKC
2250

1PC (frog)

AP00471
P82844, Brevinin-
FLPIIASVAANVFSKIFCAISKKC
2251

1PD (frog)

AP00472
P82845, Brevinin-
FLPIIASVAAKVFPKIFCAISKKC
2252

1PE (frog)

AP00121
P82847,
GLMDTVKNVAKNLAGHMLDKLK
2253

RANATUERIN 2P
CKITGC

(Ranatuerin-2P,

frog)

AP00112
P82848, Temporin-
FLPIVGKLLSGLL
2254

1P (Temporin 1P,

frog)

AP00452
P82871, Brevinin-
FLPVVAGLAAKVLPSIICAVTKKC
2255

1SY (frog)

AP00122
P82875,
SMLSVLKNLGKVGLGLVACKINK
2256

Ranatuerin-1C
QC

(Ranatuerin 1C,

frog)

AP00514
P82876, Ranalexin-
FLGGLMKAFPALICAVTKKC
2257

1Ca (frog)

AP00515
P82877, Ranalexin-
FLGGLMKAFPAIICAVTKKC
2258

1Cb (frog)

AP00124
P82878,
GLFLDTLKGAAKDVAGKLLEGLK
2259

Ranatuerin-2Ca
CKIAGCKP

(Ranatuerin 2Ca,

frog)

AP00123
P82879,
GLFLDTLKGLAGKLLQGLKCIKAG
2260

Ranatuerin-2Cb
CKP

(Ranatuerin 2Cb,

frog)

AP00104
P82880, Temporin-
FLPFLAKILTGVL
2261

1Ca (Temporin

1Ca, frog)

AP00105
P82881, Temporin-
FLPLFASLIGKLL
2262

1Cb (Temporin

1Cb, frog)

AP00106
P82882, Temporin-
FLPFLASLLTKVL
2263

1Cc (Temporin

1Cc, frog)

AP00107
P82883, Temporin-
FLPFLASLLSKVL
2264

1Cd (Temporin

1Cd, frog)

AP00108
P82884, Temporin-
FLPFLATLLSKVL
2265

1Ce (Temporin

1Ce, frog)

AP00453
P82904, Brevinin-
FLPAIVGAAGQFLPKIFCAISKKC
2266

1SA (frog)

AP00454
P82905, Brevinin-
FLPAIVGAAGKFLPKIFCAISKKC
2267

1SB (frog)

AP00455
P82906, Brevinin-
FFPIVAGVAGQVLKKIYCTISKKC
2268

1SC (frog)

AP00996
P82907, Lichenin
ISLEICAIFHDN
2269

(bacteria)

AP00302
P82951, Hepcidin
GCRFCCNCCPNMSGCGVCCRF
2270

(fish)

AP00058
P83080, Maximin 1
GIGTKILGGVKTALKGALKELAST
2271

(toad)
YAN

AP00059
P83081, Maximin 2
GIGTKILGGVKTALKGALKELAST
2272

(toad)
YVN

AP00060
P83082, Maximin 3
GIGGKILSGLKTALKGAAKELAST
2273

(toad, ZZHa)
YLH

AP00061
P83083, Maximin 4
GIGGVLLSAGKAALKGLAKVLAE
2274

(toad)
KYAN

AP00062
P83084, Maximin 5
SIGAKILGGVKTFFKGALKELASTY
2275

(toad)
LQ

AP00063
P83085, Maximin 6
ILGPVISTIGGVLGGLLKNL
2276

(toad)

AP00064
P83086, Maximin 7
ILGPVLGLVGNALGGLIKNE
2277

(toad)

AP00065
P83087, Maximin 8
ILGPVLSLVGNALGGLLKNE
2278

(toad)

AP00355
P83171,
ANTAFVSSAHNTQKIPAGAPFNRN
2279

Ginkbilobin
LRAMLADLRQNAAFAG

(Chinese plant)

AP00475
P83188, Pseudin 1
GLNTLKKVFQGLHEAIKLINNHVQ
2280

(frog)

AP00476
P83189, Pseudin 2
GLNALKKVFQGIHEAIKLINNHVQ
2281

(frog)

AP00477
P83190, Pseudin 3
GINTLKKVIQGLHEVIKLVSNHE
2282

(frog)

AP00478
P83191, Pseudin 4
GINTLKKVIQGLHEVIKLVSNHA
2283

(frog)

AP00410
P83287,
SKGKKANKDVELARG
2284

Oncorhyncin III

(fish)

AP00357
P83305, Japonicin-
FFPIGVFCKIFKTC
2285

1 (amphibian, frog)

AP00358
P83306, Japonicin-
FGLPMLSILPKALCILLKRKC
2286

2 (amphibian, frog)

AP00385
P83312,
FKLGSFLKKAWKSKLAKKLRAKG
2287

Parabutoporin
KEMLKDYAKGLLEGGSEEVPGQ

(scorpion)

AP00374
P83313,
GKVWDWIKSTAKKLWNSEPVKEL
2288

Opistoporin 1
KNTALNAAKNLVAEKIGATPS

(scorpion)

AP00375
P83314,
GKVWDWIKSTAKKLWNSEPVKEL
2289

Opistoporin 2
KNTALNAAKNFVAEKIGATPS

(scorpion)

AP00336
P83327, Histone
AERVGAGAPVYL
2290

H2A (fish)

AP00335
P83338, Histone
PKRKSATKGDEPA
2291

H6-like protein

(fish)

AP00411
P83374,
KAVAAKKSPKKAKKPAT
2292

Oncorhyncin II

(fish)

AP00999
P83375, Serracin-P
DYHHGVRVL
2293

43 kDa subunit

(bacteria)

AP00284
P83376,
SHQDCYEALHKCMASHSKPFSCS
2294

Dolabellanin B2
MKFHMCLQQQ

(sea hare)

AP00998
P83378, Serracin-P
ALPKKLKYLNLFNDGFNYMGVV
2295

23 kDa subunit

(bacteriocin,

bacteria)

AP00129
P83403, Cecropin
GWLKKIGKKIERVGQNTRDATVK
2296

(insect, moth)
GLEVAQQAANVAATVR

AP00127
P83413, Cecropin
RWKVFKKIEKVGRNIRDGVIKAAP
2297

A (insect, moth)
AIEVLGQAKAL

AP00372
P83416, Virescein
GKIPIGAIKKAGKAIGKGLRAVNIA
2298

(insect)
STAHDVYTFFKPKKRH

AP00356
P83427, Heliocin
QRFIHPTYRPPPQPRRPVIMRA
2299

(insect)

AP00409
P83428, Locustin
ATTGCSCPQCIIFDPICASSYKNGRR
2300

(insect)
GFSSGCHMRCYNRCHGTDYFQISK

GSKCI

AP00339
P83545,
FFGWLIKGAIHAGKAIHGLIHRRRH
2301

Chrysophsin-1

(Red sea bream,

madai)

AP00340
P83546,
FFGWLIRGAIHAGKAIHGLIHRRRH
2302

Chrysophsin-2

(Red sea bream,

madai)

AP00341
P83547,
FIGLLISAGKAIHDLIRRRH
2303

Chrysophsin-3

(Red sea bream,

madai)

AP01004
P84763, Thuricin-S
DWTAWSALVAAACSVELL
2304

(bacteria)

AP00553
P84868, Sesquin
KTCENLADTY
2305

(plant, ZZHp)

AP00132
Q06589, Cecropin
GWLKKIGKKIERVGQHTRDATIQTI
2306

1 (insect, fly)
AVAQQAANVAATAR

AP00135
Q06590, Cecropin
GWLKKIGKKIERVGQHTRDATIQTI
2307

2 (insect fly)
GVAQQAANVAATLK

AP00416
Q17313,
SLGGVISGAKKVAKVAIPIGKAVLP
2308

Ceratotoxin C
VVAKLVG

(insect, fly)

AP00171
Q24395,
HRHQGPIFDTRPSPFNPNQPRPGPIY
2309

Metchnikowin

(insect)

AP00354
Q27023, Tenecin 1
VTCDILSVEAKGVKLNDAACAAH
2310

(insect)
CLFRGRSGGYCNGKRVCVCR

AP00401
Q28880, Lingual
GFTQGVRNSQSCRRNKGICVPIRCP
2311

antimicrobial
GSMRQIGTCLGAQVKCCRRK

peptide (LAP, beta

defensin, cow)

AP00224
Q62713, RatNP-3
CSCRTSSCRFGERLSGACRLNGRIY
2312

(rat)
RLCC

AP00225
Q62714, RatNP-4
ACYCRIGACVSGERLTGACGLNGR
2313

(rat)
IYRLCCR

AP00223
Q62715, RatNP-2
VTCYCRSTRCGFRERLSGACGYRG
2314

(rat)
RIYRLCCR

AP00222
Q62716, RatNP-1
VTCYCRRTRCGFRERLSGACGYRG
2315

(rat)
RIYRLCCR

AP00174
Q64365, GNCP-1
RRCICTTRTCRFPYRRLGTCIFQNR
2316

(Guinea pig
VYTFCC

neutrophil cationic

peptide 1)

AP00311
Q90W78, Galensin
CYSAAKYPGFQEFINRKYKSSRF
2317

(frog)

AP00395
Q95NT0,
HSSGYTRPLPKPSRPIFIRPIGCDVC
2318

Penaeidin-4a
YGIPSSTARLCCFRYGDCCHR

(shrimp, Crustacea)

AP00423
Q962B0,
QGYKGPYTRPILRPYVRPVVSYNA
2319

Penaeidin-3n
CTLSCRGITTTQARSCSTRLGRCCH

(shrimp, Crustacea)
VAKGYS

AP00422
Q962B1,
QGCKGPYTRPILRPYVRPVVSYNA
2320

Penaeidin-3m
CTLSCRGITTTQARSCCTRLGRCCH

(shrimp, Crustacea)
VAKGYS

AP00421
Q963C3,
YSSGYTRPLPKPSRPIFIRPIGCDVC
2321

Penaeidin-4C
YGIPSSTARLCCFRYGDCCHR

(shrimp, Crustacea)

AP00210
Q99134, PGLa
GMASKAGAIAGKIAKVALKAL
2322

(African clawed

frog, XXA)

AP00054
Q9DET7,
GIGGALLSAGKSALKGLAKGLAEH
2323

Bombinin-like
FAN

peptide 7 (BLP-7,

toad)

AP00315
Q9PT75,
SLGSFLKGVGTTLASVGKVVSDQF
2324

Dermatoxin (Two-
GKLLQAGQ

colored leaf frog)

AP00133
Q9Y0Y0, Cecropin
GGLKKLGKKLEGVGKRVFKASEK
2325

B (insect,
ALPVLTGYKAIG

mosquito)

AP00004
Ref, Ct-AMP1
NLCERASLTWTGNCGNTGHCDTQ
2326

(CtAMP1, C.
CRNWESAKHGACHKRGNWKCFC

ternatea-
YFDC

antimicrobial

peptide 1, plant

defensin)

AP00027
Ref, hexapeptide
RRWQWR
2327

(synthetic)

AP00529
Ref, Lantibiotic
WKSESVCTPGCVTGVLQTCFLQTI
2328

Ericin S (bacteria)
TCNCHISK

AP00306
Ref, Tigerinin-4
RVCYAIPLPIC
2329

(frog)

AP00309
Ref, Human KS-27
KSKEKIGKEFKRIVQRIKDFLRNLV
2330

(KS27 from LL-37)
PR

AP00344
Ref, Apidaecin II
GNNRPIYIPQPRPPHPRL
2331

(honeybee, insect)

AP00424
Ref, XT1 (frog)
GFLGPLLKLAAKGVAKVIPHLIPSR
2332

QQ

AP00425
Ref, XT 2 (frog)
GCWSTVLGGLKKFAKGGLEAIVNPK
2333

AP00426
Ref, XT 4 (frog)
GVFLDALKKFAKGGMNAVLNPK
2334

AP00427
Ref, XT 7 (frog)
GLLGPLLKIAAKVGSNLL
2335

AP00431
Ref, human LLP 1
RVIEVVQGACRAIRHIPRRIRQGLE
2336

RIL

AP00432
Ref, human LLP
RIAGYGLRGLAVIIRICIRGLNLIFEI
2337

IR

AP00447
Ref, Anoplin
GLLKRIKTLL
2338

(insect)

AP00474
Ref, Piscidin 3
FIHHIFRGIVHAGRSIGRFLTG
2339

(fish)

AP00481
Ref, Kaliocin-1
FFSASCVPGADKGQFPNLCRLCAG
2340

(synthetic)
TGENKCA

AP00482
Ref, Thionin
KSCCRNTWARNCYNVCRLPGTISR
2341

mutation
EICAKKCRCKIISGTTCPSDYPK

(synthetic)

AP00484
Ref, Stomoxyn
RGFRKHFNKLVKKVKHTISETAHV
2342

(insect, fly)
AKDTAVIAGSGAAVVAAT

AP00486
Ref, Cupiennin 1b
GFGSLFKFLAKKVAKTVAKQAAK
2343

(spider)
QGAKYIANKQME

AP00487
Ref, Cupiennin 1c
GFGSLFKFLAKKVAKTVAKQAAK
2344

(spider)
QGAKYIANKQTE

AP00488
Ref, Cupiennin 1D
GFGSLFKFLAKKVAKTVAKQAAK
2345

(spider)
QGAKYVANKHME

AP00489
Ref, Hipposin
SGRGKTGGKARAKAKTRSSRAGL
2346

(fish)
QFPVGRVHRLLRKGNYAHRVGAG

APVYL

AP00923
Ref,
AISYGNGVYCNKEKCWVNKAENK
2347

Carnobacteriocin
QAITGIVIGGWASSLAGMGH

B1 (XXO, class IIa

bacteriocin,

bacteria)

AP00496
Ref, HP 2-20
AKKVFKRLEKLFSKIQNDK
2348

(synthetic)

AP00497
Ref, Maximin H5
ILGPVLGLVSDTLDDVLGIL
2349

(toad)

AP00498
Ref, rCRAMP (rat
GLVRKGGEKFGEKLRKIGQKIKEF
2350

cathelicidin)
FQKLALEIEQ

AP00500
Ref, S9-P18
KWKLFKKISKFLHLAKKF
2351

(synthetic)

AP00501
Ref, L9-P18
KWKLFKKILKFLHLAKKF
2352

(synthetic)

AP00502
Ref, Clavaspirin
FLRFIGSVIHGIGHLVHHIGVAL
2353

(sea squirt,

tunicate)

AP00503
Ref, human P-
AKRHHGYKRKFH
2354

113D

AP00504
Ref, human MUC7
LAHQKPFIRKSYKCLHKRCR
2355

20-Mer

AP00507
Ref, Nigrocin 2
GLLSKVLGVGKKVLCGVSGLC
2356

(frog)

AP00508
Ref, Nigrocin 1
GLLDSIKGMAISAGKGALQNLLKV
2357

(frog)
ASCKLDKTC

AP00509
Ref, human
VAIALKAAHYHTHKE
2358

Calcitermin

AP00510
Ref, Dicynthaurin
ILQKAVLDCLKAAGSSLSKAAITAI
2359

(sea peach)
YNKIT

AP00511
Ref, KIGAKI
KIGAKIKIGAKIKIGAKI
2360

(synthetic)

AP00516
Ref, Lycotoxin I
IWLTALKFLGKHAAKHLAKQQLS
2361

(spider)
KL

AP00517
Ref, Lycotoxin II
KIKWFKTMKSIAKFIAKEQMKKHL
2362

(spider)
GGE

AP00518
Ref, Ib-AMP3
QYRHRCCAWGPGRKYCKRWC
2363

(plant defensin,

balsam)

AP00519
Ref, Ib-AMP4
EWGRRCCGWGPGRRYCRRWC
2364

(plant defensin,

balsam)

AP00521
Ref, Dhvar4
KRLFKKLLFSLRKY
2365

(synthetic)

AP00522
Ref, Dhvar5
LLLFLLKKRKKRKY
2366

(synthetic)

AP00525
Ref, Maximin H2
ILGPVLSMVGSALGGLIKKI
2367

(toad)

AP00526
Ref, Maximin H3
ILGPVLGLVGNALGGLIKKI
2368

(toad)

AP00527
Ref, Maximin H4
ILGPVISKIGGVLGGLLKNL
2369

(toad)

AP00528
Ref, Anionic
DDDDDD
2370

peptide SAAP

(sheep)

AP00530
Ref, Lantibiotic
VLSKSLCTPGCITGPLQTCYLCFPT
2371

Ericin A (bacteria)
FAKC

AP00531
Ref, Kenojeinin I
GKQYFPKVGGRLSGKAPLAAKTH
2372

(sea skate)
RRLKP

AP00532
Ref, Lunatusin
KTCENLADTFRGPCFATSNC
2373

(plant, ZZHp)

AP00533
Ref, Fallaxin (frog)
GVVDILKGAAKDIAGHLASKVMN
2374

KL

AP00534
Ref, Tu-AMP 2
KSCCRNTTARNCYNVCRIPG
2375

(TuAMP2, thionin-

like antimicrobial

peptides, plant

defensin, tulip)

AP00535
Ref, Pilosulin 1
GLGSVFGRLARILGRVIPKVAKKL
2376

(Myr b I)
GPKVAKVLPKVMKEAIPMAVEMA

(Australian ants)
KSQEEQQPQ

AP00536
Ref, Luxuriosin
SVRTQDNAVNRQIFGSNGPYRDFQ
2377

(insect)
LSDCYLPLETNPYCNEWQFAYHW

NNALMDCERAIYHGCNRTRNNFIT

LTACKNQAGPICNRRRH

AP00537
Ref, SAMP H1
AEVAPAPAAAAPAKAPKKKAAAK
2378

(fish, Atlantic
PKKAGPS

salmon)

AP00538
Ref, Halocidin
WLNALLHHGLNCAKGVLA
2379

(dimer Hal18 +

Hal15) (tunicate)

AP00539
Ref, AOD
GFGCPWNRYQCHSHCRSIGRLGGY
2380

(American oyster
CAGSLRLTCTCYRS

defensin, animal

defensin)

AP00540
Ref, Pentadactylin
GLLDTLKGAAKNVVGSLASKVME
2381

(frog)
KL

AP00541
Ref, Polybia-MPI
IDWKKLLDAAKQIL
2382

(insect, social

wasp)

AP00542
Ref, Polybia-CP
ILGTILGLLKSL
2383

(insect, social

wasp)

AP00543
Ref, Ocellatin-1
GVVDILKGAGKDLLAHLVGKISEKV
2384

(XXA, frog)

AP00544
Ref, Ocellatin-2
GVLDIFKDAAKQILAHAAEKQI
2385

(XXA, frog)

AP00545
Ref, Ocellatin-3
GVLDILKNAAKNILAHAAEQI
2386

(frog)

AP00548
Ref, CMAP 27
RFGRFLRKIRRFRPKVTITIQGSARFG
2387

(chicken myeloid

antimicrobial

peptide 27, bird

cathelicidin,

chicken

cathelicidin)

AP00550
Ref, Tu-AMP-1
KSCCRNTVARNCYNVCRIPGTPRP
2388

(TuAMP1, thionin-
VCAATCDCKLITGTKCPPGYEK

like antimicrobial

peptides, plant

defensin, tulip)

AP00551
Ref, Combi-2
FRWWHR
2389

(synthetic)

AP00552
Ref, Maximin 9
GIGRKFLGGVKTTFRCGVKDFASK
2390

(frog)
HLY

AP00554
Ref, Sl moricin
GKIPVKAIKKAGAAIGKGLRAINIA
2391

(insect)
STAHDVYSFFKPKHKKK

AP00555
Ref, Parasin I
KGRGKQGGKVRAKAKTRSS
2392

(catfish)

AP00556
Ref, Kassinatuerin-
GFMKYIGPLIPHAVKAISDLI
2393

1 (frog)

AP00557
Ref, Fowlicidin-1
RVKRVWPLVIRTVIAGYNLYRAIK
2394

(chCATH-1, bird
KK

cathelicidin,

chicken

cathelicidin)

AP00559
Ref, Eryngin
ATRVVYCNRRSGSVVGGDDTVYY
2395

(mushroom, fungi)
EG

AP00560
Ref, Dendrocin
TTLTLHNLCPYPVWWLVTPNNGG
2396

(plant, bamboo)
FPIIDNTPVVLG

AP00561
Ref, Coconut
EQCREEEDDR
2397

antifungal peptide

(plant)

AP00562
Ref, Pandinin 1
GKVWDWIKSAAKKIWSSEPVSQL
2398

(African scorpion)
KGQVLNAAKNYVAEKIGATPT

AP00563
Ref, White cloud
KTCENLADTFRGPCFATSNCDDHC
2399

bean defensin
KNKEHLLSGRCRDDFRCWCTRNC

(plant defensin)

AP00564
Ref, Dybowskin-1
FLIGMTHGLICLISRKC
2400

(frog)

AP00565
Ref, Dybowskin-2
FLIGMTQGLICLITRKC
2401

(frog)

AP00566
Ref, Dybowskin-3
GLFDVVKGVLKGVGKNVAGSLLE
2402

(frog)
QLKCKLSGGC

AP00567
Ref, Dybowskin-4
VWPLGLVICKALKIC
2403

(frog)

AP00568
Ref, Dybowskin-5
GLFSVVTGVLKAVGKNVAKNVGG
2404

(frog)
SLLEQLKCKKISGGC

AP00569
Ref, Dybowskin-6
FLPLLLAGLPLKLCFLFKKC
2405

(frog)

AP00570
Ref, Pleurain-A1
SIITMTKEAKLPQLWKQIACRLYNTC
2406

(frog)

AP00571
Ref, Pleurain-A2
SIITMTKEAKLPQSWKQIACRLYNTC
2407

(frog)

AP00574
Ref, Esculentin-
GLFSKFAGKGIKNLIFKGVKHIGKE
2408

IGRa (frog)
VGMDVIRTGIDVAGCKIKGEC

AP00575
Ref, Brevinin-
GLLDTFKNLALNAAKSAGVSVLNS
2409

2GRa (frog)
LSCKLSKTC

AP00576
Ref, Brevinin-
GVLGTVKNLLIGAGKSAAQSVLKT
2410

2GRb (frog)
LSCKLSNDC

AP00577
Ref, Brevinin-
GLFTLIKGAAKLIGKTVAKEAGKT
2411

2GRc (frog)
GLELMACKITNQC

AP00578
Ref, Brevinin-
FLPLLAGLAANFLPKIFCKITKKC
2412

1GRa (frog)

AP00579
Ref, Nigrocin-
GLLSGILGAGKHIVCGLSGLC
2413

2GRa (frog)

AP00580
Ref, Nigrocin-
GLFGKILGVGKKVLCGLSGMC
2414

2GRb (frog)

AP00581
Ref, Nigrocin-
GLLSGILGAGKNIVCGLSGLC
2415

2GRc (frog)

AP00582
Ref, Brevinin-
GFSSLFKAGAKYLLKSVGKAGAQ
2416

2GHa (frog)
QLACKAANNCA

AP00583
Ref, Brevinin-
GVITDALKGAAKTVAAELLRKAH
2417

2GHb (frog)
CKLTNSC

AP00584
Ref, Guentherin
VIDDLKKVAKKVRRELLCKKHHK
2418

(frog)
KLN

AP00585
Ref, Brevinin-
SIWEGIKNAGKGFLVSILDKVRCK
2419

2GHc (frog)
VAGGCNP

AP00586
Ref, Temporin-GH
FLPLLFGAISHLL
2420

(frog)

AP00587
Ref, Brevinin-2TSa
GIMSLFKGVLKTAGKHVAGSLVD
2421

(frog)
QLKCKITGGC

AP00588
Ref, Brevinin-1TSa
FLGSIVGALASALPSLISKIRN
2422

(frog)

AP00589
Ref, Temporin-
FLGALAKIISGIF
2423

1TSa (frog)

AP00593
Ref, Brevinin-1CSa
FLPILAGLAAKIVPKLFCLATKKC
2424

(frog)

AP00594
Ref, Temporin-
FLPIVGKLLSGLL
2425

1CSa (frog)

AP00595
Ref, Temporin-
FLPIIGKLLSGLL
2426

1CSb (frog)

AP00596
Ref, Temporin-
FLPLVTGLLSGLL
2427

1CSc (frog)

AP00597
Ref, Temporin-
NFLGTLVNLAKKIL
2428

1CSd (frog)

AP00598
Ref, Temporin-
FLSAITSLLGKLL
2429

1SPb (frog)

AP00599
Ref, Brevinin-2-
GIWDTIKSMGKVFAGKILQNL
2430

related (frog)

AP00600
Ref, Odorranain-
GLLRASSVWGRKYYVDLAGCAKA
2431

HP (frog)

AP00601
Ref, Brevinin-
FLSLALAALPKFLCLVFKKC
2432

1DYa (frog)

AP00602
Ref, Brevinin-
FLSLALAALPKLFCLIFKKC
2433

1DYb (frog)

AP00603
Ref, Brevinin-
FLPLLLAGLPKLLCLFFKKC
2434

1DYc (frog)

AP00607
Ref, Brevinin-
GLFDVVKGVLKGAGKNVAGSLLE
2435

2DYb (frog)
QLKCKLSGGC

AP00608
Ref, Brevinin-
GLFDVVKGVLKGVGKNVAGSLLE
2436

2DYc (frog)
QLKCKLSGGC

AP00609
Ref, Brevinin-
GIFDVVKGVLKGVGKNVAGSLLE
2437

2DYd (frog)
QLKCKLSGGC

AP00610
Ref, Brevinin-
GLFSVVTGVLKAVGKNVAKNVGG
2438

2DYe (frog)
SLLEQLKCKISGGC

AP00611
Ref, Temporin-
FIGPIISALASLFG
2439

1DYa (frog)

AP00615
Ref, Palustrin-1b
ALFSILRGLKKLGNMGQAFVNCKI
2440

(frog)
YKKC

AP00616
Ref, Palustrin-1c
ALSILRGLEKLAKMGIALTNCKAT
2441

(frog)
KKC

AP00617
Ref, Palustrin-1d
ALSILKGLEKLAKMGIALTNCKAT
2442

(frog)
KKC

AP00619
Ref, Palustrin-2b
GFFSTVKNLATNVAGTVIDTLKCK
2443

(frog)
VTGGCRS

AP00620
Ref, Palustrin-2c
GFLSTVKNLATNVAGTVIDTLKCK
2444

(frog)
VTGGCRS

AP00621
Ref, Palustrin-3a
GIFPKIIGKGIKTGIVNGIKSLVKGV
2445

(frog)
GMKVFKAGLNNIGNTGCNEDEC

AP00622
Ref, Palustrin-3b
GIFPKIIGKGIKTGIVNGIKSLVKGV
2446

(frog)
GMKVFKAGLSNIGNTGCNEDEC

AP00624
Ref, human ALL-
ALLGDFFRKSKEKIGKEFKRIVQRI
2447

38 (an LL-37
KDFLRNLVPRTES

analog released

from its precursor

hCAP-18 by

gastricsin in vivo)

AP00625
Ref, human KR-20
KRIVQRIKDFLRNLVPRTES
2448

(KR20 from LL-

37)

AP00626
Ref, human KS-30
KSKEKIGKEFKRIVQRIKDFLRNLV
2449

(KS30 from LL-37)
PRTES

AP00627
Ref, human RK-31
RKSKEKIGKEFKRIVQRIKDFLRNL
2450

(RK31 from LL-
VPRTES

37)

AP00628
Ref, human LL-23
LLGDFFRKSKEKIGKEFKRIVQR
2451

(LL23 from LL-37)

AP00629
Ref, human LL-29
LLGDFFRKSKEKIGKEFKRIVQRIK
2452

(LL29 from LL-37)
DFLR

AP00630
Ref, Amoeba
GEILCNLCTGLINTLENLLTTKGAD
2453

peptide (protozoan

para

AP00631
Ref, Mundticin
KYYGNGVSCNKKGCSVDWGKAIG
2454

(bacteria)
IIGNNSAANLATGGAAGWSK

AP00638
Ref, Citropin 2.1
GLIGSIGKALGGLLVDVLKPKL
2455

(frog)

AP00639
Ref, Citropin 2.1.3
GLIGSIGKALGGLLVDVLKPKLQA
2456

(frog)
AS

AP00640
Ref, Maculatin 1.3
GLLGLLGSVVSHVVPAIVGHF
2457

(frog)

AP00641
Ref, Pardaxin 1
GFFALIPKIISSPLFKTLLSAVGSALS
2458

(Pardaxin P-1,
SSGEQE

Pardaxin P1, Pa1,

flat fish)

AP00642
Ref, Pardaxin 2
GFFALIPKIISSPIFKTLLSAVGSALS
2459

(Pardaxin P-2,
SSGGQE

Pardaxin P2, Pa2,

flat fish)

AP00643
Ref, Pardaxin 3
GFFAFIPKIISSPLFKTLLSAVGSALS
2460

(Pardaxin P-3,
SSGEQE

Pardaxin P3, Pa3,

flat fish)

AP00645
Ref, Pardaxin 5
GFFAFIPKIISSPLFKTLLSAVGSALS
2461

(Pardaxin P-5,
SSGDQE

Pardaxin P5, Pa5,

flat fish)

AP00647
Ref, Brevinin-1PLb
FLPLIAGLAANFLPKIFCAITKKC
2462

(frog)

AP00648
Ref, Brevinin-1PLc
FLPVIAGVAAKFLPKIFCAITKKC
2463

(frog)

AP00649
Ref, Esculentin-
GLFPKINKKKAKTGVFNIIKTVGKE
2464

1PLa (frog)
AGMDLIRTGIDTIGCKIKGEC

AP00650
Ref, Esculentin-
GIFTKINKKKAKTGVFNIIKTIGKEA
2465

1PLb (frog)
GMDVIRAGIDTISCKIKGEC

AP00651
Ref, Esculentin-
GLFSILKGVGKIALKGLAKNMGK
2466

2PLa (frog)
MGLDLVSCKISKEC

AP00652
Ref, Ranatuerin-
GIMDTVKNVAKNLAGQLLDKLKC
2467

2PLa (frog)
KITAC

AP00653
Ref, Ranatuerin-
GIMDTVKNAAKDLAGQLLDKLKC
2468

2PLb (frog)
RITGC

AP00654
Ref, Ranatuerin-
GLLDTIKNTAKNLAVGLLDKIKCK
2469

2PLc (frog)
MTGC

AP00655
Ref, Ranatuerin-
GIMDSVKNVAKNIAGQLLDKLKC
2470

2PLd (frog)
KITGC

AP00656
Ref, Ranatuerin-
GIMDSVKNAAKNLAGQLLDTIKCK
2471

2PLe (frog)
ITAC

AP00657
Ref, Ranatuerin-
GIMDTVKNAAKDLAGQLDKLKCR
2472

2PLf (frog)
ITGC

AP00658
Ref, Temporin-
FLPLVGKILSGLI
2473

1PLa (frog)

AP00659
Ref, Ranatuerin 5
FLPIASLLGKYL
2474

(frog)

AP00661
Ref, Esculentin-2L
GILSLFTGGIKALGKTLFKMAGKA
2475

(frog)
GAEHLACKATNQC

AP00662
Ref, Esculentin-2B
GLFSILRGAAKFASKGLGKDLTKL
2476

(ESC2B-RANBE,
GVDLVACKISKQC

frog)

AP00663
Ref, Esculentin-2P
GFSSIFRGVAKFASKGLGKDLARL
2477

(frog)
GVNLVACKISKQC

AP00664
Ref, Peptide A1
FLPAIAGILSQLF
2478

(frog)

AP00665
Ref, Peptide B9
FLPLIAGLIGKLF
2479

(frog)

AP00666
Ref, PG-L ( frog)
EGGGPQWAVGHFM
2480

AP00667
Ref, PG-KI (frog)
EPHPDEFVGLM
2481

AP00668
Ref, PG-KII (frog)
EPNPDEFVGLM
2482

AP00669
Ref, PG-KIII (frog)
EPHPNEFVGLM
2483

AP00670
Ref, PG-SPI (frog)
EPNPDEFFGLM
2484

AP00660
Ref, Pandinin 2
FWGALAKGALKLIPSLFSSFSKKD
2485

(African scorpion)

AP00671
Ref, PG-SPII (frog)
EPNPNEFFGLM
2486

AP00673
Ref, Lantibiotic
WKSESVCTPGCVTGVLQTCFLQTI
2487

Ericin S (bacteria
TCNCHISK

AP00674
Ref, Lantibiotic
VLSKSLCTPGCITGPLQTCYLCFPT
2488

Ericin A (bacteria
FAKC

AP00675
Ref, Human beta
FELDRICGYGTARCRKKCRSQEYRI
2489

defensin 4 (HBD-4,
GRCPNTYACCLRKWDESLLNRTKP

HBD4, human

defensin)

AP00676
Ref, RL-37 (RL37,
RLGNFFRKVKEKIGGGLKKVGQKI
2490

monkey
KDFLGNLVPRTAS

cathelicidin)

AP00677
Ref, CAP11
GLRKKFRKTRKRIQKLGRKIGKTG
2491

(Guinea pig
RKVWKAWREYGQIPYPCRI

cathelicidin)

AP00678
Ref, Canine
RLKELITTGGQKIGEKIRRIGQRIKD
2492

cathelicidin
FFKNLQPREEKS

(K9CATH) (dog)

AP00679
Ref, Esculentin
GLFSILKGVGKIAIKGLGKNLGKM
2493

2VEb (frog)
GLDLVSCKISKEC

AP00680
Ref, SMAP-34
GLFGRLRDSLQRGGQKILEKAERI
2494

(sheep cathelicidin)
WCKIKDIFR

AP00681
Ref, OaBac5
RFRPPIRRPPIRPPFRPPFRPPVRPPIR
2495

(sheep cathelicidin)
PPFRPPFRPPIGPFP

AP00682
Ref, OaBac6
RRLRPRHQHFPSERPWPKPLPLPLP
2496

(sheep cathelicidin)
RPGPRPWPKPLPLPLPRPGLRPWPK

PL

AP00683
Ref, OaBac7.5
RRLRPRRPRLPRPRPRPRPRPRSLPL
2497

(sheep cathelicidin)
PRPQPRRIPRPILLPWRPPRPIPRPQI

QPIPRWL

AP00684
Ref, OaBac11
RRLRPRRPRLPRPRPRPRPRPRSLPL
2498

(sheep cathelicidin)
PRPKPRPIPRPLPLPRPRPKPIPRPLP

LPRPRPRRIPRPLPLPRPRPRPIPRPL

PLPQPQPSPIPRPL

AP00685
Ref, Ranatuerin
GIMDTVKGVAKTVAASLLDKLKC
2499

2VEb (frog)
KITGC

AP00686
Ref, eCATH-1
KRFGRLAKSFLRMRILLPRRKILLAS
2500

(horse cathelicidin)

AP00687
Ref, eCATH-2
KRRHWFPLSFQEFLEQLRRFRDQL
2501

(horse cathelicidin)
PFP

AP00688
Ref, eCATH-3
KRFHSVGSLIQRHQQMIRDKSEAT
2502

(horse cathelicidin)
RHGIRIITRPKLLLAS

AP00689
Ref, Prophenin-1
AFPPPNVPGPRFPPPNFPGPRFPPPN
2503

(pig cathelicidin)
FPGPRFPPPNFPGPRFPPPNFPGPPFP

PPIFPGPWFPPPPPFRPPPFGPPRFP

AP00690
Ref, Prophenin-2
AFPPPNVPGPRFPPPNVPGPRFPPPN
2504

(pig cathelicidin)
FPGPRFPPPNFPGPRFPPPNFPGPPFP

PPIFPGPWFPPPPPFRPPPFGPPRFP

AP00691
Ref, HFIAP-1
GFFKKAWRKVKHAGRRVLDTAK
2505

(hagfish
GVGRHYVNNWLNRYR

cathelicidin)

AP00692
Ref, HFIAP-3
GWFKKAWRKVKNAGRRVLKGVG
2506

(hagfish
IHYGVGLI

cathelicidin)

AP00693
Ref, Trout cath
RICSRDKNCVSRPGVGSIIGRPGGG
2507

(fish cathelicidin)
SLIGRPGGGSVIGRPGGGSPPGGGS

FNDEFIRDHSDGNRFA

AP00694
Ref, MRP
AIGSILGALAKGLPTLISWIKNR
2508

(melittin-related

peptide)

AP00695
Ref, Temporin-
FLPILGKLLSGIL
2509

1TGa (frog)

AP00696
Ref, Dahlein 1.1
GLFDIIKNIVSTL
2510

(frog)

AP00697
Ref, Dahlein 1.2
GLFDIIKNIFSGL
2511

(frog)

AP00698
Ref, Dahlein 4.1
GLWQLIKDKIKDAATGFVTGIQS
2512

(frog)

AP00699
Ref, Dahlein 4.2
GLWQFIKDKLKDAATGLVTGIQS
2513

(frog)

AP00700
Ref, Dahlein 4.3
GLWQFIKDKFKDAATGLVTGIQS
2514

(frog)

AP00701
Ref, Dahlein 5.1
GLLGSIGNAIGAFIANKLKP
2515

(frog)

AP00702
Ref, Dahlein 5.2
GLLGSIGNAIGAFIANKLKPK
2516

(frog)

AP00703
Ref, Dahlein 5.3
GLLASLGKVLGGYLAEKLKP
2517

(frog)

AP00704
Ref, Dahlein 5.4
GLLGSIGKVLGGYLAEKLKPK
2518

(frog)

AP00705
Ref, Dahlein 5.5
GLLASLGKVLGGYLAEKLKPK
2519

(frog)

AP00706
Ref, Dahlein 5.6
GLLASLGKVFGGYLAEKLKPK
2520

(frog)

AP00709
Ref, Mytilus
GFGCPNDYPCHRHCKSIPGRAGGY
2521

defensin (mytilin)
CGGAHRLRCTCYR

A (mollusc)

AP00711
Ref, Mussel
GFGCPNNYACHQHCKSIRGYCGG
2522

defensin MGD2
YCAGWFRLRCTCYRCG

AP00712
Ref, scorpion
GFGCPLNQGACHRHCRSIRRRGGY
2523

defensin
CAGFFKQTCCYRN

AP00713
Ref, Androctonus
GFGCPFNQGACHRHCRSIRRRGGY
2524

defensin
CAGLFKQTCTCYR

AP00714
Ref, Orinthodoros
GYGCPFNQYQCHSHCSGIRGYKGG
2525

defensin A (soft
YCKGTFKQTCKCY

ticks)

AP00715
Ref, VaD1 (plant
RTCMKKEGWGKCLIDTTCAHSCK
2526

defensin)
NRGYIGGNCKGMTRTCYCLVNC

AP00722
Ref, Cryptonin
GLLNGLALRLGKRALKKIIKRLCR
2527

(insect, cicada)

AP00723
Ref, Decoralin
SLLSLLRKLIT
2528

(insect)

AP00724
Ref, RTD-2 (rhesus
RCLCRRGVCRCLCRRGVC
2529

theta-defensin-2,

minidefensin,

XXC, BBS, lectin,

ZZHa)

AP00725
Ref, RTD-3 (rhesus
RCICTRGFCRCICTRGFC
2530

theta-defensin-3,

minidefensin,

XXC, BBS, lectin,

ZZHa)

AP00726
Ref, Combi-1
RRWWRF
2531

(synthetic)

AP00748
Ref, Gm pro-rich
DIQIPGIKKPTHRDIIIPNWNPNVRT
2532

pept1 (insect)
QPWQRFGGNKS

AP00749
Ref, Gm anionic
EADEPLWLYKGDNIERAPTTADHP
2533

pept 1 (insect)
ILPSIIDDVKLDPNRRYA

AP00750
Ref, Gm pro-rich
EIRLPEPFRFPSPTVPKPIDIDPILPHP
2534

pept 2 (insect)
WSPRQTYPIIARRS

AP00752
Ref, Gm defensin-
DKLIGSCVWGATNYTSDCNAECK
2535

like peptide (insect)
RRGYKGGHCGSFWNVNCWCEE

AP00753
Ref, Gm
VQETQKLAKTVGANLEETNKKLA
2536

apolipophoricin
PQIKSAYDDFVKQAQEVQKKLHE

(insect)
AASKQ

AP00754
Ref, Gm anionic
ETESTPDYLKNIQQQLEEYTKNFNT
2537

pept2 (insect)
QVQNAFDSDKIKSEVNNFIESLGKI

LNTEKKEAPK

AP00755
Ref, Gm cecropin
ENFFKEIERAGQRIRDAIISAAPAVE
2538

D-like pept, insect
TLAQAQKIIKGGD

AP00756
Ref, Dermaseptin-
ALWKDILKNAGKAALNEINQLVNQ
2539

B6 (DRS-B6, DRS

B6, XXA, frog)

AP00759
Ref, Phylloseptin-
FLSLIPHAINAVSTLVHHSG
2540

O1 (PLS-O1,

Phylloseptin-4, PS-

4, XXA, frog)

AP00760
Ref, Phylloseptin-
FLSLIPHAINAVSAIAKHS
2541

O2 (PLS-O2,

Phylloseptin-5, PS-

5, XXA, frog)

AP00761
Ref, Phylloseptin-6
SLIPHAINAVSAIAKHF
2542

(Phylloseptin-H4,

PLS-H4, PS-6,

XXA, frog)

AP00762
Ref, Phylloseptin-7
FLSLIPHAINAVSAIAKHF
2543

(Phylloseptin-H5,

PLS-H5, PS-7,

XXA, frog)

AP00763
Ref, Dermaseptin
GLWSTIKNVGKEAAIAAGKAALG
2544

DPh-1 (XXA, frog)
AL

AP00764
Ref, Dermaseptin-
GLRSKIWLWVLLMIWQESNKFKKM
2545

S9 (DRS-S9, DRS

S9, frog)

AP00765
Ref, Human salvic
MHDFWVLWVLLEYIYNSACSVLS
2546

ATSSVSSRVLNRSLQVKVVKITN

AP00766
Ref, Gassericin A
IYWIADQFGIHLATGTARKLLDAM
2547

(XXC, XXD2,
ASGASLGTAFAAILGVTLPAWALA

class IV
AAGALGATAA

bacteriocin, Gram-

positive bacteria)

AP00767
Ref, Circularin A
VAGALGVQTAAATTIVNVILNAGT
2548

(XXC, class IV
LVTVLGIIASIASGGAGTLMTIGWA

bacteriocin, Gram-
TFKATVQKLAKQSMARAIAY

positive bacteria)

AP00768
Ref, Closticin 574
PNWTKIGKCAGSIAWAIGSGLFGG
2549

(bacteria)
AKLIKIKKYIAELGGLQKAAKLLV

GATTWEEKLHAGGYALINLAAELT

GVAGIQANCF

AP00769
Ref, Caerin 1.11
GLLGAMFKVASKVLPHVVPAITEHF
2550

(XXA, frog)

AP00770
Ref, Maculatin 1.4
GLLGLLGSVVSHVLPAITQHL
2551

(XXA, frog)

AP00771
Ref, Magainin 1
GIGKFLHSAGKFGKAFVGEIMKS
2552

(frog)

AP00772
Ref, Oxyopinin 1
FRGLAKLLKIGLKSFARVLKKVLP
2553

(spider)
KAAKAGKALAKSMADENAIRQQNQ

AP00773
Ref, Oxyopinin 2a
GKFSVFGKILRSIAKVFKGVGKVR
2554

(spider)
KQFKTASDLDKNQ

AP00774
Ref, Oxyopinin 2b
GKFSGFAKILKSIAKFFKGVGKVR
2555

(spider)
KGFKEASDLDKNQ

AP00775
Ref, Oxyopinin 2c
GKLSGISKVLRAIAKFFKGVGKAR
2556

(spider)
KQFKEASDLDKNQ

AP00776
Ref, Oxyopinin 2d
GKFSVFSKILRSIAKVFKGVGKVRK
2557

(spider)
GFKTASDLDKNQ

AP00777
Ref, NRC-1 (XXA,
GKGRWLERIGKAGGIIIGGALDHL
2558

fish, gene

predicted)

AP00778
Ref, NRC-2 (XXA,
WLRRIGKGVKIIGGAALDHL
2559

fish, gene

predicted)

AP00779
Ref, NRC-3 (XXA,
GRRKRKWLRRIGKGVKIIGGAALD
2560

fish, gene
HL

predicted)

AP00781
Ref, NRC-5 (XXA,
FLGALIKGAIHGGRFIHGMIQNHH
2561

fish, gene

predicted)

AP00782
Ref, NRC-6 (XXA,
GWGSIFKHGRHAAKHIGHAAVNH
2562

fish, gene
YL

predicted)

AP00783
Ref, NRC-7 (XXA,
RWGKWFKKATHVGKHVGKAALT
2563

fish, gene
AYL

predicted)

AP00784
Ref, NRC-10
FFRLLFHGVHHVGKIKPRA
2564

(XXA, fish, gene

predicted)

AP00785
Ref, NRC-11
GWKSVFRKAKKVGKTVGGLALD
2565

(XXA, fish, gene
HYL

predicted)

AP00786
Ref, NRC-12
GWKKWFNRAKKVGKTVGGLAVD
2566

(XXA, fish, gene
HYL

predicted)

AP00787
Ref, NRC-13
GWRLLLKKAEVKTVGKLALKHYL
2567

(XXA, fish, gene

predicted)

AP00788
Ref, NRC-14
AGWGSIFKHIFKAGKFIHGAIQAHND
2568

(XXA, fish, gene

predicted)

AP00789
Ref, NRC-15
GFWGKLFKLGLHGIGLLHLHL
2569

(XXA, fish, gene

predicted)

AP00790
Ref, NRC-16
GWKKWLRKGAKHLGQAAIK
2570

(XXA, fish, gene

predicted)

AP00791
Ref, NRC-17
GWKKWLRKGAKHLGQAAIKGLAS
2571

(XXA, fish, gene

predicted)

AP00792
Ref, NRC-19
FLGLLFHGVHHVGKWIHGLIHGHH
2572

(XXA, fish, gene

predicted)

AP00793
Ref, Bombinin H2
IIGPVLGLVGSALGGLLKKI
2573

(XXA, frog)

AP00794
Ref, Bombinin H3
IIGPVLGMVGSALGGLLKKI
2574

(frog, XXD, XXA)

AP00795
Ref, Bombinin H7
ILGPILGLVSNALGGLL
2575

(frog, XXD, XXA)

AP00796
Ref, Bombinin GH-
IIGPVLGLVGKPLESLLE
2576

1L (XXA, toad)

AP00797
Ref, Bombinin GH-
IIGPVLGLVGKPLESLLE
2577

1D (toad, XXD,

XXA)

AP00807
Ref, Enterocin E-
NRWYCNSAAGGVGGAAGCVLAG
2578

760 (bacteriocin,
YVGEAKENIAGEVRKGWGMAGGF

bacteria)
THNKACKSFPGSGWASG

AP00808
Ref, hepcidin (fish)
CRFCCRCCPRMRGCGLCCRF
2579

AP00809
Ref, hepcidin TH1-
GIKCRFCCGCCTPGICGVCCRF
2580

5 (fish)

AP00810
Ref, hepcidin TH2-
QSHLSLCRWCCNCCRSNKGC
2581

3 (fish)

AP00811
Ref, human LEAP-2
MTPFWRGVSLRPIGASCRDDSECIT
2582

RLCRKRRCSLSVAQE

AP00812
Ref, Enkelytin
FAEPLPSEEEGESYSKEPPEMEKRY
2583

(cow)
GGFM

AP00732
Ref, Spheniscin-1
SFGLCRLRRGSCAHGRCRFPSIPIG
2584

(Sphe-1, avian
RCSRFVQCCRRVW

defensin)

AP00733
Ref, Organgutan
LLGDFFRKAREKIGEEFKRIVQRIK
2585

ppyLL-37 (Great
DFLRNLVPRTES

Ape, primate

cathelicidin)

AP00734
Ref, Gibbon
SLGNFFRKARKKIGEEFKRIVQRIK
2586

hmdSL-37
DFLQHLIPRTEA

(hylobatidae,

primate

cathelicidin)

AP00735
Ref, pobRL-37
RLGNFFRKAKKKIGRGLKKIGQKI
2587

(cercopithecidae,
KDFLGNLVPRTES

primate

cathelicidin)

AP00736
Ref, cjaRL-37
RLGDILQKAREKIEGGLKKLVQKI
2588

(primate
KDFFGKFAPRTES

cathelicidin)

AP00737
Ref, Plasticin
GLVTSLIKGAGKLLGGLFGSVTG
2589

PBN2KF (XXA,

DRP-PBN2, frog)

AP00738
Ref, Plasticin
GLVTGLLKTAGKLLGDLFGSLTG
2590

ANCKF (XXA,

synthetic)

AP00739
Ref, Plasticin
GVVTDLLKTAGKLLGNLFGSLSG
2591

PD36KF (XXA,

synthetic)

AP00740
Ref, Plasticin
GVVTDLLKTAGKLLGNLVGSLSG
2592

PD36K (XXA,

synthetic)

AP00741
Ref, Chicken
PITYLDAILAAVRLLNQRISGPCILR
2593

cathelicidin-B1
LREAQPRPGWVGTLQRRREVSFLV

(bird cathelicidin)
EDGPCPPGVDCRSCEPGALQHCVG

TVSIEQQPTAELRCRPLRPQ

AP00742
Ref, Chicken
MRILYLLLSVLFVVLQGVAGQPYF
2594

gallinacin 4 (Gal 4)
SSPIHACRYQRGVCIPGPCRWPYY

RVGSCGSGLKSCCVRNRWA

AP00743
Ref, Chicken
MKILCFFIVLFVAVHGAVGFSRSPR
2595

gallinacin 7 (Gal 7)
YHMQCGYRGTFCTPGKCPYGNAY

LGLCRPKYSCCRWL

AP00744
Ref, Chicken
MQILPLLFAVLLLMLRAEPGLSLA
2596

gallinacin 9 (Gal 9)
RGLPQDCERRGGFCSHKSCPPGIGR

IGLCSKEDFCCRSRWYS

AP00745
Ref, Chicken
MTPFWRGVSLRPVGASCRDNSECI
2597

LEAP-2 (cLEAP-
TMLCRKNRCFLRTASE

2)

AP00814
Ref, Caerulein
GLGSILGKILNVAGKVGKTIGKVA
2598

precursor-related
DAVGNKE

fragment Ea

(CPRF-Ea, frog)

AP00815
Ref, Caerulein
GLGSFLKNAIKIAGKVGSTIGKVAD
2599

precursor-related
AIGNKE

fragment Eb

(CPRF-Eb, frog)

AP00816
Ref, Caerulein
GLGSFFKNAIKIAGKVGSTIGKVAD
2600

precursor-related
AIGNKE

fragment Ec

(CPRF-Ec, frog)

AP00817
Ref, Temporin-1Oa
FLPLLASLFSRLL
2601

(frog)

AP00818
Ref, Temporin-1Ob
FLPLIGKILGTIL
2602

(frog)

AP00819
Ref, Temporin-1Oc
FLPLLASLFSRLF
2603

(frog)

AP00820
Ref, Temporin-1Od
FLPLLASLFSGLF
2604

(frog)

AP00821
Ref, Brevinin-20a
GLFNVFKGLKTAGKHVAGSLLNQ
2605

(frog)
LKCKVSGGC

AP00822
Ref, Brevinin-20b
GIFNVFKGALKTAGKHVAGSLLNQ
2606

(frog)
LKCKVSGEC

AP00824
Ref, Temporin-1Gb
SILPTIVSFLSKFL
2607

(XXA, frog)

AP00825
Ref, Temporin-1Gc
SILPTIVSFLTKFL
2608

(XXA, frog)

AP00826
Ref, Temporin-1Gd
FILPLIASFLSKFL
2609

(XXA, frog)

AP00827
Ref, Ranatuerin-
SMISVLKNLGKVGLGFVACKVNK
2610

1Ga (frog)
QC

AP00829
Ref, Ranalexin-1G
FLGGLMKIIPAAFCAVTKKC
2611

(frog)

AP00830
Ref, Ranatuerin-2G
GLLLDTLKGAAKDIAGIALEKLKC
2612

(frog)
KITGCKP

AP00831
Ref, Odorranain-
GLLSGILGAGKHIVCGLTGCAKA
2613

NR (frog)

AP00832
Ref, Maximin H1
ILGPVISTIGGVLGGLLKNL
2614

(XXA, toad)

AP00834
Ref, G. mellonella
KVNANAIKKGGKAIGKGFKVISAA
2615

moricin-like
STAHDVYEHIKNRRH

peptide A (Gm-

mlpA, insect)

AP00835
Ref, G. mellonella
GKIPVKAIKKGGQIIGKALRGINIAS
2616

moricin-like
TAHDIISQFKPKKKKNH

peptide B (Gm-

mlpB, insect)

AP00836
Ref, G. mellonella
KVPIGAIKKGGKIIKKGLGVIGAAG
2617

moricin-like
TAHEVYSHVKNRH

peptide C1 (Gm-

mlpC1, insect)

AP00837
Ref, G. mellonella
KVPIGAIKKGGKIIKKGLGVLGAA
2618

moricin-like
GTAHEVYNHVRNRQ

peptide C2 (Gm-

mlpC2, insect)

AP00838
Ref, G. mellonella
KVPIGAIKKGGKIIKKGLGVIGAAG
2619

moricin-like
TAHEVYSHVKNRQ

peptide C3 (Gm-

mlpC3, insect)

AP00839
Ref, G. mellonella
KVPVGAIKKGGKAIKTGLGVVGA
2620

moricin-like
AGTAHEVYSHIRNRH

peptide C4/C5

(Gm-mlpC4/C5,

insect)

AP00840
Ref, G. mellonella
KGIGSALKKGGKIIKGGLGALGAIG
2621

moricin-like
TGQQVYEHVQNRQ

peptide D (Gm-

mlpD, insect)

AP00841
Ref, Enterocin A
TTHSGKYYGNGVYCTKNKCTVD
2622

(EntA, class IIA
WAKATTCIAGMSIGGFLGGAIPGKC

bacteriocin, i.e.

pediocin-like

peptide, bacteria)

AP00842
Ref, Divercin V41
TKYYGNGVYCNSKKCWVDWGQA
2623

(DvnV41, class IIa
SGCIGQTVVGGWLGGAIPGKC

bacteriocin,

pediocin-like

peptide, bacteria.

DvnRV41 is the

recombinant form)

AP00843
Ref, Divergicin
TKYYGNGVYCNSKKCWVDWGTA
2624

M35 (class IIa
QGCIDVVIGQLGGGIPGKGKC

bacteriocin,

pediocin-like

peptide, bacteria)

AP00844
Ref, Coagulin
KYYGNGVTCGKHSCSVDWGKATT
2625

(bacteriocin,
CIINNGAMAWATGGHQGTHKC

pediocin-like

peptide, bacteria)

AP00845
Ref, Listeriocin
KSYGNGVHCNKKKCWVDWGSAIS
2626

743A (class IIa
TIGNNSAANWATGGAAGWKS

bacteriocin,

pediocin-like

peptide, bacteria)

AP00846
Ref, Mundticin KS
KYYGNGVSCNKKGCSVDWGKAIG
2627

(enterocin CRL35,
IIGNNSAANLATGGAAGWKS

mundticin ATO6,

mundticin QU2,

class IIa

bacteriocin,

pediocin-like

peptide, bacteria)

AP00847
Ref, Sakacin 5X
KYYGNGLSCNKSGCSVDWSKAISII
2628

(Sak5X, class IIa
GNNAVANLTTGGAAGWKS

bacteriocin,

pediocin-like

peptide, bacteria)

AP00848
Ref, Leucocin C
KNYGNGVHCTKKGCSVDWGYAW
2629

(class IIa
ANIANNSVMNGLTGGNAGWHN

bacteriocin,

pediocin-like

peptide, bacteria)

AP00849
Ref, Lactococcin
TSYGNGVHCNKSKCWIDVSELETY
2630

MMFII (class IIa
KAGTVSNPKDILW

bacteriocin,

pediocin-like

peptide, bacteria)

AP00850
Ref, Sakacin G
KYYGNGVSCNSHGCSVNWGQAW
2631

(SakG, class IIa
TCGVNHLANGGHGVC

bacteriocin,

pediocin-like

peptide, bacteria)

AP00851
Ref, Plantaricin
KYYGNGVTCGKHSCSVNWGQAFS
2632

423 (class IIa
CSVSHLANFGHGKC

bacteriocin,

pediocin-like

peptide, bacteria)

AP00852
Ref, Plantaricin
KYYGNGLSCSKKGCTVNWGQAFS
2633

C19 (class IIa
CGVNRVATAGHHKC

bacteriocin,

pediocin-like

peptide, bacteria)

AP00853
Ref, Enterocin P
ATRSYGNGVYCNNSKCWVNWGE
2634

(EntP, class IIa
AKENIAGIVISGWASGLAGMGH

bacteriocin,

pediocin-like

peptide, bacteria)

AP00854
Ref, Bacteriocin 31
ATYYGNGLYCNKQKCWVDWNKA
2635

(Bac 31, Bac31,
SREIGKIIVNGWVQHGPWAPR

class IIa

bacteriocin,

pediocin-like

peptide, bacteria)

AP00855
Ref, MSI-78
GIGKFLKKAKKFGKAFVKILKK
2636

(XXA, synthetic)

AP00856
Ref, MSI-594
GIGKFLKKAKKGIGAVLKVLTTGL
2637

(XXA, synthetic)

AP00857
Ref, Catestatin
SSMKLSFRARAYGFRGPGPQL
2638

(human

CHGA(352-372),

human Cst)

AP00858
Ref, Temporin D
LLPIVGNLLNSLL
2639

(XXA, frog)

AP00859
Ref, Temporin H
LSPNLLKSLL
2640

(XXA, frog)

AP00861
Ref, Brevinin-ALb
FLPLAVSLAANFLPKLFCKITKKC
2641

(frog)

AP00862
Ref, Brevinin 1E
FLPLLAGLAANFLPKIFCKITKRC
2642

(frog)

AP00863
Ref, Temporin-
FLPIVGKLLSGLSGLL
2643

ALa (XXA, frog)

AP00864
Ref, Temporin
FLPIVGRLISGLL
2644

1ARa (XXA, frog)

AP00865
Ref, Temporin
FLPIIGQLLSGLL
2645

1AUa (XXA,

Temporin-1AUa)

(frog)

AP00866
Ref, Temporin
FLPIIAKVLSGLL
2646

1Bya (XXA,

Temporin-1Bya,

frog)

AP00867
Ref, Temporin 1Ec
FLPVIAGLLSKLF
2647

(XXA, frog)

AP00869
Ref, Temporin 1Ja
ILPLVGNLLNDLL
2648

(XXA, Temporin-

1Ja, frog)

AP00873
Ref, Temporin 1Pra
ILPILGNLLNGLL
2649

(XXA, frog)

AP00874
Ref, Temporin 1VE
FLPLVGKILSGLI
2650

(XXA, frog)

AP00875
Ref, Temporin 1Va
FLSSIGKILGNLL
2651

(XXA, frog)

AP00876
Ref, Temporin 1Vb
FLSIIAKVLGSLF
2652

(XXA, frog)

AP00877
Ref, Brevinin-1Ja
FLGSLIGAAIPAIKQLLGLKK
2653

(frog)

AP00878
Ref, Brevinin-
FLPILASLAAKFGPKLFCLVTKKC
2654

1BYa (frog)

AP00884
Ref, Ixosin-B (tick)
QLKVDLWGTRSGIQPEQHSSGKSD
2655

VRRWRSRY

AP00885
Ref, Brevinin-
FLPILASLAAKLGPKLFCLVTKKC
2656

1BYb (frog)

AP00886
Ref, Brevinin-
FLPILASLAATLGPKLLCLITKKC
2657

1BYc (frog)

AP00887
Ref, Brevinin-
GILSTFKGLAKGVAKDLAGNLLDK
2658

2BYa (frog)
FKCKITGC

AP00888
Ref, Brevinin-
GIMDSVKGLAKNLAGKLLDSLKC
2659

2BYb (frog)
KITGC

AP00891
Ref, Pilosulin 3
IIGLVSKGTCVLVKTVCKKVLKQG
2660

(Myr b III)(ants)

AP00892
Ref, Pilosulin 4
PDITKLNIKKLTKATCKVISKGASM
2661

(Myr b IV)(ants)
CKVLFDKKKQE

AP00893
Ref, Pilosulin 5
DVKGMKKAIKGILDCVIEKGYDKL
2662

(Myr b III)(ants)
AAKLKKVIQQLWE

AP00894
Ref, Ocellatin 4
GLLDFVTGVGKDIFAQLIKQI
2663

(XXA, frog)

AP00895
Ref, OH-CATH
KRFKKFFKKLKNSVKKRAKKFFK
2664

(snake cathelicidin,
KPRVIGVSIPF

reptile cathelicidin,

or elapid

cathelicidins)

AP00896
Ref, BF-CATH
KRFKKFFKKLKKSVKKRAKKFFK
2665

(snake cathelicidin)
KPRVIGVSIPF

AP00897
Ref, NA-CATH
KRFKKFFKKLKNSVKKRAKKFFK
2666

(snake cathelicidin)
KPKVIGVTFPF

AP00898
Ref, Temporin-1Sa
FLSGIVGMLGKLF
2667

(XXA, frog)

AP00899
Ref, Temporin-1Sb
FLPIVTNLLSGLL
2668

(XXA, frog)

AP00900
Ref, Temporin-1Sc
FLSHIAGFLSNLF
2669

(XXA, frog)

AP00913
Ref, Ib-AMP1
EWGRRCCGWGPGRRYCVRWC
2670

(IbAMP1, plant

defensin)

AP00914
Ref, Ib-AMP2
QYGRRCCNWGPGRRYCKRWC
2671

(IBAMP2, plant

defensin)

AP00915
Ref, Ee-CBP
QQCGRQAGNRRCANNLCCSQYGY
2672

(EeCBP, plant
CGRTNEYCCTSQGCQSQCRRCG

defensin, hevein-

type, E. europaeus

chitin-binding

protein)

AP00916
Ref, Pa-AMP1
AGCIKNGGRCNASAGPPYCCSSYC
2673

(PaAMP1, plant
FQIAGQSYGVCKNR

defensin, C6 type)

AP00917
Ref, Pa-AMP2
ACIKNGGRCVASGGPPYCCSNYCL
2674

(PaAMP2, plant
QIAGQSYGVCKKH

defensin, C6 type)

AP00924
Ref, Ornithodoros
GYGCPFNQYQCHSHCRGIRGYKG
2675

defensin B (soft
GYCTGRFKQTCKCY

ticks)

AP00925
Ref, Ornithodoros
GYGCPFNQYQCHSHCSGIRGYKGG
2676

defensin C (soft
YCKGLFKQTCNCY

ticks)

AP00926
Ref, Ornithodoros
GFGCPFNQYECHAHCSGVPGYKG
2677

defensin D (soft
GYCKGLFKQTCNCY

ticks)

AP00927
Ref,
IYFIADKMGIQLAPAWYQDIVNWV
2678

Butyrivibriocin
SAGGTLTTGFAIIVGVTVPAWIAEA

AR10 (XXC, class
AAAFGIASA

IV bacteriocin,

gram-positive

bacteria)

AP00929
Ref, AS-48
ASLQFLPIAHMAKEFGIPAAVAGT
2679

(enterocin 4, XXC,
VINVVEAGGWVTTIVSILTAVGSG

class IV bacteriocin
GLSLLAAAGRESIKAYLKKEIKKK

or class IId
GKRAVIAW

bacteriocin, Gram-

positive bacteria)

AP00930
Ref, Reutericin 6
IYWIADQFGIHLATGTARKLLDAM
2680

(XXC, XXD1,
ASGASLGTAFAAILGVTLPAWALA

class IV
AAGALGATAA

bacteriocin, Gram-

positive bacteria)

AP00931
Ref, Uberolysin
LAGYTGIASGTAKKVVDAIDKGAA
2681

(XXC, class IV
AFVIISIISTVISAGALGAVSASADFI

bacteriocin, Gram-
ILTVKNYISRNLKAQAVIW

positive bacteria)

AP00932
Ref, Acidocin B
IYWIADQFGIHLATGTARKLLDAV
2682

(XXC, class IV
ASGASLGTAFAAILGVTLPAWALA

bacteriocin, Gram-
AAGALGATAA

positive bacteria)

AP00980
Ref, Phormia
ATCDLLSGTGINHSACAAHCLLRG
2683

defensin B (insect
NRGGYCNRKGVCVCRN

defensin B)

AP00990
Ref, Pth-St1 (plant
RNCESLSHRFKGPCTRDSN
2684

defensin)

AP00991
Ref, Snakin-1
GSNFCDSKCKLRCSKAGLADRCLK
2685

(StSN1, plant
YCGICCEECKCVPSGTYGNKHECP

defensin)
CYRDKKNSKGKSKCP

AP00992
Ref, Snakin-2
YSYKKIDCGGACAARCRLSSRPRL
2686

(StSN2, plant
CNRACGTCCARCNCVPPGTSGNTE

defensin)
TCPCYASLTTHGNKRKCP

AP00993
Ref, So-D2 (S. oleracea
GIFSSRKCKTPSKTFKGICTRDSNC
2687

defensin
DTSCRYEGYPAGDCKGIRRRCMCS

D2, plant defensin)
KPC

AP00994
Ref, So-D6 (S. oleracea
GIFSNMYARTPAGYFRGP
2688

defensin

D6, plant defensin)

AP00997
Ref, Nisin Q
ITSISLCTPGCKTGVLMGCNLKTAT
2689

(lantibiotic,
CNCSVHVSK

bacteriocins,

bacteria)

AP01008
Ref, Tachystatin
YSRCQLQGFNCVVRSYGLPTIPCC
2690

A1 (BBS,
RGLTCRSYFPGSTYGRCQRF

horseshoe crabs)

AP01009
Ref, Tachystatin C
DYDWSLRGPPKCATYGQKCRTWS
2691

(BBS, horseshoe
PRNCCWNLRCKAFRCRPR

crabs)

AP01012
Ref, Latarcin 3a
SWKSMAKKLKEYMEKLKQRA
2692

(Ltc3a, XXA,

BBM, spider)

AP01013
Ref, Latarcin 3b
SWASMAKKLKEYMEKLKQRA
2693

(Ltc3b, XXA,

BBM, spider)

AP01014
Ref, Latarcin 4a
GLKDKFKSMGEKLKQYIQTWKAKF
2694

(Ltc4a, XXA,

BBM, spider)

AP01015
Ref, Latarcin 4b
SLKDKVKSMGEKLKQYIQTWKAKF
2695

(Ltc4b, XXA,

BBM, spider)

AP01016
Ref, Latarcin 5
GFFGKMKEYFKKFGASFKRRFANL
2696

(Ltc5, XXA, BBM,
KKRL

spider)

AP01018
Ref, Latarcin 6a
QAFQTFKPDWNKIRYDAMKMQTS
2697

(Ltc6a, BBM,
LGQMKKRFNL

spider)

AP01019
Ref, Latarcin 7
GETFDKLKEKLKTFYQKLVEKAED
2698

(Ltc7, BBM,
LKGDLKAKLS

spider)

AP01049
Ref, Kalata B2
VCGETCFGGTCNTPGCSCTWPICT
2699

(plant cyclotides,
RDGLP

XXC)

AP01141
Ref, Cryptdin-6
LRDLVCYCRARGCKGRERMNGTC
2700

(Crp6, animal
RKGHLLYMLCCR

defensin, alpha,

mouse)

AP01142
Ref, Rabbit kidney
KPYCSCKWRCGIGEEEKGICHKFPI
2701

defensin RK-2
VTYVCCRRP

(animal defensin,

alpha-defensin)

AP01146
Ref, Gallinacin 6
DTLACRQSHGSCSFVACRAPSVDI
2702

(Gal6, Gal-6, avian
GTCRGGKLKCCKWAPSS

beta defensin, bird)

AP01147
Ref, Gallinacin 8
DTVACRIQGNFCRAGACPPTFTISG
2703

(Gal8, Gal-8, avian
QCHGGLLNCCAKIPAQ

beta defensin, bird)

AP01148
Ref, Gallinacin 3
IATQCRIRGGFCRVGSCRFPHIAIGK
2704

(Gal3, Gal-3, avian
CATFISCCGRAY

beta defensin, bird)

AP01152
Ref, Lactococcin Q
SIWGDIGQGVGKAAYWVGKAMG
2705

(class IIb
NMSDVNQASRINRKKKH

bacteriocin,

bacteria, chain a.

For chain b, see

Info)

AP01155
Ref, Enterocin
ESVFSKIGNAVGPAAYWILKGLGN
2706

1071 (Ent1071A,
MSDVNQADRINRKKH

class IIb

bacteriocin,

bacteria; chain B is

Enterocin 1071B or

Ent1071B, see

info)

AP01156
Ref, Plantaricin S
NKLAYNMGHYAGKATIFGLAAW
2707

(chain a, class IIb
ALLA

bacteriocin,

bacteria)

AP01159
Ref, Hinnavin II
KWKIFKKIEHMGQNIRDGLIKAGP
2708

(Hin II, XXA,
AVQVVGQAATIYK

insect)

AP01160
Ref, NK-2
KILRGLCKKIMRSFLRRISWDILTG
2709

(synthetic, XXA)
KK

AP01167
Ref, Plantaricin
LTTKLWSSWGYYLGKKARWNLK
2710

NC8 (PLNC8,
HPYVQF

chain a, class IIb

bacteriocin,

bacteria. For chain

b, see Info)

AP01168
Ref, Carnocyclin A
LVAYGIAQGTAEKVVSLINAGLTV
2711

(a circular
GSIISILGGVTVGLSGVFTAVKAAI

bacteriocin, XXC,
AKQGIKKAIQL

bacteria)

AP01169
Ref, Lactacin F
NRWGDTVLSAASGAGTGIKACKSF
2712

(LafX, class IIb
GPWGMAICGVGGAAIGGYFGYTHN

bacteriocin,

bacteria. For LafA,

see Info)

AP01170
Ref, Brochocin C
YSSKDCLKDIGKGIGAGTVAGAAG
2713

(BrcC, chain BrcA,
GGLAAGLGAIPGAFVGAHFGVIGG

class IIb
SAACIGGLLGN

bacteriocin,

bacteria. For BrcB,

see Info)

AP01171
Ref, Thermophilin
YSGKDCLKDMGGYALAGAGSGAL
2714

13 (chain a ThmA,
WGAPAGGVGALPGAFVGAHVGAI

2-chain class IIb
AGGFACMGGMIGNKFN

bacteriocin,

bacteria. For chain

B ThmB, see Info)

AP01172
Ref, ABP-118
KRGPNCVGNFLGGLFAGAAAGVP
2715

(chain a:
LGPAGIVGGANLGMVGGALTCL

Abp118alpha, class

IIb bacteriocin,

bacteria. For chain

b: Abp118beta, see

Info)

AP01173
Ref, Salivaricin P
KRGPNCVGNFLGGLFAGAAAGVP
2716

(chain a: Sln1;
LGPAGIVGGANLGMVGGALTCL

class IIb

bacteriocin,

bacteria. For chain

b: Sln2, see Info)

AP01174
Ref, Mutacin IV
KVSGGEAVAAIGICATASAAIGGL
2717

(chain a: NlmA,
AGATLVTPYCVGTWGLIRSH

class IIb

bacteriocin,

bacteria. For chain

b: NLmB, see Info)

AP01175
Ref, Lactocin 705
GMSGYIQGIPDFLKGYLHGISAAN
2718

(chain a:
KHKKGRLGY

Lac705alpha; class

IIb bacteriocin,

bacteria. For chain

b: Lac705beta, see

Info)

AP01176
Ref, Cytolysin
TTPACFTIGLGVGALFSAKFC
2719

(CylLS, bacteria;

Chain B: CylLL)

AP01177
Ref, Plantaricin EF
FNRGGYNFGKSVRHVVDAIGSVA
2720

(chain a. PlnE,
GILKSIR

class IIb

bacteriocin,

bacteria. Chain b:

PlnF)

AP01178
Ref, Plantaricin JK
GAWKNFWSSLRKGFYDGEAGRAI
2721

(chain a: PlnJ; class
RR

IIb bacteriocin,

bacteria. Chain b:

PlnK)

AP01179
Ref, Enterocin SE-
NGVYCNKQKCWVDWSRARSEIID
2722

K4 (class IIa
RGVKAYVNGFTKVLGGIGGR

bacteriocin,

bacteria)

AP01180
Ref, Acidocin
NPKVAHCASQIGRSTAWGAVSGA
2723

J1132 (class IIb

bacteriocin,

bacteria)

AP01181
Ref, Curvaticin
AYPGNGVHCGKYSCTVDKQTAIG
2724

L442 (class IIa
NIGNNAA

bacteriocin,

bacteria)

AP01182
Ref, Bacteriocin 32
FTPSVSFSQNGGVVEAAAQRGYIY
2725

(Bac 32, class IIa
KKYPKGAKVPNKVKMLVNIRGKQ

bacteriocin,
TMRTCYLMSWTASSRTAKYYYYI

bacteria)

AP01183
Ref, Bacteriocin 43
ATYYGNGLYCNKEKCWVDWNQA
2726

(Bac 43,
KGEIGKIIVNGWVNHGPWAPRR

bacteriocin,

bacteria)

AP01184
Ref, Bacteriocin T8
ATYYGNGLYCNKEKCWVDWNQA
2727

(Bac T8, class IIa
KGEIGKIIVNGWVNHGPWAPRR

bacteriocin,

bacteria)

AP01185
Ref, Enterocin B
ENDHRMPNNLNRPNNLSKGGAKC
2728

(EntB, bacteriocin,
GAAIAGGLFGIPKGPLAWAAGLAN

bacteria)
VYSKCN

AP01186
Ref, Acidocin A
KTYYGTNGVHCTKKSLWGKVRLK
2729

(bacteriocin,
NVIPGTLCRKQSLPIKQDLKILLGW

bacteria)
ATGAFGKTFH

AP01187
Ref, Enterocin Q
MNFLKNGIAKWMTGAELQAYKK
2730

(EntQ, class IIc
KYGCLPWEKISC

bacteriocin,

leaderless, i.e. no

signal peptide,

bacteria)

AP01188
Ref, Enterocin
MLAKIKAMIKKFPNPYTLAAKLTT
2731

EJ97 (EntEJ97,
YEINWYKQQYGRYPWERPVA

class IIc

bacteriocin,

leaderless, i.e. no

signal peptide,

bacteria)

AP01189
Ref, Enterocin RJ-
APAGLVAKFGRPIVKKYYKQIMQF
2732

11 (EntRJ-11, class
IGEGSAINKIIPWIARMWRT

IIc bacteriocin,

leaderless, i.e. no

signal sequence,

bacteria)

AP01190
Ref, Enterocin L50
MGAIAKLVAKFGWPIVKKYYKQI
2733

(old name:
MQFIGEGWAINKIIEWIKKHI

pediocin L50,

EntL50A, a two-

chain class IIc

bacteriocin,

leaderless, i.e. no

signal peptide,

bacteria. The

sequence of

EntL50B is

provided in Info)

AP01191
Ref, MR10
MGAIAKLVAKFGWPIVKKYYKQI
2734

(MR10A, class IIc
MQFIGEGWAINKIIDWIKKHI

bacteriocin,

leaderless, i.e. no

signal peptide,

bacteria. For the

sequence of chain

b, see Info)

AP01192
Ref, Halocin S8
SDCNINSNTAADVILCFNQVGSCA
2735

(HalS8,
LCSPTLVGGPVP

microhalocin,

archaeocins,

archeae)

AP01193
Ref, Halocin C8
DIDITGCSACKYAAGQVCTIGCSA
2736

(HalC8,
AGGFICGLLGITIPVAGLSCLGFVEI

microhalocins,
VCTVADEYSGCGDAVAKEACNRA

archaeocins,
GLC

archaea)

AP01194
Ref, Lacticin 3147
CSTNTFSLSDYWGNNGAWCTLTH
2737

(chain A1, a two-
ECMAWCK

chain lantibiotic,

bacteriocin,

bacteria. The

sequence of chain

A2 is given in Info;

XXD3)

AP01195
Ref, Salivaricin A
KRGSGWIATITDDCPNSVFVCC
2738

(SalA, lantibiotic,

bacteriocin,

bacteria)

AP01196
Ref, Microcin E492
ATYYGNGLYCNKEKCWVDWNQA
2739

(MccE492, class
KGEIGKIIVNGWVNHGPWAPRR

IIb microcins,

bacteriocin,

bacteria; BBM; u-

MccE492,

siderophore

peptide, BBI, XXG)

AP01197
Ref, Hiracin JM79
ATYYGNGLYCNKEKCWVDWNQA
2740

(HirJM79, a Sec-
KGEIGKIIVNGWVNHGPWAPRR

dependent class II

bacteriocin,

bacteria)

AP01198
Ref, Thermophilin
LSCDEGMLAVGGLGAVGGPWGA
2741

9 (BlpDst, class IIb
AVGVLVGAALYCF

bacteriocin,

bacteria. beta-

chains: BlpUst,

BlpEst, BapFst)

AP01199
Ref, Penocin A
KYYGNGVHCGKKTCYVDWGQAT
2742

(PenA, class IIa
ASIGKIIVNGWTQHGPWAHR

bacteriocin,

bacteria)

AP01200
Ref, Salivaricin B
GGGVIQTISHECRMNSWQFLFTCCS
2743

(SalB, lantibotic,

bacteriocin,

bacteria)

AP01201
Ref, Lacticin 481
KGGSGVIHTISHECNMNSWQFVFT
2744

(lantibiotic, class I
CCS

bacteriocin,

bacteria)

AP01202
Ref, Bacteriocin
KGGSGVIHTISHEVIYNSWNFVFTC
2745

J46 (BacJ46,
CS

bacteriocin,

bacteria)

AP01203
Ref, Nukacin A
KKKSGVIPTVSHDCHMNSFQFVFT
2746

(NucA, Nukacin
CCS

ISK-1, NukISK-1,

bacteriocin,

bacteria)

AP01204
Ref, Streptococcin
GKNGVFKTISHECHLNTWAFLATC
2747

A-FF22
CS

(LANTIBIOTIC,

class I bacteriocin,

bacteria)

AP01210
Ref, Jelleine-I
PFKLSLHL
2748

(honeybees, insect,

XXA)

AP01211
Ref, Jelleine-II
TPFKLSLHL
2749

(honeybees, insect,

XXA)

AP01212
Ref, Jelleine-III
EPFKLSLHL
2750

(honeybees, insect,

XXA)

AP01213
Ref,
EFRGSIVIQGTKEGKSRPSLDIDYK
2751

Hymenoptaecin
QRVYDKNGMTGDAYGGLNIRPGQ

(honeybees, insect
PSRQHAGFEFGKEYKNGFIKGQSE

defensin, XXcooh)
VQRGPGGRLSPYFGINGGFRF

AP01216
Ref, Ascaphin-1
GFRDVLKGAAKAFVKTVAGHIAN
2752

(frog, XXA)

AP01218
Ref, Ascaphin-3
GFRDVLKGAAKAFVKTVAGHIANI
2753

(frog)

AP01220
Ref, Ascaphin-5
GIKDWIKGAAKKLIKTVASNIANQ
2754

(frog)

AP01222
Ref, Ascaphin-7
GFKDWIKGAAKKLIKTVASSIANQ
2755

(frog)

AP01223
Ref, Ascaphin-8
GFKDLLKGAAKALVKTVLF
2756

(frog, XXA)

AP01226
Ref, Microcin C7
MRTGNAD
2757

(MccC7, microcin

C51, MccC51,

class I microcins,

bacteriocins,

bacteria. Others:

MccA; XXamp;

BBPe)

AP01227
Ref, Microcin B17
VGIGGGGGGGGGGSCGGQGGGCG
2758

(MccB17, class I
GCSNGCSGGNGGSGGSGSHI

microcins,

bacteriocins, Gram-

negative bacteria;

BBPe)

AP01228
Ref, Microcin V
ASGRDIAMAIGTLSGQFVAGGIGA
2759

(MccV, (old name)
AAGGVAGGAIYDYASTHKPNPAM

Colicin V, ColV;
SPSGLGGTIKQKPEGIPSEAWNYAA

class II microcins,
GRLCNWSPNNLSDVCL

bacteriocins, Gram-

negative bacteria)

AP01229
Ref, Microcin L
GDVNWVDVGKTVATNGAGVIGG
2760

(MccL, class IIa
AFGAGLCGPVCAGAFAVGSSAAV

microcins,
AALYDAAGNSNSAKQKPEGLPPEA

bacteriocins, Gram-
WNYAEGRMCNWSPNNLSDVCL

negative bacteria)

AP01230
Ref, Microcin M
DGNDGQAELIAIGSLAGTFISPGFG
2761

(MccM, class IIb
SIAGAYIGDKVHSWATTATVSPSM

microcins,
SPSGIGLSSQFGSGRGTSSASSSAGS

bacteriocins, Gram-
GS

negative bacteria)

AP01231
Ref, Microcin H47
GGAPATSANAAGAAAIVGALAGIP
2762

(MccH47, class IIb
GGPLGVVVGAVSAGLTTGIGSTVG

microcins,
SGSASSSAGGGS

bacteriocins, Gram-

negative bacteria)

AP01232
Ref, Microcin I47
MNLNGLPASTNVIDLRGKDMGTYI
2763

(MccI47, class IIb
DANGACWAPDTPSIIMYPGGSGPS

microcins,
YSMSSSTSSANSGS

bacteriocins, Gram-

negative bacteria)

Aibellin
*Ac U A U A U A Q U F U G U U P V U U E E
2764

[NHC(CH2Ph)HCH2NHCH2CH2]OH

Alamethicin_F-30
* Ac U P U A U A Q U V U G L U P V U U E Q F
2765

OH

Alamethicin_F-50
* Ac U P U A U A Q U V U G L U P V U U Q Q F
2766

OH

Alamethicin_II
* Ac U P U A U U Q U V U G L U P V U U E Q F
2767

OH

Ampullosporin
* Ac W A U U L U Q U U U Q L U Q L OH
2768

Ampullosporin_B
* Ac W A U U L U Q A U U Q L U Q L OH
2769

Ampullosporin_C
* Ac W A U U L U Q U A U Q L U Q L OH
2770

Ampullosporin_D
* Ac W A U U L U Q U U A Q L U Q L OH
2771

Ampullosporin_E1
* Ac W A U U L U Q A U U Q L A Q L OH
2772

Ampullosporin_E2
* Ac W A U U L U Q U A A Q L U Q L OH
2773

Ampullosporin_E3
* Ac W A U U L U Q U U A Q L A Q L OH
2774

Ampullosporin_E4
* Ac W A U U L U Q A A U Q L U Q L OH
2775

Antiamoebin_I
* Ac F U U U J G L U U O Q J O U P F OH
2776

Antiamoebin_II
* Ac F U U U J G L U U O Q J P U P F OH
2777

Antiamoebin_III
* Ac F U U U U G L U U O Q J O U P F OH
2778

Antiamoebin_IV
* Ac F U U U J G L U U O Q J O U P F OH
2779

Antiamoebin_V
* Ac F U U U J A L U U O Q J O U P F OH
2780

Antiamoebin_VI
* Ac F U U U U G L U U O Q U O U P F OH
2781

Antiamoebin_VII
* Ac F A U J U G L U U O Q J O U P F OH
2782

Antiamoebin_VIII
* Ac F U U U J G L U U O Q U O U P F OH
2783

Antiamoebin_IX
* Ac F U A U J G L U U O Q J O U P F OH
2784

Antiamoebin_X
* Ac F U U U J G L J U O Q U O U P F OH
2785

Antiamoebin_XI
* Ac F U U U U A L U U O Q J O U P F OH
2786

Antiamoebin_XII
* Ac F U U U U G L A U O Q J O U P F OH
2787

Antiamoebin_XIII
* Ac V U U U U G L U U O Q J O U P F OH
2788

Antiamoebin_XIV
* Ac V U U U V G L U U O Q J O U P F OH
2789

Antiamoebin_XV
* Ac L U U U U G L U U O Q J O U P F OH
2790

Antiamoebin_XVI
* Ac L U U U J G L U U O Q J O U P F OH
2791

Atroviridin_A
* Ac U P U A U A Q U V U G L U P V U U Q Q F
2792

OH

Atroviridin_B
* Ac U P U A U A Q U V U G L U P V U J Q Q F
2793

OH

Atroviridin_C
* Ac U P U A U U Q U V U G L U P V U J Q Q F
2794

OH

Bergofungin_A
* Ac V U U U V G L U U O Q J O U F OH
2795

Bergofungin_B
* Ac V U U U V G L V U O Q U O U F OH
2796

Bergofungin_C
* Ac V U U U V G L U U O Q U O U F OH
2797

Bergofungin_D
* Ac V U U V G L U U O Q U O U F OH
2798

Boletusin
* Ac F U A U J L Q G U U A A U P U U U Q W
2799

OH

Cephaibol_A
* Ac F U U U U G L J U O Q J O U P F OH
2800

Cephaibol_A2
* Ac F U U U U A L J U O Q J O U P F OH
2801

Cephaibol_B
* Ac F U U U J G L J U O Q J O U P F OH
2802

Cephaibol_C
* Ac F U U U U G L J U O Q U O U P F OH
2803

Cephaibol_D
* Ac F U U U U G L U U O Q U O U P F OH
2804

Cephaibol_E
* Ac F U U U U G L U U O Q J O U P F OH
2805

Cephaibol_P
* Ac F J Q U I T U L U O Q U O U P F S OH
2806

Cephaibol_Q
* Ac F J Q U I T U L U P Q U O U P F S OH
2807

Cervinin_1
* Ac L U P U L U P A U P V L OH
2808

Cervinin_2
* Ac L U P U L U P A U P V L OCOCH3
2809

Chrysospermin_A
* Ac F U S U U L Q G U U A A U P U U U Q W
2810

OH

Chrysospermin_B
* Ac F U S U U L Q G U U A A U P J U U Q W
2811

OH

Chrysospermin_C
* Ac F U S U J L Q G U U A A U P U U U Q W
2812

OH

Chrysospermin_D
* Ac F U S U J L Q G U U A A U P J U U Q W
2813

OH

Clonostachin
* Ac U O L J O L J O U J U O J I
2814

O[CH(CH(OH)CH2OH)CH(OH)CH(OH)CH2]OH

Emerimicin_II_A
* Ac W I Q U I T U L U O Q U O U P F OH
2815

Emerimicin_II_B
* Ac W I Q J I T U L U O Q U O U P F OH
2816

Emerimicin_III
* Ac F U U U V G L U U O Q J O U F OH
2817

Emerimicin_IV
* Ac F U U U V G L U U O Q J O A F OH
2818

Harzianin_HB_I
* Ac U N L I U P J L U P L OH
2819

Harzianin_HC_I
* Ac U N L U P S V U P U L U P L OH
2820

Harzianin_HC_III
* Ac U N L U P S V U P J L U P L OH
2821

Harzianin_HC_IX
* Ac U N L U P A I U P J L U P L OH
2822

Harzianin_HC_VI
* Ac U N L U P A V U P U L U P L OH
2823

Harzianin_HC_VIII
* Ac U N L U P A V U P J L U P L OH
2824

Harzianin_HC_VIII
* Ac U N L U P A V U P J L U P L OH
2825

Harzianin_HC_X
* Ac U Q L U P A V U P J L U P L OH
2826

Harzianin_HC_XI
* Ac U N L U P S I U P U L U P L OH
2827

Harzianin_HC_XII
* Ac U N L U P S I U P J L U P L OH
2828

Harzianin_HC_XIII
* Ac U Q L U P S I U P J L U P L OH
2829

Harzianin_HC_XIV
* Ac U N L U P A I U P U L U P L OH
2830

Harzianin_HC_XV
* Ac U Q L U P A I U P J L U P L OH
2831

Harzianin_HK_VI
* Ac U N I I U P L L U P L OH
2832

Harzianin_PCU4
* Ac U N L U P S I U P U L U P V OH
2833

Helioferin_A
* Fa P ZZ A U I I U U AAE
2834

Helioferin_B
* Fa P ZZ A U I I U U AMAE
2835

Heptaibin
* Ac F U U U V G L U U O Q U O U F OH
2836

Hypelcin_A
* Ac U P U A U U Q L U G U U U P V U U Q Q L
2837

OH

Hypelcin_A_I
* Ac U P U A U U Q U L U G U U P V U U Q Q L
2838

OH

Hypelcin_A_II
* Ac U P U A U A Q U L U G U U P V U U Q Q L
2839

OH

Hypelcin_A_III
* Ac U P U A U U Q U L U G U U P V U U Q Q
2840

[C7H16NO]

Hypelcin_A_IV
* Ac U P U A U U Q U I U G U U P V U U Q Q L
2841

OH

Hypelcin_A-III
* Ac U P U A U U Q U L U G U U P V U J Q Q L
2842

OH

Hypelcin_A-IX
* Ac U P U A U U Q U I U G U U P V U J Q Q L
2843

OH

Hypelcin_A-V
* Ac U P U A U U Q U L U G U U P V U U Q Q I
2844

OH

Hypelcin_A-VI
* Ac U P U A U A Q U L U G U U P V U U Q Q I
2845

OH

Hypelcin_A-VII
* Ac U P U A U A Q U L U G U U P V U J Q Q L
2846

OH

Hypelcin_A-VIII
* Ac U P U A U A Q U I U G U U P V U U Q Q L
2847

OH

Hypelcin_B_I
* Ac U P U A U U Q U L U G U U P V U U E Q L
2848

OH

Hypelcin_B_II
* Ac U P U A U A Q U L U G U U P V U U E Q L
2849

OH

Hypelcin_B_III
* Ac U P U A U U Q U L U G U U P V U J E Q L
2850

OH

Hypelcin_B_IV
* Ac U P U A U U Q U I U G U U P V U U E Q L
2851

OH

Hypelcin_B_V
* Ac U P U A U U Q U L U G U U P V U U E Q I
2852

OH

Hypomurocin_A_I
* Ac U Q V V U P L L U P L OH
2853

Hypomurocin_A_II
* Ac J Q V V U P L L U P L OH
2854

Hypomurocin_A_III
* Ac U Q V L U P L I U P L OH
2855

Hypomurocin_A_IV
* Ac U Q I V U P L L U P L OH
2856

Hypomurocin_A_V
* Ac U Q I I U P L L U P L OH
2857

Hypomurocin_A_Va
* Ac U Q I L U P L I U P L OH
2858

Hypomurocin_B_I
* Ac U S A L U Q U V U G U U P L U U Q V OH
2859

Hypomurocin_B_II
* Ac U S A L U Q U V U G U U P L U U Q L OH
2860

Hypomurocin_B_IIIa
* Ac U A A L U Q U V U G U U P L U U Q V OH
2861

Hypomurocin_B_IIIb
* Ac U S A L U Q J V U G U U P L U U Q V OH
2862

Hypomurocin_B_IV
* Ac U S A L U Q U V U G J U P L U U Q V OH
2863

Hypomurocin_B_V
* Ac U S A L U Q U V U G J U P L U U Q L OH
2864

Leul_Zervamicin
* Ac L I Q J I T U L U O Q U O U P F OH
2865

Longibrachin_A_I
* Ac U A U A U A Q U V U G L U P V U U Q Q F
2866

OH

Longibrachin_A_II
* Ac U A U A U A Q U V U G L U P V U J Q Q F
2867

OH

Longibrachin_A_III
* Ac U A U A U U Q U V U G L U P V U U Q Q F
2868

OH

Longibrachin_A_IV
* Ac U A U A U U Q U V U G L U P V U J Q Q F
2869

OH

Longibrachin_B_II
* Ac U A U A U A Q U V U G L U P V U U E Q F
2870

OH

Longibrachin_B_III
* Ac U A U A U A Q U V U G L U P V U J E Q F
2871

OH

LP237_F5
* Oc U P Y U Q Q U Zor Q A L OH
2872

LP237_F7
* Ac U P F U Q Q U U Q A L OH
2873

LP237_F8
* Oc U P F U Q Q U Zor Q A L OH
2874

NA_VII
* Ac U A A U J Q U U U S L U OCH3
2875

Paracelsin_A
* Ac U A U A U A Q U V U G U U P V U U Q Q
2876

F OH

Paracelsin_B
* Ac U A U A U A Q U L U G U U P V U U Q Q F
2877

OH

Paracelsin_C
* Ac U A U A U U Q U V U G U U P V U U Q Q
2878

F OH

Paracelsin_D
* Ac U A U A U U Q U L U G U U P V U U Q Q F
2879

OH

Paracelsin_E
* Ac U A U A U A Q U L U G U A P V U U Q Q F
2880

OH

Peptaibolin
* Ac L U L U F OH
2881

Peptaivirin_A
* Ac F U A U J L Q G U U A A U P J U U Q W
2882

OH

Peptaivirin_B
* Ac F U S U J L Q G U U A A U P J U U Q F OH
2883

Polysporin_A
* Ac U P U A U U Q U V U G V U P V U U Q Q F
2884

OH

Polysporin_B
* Ac U P U A U U Q U V U G L U P V U U Q Q F
2885

OH

Polysporin_C
* Ac U P U A U U Q U I U G L U P V U U Q Q F
2886

OH

Polysporin_D
* Ac U P U A U U Q U I U G L U P V U V Q Q F
2887

OH

Pseudokinin_KLIII
* Ac U N I I U P L L U P NH2
2888

Pseudokinin_KLVI
* Ac U N I I U P L V hydroxyketopiperazine
2889

Samarosporin_I
* Ac F U U U V G L U U O Q J O A F OH
2890

Samarosporin_II
* Ac F U U U V G L U U O Q J O U F OH
2891

Saturnisporin_SA_I
* Ac U A U A U A Q U L U G U U P V U U Q Q F
2892

OH

Saturnisporin_SA_II
* Ac U A U A U A Q U L U G U U P V U J Q Q F
2893

OH

Saturnisporin_SA_III
* Ac U A U A U U Q U L U G U U P V U U Q Q F
2894

OH

Saturnisporin_SA_IV
* Ac U A U A U U Q U L U G U U P V U J Q Q F
2895

OH

Stilbellin_I
* Ac F U U U V G L U U O Q J O A F OH
2896

Stilbellin_II
* Ac F U U U V G L U U O Q J O U F OH
2897

Stilboflavin_A_1
* Ac U P U A U A Q U V U G U U P V U U E Q V
2898

OH

Stilboflavin_A_2
* Ac U P U A U A Q U L U G U U P V U U E Q V
2899

OH

Stilboflavin_A_3
* Ac U P U A U U Q U V U G U A P V U U E Q L
2900

OH

Stilboflavin_A_4
* Ac U P U A U A Q U L U G U U P V U U E Q L
2901

OH

Stilboflavin_A_5
* Ac U P U A U U Q U L U G U U P V U U E Q V
2902

OH

Stilboflavin_A_6
* Ac U P U A U A Q U L U G U U P V U U E Q J
2903

OH

Stilboflavin_A_7
* Ac U P U A U U Q U L U G U U P V U U E Q I
2904

OH

Stilboflavin_B_1
* Ac U P U A U A Q U V U G U U P V U U Q Q
2905

V OH

Stilboflavin_B_2
* Ac U P U A U A Q U L U G U U P V U U Q Q V
2906

OH

Stilboflavin_B_3
* Ac U P U A U A Q U V U G U U P V U U Q Q L
2907

OH

Stilboflavin_B_4
* Ac U P U A U A Q U L U G U U P V U U Q Q L
2908

OH

Stilboflavin_B_5
* Ac U P U A U U Q U L U G U U P V U U Q Q V
2909

OH

Stilboflavin_B_6
* Ac U P U A U U Q U V U G U U P V U U Q Q
2910

V OH

Stilboflavin_B_7
* Ac U P U A U U Q U L U G U U P V U U Q Q L
2911

OH

Stilboflavin_B_8
* Ac U P U A U U Q U V U G U U P V U U Q Q L
2912

OH

Stilboflavin_B_9
* Ac U P U A U U Q U L U G U U P V U U Q Q I
2913

OH

Stilboflavin_B_10
* Ac U P U A U U Q U V U G U U P V U U Q Q I
2914

OH

Suzukacillin
* Ac U A U A U A Q U U U G L U P V U U Q Q F
2915

OH

Trichobrachin_A-I
* Ac U N L L U P L U U P L OH
2916

Trichobrachin_A-II
* Ac U N L L U P V L U P V OH
2917

Trichobrachin_A-III
* Ac U N V L U P L L U P V OH
2918

Trichobrachin_A-IV
* Ac U N L V U P L L U P V OH
2919

Trichobrachin_B-I
* Ac U N L L U P V U V P L OH
2920

Trichobrachin_B-II
* Ac U N V L U P L U V P L OH
2921

Trichobrachin_B-III
* Ac U N L V U P L U V P L OH
2922

Trichobrachin_B-IV
* Ac U N L L U P L U V P V OH
2923

Trichocellin_TC-A-I
* Ac U A U A U A Q U L U G U U P V U U Q Q F
2924

OH

Trichocellin_TC-A-II
* Ac U A U A U A Q U L U G U U P V U J Q Q F
2925

OH

Trichocellin_TC-A-III
* Ac U A U A U A Q U I U G U U P V U U Q Q F
2926

OH

Trichocellin_TC-A-IV
* Ac U A U A U A Q U I U G U U P V U J Q Q F
2927

OH

Trichocellin_TC-A-V
* Ac U A U A U A Q U L U G L U P V U U Q Q F
2928

OH

Trichocellin_TC-A-VI
* Ac U A U A U A Q U L U G L U P V U J Q Q F
2929

OH

Trichocellin_TC-A-
* Ac U A U A U A Q U I U G L U P V U U Q Q F
2930

VII
OH

Trichocellin_TC-A-
* Ac U A U A U A Q U I U G L U P V U J Q Q F
2931

VIII
OH

Trichocellin_TC-B-I
* Ac U A U A U A Q U L U G U U P V U U E Q F
2932

OH

Trichocellin_TC-B-II
* Ac U A U A U A Q U L U G U U P V U J E Q F
2933

OH

Trichodecenin_TD_I
* (Z)-4-decenoyl G G L U G I L OH
2934

Trichodecenin_TD_II
* (Z)-4-decenoyl G G L U G L L OH
2935

Trichogin_A_IV
* Oc U G L U G G L U G I L OH
2936

Trichokindin_Ia
* Ac U S A U U Q J L U A U U P L U U Q I OH
2937

Trichokindin_Ib
* Ac U S A U J Q U L U A U U P L U U Q I OH
2938

Trichokindin_IIa
* Ac U S A U U Q U L U A J U P L U U Q I OH
2939

Trichokindin_IIb
* Ac U S A U J Q J L U A U U P L U U Q L OH
2940

Trichokindin_IIIa
* Ac U S A U U Q J L U A J U P L U U Q L OH
2941

Trichokindin_IIIb
* Ac U S A U J Q U L U A J U P L U U Q L OH
2942

Trichokindin_IV
* Ac U S A U J Q J L U A U U P L U U Q I OH
2943

Trichokindin_Va
* Ac U S A U U Q J L U A J U P L U U Q I OH
2944

Trichokindin_Vb
* Ac U S A U J Q U L U A J U P L U U Q I OH
2945

Trichokindin_VI
* Ac U S A U J Q J L U A J U P L U U Q L OH
2946

Trichokindin_VII
* Ac U S A U J Q J L U A J U P L U U Q I OH
2947

Trichokonin_Ia
* Ac U A U A U A Q U V U G L A P V U U Q Q F
2948

OH

Trichokonin_Ib
* Ac U G U A U A Q U V U G L U P V U U Q Q F
2949

OH

Trichokonin_IIa
* Ac U A U A U A Q U V U G L U P A U U Q Q F
2950

OH

Trichokonin_IIb
* Ac A A U A U A Q U V U G L U P V U U Q Q F
2951

OH

Trichokonin_IIc
* Ac U A A A U A Q U V U G L U P V U U Q Q F
2952

OH

Trichokonin_V
* Ac U A U A U Q U V U G L U P V U U Q Q F
2953

OH

Trichokonin_VII
* Ac U A U A U A Q U V U G L U P V U J Q Q F
2954

OH

Trichokonin_VIII
* Ac U A U A U U Q U V U G L U P V U U Q Q F
2955

OH

Trichokonin_IX
* Ac U A U A U A Q U V U G L U P V U J Q Q F
2956

OH

Tricholongin_BI
* Ac U G F U U Q U U U S L U P V U U Q Q L
2957

OH

Tricholongin_BII
* Ac U G F U U Q U U U S L U P V U J Q Q L
2958

OH

Trichopolyn_I
* Fa P ZZ A U U I A U U AMAE
2959

Trichopolyn_II
* Fa P ZZ A U U V A U U AMAE
2960

Trichopolyn_III
* Fa P ZZ A U U I A U A AMAE
2961

Trichopolyn_IV
* Fa P ZZ A U U V A U A AMAE
2962

Trichopolyn_V
* Fa′ P ZZ A U U I A U U AMAE
2963

Trichorovin_TV_Ia
* Ac U N V Lx U P Lx Lx U P V OH
2964

Trichorovin_TV_Ib
* Ac U N V V U P Lx Lx U P Lx OH
2965

Trichorovin_TV_IIa
* Ac U N V V U P Lx Lx U P Lx OH
2966

Trichorovin_TV_IIb
* Ac U N Lx V U P Lx Lx U P V OH
2967

Trichorovin_TV_IIIa
* Ac U Q V V U P Lx Lx U P Lx OH
2968

Trichorovin_TV_IIIb
* Ac U Q V Lx U P Lx Lx U P V OH
2969

Trichorovin_TV_IVa
* Ac U Q V V U P Lx Lx U P Lx OH
2970

Trichorovin_TV_IVb
* Ac U Q Lx V U P Lx Lx U P V OH
2971

Trichorovin_TV_IVc
* Ac U N V Lx U P Lx Lx U P Lx OH
2972

Trichorovin_TV_IXa
* Ac U Q V Lx U P Lx Lx U P Lx OH
2973

Trichorovin_TV_IXb
* Ac U Q Lx Lx U P Lx Lx U P V OH
2974

Trichorovin_TV_Va
* Ac U N V Lx U P Lx Lx U P Lx OH
2975

Trichorovin_TV_Vb
* Ac U N Lx Lx U P Lx Lx U P V OH
2976

Trichorovin_TV_VIa
* Ac U N V Lx U P Lx Lx U P Lx OH
2977

Trichorovin_TV_VIb
* Ac U N Lx Lx U P Lx Lx U P V OH
2978

Trichorovin_TV_VIIa
* Ac U N Lx V U P Lx Lx U P Lx OH
2979

Trichorovin_TV_VIIb
* Ac U Q V Lx U P Lx Lx U P V OH
2980

Trichorovin_TV_VIII
* Ac U Q V Lx U P Lx Lx U P Lx OH
2981

Trichorovin_TV_Xa
* Ac U Q Lx V U P Lx Lx U P Lx OH
2982

Trichorovin_TV_Xb
* Ac U N Lx Lx U P Lx Lx U P Lx OH
2983

Trichorovin_TV_XIIa
* Ac U N I I U P L L U P I OH
2984

Trichorovin_TV_XIIb
* Ac U N Lx Lx U P Lx Lx U P L OH
2985

Trichorovin_TV_XIII
* Ac U Q Lx Lx U P Lx Lx U P Lx OH
2986

Trichorovin_TV_XIV
* Ac U Q Lx Lx U P Lx Lx U P Lx OH
2987

Trichorozin_I
* Ac U N I L U P I L U P V OH
2988

Trichorozin_II
* Ac U Q I L U P I L U P V OH
2989

Trichorozin_III
* Ac U N I L U P I L U P L OH
2990

Trichorozin_IV
* Ac U Q I L U P I L U P L OH
2991

Trichorzianine_TA_IIIc
* Ac U A A U U Q U U U S L U P V U I Q Q W
2992

OH

Trichorzianine_TB_IIa
* Ac U A A U U Q U U U S L U P L U I Q E W
2993

OH

Trichorzianine_TB_IIIc
* Ac U A A U U Q U U U S L U P V U I Q E W
2994

OH

Trichorzianine_TB_IVb
* Ac U A A U J Q U U U S L U P V U I Q E W
2995

OH

Trichorzianine_TB_Vb
* Ac U A A U U Q U U U S L U P L U I Q E F OH
2996

Trichorzianine_TB_VIa
* Ac U A A U J Q U U U S L U P L U I Q E F OH
2997

Trichorzianine_TB_VIb
* Ac U A A U U Q U U U S L U P V U I Q E F
2998

OH

Trichorzianine_TB_VII
* Ac U A A U J Q U U U S L U P V U I Q E F OH
2999

Trichorzin_HA_I
* Ac U G A U U Q U V U G L U P L U U Q L OH
3000

Trichorzin_HA_II
* Ac U G A U U Q U V U G L U P L U J Q L OH
3001

Trichorzin_HA_III
* Ac U G A U J Q U V U G L U P L U U Q L OH
3002

Trichorzin_HA_V
* Ac U G A U J Q U V U G L U P L U J Q L OH
3003

Trichorzin_HA_VI
* Ac U G A U J Q J V U G L U P L U J Q L OH
3004

Trichorzin_HA_VII
* Ac U G A U J Q V V U G L U P L U J Q L OH
3005

Trichorzin_MA_I
* Ac U S A U U Q U L U G L U P L U U Q V OH
3006

Trichorzin_MA_II
* Ac U S A U J Q U L U G L U P L U U Q V OH
3007

Trichorzin_MA_III
* Ac U S A U J Q J L U G L U P L U U Q V OH
3008

Trichorzin_PA_II
* Ac U S A U J Q U V U G L U P L U U Q W OH
3009

Trichorzin_PA_IV
* Ac U S A U J Q J V U G L U P L U U Q W OH
3010

Trichorzin_PA_V
* Ac U S A J J Q U V U G L U P L U U Q W OH
3011

Trichorzin_PA_VI
* Ac U S A U J Q U V U G L U P L U U Q F OH
3012

Trichorzin_PA_VII
* Ac U S A J J Q U V U G L U P L U U Q W OH
3013

Trichorzin_PA_VIII
* Ac U S A U J Q J V U G L U P L U U Q F OH
3014

Trichorzin_PA_IX
* Ac U S A J J Q U V U G L U P L U U Q F OH
3015

Trichorzin_PAU4
* Ac U S A U U Q U V U G L U P L U U Q W OH
3016

Trichosporin_TS-B-
* Ac U A G U A U Q U Lx A A Vx A P V U Vx Q
3017

1a-1
Q F OH

Trichosporin_TS-B-
* Ac U A G A U U Q U Lx A A Vx A P V U Vx Q
3018

1a-2
Q F OH

Trichosporin_TS-B-
* Ac U A G A U U Q U Lx U G Lx A P V U A Q
3019

1b
Q F OH

Trichosporin_TS-B-
* Ac U A S A U U Q U Lx U G Lx A P V U U Q Q
3020

1d
F OH

Trichosporin_TS-B-
* Ac U A G A U U Q U Lx U G Lx U P V U U Q
3021

1e
Q F OH

Trichosporin_TS-B-1f
* Ac U A S A U U Q U Lx U G Lx U P V U U Q Q
3022

F OH

Trichosporin_TS-B-
* Ac U A G A U U Q U Lx U G Lx A P V U U Q
3023

1g
Q F OH

Trichosporin_TS-B-
* Ac U A G A U U Q U Lx U G Lx U P V U Vx Q
3024

1h
Q F OH

Trichosporin_TS-B-Ia
* Ac U A S A U U Q U L U G L U P V U U Q Q F
3025

OH

Trichosporin_TS-B-
* Ac U A A A U U Q U L U G L U P V U U Q Q F
3026

IIIa
OH

Trichosporin_TS-B-
* Ac U A A A U U Q U I U G L U P V U A Q Q F
3027

IIIb
OH

Trichosporin_TS-B-
* Ac U A A A A U Q U I U G L U P V U U Q Q F
3028

IIIc
OH

Trichosporin_TS-B-
* Ac U A A A U U Q U V U G L U P V U U Q Q F
3029

IIId
OH

Trichosporin_TS-B-
* Ac U A A A U U Q U L U G L U P V U J Q Q F
3030

IVb
OH

Trichosporin_TS-B-
* Ac U A U A U U Q U V U G L U P V U U Q Q F
3031

IVc
OH

Trichosporin_TS-B-
* Ac U A A A U U Q U V U G L U P V U J Q Q F
3032

IVd
OH

Trichosporin_TS-B-V
* Ac U A A A U U Q U I U G L U P V U U Q Q F
3033

OH

Trichosporin_TS-B-
* Ac U A U A U U Q U I U G L U P V U U Q Q F
3034

VIa
OH

Trichosporin_TS-B-
* Ac U A A A U U Q U I U G L U P V U J Q Q F
3035

VIb
OH

Trichotoxin_A-40
* Ac U G U L U E U U U A U U P L U J Q V OH
3036

Trichotoxin_A-40_I
* Ac U G U L U Q U U A A U U P L U U E V OH
3037

Trichotoxin_A-40_II
* Ac U G U L U Q U U U A A U P L U U E V OH
3038

Trichotoxin_A-40_III
* Ac U G U L U Q U U A A U U P L U J E V OH
3039

Trichotoxin_A-40_IV
* Ac U G U L U Q U U U A U U P L U U E V OH
3040

Trichotoxin_A-40_V
* Ac U G U L U Q U U U A U U P L U J E V OH
3041

Trichotoxin_A-40_Va
* Ac U A U L U Q U U U A U U P L U U E V OH
3042

Trichotoxin_A-50_E
* Ac U G U L U Q U U U A A U P L U U Q V OH
3043

Trichotoxin_A-50_F
* Ac U G U L U Q U U A A A U P L U J Q V OH
3044

Trichotoxin_A-50_G
* Ac U G U L U Q U U U A A U P L U J Q V OH
3045

Trichotoxin_A-50_H
* Ac U A U L U Q U U U A A U P L U J Q V OH
3046

Trichotoxin_A-50_I
* Ac U G U L U Q U U U A U U P L U J Q V OH
3047

Trichotoxin_A-50_J
* Ac U A U L U Q U U U A U U P L U J Q V OH
3048

Trichovirin-Ia
* Ac U G A L A Q Vx V U G U U P L U U Q L
3049

OH

Trichovirin-Ib
* Ac U G A L U Q A V U G J U P L U U Q L OH
3050

Trichovirin-IIa
* Ac U G A L A Q U V U G J U P L U U Q L OH
3051

Trichovirin-IIb
* Ac U G A L U Q U V U G U U P L U U Q L OH
3052

Trichovirin-IIc
* Ac U G A L U Q Vx V U G U U P L U U Q L
3053

OH

Trichovirin-IIIa
* Ac U G A L U Q J V U G U U P L U U Q L OH
3054

Trichovirin-IIIb
* Ac U G A L J Q J U U G U U P L U U Q L OH
3055

Trichovirin-IVa
* Ac U G A L J Q J V U G U U P L U U Q L OH
3056

Trichovirin-IVb
* Ac U G A L U Q U V U G J U P L U U Q L OH
3057

Trichovirin-V
* Ac U G A L U Q J V U G J U P L U U Q L OH
3058

Trichovirin-VIa
* Ac U G A L U Q J L U G J U P L U U Q L OH
3059

Trichovirin-VIb
* Ac U G A L J Q J V U G J U P L U U Q L OH
3060

Trikoningin_KA_V
* Ac U G A U I Q U U U S L U P V U I Q Q L OH
3061

Trikoningin_KB_I
* Oc U G V U G G V U G I L OH
3062

Trikoningin_KB_II
* Oc J G V U G G V U G I L OH
3063

Tylopeptin_A
* Ac W V U J A Q A U S U A L U Q L OH
3064

Tylopeptin_B
* Ac W V U U A Q A U S U A L U Q L OH
3065

XR586
* Ac W J Q U I T U L U P Q U O J P F G OH
3066

Zervamicin_A-1-16
* Boc W I A U I V U L U P A U P U P F OCH3
3067

Zervamicin_ZIA
* Ac W I E J V T U L U O Q U O U P F OH
3068

Zervamicin_ZIB
* Ac W V E J I T U L U O Q U O U P F OH
3069

Zervamicin_ZIB′
* Ac W I E U I T U L U O Q U O U P F OH
3070

Zervamicin_ZIC
* Ac W I E J I T U L U O Q U O U P F OH
3071

Zervamicin_ZII-1
* Ac W I Q U V T U L U O Q U O U P F OH
3072

Zervamicin_ZII-2
* Ac W I Q U I T U V U O Q U O U P F OH
3073

Zervamicin_ZII-3
* Ac W V Q U I T U L U O Q U O U P F OH
3074

Zervamicin_ZII-4
* Ac W I Q J V T U L U O Q U O U P F OH
3075

Zervamicin_ZII-5
* Ac W I Q J I T U V U O Q U O U P F OH
3076

Zervamicin_ZIIA
* Ac W I Q U I T U L U O Q U O U P F OH
3077

Zervamicin_ZIIB
* Ac W I Q J I T U L U O Q U O U P F OH
3078

CAMEL135
GWRLIKKILRVFKGL
3079

(CAM135)

Novispirin G2
KNLRIIRKGIHIIKKY*
3080

B-33
FKKFWKWFRRF
3081

B-34
LKRFLKWFKRF
3082

B-35
KLFKRWKHLFR
3083

B-36
RLLKRFKHLFK
3084

B-37
FKTFLKWLHRF
3085

B-38
IKQLLHFFQRF
3086

B-39
KLLQTFKQIFR
3087

B-40
RILKELKNLFK
3088

B-41
LKQFVHFIHRF
3089

B-42
VKTLLHIFQRF
3090

B-43
KLVEQLKEIFR
3091

B-44
RVLQEIKQILK
3092

B-45
VKNLAELVHRF
3093

B-46
ATHLLHALQRF
3094

B-47
KLAENVKEILR
3095

B-48
RALHEAKEALK
3096

B-49
FHYFWHWFHRF
3097

B-50
LYHFLHWFQRF
3098

B-51
YLFQTWQHLFR
3099

B-52
YLLTEFQHLFK
3100

B-53
FKTFLQWLHRF
3101

B-54
IKTLLHFFQRF
3102

B-55
KLLQTFNQIFR
3103

B-56
TILQSLKNIFK
3104

B-57
LKQFVKFIHRF
3105

B-58
VKQLLKIFNRF
3106

B-59
KLVQQLKNIFR
3107

B-60
RVLNQVKQILK
3108

B-61
VKKLAKLVRRF
3109

B-62
AKRLLKVLKRF
3110

B-63
KLAQKVKRVLR
3111

B-64
RALKRIKHVLK
3112

1C-1
RRRRWWW
3113

1C-2
RRWWRRW
3114

1C-3
RRRWWWR
3115

1C-4
RWRWRWR
3116

2C-1
RRRFWWR
3117

2C-2
RRWWRRF*
3118

2C-3
RRRWWWF*
3119

2C-4
RWRWRWF*
3120

3C-1
RRRRWWK
3121

3C-2
RRWWRRK
3122

3C-3
RRRWWWK
3123

3C-4
RWRWRWK
3124

4C-1
RRRKWWK
3125

4C-2
RRWKRRK
3126

4C-3
RRRKWWK
3127

4C-4
RWRKRWK
3128

a-3
LHLLHQLLHLLHQF*
3129

a-4
AQAAHQAAHAAHQF*
3130

a-5
KLKKLLKKLKKLLK
3131

a-6
LKLLKKLLKLLKKF*
3132

a-7
LQLLKQLLKLLKQF*
3133

a-8
AQAAKQAAKAAKQF*
3134

a-9
RWRRWWRHFHHFFH*
3135

a-10
KLKKLLKRWRRWWR
3136

a-11
RWRRLLKKLHHLLH*
3137

a-12
KLKKLLKHLHHLLH*
3138

BD-1
FVF RHK WVW KHR FLF
3139

BD-2
VFI HRH VWV HKH VLF
3140

BD-3
WR WR AR WR WR LR WR F
3141

BD-4
WR IH LR AR LH VK FR F
3142

BD-5
LR IH AR FK VH IR LK F
3143

BD-6
FH IK FR VH LK VR FH F
3144

BD-7
FH VK IH FR LH VK FH F
3145

BD-8
LH IH AH FH VH IH LH F
3146

BD-9
FK IH FR LK VH IR FK F
3147

BD-10
FK AH IR FK LR VK FH F
3148

BD-11
LK AK IK FK VK LK IK F
3149

BD-12
WIW KHK FL HRH FLF
3150

BD-13
VFL HRH VI KHK LVF
3151

BD-14
FL HKH VL RHR IVF
3152

BD-15
VF KHK IV HRH ILF
3153

BD-16
FLF KH LFL HR IFF
3154

BD-17
LF KH ILI HR VIF
3155

BD-18
FL HKH LF KHK LF
3156

BD-19
VF RHR FI HRH VF
3157

BD-20
FI HK LV HKH VLF
3158

BD-21
VL RH LF RHR IVF
3159

BD-22
LV HK LIL RH LLF
3160

BD-23
VF KR VLI HK LIF
3161

BD-24
IV RK FLF RHK VF
3162

BD-25
VL KH VIA HKR LF
3163

BD-26
FI RK FLF KH LF
3164

BD-27
VI RH VWV RK LF
3165

BD-28
FLF RHR F RHR LVF
3166

BD-29
LFL HKH A KHK FLF
3167

BD-30
F KHK F KHK FIF
3168

BD-31
L RHR L RHR LIF
3169

BD-32
LIL K FLF K FVF
3170

BD-33
VLI R ILV R VIF
3171

BD-34
F RHR F RHR F
3172

BD-35
L KHK L KHK F
3173

BD-36
F K F KHK LIF
3174

BD-37
L R L RHR VLF
3175

BD-38
F K FLF K FLF
3176

BD-39
L R LFL R WLF
3177

BD-40
F K FLF KHK F
3178

BD-41
L R LFL RHR F
3179

BD-42
F K FLF K F
3180

BD-43
L R LFL R F
3181

AA-1
HHFFHHFHHFFHHF*
3182

AA-2
FHFFHHFFHFFHHF*
3183

AA-3
KLLK-GAT-FHFFHHFFHFFHHF
3184

AA-4
KLLK-FHFFHHFFHFFHHF
3185

AA-5
FHFFHHFFHFFHHFKLLK
3186

RIP
YSPWTNF*
3187

Lariatin A
c(Gly-Ser-Gln-Leu-Val-Tyr-Arg-Glu)-Trp-Val-
3188

(anti-mycobacteria)
Gly-His-Ser-Asn-Val-Ile-Lys-Pro

Lariatin B
c(Gly-Ser-Gln-Leu-Val-Tyr-Arg-Glu)-Trp-Val-
3189

(anti-mycobacteria)
Gly-His-Ser-Asn-Val-Ile-Lys-Gly-Pro-Pro

Abreviations:

U - Aminoisobutyric Acid (Aib);

J - Isovaline (Iva);

O - Hydroxyproline (Hyp);

Z - Ethylnorvaline (EtNor);

x or xx means L or I at that position;

Ac - optionally acetylated N-term;

OH, OCH3 - optional C-term; Alkane long chains are noted in brackets;

*optionally amidated C-terminus. Where protecting groups are shown, the gropus are optional. Conversely any of the peptides shown without protecting groups can, optionally bear one or more protecting groups. Where peptides are shown circularized, linear forms are also contemplated. Conversely, where linear peptides are shown circularlized versions are also contemplated.

In certain embodiments the antimicrobial peptide consists of or comprises the amino acid sequence of LL-37 (LLGDFFRK SKEKIGKEFKRIVQRIKD FLRNL VPRTES, SEQ ID NO:3190) or a variant of LL-37. LL-37 is a cathelicidin anti-microbial corresponding to amino acids 134-170 of the human cationic antimicrobial protein 18 (hCAP18). In certain embodiments the antimicrobial peptide consists of or comprises the amino acid sequence of an LL-37 variant as described in U.S. Patent Publication No: 2009/0156499 A1). Illustrative variants comprise or consist of the amino acid sequence having at least 90%, 95%, or 98% sequence identity with the amino acid sequence FKRIVQRIKDFLRX₁(SEQ ID NO:3191), where X₁is selected from the group consisting of 0, 1, 2, 3, 4, 5, 6, 7, and 8 amino acids. In certain embodiments illustrative variants comprise or consist of the amino acid sequence having at least 90%, 95%, or 98% sequence identity with the amino acid sequence X₁RLFDKIRQVIRKFX₂(SEQ ID NO:3192) where X₁is 0, 1, 2, 3, 4, 5, 6, 7, or 8 amino acids and X₂is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or 16 amino acids.

In certain embodiments the antimicrobial peptide consists of or comprises the amino acid sequence of an LL-37 variant shown in Table 15.

TABLE 15

LL-37 peptide and variants.

SEQ

ID
Amino acid sequence
ID NO

LL-37
LLGDFFRKSKEKIGKEFKRIVQRIKDFLR
3193

NLVPRTES

Cys-LL-37
CLLGDFFRKSKEKIGKEFKRIVQRIKDF
3194

LRNLVPRTES

LL-37(17-32)

FKRIVQRIKDFLRNLV

3195

Cys-LL-37-Cys
CLLGDFFRKSKEKIGKEFKRIVQRIKDFL
3196

RNLVPRTESC

LL-37FK-13
FKRIVQRIKDFLR
3197

LL-37FKR
FKRIVQRIKDFLRNLVPRTES
3198

LL-37GKE
GKEFKRIVQRIKDFLRNLVPR
3199

LL-37KRI
KRIVQRIKDFLRNLVPRTES
3200

LL-37LLG
LLGDFFRKSKEKIGKEFKRIV
3201

LL-37RKS
RKSKEKIGKEFKRIVQRIKDFLRNLVPRTES
3202

LL-37SKE
SKEKIGKEFKRIVQRIKDFLR
3203

LL-37-Cys
LLGDFFRKSKEKIGKEFKRIVQRIKDFL
3204

RNLVPRTESC

A number of antimicrobial peptides are also disclosed in U.S. Pat. Nos. 7,271,239, 7,223,840, 7,176,276, 6,809,181, 6,699,689, 6,420,116, 6,358,921, 6,316,594, 6,235,973, 6,183,992, 6,143,498, 6,042,848, 6,040,291, 5,936,063, 5,830,993, 5,428,016, 5,424,396, 5,032,574, 4,623,733, which are incorporated herein by reference for the disclosure of particular antimicrobial peptides.

v. Ligands.

In certain embodiments the effector can comprise one or more ligands, epitope tags, and/or antibodies. In certain embodiments preferred ligands and antibodies include those that bind to surface markers on immune cells. Chimeric moieties utilizing such antibodies as effector molecules act as bifunctional linkers establishing an association between the immune cells bearing binding partner for the ligand or antibody and the target microorganism(s).

The terms “epitope tag” or “affinity tag” are used interchangeably herein, and used refers to a molecule or domain of a molecule that is specifically recognized by an antibody or other binding partner. The term also refers to the binding partner complex as well. Thus, for example, biotin or a biotin/avidin complex are both regarded as an affinity tag. In addition to epitopes recognized in epitope/antibody interactions, affinity tags also comprise “epitopes” recognized by other binding molecules (e.g. ligands bound by receptors), ligands bound by other ligands to form heterodimers or homodimers, His₆bound by Ni-NTA, biotin bound by avidin, streptavidin, or anti-biotin antibodies, and the like.

Epitope tags are well known to those of skill in the art. Moreover, antibodies specific to a wide variety of epitope tags are commercially available. These include but are not limited to antibodies against the DYKDDDDK (SEQ ID NO:3205) epitope, c-myc antibodies (available from Sigma, St. Louis), the HNK-1 carbohydrate epitope, the HA epitope, the HSV epitope, the His₄(SEQ ID NO:3206), His_s(SEQ ID NO:3207), and His₆(SEQ ID NO:3208) epitopes that are recognized by the His epitope specific antibodies (see, e.g., Qiagen), and the like. In addition, vectors for epitope tagging proteins are commercially available. Thus, for example, the pCMV-Tag1 vector is an epitope tagging vector designed for gene expression in mammalian cells. A target gene inserted into the pCMV-Tag1 vector can be tagged with the FLAG® epitope (N-terminal, C-terminal or internal tagging), the c-myc epitope (C-terminal) or both the FLAG (N-terminal) and c-myc (C-terminal) epitopes.

vi. Lipids and Liposomes.

In certain embodiments the effectors comprise one or more microparticles or nanoparticles that can be loaded with an effector agent (e.g., a pharmaceutical, a label, etc.). In certain embodiments the microparticles or nanoparticles are lipidic particles. Lipidic particles are microparticles or nanoparticles that include at least one lipid component forming a condensed lipid phase. Typically, a lipidic nanoparticle has preponderance of lipids in its composition. Various condensed lipid phases include solid amorphous or true crystalline phases; isomorphic liquid phases (droplets); and various hydrated mesomorphic oriented lipid phases such as liquid crystalline and pseudocrystalline bilayer phases (L-alpha, L-beta, P-beta, Lc), interdigitated bilayer phases, and nonlamellar phases (see, e.g., The Structure of Biological Membranes, ed. by P. Yeagle, CRC Press, Bora Raton, Fla., 1991). Lipidic microparticles include, but are not limited to a liposome, a lipid-nucleic acid complex, a lipid-drug complex, a lipid-label complex, a solid lipid particle, a microemulsion droplet, and the like. Methods of making and using these types of lipidic microparticles and nanoparticles, as well as attachment of affinity moieties, e.g., antibodies, to them are known in the art (see, e.g., U.S. Pat. Nos. 5,077,057; 5,100,591; 5,616,334; 6,406,713; 5,576,016; 6,248,363; Bondi et al. (2003) Drug Delivery 10: 245-250; Pedersen et al., (2006) Eur. J. Pharm. Biopharm. 62: 155-162, 2006 (solid lipid particles); U.S. Pat. Nos. 5,534,502; 6,720,001; Shiokawa et al. (2005) Clin. Cancer Res. 11: 2018-2025 (microemulsions); U.S. Pat. No. 6,071,533 (lipid-nucleic acid complexes), and the like).

A liposome is generally defined as a particle comprising one or more lipid bilayers enclosing an interior, typically an aqueous interior. Thus, a liposome is often a vesicle formed by a bilayer lipid membrane. There are many methods for the preparation of liposomes. Some of them are used to prepare small vesicles (d<0.05 micrometer), some for larger vesicles (d>0.05 micrometer). Some are used to prepare multilamellar vesicles, some for unilamellar ones. Methods for liposome preparation are exhaustively described in several review articles such as Szoka and Papahadjopoulos (1980) Ann. Rev. Biophys. Bioeng., 9: 467, Deamer and Uster (1983) Pp. 27-51 In: Liposomes, ed. M. J. Ostro, Marcel Dekker, New York, and the like.

In various embodiments the liposomes include a surface coating of a hydrophilic polymer chain. “Surface-coating” refers to the coating of any hydrophilic polymer on the surface of liposomes. The hydrophilic polymer is included in the liposome by including in the liposome composition one or more vesicle-forming lipids derivatized with a hydrophilic polymer chain. In certain embodiments, vesicle-forming lipids with diacyl chains, such as phospholipids, are preferred. One illustrative phospholipid is phosphatidylethanolamine (PE), which contains a reactive amino group convenient for coupling to the activated polymers. One illustrative PE is distearoyl PE (DSPE). Another example is non-phospholipid double chain amphiphilic lipids, such as diacyl- or dialkylglycerols, derivatized with a hydrophilic polymer chain.

In certain embodiments a hydrophilic polymer for use in coupling to a vesicle forming lipid is polyethyleneglycol (PEG), preferably as a PEG chain having a molecular weight between 1,000-10,000 Daltons, more preferably between 1,000-5,000 Daltons, most preferably between 2,000-5,000 Daltons. Methoxy or ethoxy-capped analogues of PEG are also useful hydrophilic polymers, commercially available in a variety of polymer sizes, e.g., 120-20,000 Daltons.

Other hydrophilic polymers that can be suitable include, but are not limited to polylactic acid, polyglycolic acid, polyvinylpyrrolidone, polymethyloxazoline, polyethyloxazoline, polyhydroxypropyl methacrylamide, polymethacrylamide, polydimethylacrylamide, and derivatized celluloses, such as hydroxymethylcellulose or hydroxyethylcellulose.

Preparation of Lipid-Polymer Conjugates Containing these Polymers Attached to a suitable lipid, such as PE, have been described, for example in U.S. Pat. No. 5,395,

The liposomes can, optionally be prepared for attachment to one or more targeting moieties described herein. Here the lipid component included in the liposomes would include either a lipid derivatized with the targeting moiety, or a lipid having a polar-head chemical group, e.g., on a linker, that can be derivatized with the targeting moiety in preformed liposomes, according to known methods.

Methods of functionalizing lipids and liposomes with affinity moieties such as antibodies are well known to those of skill in the art (see, e.g., DE 3,218,121; Epstein et al. (1985) Proc. Natl. Acad. Sci., USA, 82:3688 (1985); Hwang et al. (1980) Proc. Natl. Acad. Sci., USA, 77: 4030; EP 52,322; EP 36,676; EP 88,046; EP 143,949; EP 142,641; Japanese patent application 83-118008; U.S. Pat. Nos. 4,485,045 and 4,544,545; and EP 102,324, all of which are incorporated herein by reference).

vii. Agents that Physically Disrupt the Extracellular Matrix within a Community of Microorganisms

In certain embodiments, peptides can be coupled to agents that physically disrupt the extracellular matrix within a community of microorganisms, for example a biofilm. In certain preferred embodiments, such an agent could be a bacterial cell-wall degrading enzyme, for example SAL-2, or any species of glycosidase, alginase, peptidase, proteinase, lipase, or DNA or RNA degrading enzyme or compound, for example rhRNase. Disruption of extracellular matrix of biofilms can result in clearance and therapeutic benefit.

Peptides can also be attached to antimicrobial proteins, such as Protein Inhibitor C or Colicin, or fragments thereof, for example the IIa domain of Colicin, or the heparin-binding domain of Protein Inhibitor C.

viii. Polymeric Microparticles and/or Nanoparticles.

In certain embodiments the effector(s) comprise polymeric microparticles and/or nanoparticles and/or micelles.

Microparticle and nanoparticle-based drug delivery systems have considerable potential for treatment of various microorganisms. Technological advantages of polymeric microparticles or nanoparticles used as drug carriers are high stability, high carrier capacity, feasibility of incorporation of both hydrophilic and hydrophobic substances, and feasibility of variable routes of administration, including oral application and inhalation. Polymeric nanoparticles can also be designed to allow controlled (sustained) drug release from the matrix. These properties of nanoparticles enable improvement of drug bioavailability and reduction of the dosing frequency.

Polymeric nanoparticles are typically micron or submicron (<1 μm) colloidal particles. This definition includes monolithic nanoparticles (nanospheres) in which the drug is adsorbed, dissolved, or dispersed throughout the matrix and nanocapsules in which the drug is confined to an aqueous or oily core surrounded by a shell-like wall. Alternatively, in certain embodiments, the drug can be covalently attached to the surface or into the matrix.

Polymeric microparticles and nanoparticles are typically made from biocompatible and biodegradable materials such as polymers, either natural (e.g., gelatin, albumin) or synthetic (e.g., polylactides, polyalkylcyanoacrylates), or solid lipids. In the body, the drug loaded in nanoparticles is usually released from the matrix by diffusion, swelling, erosion, or degradation. One commonly used material is poly(lactide-co-glycolide) (PLG).

Methods of fabricating and loading polymeric nanoparticles or microparticles are well known to those of skill in the art. Thus, for example, Matsumoto et al. (1999) Intl. J. Pharmaceutics, 185: 93-101 teaches the fabrication of poly(L-lactide)-poly(ethylene glycol)-poly(L-lactide) nanoparticles, Chawla et al. (2002) Intl. J. Pharmaceutics 249: 127-138, teaches the fabrication and use of poly(ε-caprolactone) nanoparticles delivery of tamifoxen, and Bodmeier et al. (1988) Intl. J. Pharmaceutics, 43: 179-186, teaches the preparation of poly(D,L-lactide) microspheres using a solvent evaporation method. “Intl. J. Pharmaceutics, 1988, 43, 179-186. Other nanoparticle formulations are described, for example, by Williams et al. (2003) J. Controlled Release, 91: 167-172; Leroux et al. (1996) J. Controlled Release, 39: 339-350; Soppimath et al. (2001) J. Controlled Release, 70:1-20; Brannon-Peppas (1995) Intl. J. Pharmaceutics, 116: 1-9; and the like.

C) Peptide Preparation.

The peptides described herein can be chemically synthesized using standard chemical peptide synthesis techniques or, particularly where the peptide does not comprise “D” amino acid residues, the peptide can be recombinantly expressed. Where the “D” polypeptides are recombinantly expressed, a host organism (e.g. bacteria, plant, fungal cells, etc.) can be cultured in an environment where one or more of the amino acids is provided to the organism exclusively in a D form. Recombinantly expressed peptides in such a system then incorporate those D amino acids.

In certain embodiments, D amino acids can be incorporated in recombinantly expressed peptides using modified amino acyl-tRNA synthetases that recognize D-amino acids.

In certain embodiments the peptides are chemically synthesized by any of a number of fluid or solid phase peptide synthesis techniques known to those of skill in the art. Solid phase synthesis in which the C-terminal amino acid of the sequence is attached to an insoluble support followed by sequential addition of the remaining amino acids in the sequence is a preferred method for the chemical synthesis of the polypeptides of this invention. Techniques for solid phase synthesis are well known to those of skill in the art and are described, for example, by Barany and Merrifield (1963) Solid-Phase Peptide Synthesis; pp. 3-284 in The Peptides: Analysis, Synthesis, Biology. Vol. 2: Special Methods in Peptide Synthesis, Part A.; Merrifield et al. (1963) J. Am. Chem. Soc., 85: 2149-2156, and Stewart et al. (1984) Solid Phase Peptide Synthesis, 2nd ed. Pierce Chem. Co., Rockford, Ill.

In one embodiment, the peptides can be synthesized by the solid phase peptide synthesis procedure using a benzhyderylamine resin (Beckman Bioproducts, 0.59 mmol of NH₂/g of resin) as the solid support. The COOH terminal amino acid (e.g., t-butylcarbonyl-Phe) is attached to the solid support through a 4-(oxymethyl)phenacetyl group. This is a more stable linkage than the conventional benzyl ester linkage, yet the finished peptide can still be cleaved by hydrogenation. Transfer hydrogenation using formic acid as the hydrogen donor can be used for this purpose.

It is noted that in the chemical synthesis of peptides, particularly peptides comprising D amino acids, the synthesis usually produces a number of truncated peptides in addition to the desired full-length product. Thus, the peptides are typically purified using, e.g., HPLC.

D-amino acids, beta amino acids, non-natural amino acids, and the like can be incorporated at one or more positions in the peptide simply by using the appropriately derivatized amino acid residue in the chemical synthesis. Modified residues for solid phase peptide synthesis are commercially available from a number of suppliers (see, e.g., Advanced Chem Tech, Louisville; Nova Biochem, San Diego; Sigma, St Louis; Bachem California Inc., Torrance, etc.). The D-form and/or otherwise modified amino acids can be completely omitted or incorporated at any position in the peptide as desired. Thus, for example, in certain embodiments, the peptide can comprise a single modified acid, while in other embodiments, the peptide comprises at least two, generally at least three, more generally at least four, most generally at least five, preferably at least six, more preferably at least seven or even all modified amino acids. In certain embodiments, essentially every amino acid is a D-form amino acid.

As indicated above, the peptides and/or fusion proteins of this invention can also be recombinantly expressed. Accordingly, in certain embodiments, the antimicrobial peptides and/or targeting moieties, and/or fusion proteins of this invention are synthesized using recombinant expression systems. Generally this involves creating a DNA sequence that encodes the desired peptide or fusion protein, placing the DNA in an expression cassette under the control of a particular promoter, expressing the peptide or fusion protein in a host, isolating the expressed peptide or fusion protein and, if required, renaturing the peptide or fusion protein.

DNA encoding the peptide(s) or fusion protein(s) described herein can be prepared by any suitable method as described above, including, for example, cloning and restriction of appropriate sequences or direct chemical synthesis.

This nucleic acid can be easily ligated into an appropriate vector containing appropriate expression control sequences (e.g. promoter, enhancer, etc.), and, optionally, containing one or more selectable markers (e.g. antibiotic resistance genes).

The nucleic acid sequences encoding the peptides or fusion proteins described herein can be expressed in a variety of host cells, including, but not limited to, E. coli, other bacterial hosts, yeast, fungus, and various higher eukaryotic cells such as insect cells (e.g. SF3), the COS, CHO and HeLa cells lines and myeloma cell lines. The recombinant protein gene will typically be operably linked to appropriate expression control sequences for each host. For E. coli this can include a promoter such as the T7, tip, or lambda promoters, a ribosome binding site and preferably a transcription termination signal. For eukaryotic cells, the control sequences can include a promoter and often an enhancer (e.g., an enhancer derived from immunoglobulin genes, SV40, cytomegalovirus, etc.), and a polyadenylation sequence, and may include splice donor and acceptor sequences.

The plasmids can be transferred into the chosen host cell by well-known methods such as calcium chloride transformation for E. coli and calcium phosphate treatment or electroporation for mammalian cells. Cells transformed by the plasmids can be selected by resistance to antibiotics conferred by genes contained on the plasmids, such as the amp, gpt, neo and hyg genes.

Once expressed, the recombinant peptide(s) or fusion protein(s) can be purified according to standard procedures of the art, including ammonium sulfate precipitation, affinity columns, column chromatography, gel electrophoresis and the like (see, generally, R. Scopes, (1982) Protein Purification, Springer-Verlag, N.Y.; Deutscher (1990) Methods in Enzymology Vol. 182: Guide to Protein Purification., Academic Press, Inc. N.Y.). Substantially pure compositions of at least about 90 to 95% homogeneity are preferred, and 98 to 99% or more homogeneity are most preferred.

One of skill in the art would recognize that after chemical synthesis, biological expression, or purification, the peptide(s) or fusion protein(s) may possess a conformation substantially different than desired native conformation. In this case, it may be necessary to denature and reduce the peptide or fusion protein and then to cause the molecule to re-fold into the preferred conformation. Methods of reducing and denaturing proteins and inducing re-folding are well known to those of skill in the art (see, e.g., Debinski et al. (1993) J. Biol. Chem., 268: 14065-14070; Kreitman and Pastan (1993) Bioconjug. Chem., 4: 581-585; and Buchner, et al., (1992) Anal. Biochem., 205: 263-270). Debinski et al., for example, describes the denaturation and reduction of inclusion body proteins in guanidine-DTE. The protein is then refolded in a redox buffer containing oxidized glutathione and L-arginine.

One of skill would recognize that modifications can be made to the peptide(s) and/or fusion protein(s) proteins without diminishing their biological activity. Some modifications may be made to facilitate the cloning, expression, or incorporation of the targeting molecule into a fusion protein. Such modifications are well known to those of skill in the art and include, for example, a methionine added at the amino terminus to provide an initiation site, or additional amino acids (e.g., poly His) placed on either terminus to create conveniently located restriction sites or termination codons or purification sequences.

D) Joining Targeting Moieties to Effectors.

i. Chemical Conjugation.

Chimeric moieties are formed by joining one or more of the targeting moieties described herein to one or more effectors. In certain embodiments the targeting moieties are attached directly to the effector(s) via naturally occurring reactive groups or the targeting moiety and/or the effector(s) can be functionalized to provide such reactive groups.

In various embodiments the targeting moieties are attached to effector(s) via one or more linking agents. Thus, in various embodiments the targeting moieties and the effector(s) can be conjugated via a single linking agent or multiple linking agents. For example, the targeting moiety and the effector can be conjugated via a single multifunctional (e.g., bi-, tri-, or tetra-) linking agent or a pair of complementary linking agents. In another embodiment, the targeting moiety and the effector are conjugated via two, three, or more linking agents. Suitable linking agents include, but are not limited to, e.g., functional groups, affinity agents, stabilizing groups, and combinations thereof.

In certain embodiments the linking agent is or comprises a functional group. Functional groups include monofunctional linkers comprising a reactive group as well as multifunctional crosslinkers comprising two or more reactive groups capable of forming a bond with two or more different functional targets (e.g., labels, proteins, macromolecules, semiconductor nanocrystals, or substrate). In some preferred embodiments, the multifunctional crosslinkers are heterobifunctional crosslinkers comprising two or more different reactive groups.

Suitable reactive groups include, but are not limited to thiol (—SH), carboxylate (COOH), carboxyl (—COOH), carbonyl, amine (NH₂), hydroxyl (—OH), aldehyde (—CHO), alcohol (ROH), ketone (R₂CO), active hydrogen, ester, sulfhydryl (SH), phosphate (—PO₃), or photoreactive moieties. Amine reactive groups include, but are not limited to e.g., isothiocyanates, isocyanates, acyl azides, NHS esters, sulfonyl chlorides, aldehydes and glyoxals, epoxides and oxiranes, carbonates, arylating agents, imidoesters, carbodiimides, and anhydrides. Thiol-reactive groups include, but are not limited to e.g., haloacetyl and alkyl halide derivates, maleimides, aziridines, acryloyl derivatives, arylating agents, and thiol-disulfides exchange reagents. Carboxylate reactive groups include, but are not limited to e.g., diazoalkanes and diazoacetyl compounds, such as carbonyldiimidazoles and carbodiimides. Hydroxyl reactive groups include, but are not limited to e.g., epoxides and oxiranes, carbonyldiimidazole, oxidation with periodate, N,N′-disuccinimidyl carbonate or N-hydroxylsuccimidyl chloroformate, enzymatic oxidation, alkyl halogens, and isocyanates. Aldehyde and ketone reactive groups include, but are not limited to e.g., hydrazine derivatives for schiff base formation or reduction amination. Active hydrogen reactive groups include, but are not limited to e.g., diazonium derivatives for mannich condensation and iodination reactions. Photoreactive groups include, but are not limited to e.g., aryl azides and halogenated aryl azides, benzophenones, diazo compounds, and diazirine derivatives.

Other suitable reactive groups and classes of reactions useful in forming chimeric moieties include those that are well known in the art of bioconjugate chemistry. Currently favored classes of reactions available with reactive chelates are those which proceed under relatively mild conditions. These include, but are not limited to, nucleophilic substitutions (e.g., reactions of amines and alcohols with acyl halides, active esters), electrophilic substitutions (e.g., enamine reactions), and additions to carbon-carbon and carbon-heteroatom multiple bonds (e.g., Michael reaction, Diels-Alder addition). These and other useful reactions are discussed in, for example, March (1985) Advanced Organic Chemistry, 3rd Ed., John Wiley & Sons, New York, Hermanson (1996) Bioconjugate Techniques, Academic Press, San Diego; and Feeney et al. (1982) Modification of Proteins; Advances in Chemistry Series, Vol. 198, American Chemical Society, Washington, D.C.

In certain embodiments, the linking agent comprises a chelator. For example, the chelator comprising the molecule, DOTA (DOTA=1,4,7,10-tetrakis(carboxymethyl)-1,4,7,10-tetraazacyclododecane), can readily be labeled with a radiolabel, such as Gd³⁺ and ⁶⁴Cu, resulting in Gd³⁺-DOTA and ⁶⁴Cu-DOTA respectively, attached to the targeting moiety. Other suitable chelates are known to those of skill in the art, for example, 1,4,7-triazacyclononane-N,N′,N″-triacetic acid (NOTA) derivatives being among the most well known (see, e.g., Lee et al. (1997) Nucl Med. Biol. 24: 2225-23019).

A “linker” or “linking agent” as used herein, is a molecule that is used to join two or more molecules. In certain embodiments the linker is typically capable of forming covalent bonds to both molecule(s) (e.g., the targeting moiety and the effector). Suitable linkers are well known to those of skill in the art and include, but are not limited to, straight or branched-chain carbon linkers, heterocyclic carbon linkers, or peptide linkers. In certain embodiments the linkers can be joined to the constituent amino acids through their side groups (e.g., through a disulfide linkage to cysteine). However, in certain embodiments, the linkers will be joined to the alpha carbon amino and carboxyl groups of the terminal amino acids.

A bifunctional linker having one functional group reactive with a group on one molecule (e.g., a targeting peptide), and another group reactive on the other molecule (e.g., an antimicrobial peptide), can be used to form the desired conjugate. Alternatively, derivatization can be performed to provide functional groups. Thus, for example, procedures for the generation of free sulfhydryl groups on peptides are also known (See U.S. Pat. No. 4,659,839).

In certain embodiments the linking agent is a heterobifunctional crosslinker comprising two or more different reactive groups that form a heterocyclic ring that can interact with a peptide. For example, a heterobifunctional crosslinker such as cysteine may comprise an amine reactive group and a thiol-reactive group can interact with an aldehyde on a derivatized peptide. Additional combinations of reactive groups suitable for heterobifunctional crosslinkers include, for example, amine- and sulfhydryl reactive groups; carbonyl and sulfhydryl reactive groups; amine and photoreactive groups; sulfhydryl and photoreactive groups; carbonyl and photoreactive groups; carboxylate and photoreactive groups; and arginine and photoreactive groups. In one embodiment, the heterobifunctional crosslinker is SMCC.

Many procedures and linker molecules for attachment of various molecules to peptides or proteins are known (see, e.g., European Patent Application No. 188,256; U.S. Pat. Nos. 4,671,958, 4,659,839, 4,414,148, 4,699,784; 4,680,338; 4,569,789; and 4,589,071; and Borlinghaus et al. (1987) Cancer Res. 47: 4071-4075). Illustrative linking protocols are provided herein in Examples 2 and 3.

ii. Fusion Proteins.

In certain embodiments where the targeting moiety and effector are both peptides or both comprise peptides, the chimeric moiety can be chemically synthesized or recombinantly expressed as a fusion protein (i.e., a chimeric fusion protein).

In certain embodiments the chimeric fusion proteins are synthesized using recombinant DNA methodology. Generally this involves creating a DNA sequence that encodes the fusion protein, placing the DNA in an expression cassette under the control of a particular promoter, expressing the protein in a host, isolating the expressed protein and, if required, renaturing the protein.

DNA encoding the fusion proteins can be prepared by any suitable method, including, for example, cloning and restriction of appropriate sequences or direct chemical synthesis by methods such as the phosphotriester method of Narang et al. (1979) Meth. Enzymol. 68: 90-99; the phosphodiester method of Brown et al. (1979) Meth. Enzymol. 68: 109-151; the diethylphosphoramidite method of Beaucage et al. (1981) Tetra. Lett., 22: 1859-1862; and the solid support method of U.S. Pat. No. 4,458,066.

Chemical synthesis produces a single stranded oligonucleotide. This can be converted into double stranded DNA by hybridization with a complementary sequence or by polymerization with a DNA polymerase using the single strand as a template. One of skill would recognize that while chemical synthesis of DNA is limited to sequences of about 100 bases, longer sequences can be obtained by the ligation of shorter sequences.

Alternatively, subsequences can be cloned and the appropriate subsequences cleaved using appropriate restriction enzymes. The fragments can then be ligated to produce the desired DNA sequence.

In certain embodiments, DNA encoding fusion proteins of the present invention may be cloned using DNA amplification methods such as polymerase chain reaction (PCR). Thus, for example, the nucleic acid encoding a targeting antibody, a targeting peptide, and the like is PCR amplified, using a sense primer containing the restriction site for NdeI and an antisense primer containing the restriction site for HindIII. This produces a nucleic acid encoding the targeting sequence and having terminal restriction sites. Similarly an effector and/or effector/linker/spacer can be provided having complementary restriction sites. Ligation of sequences and insertion into a vector produces a vector encoding the fusion protein.

While the targeting moieties and effector(s) can be directly joined together, one of skill will appreciate that they can be separated by a peptide spacer/linker consisting of one or more amino acids. Generally the spacer will have no specific biological activity other than to join the proteins or to preserve some minimum distance or other spatial relationship between them. However, the constituent amino acids of the spacer may be selected to influence some property of the molecule such as the folding, net charge, or hydrophobicity.

The nucleic acid sequences encoding the fusion proteins can be expressed in a variety of host cells, including E. coli, other bacterial hosts, yeast, and various higher eukaryotic cells such as the COS, CHO and HeLa cells lines and myeloma cell lines. The recombinant protein gene will be operably linked to appropriate expression control sequences for each host. For E. coli this includes a promoter such as the T7, tip, or lambda promoters, a ribosome binding site and preferably a transcription termination signal. For eukaryotic cells, the control sequences will include a promoter and preferably an enhancer derived from immunoglobulin genes, SV40, cytomegalovirus, etc., and a polyadenylation sequence, and may include splice donor and acceptor sequences.

Once expressed, the recombinant fusion proteins can be purified according to standard procedures of the art, including ammonium sulfate precipitation, affinity columns, column chromatography, gel electrophoresis and the like (see, generally, R. Scopes (1982) Protein Purification, Springer-Verlag, N.Y.; Deutscher (1990) Methods in Enzymology Vol. 182: Guide to Protein Purification., Academic Press, Inc. N.Y.). Substantially pure compositions of at least about 90 to 95% homogeneity are preferred, and 98 to 99% or more homogeneity are most preferred for pharmaceutical uses. Once purified, partially or to homogeneity as desired, the polypeptides may then be used therapeutically.

One of skill in the art would recognize that after chemical synthesis, biological expression, or purification, the fusion protein may possess a conformation substantially different than the native conformations of the constituent polypeptides. In this case, it may be necessary to denature and reduce the polypeptide and then to cause the polypeptide to re-fold into the preferred conformation. Methods of reducing and denaturing proteins and inducing re-folding are well known to those of skill in the art (See, Debinski et al. (1993) J. Biol. Chem., 268: 14065-14070; Kreitman and Pastan (1993) Bioconjug. Chem., 4: 581-585; and Buchner, et al. (1992) Anal. Biochem., 205: 263-270).

One of skill would recognize that modifications can be made to the fusion proteins without diminishing their biological activity. Some modifications may be made to facilitate the cloning, expression, or incorporation of the targeting molecule into a fusion protein. Such modifications are well known to those of skill in the art and include, for example, a methionine added at the amino terminus to provide an initiation site, or additional amino acids placed on either terminus to create conveniently located restriction sites or termination codons.

As indicated above, in various embodiments a peptide linker/spacer is used to join the one or more targeting moieties to one or more effector(s). In various embodiments the peptide linker is relatively short, typically less than about 10 amino acids, preferably less than about 8 amino acids and more preferably about 3 to about 5 amino acids. Suitable illustrative linkers include, but are not limited to PSGSP ((SEQ ID NO:3209), ASASA (SEQ ID NO: 3210), or GGG. In certain embodiments longer linkers such as (GGGGS)₃(SEQ ID NO:3211) can be used. Illustrative peptide linkers and other linkers are shown in Table 16.

TABLE 16

Illustrative peptide and non-peptide linkers.

Linker
SEQ ID NO:

AAA

GGG

GGGG
3212

SGG

GGSGGS
3213

SAT

PYP

PSPSP
3214

ASA

ASASA
3215

PSPSP
3216

KKKK
3217

RRRR
3218

GGGGS
3219

GGGGS GGGGS
3220

GGGGS GGGGS GGGGS
3221

GGGGS GGGGS GGGGS GGGGS
3222

GGGGS GGGGS GGGGS GGGGS GGGGS
3223

GGGGS GGGGS GGGGS GGGGS GGGGS GGGGS
3224

2-nitrobenzene or O-nitrobenzyl

Nitropyridyl disulfide

Dioleoylphosphatidylethanolamine (DOPE)

S-acetylmercaptosuccinic acid

1,4,7,10-tetraazacyclododecane-1,4,7,10-tetracetic acid (DOTA)

β-glucuronide and β-glucuronide variants

Poly(alkylacrylic acid)

Benzene-based linkers (for example: 2,5-Bis(hexyloxy)-1,4-bis[2,5-

bis(hexyloxy)-4-formyl-phenylenevinylene]benzene) and like

molecules

Disulfide linkages

Poly(amidoamine) or like dendrimers linking multiple target and killing

peptides in one molecule

Carbon nanotubes

Hydrazone and hydrazone variant linkers

PEG of any chain length

Succinate, formate, acetate butyrate, other like organic acids

Aldols, alcohols, or enols

Peroxides

alkane or alkene groups of any chain length

One or more porphyrin or dye molecules containing free amide and

carboxylic acid groups

One or more DNA or RNA nucleotides, including polyamine and

polycarboxyl-containing variants

Inulin, sucrose, glucose, or other single, di or polysaccharides

Linoleic acid or other polyunsaturated fatty acids

Variants of any of the above linkers containing halogen or thiol

groups

(All amino-acid-based linkers could be L, D, combinations of L and D forms, β-form, and the like)

E) Multiple Targeting Moieties and/or Effectors.

As indicated above, in certain embodiments, the chimeric moieties described herein comprise multiple targeting moieties attached to a single effector or multiple effectors attached to a single targeting moiety, or multiple targeting moieties attached to multiple effectors.

Where the chimeric construct is a fusion protein this is easily accomplished by providing multiple domains that are targeting domains attached to one or more effector domains. FIG. 14 schematically illustrates a few, but not all, configurations. In various embodiments the multiple targeting domains and/or multiple effector domains can be attached to each other directly or can be separated by linkers (e.g., amino acid or peptide linkers as described above).

When the chimeric construct is a chemical conjugate linear or branched configurations (e.g., as illustrated in FIG. 14) are readily produced by using branched or multifunctional linkers and/or a plurality of different linkers.

F) Protecting Groups.

While the various peptides (e.g., targeting peptides, antimicrobial peptides, STAMPs) described herein may be shown with no protecting groups, in certain embodiments they can bear one, two, three, four, or more protecting groups. In various embodiments, the protecting groups can be coupled to the C- and/or N-terminus of the peptide(s) and/or to one or more internal residues comprising the peptide(s) (e.g., one or more R-groups on the constituent amino acids can be blocked). Thus, for example, in certain embodiments, any of the peptides described herein can bear, e.g., an acetyl group protecting the amino terminus and/or an amide group protecting the carboxyl terminus. One example of such a protected peptide is the 1845L6-21 STAMP having the amino acid sequence KFINGVLSQFVLERKPYPKLFKFLRKHLL* (SEQ ID NO:3225), where the asterisk indicates an amidated carboxyl terminus. Of course, this protecting group can be can be eliminated and/or substituted with another protecting group as described herein.

Without being bound by a particular theory, it was discovered that addition of a protecting group, particularly to the carboxyl and in certain embodiments the amino terminus can improve the stability and efficacy of the peptide.

A wide number of protecting groups are suitable for this purpose. Such groups include, but are not limited to acetyl, amide, and alkyl groups with acetyl and alkyl groups being particularly preferred for N-terminal protection and amide groups being preferred for carboxyl terminal protection. In certain particularly preferred embodiments, the protecting groups include, but are not limited to alkyl chains as in fatty acids, propionyl, formyl, and others. Particularly preferred carboxyl protecting groups include amides, esters, and ether-forming protecting groups. In one preferred embodiment, an acetyl group is used to protect the amino terminus and an amide group is used to protect the carboxyl terminus. These blocking groups enhance the helix-forming tendencies of the peptides. Certain particularly preferred blocking groups include alkyl groups of various lengths, e.g., groups having the formula: CH₃—(CH₂)_n—CO— where n ranges from about 1 to about 20, preferably from about 1 to about 16 or 18, more preferably from about 3 to about 13, and most preferably from about 3 to about 10.

In certain embodiments, the protecting groups include, but are not limited to alkyl chains as in fatty acids, propionyl, formyl, and others. Particularly preferred carboxyl protecting groups include amides, esters, and ether-forming protecting groups. In one embodiment, an acetyl group is used to protect the amino terminus and/or an amino group is used to protect the carboxyl terminus (i.e., amidated carboxyl terminus). In certain embodiments blocking groups include alkyl groups of various lengths, e.g., groups having the formula: CH₃—(CH₂)_n—CO— where n ranges from about 3 to about 20, preferably from about 3 to about 16, more preferably from about 3 to about 13, and most preferably from about 3 to about 10.

In certain embodiments, the acid group on the C-terminal can be blocked with an alcohol, aldehyde or ketone group and/or the N-terminal residue can have the natural amide group, or be blocked with an acyl, carboxylic acid, alcohol, aldehyde, or ketone group.

Other protecting groups include, but are not limited to Fmoc, t-butoxycarbonyl (t-BOC), 9-fluoreneacetyl group, 1-fluorenecarboxylic group, 9-florenecarboxylic group, 9-fluorenone-1-carboxylic group, benzyloxycarbonyl, xanthyl (Xan), trityl (Trt), 4-methyltrityl (Mtt), 4-methoxytrityl (Mmt), 4-methoxy-2,3,6-trimethyl-benzenesulphonyl (Mtr), Mesitylene-2-sulphonyl (Mts), 4,4-dimethoxybenzhydryl (Mbh), Tosyl (Tos), 2,2,5,7,8-pentamethyl chroman-6-sulphonyl (Pmc), 4-methylbenzyl (MeBzl), 4-methoxybenzyl (MeOBzl), benzyloxy (BzlO), benzyl (Bzl), benzoyl (Bz), 3-nitro-2-pyridinesulphenyl (Npys), 1-(4,4-dimentyl-2,6-diaxocyclohexylidene)ethyl (Dde), 2,6-dichlorobenzyl (2,6-DiCl—Bzl), 2-chlorobenzyloxycarbonyl (2-Cl—Z), 2-bromobenzyloxycarbonyl (2-Br—Z), Benzyloxymethyl (Bom), cyclohexyloxy (cHxO), t-butoxymethyl (Bum), t-butoxy (tBuO), t-Butyl (tBu), Acetyl (Ac), and Trifluoroacetyl (TFA).

Protecting/blocking groups are well known to those of skill as are methods of coupling such groups to the appropriate residue(s) comprising the peptides of this invention (see, e.g., Greene et al., (1991) Protective Groups in Organic Synthesis, 2nd ed., John Wiley & Sons, Inc. Somerset, N.J.). In illustrative embodiment, for example, acetylation is accomplished during the synthesis when the peptide is on the resin using acetic anhydride. Amide protection can be achieved by the selection of a proper resin for the synthesis. For example, a rink amide resin can be used. After the completion of the synthesis, the semipermanent protecting groups on acidic bifunctional amino acids such as Asp and Glu and basic amino acid Lys, hydroxyl of Tyr are all simultaneously removed. The peptides released from such a resin using acidic treatment comes out with the n-terminal protected as acetyl and the carboxyl protected as NH₂and with the simultaneous removal of all of the other protecting groups.

Where amino acid sequences are disclosed herein, amino acid sequences comprising, one or more protecting groups, e.g., as described above (or any other commercially available protecting groups for amino acids used, e.g., in boc or fmoc peptide synthesis) are also contemplated.

G) Peptide Circularization.

In certain embodiments the peptides described herein (e.g., AMPs, compound AMPs, STAMPs, etc.) are circularized/cyclized to produce cyclic peptides. Cyclic peptides, as contemplated herein, include head/tail, head/side chain, tail/side chain, and side chain/side chain cyclized peptides. In addition, peptides contemplated herein include homodet, containing only peptide bonds, and heterodet containing in addition disulfide, ester, thioester-bonds, or other bonds.

The cyclic peptides can be prepared using virtually any art-known technique for the preparation of cyclic peptides. For example, the peptides can be prepared in linear or non-cyclized form using conventional solution or solid phase peptide syntheses and cyclized using standard chemistries. Preferably, the chemistry used to cyclize the peptide will be sufficiently mild so as to avoid substantially degrading the peptide. Suitable procedures for synthesizing the peptides described herein as well as suitable chemistries for cyclizing the peptides are well known in the art.

In various embodiments cyclization can be achieved via direct coupling of the N- and C-terminus to form a peptide (or other) bond, but can also occur via the amino acid side chains. Furthermore it can be based on the use of other functional groups, including but not limited to amino, hydroxy, sulfhydryl, halogen, sulfonyl, carboxy, and thiocarboxy. These groups can be located at the amino acid side chains or be attached to their N- or C-terminus.

Accordingly, it is to be understood that the chemical linkage used to covalently cyclize the peptides of the invention need not be an amide linkage. In many instances it may be desirable to modify the N- and C-termini of the linear or non-cyclized peptide so as to provide, for example, reactive groups that may be cyclized under mild reaction conditions. Such linkages include, by way of example and not limitation amide, ester, thioester, CH₂—NH, etc. Techniques and reagents for synthesizing peptides having modified termini and chemistries suitable for cyclizing such modified peptides are well-known in the art.

Alternatively, in instances where the ends of the peptide are conformationally or otherwise constrained so as to make cyclization difficult, it may be desirable to attach linkers to the N- and/or C-termini to facilitate peptide cyclization. Of course, it will be appreciated that such linkers will bear reactive groups capable of forming covalent bonds with the termini of the peptide. Suitable linkers and chemistries are well-known in the art and include those previously described.

Cyclic peptides and depsipeptides (heterodetic peptides that include ester (depside) bonds as part of their backbone) have been well characterized and show a wide spectrum of biological activity. The reduction in conformational freedom brought about by cyclization often results in higher receptor-binding affinities. Frequently in these cyclic compounds, extra conformational restrictions are also built in, such as the use of D- and N-alkylated-amino acids, α,β-dehydro amino acids or α,α-disubstituted amino acid residues.

Methods of forming disulfide linkages in peptides are well known to those of skill in the art (see, e.g., Eichler and Houghten (1997) Protein Pept. Lett. 4: 157-164).

Reference may also be made to Marlowe (1993) Biorg. Med. Chem. Lett. 3: 437-44 who describes peptide cyclization on TFA resin using trimethylsilyl (TMSE) ester as an orthogonal protecting group; Pallin and Tam (1995) J. Chem. Soc. Chem. Comm. 2021-2022) who describe the cyclization of unprotected peptides in aqueous solution by oxime formation; Algin et al. (1994) Tetrahedron Lett. 35: 9633-9636 who disclose solid-phase synthesis of head-to-tail cyclic peptides via lysine side-chain anchoring; Kates et al. (1993) Tetrahedron Lett. 34: 1549-1552 who describe the production of head-to-tail cyclic peptides by three-dimensional solid phase strategy; Tumelty et al. (1994) J. Chem. Soc. Chem. Comm. 1067-1068, who describe the synthesis of cyclic peptides from an immobilized activated intermediate, where activation of the immobilized peptide is carried out with N-protecting group intact and subsequent removal leading to cyclization; McMurray et al. (1994) Peptide Res. 7: 195-206) who disclose head-to-tail cyclization of peptides attached to insoluble supports by means of the side chains of aspartic and glutamic acid; Hruby et al. (1994) Reactive Polymers 22: 231-241) who teach an alternate method for cyclizing peptides via solid supports; and Schmidt and Langer (1997) J. Peptide Res. 49: 67-73, who disclose a method for synthesizing cyclotetrapeptides and cyclopentapeptides.

These methods of peptide cyclization are illustrative and non-limiting. Using the teaching provide herein, other cyclization methods will be available to one of skill in the art.

H) Identification/Verification of Active Peptides

The active AMPs, STAMPs and the like can be identified and/or validated using an in vitro screening assay. Indeed, in many instances the AMPs and/or STAMPS described herein will be used in vitro as preservatives, topical antimicrobial treatments, and the like. Additionally, despite certain apparent limitations of in vitro susceptibility tests, clinical data indicate that a good correlation exists between minimal inhibitory concentration (MIC) test results and in vivo efficacy of antibiotic compounds (see, e.g., Murray et al. (1994) Antimicrobial Susceptibility Testing, Poupard et al., eds., Plenum Press, New York; Knudsen et al. (1995) Antimicrob. Agents Chemother. 39(6): 1253-1258; and the like). Thus, AMPs useful for treating infections and diseases related thereto are also conveniently identified by demonstrated in vitro antimicrobial activity against specified microbial targets, e.g., as illustrated in Table 4).

Typically, the in vitro antimicrobial activity of antimicrobial agents is tested using standard NCCLS bacterial inhibition assays, or MIC tests (see, National Committee on Clinical Laboratory Standards “Performance Standards for Antimicrobial Susceptibility Testing,” NCCLS Document M100-S5 Vol. 14, No. 16, December 1994; “Methods for dilution antimicrobial susceptibility test for bacteria that grow aerobically-Third Edition,” Approved Standard M7-A3, National Committee for Clinical Standards, Villanova, Pa.).

It will be appreciated that other assays as are well known in the art or that will become apparent to those having skill in the art upon review of this disclosure may also be used to identify active AMPs. Such assays include, for example, the assay described in Lehrer et al. (1988) J. Immunol. Meth., 108: 153 and Steinberg and Lehrer, “Designer Assays for Antimicrobial Peptides: Disputing the ‘One Size Fits All’ Theory,” In: Antibacterial Peptide Protocols, Shafer, Ed., Humana Press, N.J. Generally, active peptides of the invention will exhibit MICs (as measured using the assays described in the examples) of less than about 100 μM, preferably less than about 80 or 60 μM, more preferably about 50 μM or less, about 25 μM or less, or about 15 μM or less, or about 10 μM or less.

IV. Administration and Formulations.

A) Pharmaceutical Formulations.

In certain embodiments, the antimicrobial peptides and/or the chimeric constructs (e.g., targeting moieties attached to antimicrobial peptide(s), targeting moieties attached to detectable label(s), etc.) are administered to a mammal in need thereof, to a cell, to a tissue, to a composition (e.g., a food), etc.). In various embodiments the compositions can be administered to detect and/or locate, and/or quantify the presence of particular microorganisms, microorganism populations, biofilms comprising particular microorganisms, and the like. In various embodiments the compositions can be administered to inhibit particular microorganisms, microorganism populations, biofilms comprising particular microorganisms, and the like.

These active agents (antimicrobial peptides and/or chimeric moieties) can be administered in the “native” form or, if desired, in the form of salts, esters, amides, prodrugs, derivatives, and the like, provided the salt, ester, amide, prodrug or derivative is suitable pharmacologically, i.e., effective in the present method(s). Salts, esters, amides, prodrugs and other derivatives of the active agents can be prepared using standard procedures known to those skilled in the art of synthetic organic chemistry and described, for example, by March (1992) Advanced Organic Chemistry; Reactions, Mechanisms and Structure, 4th Ed. N.Y. Wiley-Interscience.

Methods of formulating such derivatives are known to those of skill in the art. For example, the disulfide salts of a number of delivery agents are described in PCT Publication WO 2000/059863 which is incorporated herein by reference. Similarly, acid salts of therapeutic peptides, peptoids, or other mimetics, and can be prepared from the free base using conventional methodology that typically involves reaction with a suitable acid. Generally, the base form of the drug is dissolved in a polar organic solvent such as methanol or ethanol and the acid is added thereto. The resulting salt either precipitates or can be brought out of solution by addition of a less polar solvent. Suitable acids for preparing acid addition salts include, but are not limited to both organic acids, e.g., acetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, malic acid, malonic acid, succinic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, salicylic acid, and the like, as well as inorganic acids, e.g., hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and the like. An acid addition salt can be reconverted to the free base by treatment with a suitable base. Certain particularly preferred acid addition salts of the active agents herein include halide salts, such as may be prepared using hydrochloric or hydrobromic acids. Conversely, preparation of basic salts of the active agents of this invention are prepared in a similar manner using a pharmaceutically acceptable base such as sodium hydroxide, potassium hydroxide, ammonium hydroxide, calcium hydroxide, trimethylamine, or the like. In certain embodiments basic salts include alkali metal salts, e.g., the sodium salt, and copper salts.

For the preparation of salt forms of basic drugs, the pKa of the counterion is preferably at least about 2 pH lower than the pKa of the drug. Similarly, for the preparation of salt forms of acidic drugs, the pKa of the counterion is preferably at least about 2 pH higher than the pKa of the drug. This permists the counterion to bring the solution's pH to a level lower than the pHmax to reach the salt plateau, at which the solubility of salt prevails over the solubility of free acid or base. The generalized rule of difference in pKa units of the ionizable group in the active pharmaceutical ingredient (API) and in the acid or base is meant to make the proton transfer energetically favorable. When the pKa of the API and counterion are not significantly different, a solid complex may form but may rapidly disproportionate (i.e., break down into the individual entities of drug and counterion) in an aqueous environment.

Preferably, the counterion is a pharmaceutically acceptable counterion. Suitable anionic salt forms include, but are not limited to acetate, benzoate, benzylate, bitartrate, bromide, carbonate, chloride, citrate, edetate, edisylate, estolate, fumarate, gluceptate, gluconate, hydrobromide, hydrochloride, iodide, lactate, lactobionate, malate, maleate, mandelate, mesylate, methyl bromide, methyl sulfate, mucate, napsylate, nitrate, pamoate (embonate), phosphate and diphosphate, salicylate and disalicylate, stearate, succinate, sulfate, tartrate, tosylate, triethiodide, valerate, and the like, while suitable cationic salt forms include, but are not limited to aluminum, benzathine, calcium, ethylene diamine, lysine, magnesium, meglumine, potassium, procaine, sodium, tromethamine, zinc, and the like.

In various embodiments preparation of esters typically involves functionalization of hydroxyl and/or carboxyl groups that are present within the molecular structure of the active agent. In certain embodiments, the esters are typically acyl-substituted derivatives of free alcohol groups, i.e., moieties that are derived from carboxylic acids of the formula RCOOH where R is alky, and preferably is lower alkyl. Esters can be reconverted to the free acids, if desired, by using conventional hydrogenolysis or hydrolysis procedures.

Amides can also be prepared using techniques known to those skilled in the art or described in the pertinent literature. For example, amides may be prepared from esters, using suitable amine reactants, or they may be prepared from an anhydride or an acid chloride by reaction with ammonia or a lower alkyl amine.

In various embodiments, the active agents identified herein are useful for parenteral, topical, oral, nasal (or otherwise inhaled), rectal, or local administration, such as by aerosol or transdermally, for detection and/or quantification, and or localization, and/or prophylactic and/or therapeutic treatment of infection (e.g., microbial infection). The compositions can be administered in a variety of unit dosage forms depending upon the method of administration. Suitable unit dosage forms, include, but are not limited to powders, tablets, pills, capsules, lozenges, suppositories, patches, nasal sprays, injectibles, implantable sustained-release formulations, lipid complexes, etc.

The active agents (e.g., antimicrobial peptides and/or chimeric constructs) described herein can also be combined with a pharmaceutically acceptable carrier (excipient) to form a pharmacological composition. In certain embodiments, pharmaceutically acceptable carriers include those approved by a regulatory agency of the Federal or a state government or listed in the U.S. Pharmacopeia or other generally recognized pharmacopeia for use in/on animals, and more particularly in/on humans. A “carrier” refers to, for example, a diluent, adjuvant, excipient, auxiliary agent or vehicle with which an active agent of the present invention is administered.

Pharmaceutically acceptable carriers can contain one or more physiologically acceptable compound(s) that act, for example, to stabilize the composition or to increase or decrease the absorption of the active agent(s). Physiologically acceptable compounds can include, for example, carbohydrates, such as glucose, sucrose, or dextrans, antioxidants, such as ascorbic acid or glutathione, chelating agents, low molecular weight proteins, protection and uptake enhancers such as lipids, compositions that reduce the clearance or hydrolysis of the active agents, or excipients or other stabilizers and/or buffers.

Other physiologically acceptable compounds, particularly of use in the preparation of tablets, capsules, gel caps, and the like include, but are not limited to binders, diluent/fillers, disentegrants, lubricants, suspending agents, and the like.

In certain embodiments, to manufacture an oral dosage form (e.g., a tablet), an excipient (e.g., lactose, sucrose, starch, mannitol, etc.), an optional disintegrator (e.g. calcium carbonate, carboxymethylcellulose calcium, sodium starch glycollate, crospovidone etc.), a binder (e.g. alpha-starch, gum arabic, microcrystalline cellulose, carboxymethylcellulose, polyvinylpyrrolidone, hydroxypropylcellulose, cyclodextrin, etc.), and an optional lubricant (e.g., talc, magnesium stearate, polyethylene glycol 6000, etc.), for instance, are added to the active component or components (e.g., active peptide) and the resulting composition is compressed. Where necessary the compressed product is coated, e.g., known methods for masking the taste or for enteric dissolution or sustained release. Suitable coating materials include, but are not limited to ethyl-cellulose, hydroxymethylcellulose, polyoxyethylene glycol, cellulose acetate phthalate, hydroxypropylmethylcellulose phthalate, and Eudragit (Rohm & Haas, Germany; methacrylic-acrylic copolymer).

Other physiologically acceptable compounds include wetting agents, emulsifying agents, dispersing agents or preservatives that are particularly useful for preventing the growth or action of microorganisms. Various preservatives are well known and include, for example, phenol and ascorbic acid. One skilled in the art would appreciate that the choice of pharmaceutically acceptable carrier(s), including a physiologically acceptable compound depends, for example, on the route of administration of the active agent(s) and on the particular physio-chemical characteristics of the active agent(s).

In certain embodiments the excipients are sterile and generally free of undesirable matter. These compositions can be sterilized by conventional, well-known sterilization techniques. For various oral dosage form excipients such as tablets and capsules sterility is not required. The USP/NF standard is usually sufficient.

In certain therapeutic applications, the compositions of this invention are administered, e.g., topically administered or administered to the oral or nasal cavity, to a patient suffering from infection or at risk for infection or prophylactically to prevent dental caries or other pathologies of the teeth or oral mucosa characterized by microbial infection in an amount sufficient to prevent and/or cure and/or at least partially prevent or arrest the disease and/or its complications. An amount adequate to accomplish this is defined as a “therapeutically effective dose.” Amounts effective for this use will depend upon the severity of the disease and the general state of the patient's health. Single or multiple administrations of the compositions may be administered depending on the dosage and frequency as required and tolerated by the patient. In any event, the composition should provide a sufficient quantity of the active agents of the formulations of this invention to effectively treat (ameliorate one or more symptoms in) the patient.

The concentration of active agent(s) can vary widely, and will be selected primarily based on activity of the active ingredient(s), body weight and the like in accordance with the particular mode of administration selected and the patient's needs. Concentrations, however, will typically be selected to provide dosages ranging from about 0.1 or 1 mg/kg/day to about 50 mg/kg/day and sometimes higher. Typical dosages range from about 3 mg/kg/day to about 3.5 mg/kg/day, preferably from about 3.5 mg/kg/day to about 7.2 mg/kg/day, more preferably from about 7.2 mg/kg/day to about 11.0 mg/kg/day, and most preferably from about 11.0 mg/kg/day to about 15.0 mg/kg/day. In certain preferred embodiments, dosages range from about 10 mg/kg/day to about 50 mg/kg/day. In certain embodiments, dosages range from about 20 mg to about 50 mg given orally twice daily. It will be appreciated that such dosages may be varied to optimize a therapeutic and/or phophylactic regimen in a particular subject or group of subjects.

In certain embodiments, the active agents of this invention are administered to the oral cavity. This is readily accomplished by the use of lozenges, aersol sprays, mouthwash, coated swabs, and the like.

In certain embodiments, the active agent(s) of this invention are administered topically, e.g., to the skin surface, to a topical lesion or wound, to a surgical site, and the like.

In certain embodiments the active agents of this invention are administered systemically (e.g., orally, or as an injectable) in accordance with standard methods well known to those of skill in the art. In other preferred embodiments, the agents, can also be delivered through the skin using conventional transdermal drug delivery systems, i.e., transdermal “patches” wherein the active agent(s) are typically contained within a laminated structure that serves as a drug delivery device to be affixed to the skin. In such a structure, the drug composition is typically contained in a layer, or “reservoir,” underlying an upper backing layer. It will be appreciated that the term “reservoir” in this context refers to a quantity of “active ingredient(s)” that is ultimately available for delivery to the surface of the skin. Thus, for example, the “reservoir” may include the active ingredient(s) in an adhesive on a backing layer of the patch, or in any of a variety of different matrix formulations known to those of skill in the art. The patch may contain a single reservoir, or it may contain multiple reservoirs.

In one embodiment, the reservoir comprises a polymeric matrix of a pharmaceutically acceptable contact adhesive material that serves to affix the system to the skin during drug delivery. Examples of suitable skin contact adhesive materials include, but are not limited to, polyethylenes, polysiloxanes, polyisobutylenes, polyacrylates, polyurethanes, and the like. Alternatively, the drug-containing reservoir and skin contact adhesive are present as separate and distinct layers, with the adhesive underlying the reservoir which, in this case, may be either a polymeric matrix as described above, or it may be a liquid or hydrogel reservoir, or may take some other form. The backing layer in these laminates, which serves as the upper surface of the device, preferably functions as a primary structural element of the “patch” and provides the device with much of its flexibility. The material selected for the backing layer is preferably substantially impermeable to the active agent(s) and any other materials that are present.

Other formulations for topical delivery include, but are not limited to, ointments, gels, sprays, fluids, and creams. Ointments are semisolid preparations that are typically based on petrolatum or other petroleum derivatives. Creams containing the selected active agent are typically viscous liquid or semisolid emulsions, often either oil-in-water or water-in-oil. Cream bases are typically water-washable, and contain an oil phase, an emulsifier and an aqueous phase. The oil phase, also sometimes called the “internal” phase, is generally comprised of petrolatum and a fatty alcohol such as cetyl or stearyl alcohol; the aqueous phase usually, although not necessarily, exceeds the oil phase in volume, and generally contains a humectant. The emulsifier in a cream formulation is generally a nonionic, anionic, cationic or amphoteric surfactant. The specific ointment or cream base to be used, as will be appreciated by those skilled in the art, is one that will provide for optimum drug delivery. As with other carriers or vehicles, an ointment base should be inert, stable, nonirritating and nonsensitizing.

As indicated above, various buccal, and sublingual formulations are also contemplated.

In certain embodiments, one or more active agents of the present invention can be provided as a “concentrate”, e.g., in a storage container (e.g., in a premeasured volume) ready for dilution, or in a soluble capsule ready for addition to a volume of water, alcohol, hydrogen peroxide, or other diluent.

While the invention is described with respect to use in humans, it is also suitable for animal, e.g., veterinary use. Thus certain preferred organisms include, but are not limited to humans, non-human primates, canines, equines, felines, porcines, ungulates, largomorphs, and the like.

B) Nanoemulsion Formulations.

In certain embodiments the targeting peptides, antimicrobial peptides and/or chimeric moieties (e.g., STAMPs) as described herein are formulated in a nanoemulsion. Nanoemulsions include, but are not limited to oil in water (O/W) nanoemulsions, and water in oil (W/O) nanoemulsions. Nanoemulsions can be defined as emulsions with mean droplet diameters ranging from about 20 to about 1000 nm. Usually, the average droplet size is between about 20 nm or 50 nm and about 500 nm. The terms sub-micron emulsion (SME) and mini-emulsion are used as synonyms.

Illustrative oil in water (O/W) nanoemulsions include, but are not limited to:

Surfactant micelles—micelles composed of small molecules surfactants or detergents (e.g., SDS/PBS/2-propanol) which are suitable for predominantly hydrophobic peptides.

Polymer micelles—micelles composed of polymer, copolymer, or block copolymer surfactants (e.g., Pluronic L64/PBS/2-propanol) which are suitable for predominantly hydrophobic peptides;

Blended micelles: micelles in which there is more than one surfactant component or in which one of the liquid phases (generally an alcohol or fatty acid compound) participates in the formation of the micelle (e.g., Octanoic acid/PBS/EtOH) which are suitable for predominantly hydrophobic peptides;

Integral peptide micelles—blended micelles in which the peptide serves as an auxiliary surfactant, forming an integral part of the micelle (e.g., amphipathic peptide/PBS/mineral oil) which are suitable for amphipathic peptides; and

Pickering (solid phase) emulsions—emulsions in which the peptides are associated with the exterior of a solid nanoparticle (e.g., polystyrene nanoparticles/PBS/no oil phase) which are suitable for amphipathic peptides.

Illustrative water in oil (W/O) nanoemulsions include, but are not limited to:

Surfactant micelles—micelles composed of small molecules surfactants or detergents (e.g., dioctyl sulfosuccinate/PBS/2-propanol, Isopropylmyristate/PBS/2-propanol, etc.) which are suitable for predominantly hydrophilic peptides;

Polymer micelles—micelles composed of polymer, copolymer, or block copolymer surfactants (e.g., PLURONIC® L121/PBS/2-propanol), which are suitable for predominantly hydrophilic peptides;

Blended micelles—micelles in which there is more than one surfactant component or in which one of the liquid phases (generally an alcohol or fatty acid compound) participates in the formation of the micelle (e.g., capric/caprylic diglyceride/PBS/EtOH) which are suitable for predominantly hydrophilic peptides;

Integral peptide micelles—blended micelles in which the peptide serves as an auxiliary surfactant, forming an integral part of the micelle (e.g., amphipathic peptide/PBS/polypropylene glycol) which are suitable for amphipathic peptides; and

Pickering (solid phase) emulsions—emulsions in which the peptides are associated with the exterior of a solid nanoparticle (e.g., chitosan nanoparticles/no aqueous phase/mineral oil) which are suitable for amphipathic peptides.

As indicated above, in certain embodiments the nanoemulsions comprise one or more surfactants or detergents. In some embodiments the surfactant is a non-anionic detergent (e.g., a polysorbate surfactant, a polyoxyethylene ether, etc.). Surfactants that find use in the present invention include, but are not limited to surfactants such as the TWEEN®, TRITON®, and TYLOXAPOL® families of compounds.

In certain embodiments the emulsions further comprise one or more cationic halogen containing compounds, including but not limited to, cetylpyridinium chloride. In still further embodiments, the compositions further comprise one or more compounds that increase the interaction (“interaction enhancers”) of the composition with microorganisms (e.g., chelating agents like ethylenediaminetetraacetic acid, or ethylenebis(oxyethylenenitrilo)tetraacetic acid in a buffer).

In some embodiments, the nanoemulsion further comprises an emulsifying agent to aid in the formation of the emulsion. Emulsifying agents include compounds that aggregate at the oil/water interface to form a kind of continuous membrane that prevents direct contact between two adjacent droplets. Certain embodiments of the present invention feature oil-in-water emulsion compositions that may readily be diluted with water to a desired concentration without impairing their anti-pathogenic properties.

In addition to discrete oil droplets dispersed in an aqueous phase, certain oil-in-water emulsions can also contain other lipid structures, such as small lipid vesicles (e.g., lipid spheres that often consist of several substantially concentric lipid bilayers separated from each other by layers of aqueous phase), micelles (e.g., amphiphilic molecules in small clusters of 50-200 molecules arranged so that the polar head groups face outward toward the aqueous phase and the apolar tails are sequestered inward away from the aqueous phase), or lamellar phases (lipid dispersions in which each particle consists of parallel amphiphilic bilayers separated by thin films of water).

These lipid structures are formed as a result of hydrophobic forces that drive apolar residues (e.g., long hydrocarbon chains) away from water. The above lipid preparations can generally be described as surfactant lipid preparations (SLPs). SLPs are minimally toxic to mucous membranes and are believed to be metabolized within the small intestine (see e.g., Hamouda et al., (1998) J. Infect. Disease 180: 1939).

In certain embodiments the emulsion comprises a discontinuous oil phase distributed in an aqueous phase, a first component comprising an alcohol and/or glycerol, and a second component comprising a surfactant or a halogen-containing compound. The aqueous phase can comprise any type of aqueous phase including, but not limited to, water (e.g., dionized water, distilled water, tap water) and solutions (e.g., phosphate buffered saline solution, or other buffer systems). The oil phase can comprise any type of oil including, but not limited to, plant oils (e.g., soybean oil, avocado oil, flaxseed oil, coconut oil, cottonseed oil, squalene oil, olive oil, canola oil, corn oil, rapeseed oil, safflower oil, and sunflower oil), animal oils (e.g., fish oil), flavor oil, water insoluble vitamins, mineral oil, and motor oil. In certain embodiments, the oil phase comprises 30-90 vol % of the oil-in-water emulsion (i.e., constitutes 30-90% of the total volume of the final emulsion), more preferably 50-80%.

In certain embodiments the alcohol, when present, is ethanol.

While the present invention is not limited by the nature of the surfactant, in some preferred embodiments, the surfactant is a polysorbate surfactant (e.g., TWEEN 20®, TWEEN 40®, TWEEN 60®, and TWEEN 80®), a pheoxypolyethoxyethanol (e.g., TRITON® X-100, X-301, X-165, X-102, and X-200, and TYLOXAPOL®), or sodium dodecyl sulfate, and the like.

In certain embodiments a halogen-containing component is present. the nature of the halogen-containing compound, in some preferred embodiments the halogen-containing compound comprises a chloride salt (e.g., NaCl, KCl, etc.), a cetylpyridinium halide, a cetyltrimethylammonium halide, a cetyldimethylethylammonium halide, a cetyldimethylbenzylammonium halide, a cetyltributylphosphonium halide, dodecyltrimethylammonium halides, tetradecyltrimethylammonium halides, cetylpyridinium chloride, cetyltrimethylammonium chloride, cetylbenzyldimethylammonium chloride, cetylpyridinium bromide, cetyltrimethylammonium bromide, cetyldimethylethylammonium bromide, cetyltributylphosphonium bromide, dodecyltrimethylammonium bromide, tetradecyltrimethylammonium bromide, and the like

In certain embodiments the emulsion comprises a quaternary ammonium compound. Quaternary ammonium compounds include, but are not limited to, N-alkyldimethyl benzyl ammonium saccharinate, 1,3,5-Triazine-1,3,5(2H,4H,6H)-triethanol; 1-Decanaminium, N-decyl-N,N-dimethyl-, chloride (or) Didecyl dimethyl ammonium chloride; 2-(2-(p-(Diisobuyl)cresosxy)ethoxy)ethyl dimethyl benzyl ammonium chloride; 2-(2-(p-(Diisobutyl)phenoxy)ethoxy)ethyl dimethyl benzyl ammonium chloride; alkyl 1 or 3-benzyl-1-(2-hydroxethyl)-2-imidazolinium chloride; alkyl bis(2-hydroxyethyl)benzyl ammonium chloride; alkyl demethyl benzyl ammonium chloride; alkyl dimethyl 3,4-dichlorobenzyl ammonium chloride (100% C12); alkyl dimethyl 3,4-dichlorobenzyl ammonium chloride (50% C14, 40% C12, 10% C16); alkyl dimethyl 3,4-dichlorobenzyl ammonium chloride (55% C14, 23% C12, 20% C16); alkyl dimethyl benzyl ammonium chloride; alkyl dimethyl benzyl ammonium chloride (100% C14); alkyl dimethyl benzyl ammonium chloride (100% C16); alkyl dimethyl benzyl ammonium chloride (41% C14, 28% C12); alkyl dimethyl benzyl ammonium chloride (47% C12, 18% C14); alkyl dimethyl benzyl ammonium chloride (55% C16, 20% C14); alkyl dimethyl benzyl ammonium chloride (58% C14, 28% C16); alkyl dimethyl benzyl ammonium chloride (60% C14, 25% C12); alkyl dimethyl benzyl ammonium chloride (61% C11, 23% C14); alkyl dimethyl benzyl ammonium chloride (61% C12, 23% C14); alkyl dimethyl benzyl ammonium chloride (65% C12, 25% C14); alkyl dimethyl benzyl ammonium chloride (67% C12, 24% C14); alkyl dimethyl benzyl ammonium chloride (67% C12, 25% C14); alkyl dimethyl benzyl ammonium chloride (90% C14, 5% C12); alkyl dimethyl benzyl ammonium chloride (93% C14, 4% C12); alkyl dimethyl benzyl ammonium chloride (95% C16, 5% C18); alkyl dimethyl benzyl ammonium chloride (and) didecyl dimethyl ammonium chloride; alkyl dimethyl benzyl ammonium chloride (as in fatty acids); alkyl dimethyl benzyl ammonium chloride (C12-C16); alkyl dimethyl benzyl ammonium chloride (C12-C18); alkyl dimethyl benzyl and dialkyl dimethyl ammonium chloride; alkyl dimethyl dimethybenzyl ammonium chloride; alkyl dimethyl ethyl ammonium bromide (90% C14, 5% C16, 5% C12); alkyl dimethyl ethyl ammonium bromide (mixed alkyl and alkenyl groups as in the fatty acids of soybean oil); alkyl dimethyl ethylbenzyl ammonium chloride; alkyl dimethyl ethylbenzyl ammonium chloride (60% C14); alkyl dimethyl isoproylbenzyl ammonium chloride (50% C12, 30% C14, 17% C16, 3% C18); alkyl trimethyl ammonium chloride (58% C18, 40% C16, 1% C14, 1% C12); alkyl trimethyl ammonium chloride (90% C18, 10% C16); alkyldimethyl(ethylbenzyl) ammonium chloride (C12-18); Di-(C8-10)-alkyl dimethyl ammonium chlorides; dialkyl dimethyl ammonium chloride; dialkyl dimethyl ammonium chloride; dialkyl dimethyl ammonium chloride; dialkyl methyl benzyl ammonium chloride; didecyl dimethyl ammonium chloride; diisodecyl dimethyl ammonium chloride; dioctyl dimethyl ammonium chloride; dodecyl bis(2-hydroxyethyl) octyl hydrogen ammonium chloride; dodecyl dimethyl benzyl ammonium chloride; dodecylcarbamoyl methyl dimethyl benzyl ammonium chloride; heptadecyl hydroxyethylimidazolinium chloride; hexahydro-1,3,5-thris(2-hydroxyethyl)-s-triazine; myristalkonium chloride (and) Quat RNIUM 14; N,N-Dimethyl-2-hydroxypropylammonium chloride polymer; n-alkyl dimethyl benzyl ammonium chloride; n-alkyl dimethyl ethylbenzyl ammonium chloride; n-tetradecyl dimethyl benzyl ammonium chloride monohydrate; octyl decyl dimethyl ammonium chloride; octyl dodecyl dimethyl ammonium chloride; octyphenoxyethoxyethyl dimethyl benzyl ammonium chloride; oxydiethylenebis (alkyl dimethyl ammonium chloride); quaternary ammonium compounds, dicoco alkyldimethyl, chloride; trimethoxysily propyl dimethyl octadecyl ammonium chloride; trimethoxysilyl quats, trimethyl dodecylbenzyl ammonium chloride; n-dodecyl dimethyl ethylbenzyl ammonium chloride; n-hexadecyl dimethyl benzyl ammonium chloride; n-tetradecyl dimethyl benzyl ammonium chloride; n-tetradecyl dimethyl ethylbenzyl ammonium chloride; and n-octadecyl dimethyl benzyl ammonium chloride.

Nanoemulsion formulations and methods of making such are well known to those of skill in the art and described for example in U.S. Pat. Nos. 7,476,393, 7,468,402, 7,314,624, 6,998,426, 6,902,737, 6,689,371, 6,541,018, 6,464,990, 6,461,625, 6,419,946, 6,413,527, 6,375,960, 6,335,022, 6,274,150, 6,120,778, 6,039,936, 5,925,341, 5,753,241, 5,698,219, and 5,152,923 and in Fanun et al. (2009) Microemulsions: Properties and Applications (Surfactant Science), CRC Press, Boca Ratan Fl.

C) Formulations Optimizing Activity.

In certain embodiments, formulations are selected to optimize binding specificity, and/or binding avidity, and/or antimicrobial activity, and/or stability/conformation of the targeting peptide, antimicrobial peptide, chimeric moiety, and/or STAMP. In this regard, it was a surprising discovery that the activity of certain STAMPs, and presumably the constituent targeting peptides and/or antimicrobial peptides was optimized in the presence of a salt. Accordingly, certain embodiments are contemplated where the targeting peptide and/or antimicrobial peptide, and/or STAMP is formulated in combination with one or more salts. The formulatiosn disclosed herein, however, are not limited to those containing salt(s). Embodiments, are also contemplated where the targeting peptide and/or antimicrobial peptide, and/or STAMP is formulated without the presence of a salt.

In certain embodiments, sodium chloride plus a little potassium chloride resulted in the best activity of the salts tested. However, other salts, e.g., CaCl₂, MgCl₂, MnCl₂also enhanced activity. Accordingly, in certain embodiments, it is contemplated that the targeting peptide(s), and/or antimicrobial peptide(s), and/or chimeric moieties, and/or STAMPs are formulated with one or more salts.

In certain embodiments suitable salts include any of a number of pharmaceutically acceptable salts. Representative salts include the hydrobromide, hydrochloride, sulfate, bisulfate, phosphate, nitrate, acetate, valerate, oleate, palmitate, stearate, laurate, benzoate, lactate, phosphate, tosylate, citrate, maleate, fumarate, succinate, tartrate, napthylate, mesylate, besylate, glucoheptonate, lactobionate, and laurylsulphonate salts and the like (see, e.g., Berge et al. (1977) J. Pharm. Sci. 66: 1-19), although it is noted that citrate salts appear to inhibit the activity of certain STAMPs.

In certain embodiments pharmaceutically acceptable salts of the present invention include the conventional nontoxic salts or quaternary ammonium salts of the compounds, e.g., from non-toxic organic or inorganic acids. For example, such conventional nontoxic salts include those derived from inorganic acids such as hydrochloride, hydrobromic, sulfuric, sulfamic, phosphoric, nitric, and the like; and the salts prepared from organic acids such as acetic, propionic, succinic, glycolic, stearic, lactic, malic, tartaric, citric, ascorbic, palmitic, maleic, hydroxymaleic, phenylacetic, glutamic, benzoic, salicyclic, sulfanilic, 2-acetoxybenzoic, fumaric, toluenesulfonic, methanesulfonic, benzenesulfonic, ethane disulfonic, oxalic, isothionic, and the like.

In other cases, the compounds of the present invention may contain one or more acidic functional groups and, thus, are capable of forming pharmaceutically-acceptable salts with pharmaceutically-acceptable bases. The term “pharmaceutically-acceptable salts” in these instances refers to the relatively non-toxic, inorganic and organic base addition salts of compounds of the present invention. These salts can likewise be prepared in situ in the administration vehicle or the dosage form manufacturing process, or by separately treating the compound in its free acid form with a suitable base, such as the hydroxide, carbonate or bicarbonate of a pharmaceutically-acceptable metal cation, with ammonia, or with a pharmaceutically-acceptable organic primary, secondary or tertiary amine. Representative alkali or alkaline earth salts include the lithium, sodium, potassium, calcium, magnesium, and aluminum salts and the like. Representative organic amines useful for the formation of base addition salts include ethylamine, diethylamine, ethylenediamine, ethanolamine, diethanolamine, piperazine and the like (see, for example, Berge et al., supra; and Stahl and Wermuth (2002) Handbook of Pharmaceutical Salts: Properties, Selection, and Use, Wiley-VCH, Zurich, Switzerland).

In various embodiments, the salt is simply a sodium chloride and/or a potassium chloride and can readily be prepared, for example, as a phosphate buffered saline (PBS) solution. In certain embodiments, the salt concentration is comparable to that found in 0.5×PBS to about 2.5×PBS, more preferably from about 0.5×PBS to about 1.5×PBS. In certain embodiments optimum activity has been observed in 1×PBS.

In various embodiments, the pH of the formulation ranges from about pH 5.0 to about pH 8.5, preferably from about pH 6.0 to about pH 8.0, more preferably from about pH 7.0 to about pH 8.0. In certain embodiments the pH is about pH 7.4.

While optimum results have been observed for certain STAMPs using a PBS buffer system, other buffer systems are also acceptable. Such buffers include, but are not limited to sulfate buffers, carbonate buffers, Tris buffers, CHAPS buffers, PIPES buffers, and the like, as long as the salt is included.

In various embodiments, the targeting peptide, and/or antimicrobial peptide, and/or chimeric moiety, and/or STAMP is present in the formulation at a concentration ranging from about 1 nM, to about 1, 10, or 100 mM, more preferably from about 1 nM, about 10 nM, about 100 nM, about 1 μM, or about 10 μM to about 50 μM, about 100 μM, about 200 μm, about 300 μM, about 400 μM, or about 500 μM, preferably from about 1 μL1M, about 10 μM, about 25 μM, or about 50 μM to about 1 mM, about 10 mM, about 20 mM, or about 5 mM, most preferably from about 10 μM, about 20 μM, or about 50 μM to about 100 μM, about 150 μM, or about 200 μM.

D) Home Health Care/Hygiene Product Formulations.

In certain embodiments, one or more of the targeting peptide(s), and/or antimicrobial peptides (AMPs) and/or chimeric moieties, and/or STAMPS described herein are incorporated into healthcare formulations, e.g., for home use. Such formulations include, but are not limited to toothpaste, mouthwash, tooth whitening strips or solutions, contact lens storage, wetting, or cleaning solutions, dental floss, toothpicks, toothbrush bristles, oral sprays, oral lozenges, nasal sprays, aerosolizers for oral and/or nasal application, wound dressings (e.g., bandages), and the like.

For example, chimeric moieties and/or STAMPs, and/or AMPs directed against S. mutans are well suited for inhibiting frequency or severity of dental caries formation, plaque formation, periodontal disease, and/or halitosis.

Chimeric moieties and/or STAMPs, and/or AMPs directed against Corynebacterium spp, when applied to a skin surface can reduce/eliminate Corynebacterium resulting in a reduction of odors. Such moieties are readily incorporated in soaps, antibiotics, antiseptics, disinfectants, and the like.

The formulation of such health products is well known to those of skill, and the antimicrobial peptides and/or chimeric constructs are simply added to such formulations in an effective dose (e.g., a prophylactic dose to inhibit dental carie formation, etc.).

For example, toothpaste formulations are well known to those of skill in the art. Typically such formulations are mixtures of abrasives and surfactants; anticaries agents, such as fluoride; tartar control ingredients, such as tetrasodium pyrophosphate and methyl vinyl ether/maleic anhydride copolymer; pH buffers; humectants, to prevent dry-out and increase the pleasant mouth feel; and binders, to provide consistency and shape (see, e.g., Table 17). Binders keep the solid phase properly suspended in the liquid phase to prevent separation of the liquid phase out of the toothpaste. They also provide body to the dentifrice, especially after extrusion from the tube onto the toothbrush.

TABLE 17

Typical components of toothpaste.

Ingredients
Wt %

Humectants
40-70

Water
0-50

Buffers/salts/tartar
0.5-10

control

Organic thickeners
0.4-2

(gums)

Inorganic thickeners
0-12

Abrasives
10-50

Actives (e.g., triclosan)
0.2-1.5

Surfactants
0.5-2

Flavor and sweetener
0.8-1.5

Fluoride sources provide 1000-15000 ppm fluorine.

Table 18 lists typical ingredients used in formulations; the final combination will depend on factors such as ingredient compatibility and cost, local customs, and desired benefits and quality to be delivered in the product. It will be recognized that one or more antimicrobial peptides and/or chimeric constructs described herein can simply be added to such formulations or used in place of one or more of the other ingredients.

TABLE 18

List of typical ingredients.

Tartar

Inorganic

Control

Gums
Thickeners
Abrasives
Surfactants
Humectants
Ingredient

Sodium
Silica
Hydrated
Sodium
Glycerine
Tetrasodium

carboxymethyl
thickeners
silica
lauryl sulfate

pyrophosphate

cellulose

Cellulose ethers
Sodium
Dicalcium
Sodium N-
Sorbitol
Gantrez S-70

aluminum
phosphate
lauryl

silicates
digydrate
sarcosinate

Xanthan Gum
Clays
Calcium
Pluronics
Propylene
Sodium tri-

carbonate

glycol
polyphosphate

Carrageenans

Sodium

Xylitol

bicarbonate

Sodium alginate

Calcium
Sodium
Polyethylene

pyrophosphate
lauryl
glycol

sulfoacetate

Carbopols

Alumina

One illustrative formulation described in U.S. Pat. No. 6,113,887 comprises (1) a water-soluble bactericide selected from the group consisting of pyridinium compounds, quaternary ammonium compounds and biguanide compounds in an amount of 0.001% to 5.0% by weight, based on the total weight of the composition; (2) a cationically-modified hydroxyethylcellulose having an average molecular weight of 1,000,000 or higher in the hydroxyethylcellulose portion thereof and having a cationization degree of 0.05 to 0.5 mol/glucose in an amount of 0.5% to 5.0% by weight, based on the total weight of the composition; (3) a surfactant selected from the group consisting of polyoxyethylene polyoxypropylene block copolymers and alkylolamide compounds in an amount of 0.5% to 13% by weight, based on the total weight of the composition; and (4) a polishing agent of the non-silica type in an amount of 5% to 50% by weight, based on the total weight of the composition. In certain embodiments, the antimicrobial peptide(s) and/or chimeric construct(s) described herein can be used in place of the bactericide or in combination with the bactericide.

Similarly, mouthwash formulations are also well known to those of skill in the art. Thus, for example, mouthwashes containing sodium fluoride are disclosed in U.S. Pat. Nos. 2,913,373, 3,975,514, and 4,548,809, and in US Patent Publications US 2003/0124068 A1, US 2007/0154410 A1, and the like. Mouthwashes containing various alkali metal compounds are also known: sodium benzoate (WO 9409752); alkali metal hypohalite (US 20020114851A1); chlorine dioxide (CN 1222345); alkali metal phosphate (US 2001/0002252 A1, US 2003/0007937 A1); hydrogen sulfate/carbonate (JP 8113519); cetylpyridium chloride (CPC) (see, e.g., U.S. Pat. No. 6,117,417, U.S. Pat. No. 5,948,390, and JP 2004051511). Mouthwashes containing higher alcohol (see, e.g., US 2002/0064505 A1, US 2003/0175216 A1); hydrogen peroxide (see, e.g., CN 1385145); CO₂gas bubbles (see, e.g., JP 1275521 and JP 2157215) are also known. In certain embodiments, these and other mouthwash formulations can further comprise one or more of the AMPs or compound AMPs of this invention.

Contact lens storage, wetting, or cleaning solutions, dental floss, toothpicks, toothbrush bristles, oral sprays, oral lozenges, nasal sprays, and aerosolizers for oral and/or nasal application, and the like are also well known to those of skill in the art and can readily be adapted to incorporate one or more antimicrobial peptide(s) and/or chimeric construct(s) described herein.

The foregoing pharmaceutical and/or home healthcare formulations and/or devices are meant to be illustrative and not limiting. Using teaching provided herein, the antimicrobial peptide(s) and/or chimeric construct(s) described herein can readily be incorporated into other products.

E) Illustrative Oral Care Formulations.

The targeting peptide(s), and/or antimicrobial peptide(s), and/or chimeric moieties, and/or STAMPs described herein can be used for a number of applications, e.g., as described above. In certain embodiments anti-S. mutans STAMPs, AMPs, and/or other chimeric moieties can be used to reduce the incidence or severity of dental caries, inhibit plaque formation, reduce halitosis, and the like. Accordingly, in certain embodiments, such moieties are included in devices and formulations for dental applications e.g., tea or other drinks, toothpick coatings, dental floss coatings, toothpaste, gel, mouthwash, varnish, even professional dental products.

In certain embodiments, methods of treating or reducing the incidence, duration, or severity of periodontal disease are provided. The methods can include applying to the gingival crevice or periodontal pocket a composition comprising a targeting peptide, and/or antimicrobial peptide, and/or STAMP, and/or other chimeric moiety as described herein with a carrier/stabilizing agent. In the composition applied, the carrier/stabilizing agent can provide retention, tissue penetration, deposition and sustained release of the active agent (e.g., STAMP) for reducing the population of specific bacterial species within a periodontal biofilm and associated tissues. In certain embodiments, the carrier agent provides penetration and retention into the gingival crevice or periodontal pocket and associated tissues with sustained release of the active agent to enhance the reduction in population of select bacteria within the gingival tissue and dentinal tubule tissue.

In various embodiments, carrier agents can include, but are not limited to polylactide, polyglycolide, polylactide-co-glycolide, polycaprolactone, cellulosic-based polymers, ethylene glycol polymers and its copolymers, oxyethylene polymers, polyvinyl alcohol, chitosan and hyaluronan and its copolymers. In an aspect, the carrier agents include hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, hydroxymethyl cellulose, polyvinyl alcohol, polyethylene glycol, polyethylene oxide, ethylene oxide-propylene oxide co-polymers, chitosan, hyaluronan and its copolymers, or combinations thereof. In another aspect, the carrier agents include hyaluronan or hyaluronic acid and copolymers including salts of hyaluronic acid, esters of hyaluronic acid, cross-linked gels of hyaluronic acid, enzymatic derivatives of hyaluronic acid, chemically modified derivatives of hyaluronic acid or combinations thereof. As used herein, hyaluronic acid broadly refers to naturally occurring, microbial and synthetic derivatives of acidic polysaccharides of various molecular weights constituted by residues of D-glucuronic acid polysaccharides and N-acetyl-D-glucosamine.

In certain embodiments, the active agent (e.g., STAMP, AMP, etc.) and the carrier agent are in the form of an admixture, in the form of a complex, covalently coupled, or a combination thereof. In certain embodiments, the carrier agent comprises a bioadhesive. Suitable bioadhesive carrier agents include, but are not limited to a cellulose based polymer and/or a dextrin. Suitable cellulose based polymers include, but are not limited to hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxymethyl cellulose, or a mixture thereof. In one illustrative embodiment, the bioadhesive carrier agent includes polylactide, polyglycolide, polylactide-co-glycolide, polyethylene glycol, hyaluronan, hyaluronic acid, chitosan, or a mixture thereof. In certain embodiments the bioadhesive carrier agent can include a copolymer comprising polyethylene glycol, hyaluronan, hyaluronic acid, chitosan, or a mixture thereof.

In certain embodiments, the carrier agent penetrates periodontal tissues. Suitable penetrating carrier agents include, but are not limited to hyaluronic acid, a hyaluronic acid derivative, chitosan, a chitosan derivative, or a mixture thereof. In an embodiment, the penetrating carrier agent includes a salt of hyaluronic acid, an ester of hyaluronic acid, an enzymatic derivative of hyaluronic acid, a cross-linked gel of hyaluronic acid, a chemically modified derivative of hyaluronic acid, or a mixture thereof.

V. Microorganism Detection.

As indicated above, the targeting moieties and/or STAMPs are useful in diagnostic compositions and methods to determine the presence or absence and/or to quantify the amount of one or microorganisms present in the environment, in a food stuff, in a biological sample, and the like.

For example, targeting peptide-antimicrobial peptide conjugates (e.g. Specifically targeted antimicrobial peptides (STAMPs)) can be used as diagnostic reagents. STAMPs (and other targeted antimicrobial constructs described herein) have the ability to specifically bind to microorganisms, for example, S. mutans, and permeabilize or disrupt their membrane such that cell impermeable dyes or other reagent (propidium iodide, etc.) may enter the microorganism or intracellular molecules or contents (ATP, DNA, Calcium, etc.) of the targeted microorganism are caused to be released into the environment for analysis. In one method a STAMP, for example, C16G2, can permeabilize or disrupt the membrane of target microorganisms, for example, S. mutans, in a prepared culture or clinical sample by itself, in a biofilm in vitro or in vivo. To the sample a cell impermeable dye (e.g. propidium iodide, etc.) is added to label and allow for detection of those microorganisms targeted by the STAMP. Cell permeable dyes (e.g. SYTO9) can also be added to label and detect the entire population of microorganisms in the sample. Labeled cells can then be quantified by fluorescence microscopy, fluorometry, flow cytometry or other method.

In another example, a STAMP treated sample is mixed with luciferase and luciferin which reacts with the ATP released from the STAMP treated cells and the resulting luminescence is used to detected and quantify targeted cells.

VI. Kits.

In another embodiment this invention provides kits for the inhibition of an infection and/or for the treatment and/or prevention of dental caries in a mammal. The kits typically comprise a container containing one or more of the active agents (i.e., the antimicrobial peptide(s) and/or chimeric construct(s)) described herein. In certain embodiments the active agent(s) can be provided in a unit dosage formulation (e.g., suppository, tablet, caplet, patch, etc.) and/or may be optionally combined with one or more pharmaceutically acceptable excipients.

In certain embodiments the kits comprise one or more of the home healthcare product formulations described herein (e.g., toothpaste, mouthwash, tooth whitening strips or solutions, contact lens storage, wetting, or cleaning solutions, dental floss, toothpicks, toothbrush bristles, oral sprays, oral lozenges, nasal sprays, aerosolizers for oral and/or nasal application, and the like).

In certain embodiments kits are provided for detecting and/or locating and/or quantifying certain target microorganisms and/or cells or tissues comprising certain target microorganisms, and/or prosthesis bearing certain target microorganisms, and/or biofilms comprising certain target microorganisms. In various embodiments these kits typically comprise a chimeric moiety comprising a targeting moiety and a detectable label as described herein and/or a targeting moiety attached to an affinity tag for use in a pretargeting strategy as described herein.

In addition, the kits optionally include labeling and/or instructional materials providing directions (i.e., protocols) for the practice of the methods or use of the “therapeutics” or “prophylactics” or detection reagents of this invention. Certain instructional materials describe the use of one or more active agent(s) of this invention to therapeutically or prophylactically to inhibit or prevent infection and/or to inhibit the formation of dental caries. The instructional materials may also, optionally, teach preferred dosages/therapeutic regiment, counter indications and the like.

While the instructional materials typically comprise written or printed materials they are not limited to such. Any medium capable of storing such instructions and communicating them to an end user is contemplated by this invention. Such media include, but are not limited to electronic storage media (e.g., magnetic discs, tapes, cartridges, chips), optical media (e.g., CD ROM), and the like. Such media may include addresses to internet sites that provide such instructional materials.

EXAMPLES

The following examples are offered to illustrate, but not to limit the claimed invention.

Example 1
Design and Activity of a “Dual-Targeted” Antimicrobial Peptide

Numerous reports have indicated the important role of human normal flora in the prevention of microbial pathogenesis and disease. Evidence suggests that infections at mucosal surfaces result from the outgrowth of subpopulations or clusters within a microbial community, and are not linked to one pathogenic organism alone. In order to preserve the protective normal flora while treating the majority of infective bacteria in the community, a tunable therapeutic is necessary that can discriminate between benign bystanders and multiple pathogenic organisms. Here we describe the proof-of-principle for such a multi-targeted antimicrobial: a multiple-headed specifically-targeted antimicrobial peptide (MH-STAMP). The completed MH-STAMP, M8(KH)-20, displays specific activity against targeted organisms in vitro (Pseudomonas aeruginosa and Streptococcus mutans) and can remove both species from a mixed planktonic culture with little impact against untargeted bacteria. These results demonstrate that a functional, dual-targeted molecule can be constructed from wide-spectrum antimicrobial peptide precursor.

Introduction

For nearly 30 years antimicrobial peptides (AMPs) have been rigorously investigated as alternatives to small molecule antibiotics and potential solutions to the growing crisis of antibiotic resistant bacterial infections (Ganz (2003) Nat Rev Immunol., 3: 710-720; Hancock and Lehrer (1998)., 16: 82-88). Numerous reports have characterized potential AMPs from natural sources, and a great body of work has been carried out designing “tailor-made” AMPs due to the approachable nature of solid-phase peptide synthesis (SPPS) (Genco et al. (2003) Int J Antimicrob Agents, 21: 75-78; He and Eckert (2007) Antimicrob Agents Chemother., 51: 1351-1358). Several examples of the latter have shown remarkable activities in vitro against fungi, Gram-positive and Gram-negative bacteria, as well as some enveloped viruses (Brogden (2005) Nat Rev Microbiol. 3: 238-250).

Unlike small molecule antibiotics that may lose activity when their basic structures are modified even incrementally, peptides are a convenient canvas for molecular alteration. AMPs can be optimized through the incorporation of more or less hydrophobic or charged amino acids, which has been shown to affect selectivity for Gram-positive, Gram-negative or fungal membranes (Muhle and Tam J P (2001) Biochemistry, 40: 5777-5785; Tossi et al. (2000) Biopolymers 55: 4-30). Additionally, lysine residues can be utilized to improve AMP activity per μM. In this approach, multiple AMP chains can be attached to a single peptide scaffold through branching from lysine epsilon-amines (Tam et al. (2992) Eur. J. Biochem., 269: 923-932; Pini et al. (2005) Antimicrob Agents Chemother., 2005; 49: 2665-2672). AMP activity can be specifically tuned through the attachment of a targeting peptide region, as described for a novel class of molecules, the specifically-targeted antimicrobial peptides, or STAMPs (Eckert et al. (2006) Antimicrob Agents Chemother., 50: 3651-3657; Eckert et al. (2006) Antimicrob Agents Chemother., 50: 1480-1488). These chimeric molecules can consist of functionally independent targeting and killing moieties within a linear peptide sequence. A pathogenic bacterium recognized (i.e. bound) by the targeting peptide can be eliminated from a multi-species community with little impact to bystander normal flora. As an extension of this concept, we hypothesized that a STAMP could be constructed with multiple targeting peptide “heads” attached to a single AMP by utilizing a central lysine residue branch point. Potentially, targeting “heads” could be specific for the same pathogen, or have different binding profiles. Utilizing the former approach, microbial resistance evolution linked to a targeting peptide could be inhibited or reduced, as no single microbial population would have the genetic diversity necessary to mutate multiple discrete targeting peptide receptors in one cell (Drake et al. (1998) Genetics 148: 1667-1686).

Multi-headed STAMP (MH-STAMP) molecules with differing bacterial targets may have appeal in treating poly-microbial infections, or where it may be advantageous to remove a cluster of biofilm constituents without utilizing several distinct molecules; for example in the simultaneously treatment of dental caries and periodontitis, or in the eradication of the Propionibacteria spp. and Staphylococcus spp. involved in acne and skin infections, respectively.

In this example, we present the proof-of-principle design, synthesis and in vitro activity of such a MH-STAMP, M8(KH)-20. Previously, we identified two functional STAMP targeting domains, one with specific recognition of the cariogenic pathogen S. mutans (Eckert et al. (2006) Antimicrob Agents Chemother., 50: 3651-3657), and the other with Pseudomonas spp.-level selectivity (Eckert et al. (2006) Antimicrob Agents Chemother., 50: 3833-3838). Conjoined to a normally wide-spectrum linear AMP, we observed antimicrobial effects directed specifically to P. aeruginosa and S. mutans in vitro. Additionally, treatment of mixed bacterial communities with the multi-headed MH-STAMP resulted in the specific eradication of the target organisms with little impact on bystander population levels.

Materials and Methods

Bacterial Strains and Growth Conditions

P. aeruginosa ATCC15692, Klebsiella pneumoniae KAY 2026 (Sprenger and Lengeler (1984) J Bacteriol., 157: 39-45), Escherichia coli DH5a (pFW5, spectinomycin resistance) (Podbielski et al. (1996) Gene, 177: 137-147), Staphylococcus aureus Newmann (Duthie and Lorenz (1952) J Gen Microbiol., 6: 95-107), and Staphylococcus epidermidis ATCC35984 were cultivated under aerobic conditions at 37° C. with vigorous shaking Aerobic Gram-negative organisms were grown in Lauri-Bertaini (LB) broth and Gram-positive bacteria in Brain-heart infusion (BHI) broth. Streptococcus mutans JM11 (spectinomycin resistant, UA140 background) was grown in Todd-Hewitt (TH) broth under anaerobic conditions (80% N2, 15% CO₂, 5% H2) at 37° C. Merritt et al. (2005) J Microbiol Meth., 61: 161-170. All bacteria were grown overnight to an OD600 of 0.8-1.0 prior to appropriate dilution and antimicrobial testing.

Synthesis of Multi-Head STAMP Peptides

Conventional solid-phase peptide synthesis (SPPS) methodologies were utilized for the construction of all peptides shown in FIG. 15 (Symphony Synthesizer, PTI, Tucson, Ariz.). Chemicals, amino acids, and synthesis resins were purchased from Anaspec (San Jose, Calif.). BD2.20 (FIRKFLKKWLL (SEQ ID NO:3226), amidated c-terminus, mw 1491.92), an antimicrobial peptide developed in our laboratory with robust antimicrobial activity against a number of bacterial species (Table 19), served as the root sequence to which differing targeting peptides were attached: Firstly, BD2.20 was synthesized by SPPS (Rink-Amide-MBHA resin, 0.015 mmol), followed by the stepwise coupling of a functionalized alkane (NH₂(CH₂)₇COOH), and an Fmoc-protected Lys (side-chain protected with 4-methyltrityl (Mtt)) to the N-terminus. Standard SPPS methods were then employed for the step-wise addition of the S. mutans targeting peptide M8 plus a tri-Gly linker region (TFFRFLNR-GGG (SEQ ID NO:3227)) to the N-terminal of the central Lys. After assembly of Fmoc-M8-GGG-K(Mtt)-(CH₂)₇C0-BD2.20 (SEQ ID NO:3228), the Fmoc group was removed with 25% piperidine in DMF and the N-terminal was re-protected with an acetyl group with Ac₂O/DIEA (1:1, 20 molar excess) for 2 hours. The Mtt-protected amino group of the central Lys was then selectively exposed with 2% TFA in DCM (1.5 mL) for 15 minutes (three cycles of 5 min). The resulting product was reloaded into the synthesizer and the peptide sequence built from the Lys side-chain was completed with standard Fmoc SPPS methods. As shown in FIG. 15, the completed MH-STAMP M8(KH)-20 contained the side-chain peptide KH (Pseudomonas spp.-targeting, KKHRKHRKHRKH-GGG (SEQ ID NO:3229)), while in MH-STAMP M8(BL)-20 a peptide with no bacterial binding (data not shown), BL-1 (DAANEA-GGG), was utilized. BL(KH)-20 was constructed identically to M8(KH)-20, utilizing BL-1 in place of M8 (FIG. 15).

TABLE 19

MICs of MH-STAMPs and component peptides.

MIC (μM)

P. aeruginosa

E. coli

K. pneumoniae

S. mutans

S. epidermidis

S. aureus

BD2.20
14.4 ± 4.40
5.47 ± 1.41
2.98 ± 0.47
2.86 ± 0.60
5.11 ± 1.58
5.625 ± 1.29

M8(KH)-
11.95 ± 3.32
2.72 ± 0.59
3.13
6.25
3.13
5.64 ± 1.07

20

M8(BL)-
50
5.97 ± 0.94
6.88 ± 1.98
6.25
6.25
18.05 ± 6.58

20

BL(KH)-
27.5 ± 7.90
6.25
6.25
6.25
6.25
6.25

20

Average MIC with standard deviation, n = 10 assays.

Synthesis progression was monitored by the ninhydrin test, and completed peptides cleaved from the resin with 95% TFA utilizing appropriate scavengers, and precipitated in methyl tert-butyl ether. Purification and MH-STAMP quality was confirmed by HPLC (Waters, Milford, Mass.) using a linear gradient of increasing mobile phase (acetonitrile 10 to 90% in water with 0.1% TFA) and a Waters XBridge BEH 130 C18 column (4.6×100 mm, particle size 5 μm). Absorbance at 215 nm was utilized as the monitoring wavelength, though 260 and 280 nm were also collected. LC spectra were analyzed with MassLynx Software v.4.1 (Waters). Matrix-assisted laser desorption ionization (MALDI) mass spectroscopy was utilized to confirm correct peptide mass (Voyager System 4291, Applied Biosystems) (Anderson et al. (2008) Biotechnol Lett., 30: 813-818).

MIC Assay

Peptides were evaluated for basic antimicrobial activity by broth microdilution, as described previously (Eckert et al. (2006) Antimicrob Agents Chemother., 50: 3651-3657; Eckert et al. (2006) Antimicrob Agents Chemother., 50: 1480-1488). Briefly, ˜1×105 cfu/mL bacteria were diluted in TH (S. mutans), or Mueller-Hinton (MH) broth (all other organisms) and distributed to 96-well plates. Serially-diluted (2-fold) peptides were then added and the plates incubated at 37° C. for 18-24 h. Peptide MIC was determined as the concentration of peptide that completely inhibited organism growth when examined by eye (clear well). All experiments were conducted 10 times.

Post-Antibiotic Effect Assay

The activity and selectivity of MH-STAMPs after a 10 min incubation was determined by growth retardation experiments against targeted and untargeted bacteria in monocultures, as described previously (Id.). Cells from overnight cultures were diluted to ˜5×106 cfu/mL in MH (or TH with 1% sucrose for S. mutans), normalized by OD600 0.05-0.1 and seeded to 96-well plates. Cultures were then grown under the appropriate conditions for 2 h (3 h for S. mutans) prior to the addition of peptides for 10 min. Plates were then centrifuged at 3000×g for 5 min, the supernatants discarded, fresh medium returned (MH or TH without sucrose for S. mutans), and incubation resumed. Bacterial growth after treatment was then monitored over time by OD600.

Microbial Population Shift Assay

Mixed planktonic populations of P. aeruginosa, E. coli, S. epidermidis, and S. mutans were utilized to examine the potential of MH-STAMPs to direct species composition within a culture after treatment. Samples were prepared containing: ˜6×10⁴cfu/mL S. mutans, ˜2×10⁴cfu/mL E. coli, ˜2×10⁴cfu/mL S. epidermidis, and ˜0.5×10⁴cfu/mL P. aeruginosa in BHI (mixed immediately before peptide addition). Peptide (10 μM) or mock-treatment (1×PBS) was then added and samples were incubated at 37° C. for 24 h under anaerobic conditions (80% N₂, 15% CO₂, 5% H₂). After incubation, samples were serially diluted (1:10) in 1×PBS and aliquots from each dilution were then spotted to agar plates selective for each species in the mixture: TH plus 800 μg/mL spectinomycin (S. mutans), LB plus 25 μg/mL ampicillin (P. aeruginosa), LB plus 200 μg/mL spectinomycin (E. coli), and mannitol salt agar (MSA, S. epidermidis) in order to quantitate survivors from each species. Plates were then incubated 37° C. under aerobic conditions (TH plates were incubated anaerobically) and colonies counted after 24 h to determine survivors. Expected colony morphologies were observed for each species when plated on selective media. Gram stains and direct microscopic observation (from select isolated colonies) were undertaken to confirm species identity (data not shown). The detection limit of the assay was 200 cfu/mL.

Results

Design and Synthesis of Multi-Headed STAMPs

We constructed a prototype MH-STAMP from the well-established targeting peptides KH (specific to Pseudomonas spp) and M8 (specific for Streptococcus mutans). The wide-spectrum antimicrobial peptide BD2.20 was utilized as the base AMP for all MH171 STAMP construction. BD2.20 is a novel synthetic AMP with a cationic and amphipathic residue arrangement, which has robust MICs against a variety of Gram-negative and Gram-positive organisms (Table 19). For the synthesis of MH-STMAP M8(KH)-20 (construct presented in FIG. 15), BD2.20 and a Lys (Mtt-protected side-chain) residue were joined via an activated alkane spacer, followed by addition of the M8 targeting peptide to the N-terminus of the product. Selective deprotection of the central Lys(Mtt) side chain was then undertaken and the KH targeting peptide attached. The correct molecular mass (4888.79) and ˜90% purity was confirmed by HPLC and MALDI mass spectrometry (FIG. 16).

The non-binding “blank” targeting peptide BL-1 was incorporated into the synthesis scheme in place of KH or M8 to construct variant MH-STAMPs possessing a single functional targeting head: M8(BL)-20 and BL(KH)-20. The correct MW and acceptable purity were observed for these MH-STAMPs (FIG. 15, data not shown).

General Antimicrobial Activity of Multi-Head Constructs

After synthesis, the completed MH-STAMPs were evaluated for general antimicrobial activity by MIC against a panel of bacteria. As shown in Table 19, the MH-STAMP constructs M8(KH)-20, BL(KH)-20, and M8(BL)-20 were found to have similar activity profiles to that of BD2.20 for the organisms examined (less than two titration steps in 10-fold difference). Additionally, we observed a difference in general susceptibility between P. aeruginosa and the other organisms tested, suggesting this bacterium is more resistant to BD2.20. Overall, these data indicate that the addition of the targeting domains to the base sequence was tolerated and did not completely inhibit the activity of the antimicrobial peptide.

Peptide selectivity could not be determined utilizing these methods, as STAMPs and their parent AMP molecules often display similar MICs, but have radically different antimicrobial kinetics and selectivity due to increased specific-killing mediated by the targeting regions (Id.). Therefore, we performed different experiments to test for antimicrobial selectivity and functional MH-STAMP construction.

Selectivity and Post-Antibiotic Effect of MH-STAMP Constructs

MH-STAMP antimicrobial kinetics was ascertained utilizing a variation of the classical post-antibiotic effect assay, which measures the ability of an agent to affect an organism's growth after a short exposure period. Monocultures of MH-STAMP-targeted and untargeted organisms were exposed to M8(KH)-20, M8(BL)-20, BL(KH)-20, or unmodified BD2.20, then allowed to recover. As shown in FIG. 17A, S. mutans growth was effectively retarded by M8-containing constructs (M8(KH)-20, M8(BL)-20), but was not altered by a MH-STAMP construct lacking this region (BL(KH)-20). Similarly, the growth of the other targeted bacterium, P. aeruginosa, was inhibited in a KH-dependant manner (FIG. 17B). In comparison, the non-targeted bacteria E. coli, S. aureus, and S. epidermidis were not inhibited by treatment with any MH-STAMP and were only inhibited by the base antimicrobial peptide BD2.20, which displayed robust antimicrobial activity against all examined strains. These results indicate that MH-STAMPs containing KH or M8 targeting domains have activity against P. aeruginosa or S. mutans, respectively, and not other bacteria. Furthermore, replacement of the targeting region with a non-binding peptide abolishes specific activity.

Ability of MH-STAMPs to Direct a “Population Shift” within a Mixed Species Population

We hypothesized that potential MH-STAMP dual-functionality could affect a particular set of bacteria within a mixed population, thereby promoting the outgrowth of non-targeted organisms and “shifting” the constituent makeup. To examine this possibility, defined mixed populations of planktonic cells were treated continuously and the make-up of the community examined after 24 h. As shown in FIG. 18, treatment with the wide spectrum AMP BD2.20 resulted in a significant loss of recoverable cfu/mL after 24 h from all species in the mixture. Treatment with M8(KH)-20 was found to alter this pattern; we observed ˜1×10⁵cfu/mL surviving E. coli and S. epidermidis, but did not recover S. mutans or P. aeruginosa cfu/mL. In BL(KH)-20 treated samples, P. aeruginosa cfu/mL were not observed, though we recovered higher than input cfu/mL from S. mutans and unchanged numbers of S. epidermidis and E. coli. In samples exposed to M8(BL)-20, S. mutans recoverable cfu/mL were greatly reduced compared to input cfu/mL, while other species were not affected or affected to a lesser extent. Interestingly, these results suggest that M8(KH)-20, M8(BL)-20, and BL(KH)-20 retain their ability to affect organisms recognized by the targeting regions present, even within a mixed population of bacteria.

Discussion

Our results indicate that we have successfully constructed a STAMP with dual antimicrobial specificities controlled by the targeting peptides present in the molecule; KH for Pseudomonas spp, M8 for S. mutans. In a closed multi-species system (FIG. 18), the dual specificity of M8(KH)-20 was readily discernable: the population of the culture “shifted” away from targeted organisms after MH-STAMP treatment. The targeted bacteria were eliminated and the population of untargeted organisms increased, to varying degrees, above-input cfu/mL. Additionally, interruption of KH or M8 in the MH-STAMP construct with the non-binding peptide BL-1 resulted in the expected elimination of only one targeted species. These results support the hypothesis that functional MH-STAMPs could be constructed from a wide-spectrum AMP base.

The emergence of metagenomics and the development of more sensitive molecular diagnostics has driven an increase in the understanding of human-associated microbial ecologies and host-microbe interactions (Aas et al. (2005) J Clin Microbiol., 43: 5721-5732; Boman (2000) Immunol Rev., 173: 5-16; Kreth et al. (2005) J Bacteriol., 187: 7193-7203). At mucosal surfaces, it has become clear that our bodies harbor an abundance of residential flora which may impact innate and humoral immunity, nutrient availability, protection against pathogens, and even host physiology (Metges (2000) J Nutr., 130: 1857S-64; Sears (2005) Anaerobe, 11: 247-251; Lievin-Le et al. (2006) Clin Microbiol Rev., 19: 315-337; DiBaise et al. (2008) Mayo Clinic Proceedings 83: 460-469). Furthermore, findings have indicated that shifts in the diversity of normal flora are associated with negative clinical consequences; for example the overgrowth of S. mutans in the oral cavity during cariogenesis (linked to the uptake of sucrose) or the antibiotic-assisted colonization of the intestine by Clostridium difficle (Loesche (1986) Microbiol Rev., 50: 353-380; Gould and McDonald (2998) Crit. Care 12: 203). Other population shifts may be linked to axilla odor (Corynebacteria spp) (Leyden et al. (1981) J Invest Dermatol., 77: 413-416; Elsner (2006) Curr Probl Dermatol., 33: 35-41), or even host obesity. Given the quantity and diversity of microbes present, pathogenesis at mucosal surfaces is not likely to be associated with the overgrowth of a single strain or species. More often, it is a population shift resulting in the predominance of two or more species; for example the persistence of Burkholderia cepacia and P. aeruginosa in cystic fibrosis airway or Treponema denticola and Porphymonas gingivalis and other “red cluster” organisms in gingivitis (Govan and Deretic (1996) Microbiol Rev., 60: 539-574; Paster et al. (2001) J Bacteriol., 183: 3770-3783). In many cases (such as the latter) these species may have only distant phylogenetic relationships and display differential susceptibilities to antibiotic therapies resulting in persistent disease progression despite treatment (Schlessinger (1988) Clin Microbiol Rev., 1: 54-59; Tresse et al. (1997) J Antimicrob Chemother., 40: 419-421). Currently, available treatments for infections of mucosal surfaces are largely non-specific (traditional small-molecule antibiotics, mechanical removal), and thus are not effective in retaining flora or shifting the constituent balance back to a health-associated composition (Keene and Shklair (1974) J Dent Res., 53: 1295). There is a need for a therapeutic treatment that can selectively target multiple pathogens, regardless of their phylogenetic relationship, and MH-STAMPs can help achieve this goal.

In monoculture experiments (FIG. 17), our results suggest that M8 or KH inclusion in the MH-STAMP drove activity towards S. mutans or P. aeruginosa, but also that the presence of a targeting domain reduced the activity of the parent AMP BD2.20 against untargeted organisms. In contrast, the results of our MIC assays (Table 19) indicate little difference in activity between BD2.20 and any MH-STAMP. Against untargeted organisms, the M8 and KH regions are likely to have a negative, but not completely inhibitory, impact on BD2.20 activity. Given the long duration of activity and the lower inoculum size in the MIC assay (compared with experiments in FIG. 17), it is likely that all BD2.20-containing peptides could reach equal levels of growth inhibition, despite large and target-specific differences in antimicrobial speed. This pattern of results was also observed when comparing MICs of targeted and untargeted organisms utilizing STAMPs against S. mutans and Pseudomonas mendocina (Eckert et al. (2006) Antimicrob Agents Chemother., 50: 3651-3657; Eckert et al. (2006) Antimicrob Agents Chemother., 50: 1480-1488).

Although more rigorous studies and a more medically relevant combination of pathogen targets is desirable, these findings indicate that it is possible to design an antimicrobial peptide-based therapeutic with multiple and defined fidelities in vitro. MH-STAMPs may help improve human health through the promotion of healthy microbial constituencies.

Example 2
Synthesis of Peptide—Porphyrin Conjugate

The mixture of coupling reagent HATU (5 eq. excess, 10 mg) and purpurin-18 (MW 564, 5 eq excess, 15 mg) in 600 mL dry dichloromethane (DCM):DMF:dimethylsulphoxide (DMSO) (1:1:1 (v/v)) was added to the peptide resin (1 molar equivalent, 15 mg) which was swelled by placing in minimal DMF for 30 min prior to reaction. 26 μL (10 molar equivalents) DIPEA was then added to the reaction flask to initiate the reaction. The reaction mixture was protected with argon and stirred at room temperature for 3 h.

After finishing, the reaction mixture was then passed down a sintered glass filtered vial and extensively washed with DMF and DCM to remove all waste reagents. The resin was then dried overnight in vacuum, and cleaved with 1 ml of trifluoroacetic acid (TFA)/thioanisole/water/EDT (10/0.5/0.5/025) for 2 hr at room temperature, and the cleavage solution was precipitated with 10 mL methyl-tert butyl ether. The precipitate was washed twice with the same amount of ether.

Example 3
Synthesis of Peptide—CSA Conjugate

To the fully protected peptide (solution of B43-GGG (FIDSFIRSF-GGG, 0.025 mmol) and tri-Boc-CSA-15 (0.0125 mol) in 300 μL DMF, DCC (7.7 mg), HOBt (5.1 mg) and 13 μL DIEA were added in iced-bath. After stirred at room temperature for four days, the reaction mixture was poured into 5 ml water and extracted with chloroform (5×3 mL). The CHCl₃extract was evaporated under vacuum and dried in a lyophilizer overnight. The dried CHCl₃extracts was then dissolved in 1 mL DCM followed by added 1 mL of TFA in iced-bath. The reaction mixture was further stirred at room temperature for 2 hours and precipitated with methyl tert-butyl ether (10 mL). The precipitate was further washed once with the same amount ether and dried in vacuum.

Example 4

STAMPs Against Corvnebacterium jeikeium and Streptococcus mutans

This example illustrates the development of STAMPs to selectively target and reduce or eliminate Streptococcus mutans (dental caries) or Corynebacterium jeikeium (body odor, opportunistic infections) from mixed microbial populations.

Axilla odor is caused by overgrowth of, and metabolite production from, Corynebacterium spp, which replaces Staphylococcus and Micrococcus spp associated with less odor. Current hygiene (soaps, antibiotics, antiseptics, disinfectants) practices remove all bacteria, allowing the ratio of Corynebacteria to normal flora to remain high during regrowth. Deodorants and anti-perspirants are temporary solutions that hide or even exacerbate the problem.

S. mutans is the major etiological agent of dental caries. Current methods (tooth brushing, antiseptic mouthrinses) to treat cariogenesis have focused on complete bacterial removal, i.e., elimination of S. mutans and other harmless oral bacteria. Caries have persisted despite these methods, and in many cases, S. mutans can become the dominant organism in the mouth. Several S. mutans and acid-targeted approaches (probiotic replacement, saliva pH adjustment) are under development, but none have shown clinical efficacy.

This example describes a number of STAMPs that preferentially or selectively reduce or eliminate S mutans and/or Corynebacterium spp from mixed populations.

Several lead STAMPs with specific activity against Corynebacterium jeikeium are also disclosed herein.

The STAMPs described herein comprise functional regions within a peptide molecule or a chemical conjugate. These regions include a targeting region comprising one or more targeting moieties (e.g., targeting peptides), a linker, and one or more killing moieties (e.g., antimicrobial peptides (AMPs), porphyrins, etc.).

The STAMPs function through the targeting region, which selectively accumulates STAMPs, and therefore killing regions, on or in proximity to the microorganism of interest. Other flora are not recognized by the targeting region, and therefore avoid or have reduced STAMP accumulation and cellular damage.

In certain embodiments, STAMPs against oral S. mutans are best applied formulated in a mouthrinse, toothpaste, cream, gel, or adhesive strip, and in certain preferably embodiments, are provided in a formulation that comprises 0.5 to 2.5×PBS (or other salt) and other ingredients commonly found in oral healthcare formulations (e.g., mouthrinse formulations). Certain illustrative formulations are shown in Table 20.

During the course of evaluating STAMPs, antimicrobial peptides (AMPs), and binding peptides for desired activity, it was discovered that certain formulations can attenuate or promote peptide activity, as compared to activity levels in a default buffer system (1×PBS). In some cases, 1×PBS may provide the best level of activity. Below are a number of formulations that alter, or may alter, peptide or STAMP activity. For complex buffer systems, assume the base solvent is water unless otherwise stated.

Formulation 1 (1×PBS, pH 7.4): 136.8 mM NaCl, 2.68 mM KCl, 1.01 mM Na₂HPO₄, and 1.37 mM KH₂PO₄.

Formulation 2 (HEPES/CTAB): 20 mM HEPES (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid), 150 mM NaCl, 1 mM MgCl₂, and 0.1% CTAB (Cetyl trimethylammonium bromide).

Formulation 3 (TRIS/CTAB): 20 mM Tris (tris(hydroxymethyl)aminomethane), pH 7.5, 150 mM NaCl, 1 mM MgCl₂, and 0.1% CTAB.

Formulation 4: 20 mM HEPES.

Formulation 5: 20 mM Tris, pH 7.5.

Formulation 6: 0.2% CTAB.

Formulation 7: 1% Glycerol.

Formulation 8: 1% Pluronic F108 (nonionic surfactant: α-Hydro-.omega.-hydroxypoly(oxyethylene)poly(oxypropylene)poly(oxyethylene) block copolymer).

Formulation 9: 1% Pluronic F123 (Poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol), average M_a˜5,800).

Formulation 10:1% Pluronic F17R4 (Poly(propylene glycol)-block-poly(ethylene glycol)-block-polypropylene glycol), average M_a˜2,700).

Formulation 11: 1% to 7% PEG400.

Formulation 12: 50 mM Urea.

Formulation 13: 10 mM AOT (Sodium bis(2-ethylhexyl) sulfosuccinate).

Formulation 14: 0.5-0.1% Tween 20 (nonionic detergent, also known as polysorbate 20 or PEG(20) sorbitan monolauratesorbitan monolaurate).

Formulation 15: 0.5-0.1% Tween 80 (nonionic surfactant, C₆₄H₁₂₄O₂₆, also known as polyoxyethylene (20) sorbitan monooleate, (x)-sorbitan mono-9-octadecenoate poly(oxy-1,2-ethanediyl), or POE (20) sorbitan monooleate).

Formulation 16: 5-10% Ethanol.

Formulation 17: 20% Glycerin.

Formulation 18: 20% Sorbitol.

Formulation 19: 10% Glycerin/10% Sorbitol.

Formulation 20: 0.1% SLS (Sodium lauryl sulfate).

Formulation 21: 1% Pluronic F127 (nonionic suffactant: α-Hydro-.omega.-hydroxypoly(oxyethylene)poly(oxypropylene)poly(oxyethylene) block copolymer).

Formulation 21: 0.1% Tween 20 (nonionic detergent, also known as Polysorbate 20, or PEG(20)sorbitan monolaurate).

Formulation 21: 10% PG (phospholipid gel).

Mouthrinse neat solution #1 (made in 1×PBS): 7% ETOH, 20% Glycerin, 7% PEG 400, and 1% PLURONIC® F127.

Mouthrinse neat solution #2 (made in 1×PBS): 7% ETOH, 20% Sorbitol, 7% PEG 400, and 1% PLURONIC® F127.

Mouthrinse neat solution #3 (made in 1×PBS): 7% ETOH, 20% Glycerin and 7% PEG 400.

Mouthrinse neat solution #4 (made in 1×PBS): 7% ETOH, 20% Sorbitol and 7% PEG 400.

Other illustrative, but not limiting, mouthrinse formulations are shown in Table 20.

TABLE 20

Illustrative mouthrinse formulations.

Rinse#
ETOH
Glycerin
PEG400
F127
Water¹
Fluoride

1
5
22.5
7
1
64.5
187.5

2
6
25
1
0
68
0

3
6
20
7
0
67
0

4
6
20
1
1
72
0

5
7
25
7
0
61
0

6
7
20
1
0
72
0

7
7
20
7
0
66
250

8
5
20
7
1
67
0

9
6.472
21.139
5.361
0.722
66.306
250

10
7
22.5
1
0
69.5
250

11
5
25
1
0
69
250

12
7
20
7
0
66
250

13
5
20
1
1
73
250

14
5
25
7
0.5
62.5
250

15
7
25
1
0.5
66.5
250

16
7
25
7
1
60
250

17
5
25
7
0.5
62.5
0

18
7
20
1
1
71
250

19
6
25
1
1
67
250

20
7
25
7
1
60
125

21
5
25
1
0
69
250

22
5
20
1.5
0.5
73
0

23
7
20
1
1
71
250

24
6
20
1
0
73
250

25
5
22.333
3.778
0.444
68.444
125

26
7
25
1
1
66
0

27
6
25
7
0
62
250

28
7
20
7
1
65
0

29
7
25
4
1
63
62.5

30
5
25
4
0
66
0

31
5
25
1
1
68
0

32
7
25
7
1
60
0

33
7
22.5
4
0.5
66
0

34
5
20
4.5
0
70.5
250

35
5
23
1
0
71
62.5

36
6
20
1
1
72
0

37
5
20
7
1
67
250

38
7
20
1
0
72
0

39
5
25
4
1
65
250

40
5
22.5
7
0
65.5
0

n1
7
20
7
1
65
0

n2
7
20%
7
1
65
0

Sorbitol

n3
7
20
7
0
66
0

n4
7
20%
7
0
66
0

Sorbitol

¹1xPBS can be substituted for water

In certain embodiments, Corynebacterium-specific STAMPs are formulated in any number of creams, nanoemulsions, lipid micelles, aqueous or no-aqueous gels, sprays, soaps or roll-on bars, or other products used for axilla or other hygiene.

STAMP-mediated selective antimicrobial activity can result in preservation of the normal flora at the oral or axilla mucosal surface, resulting in protective colonization and the conversion of a harmful flora to a beneficial one. Recurrence of pathogen overgrowth would be reduced, which also limits the amount and frequency (and therefore cost) of STAMP delivery. STAMPs allow for “surgical” antimicrobial precision, which limits antimicrobial resistance evolution as well due to the general mechanism of cell membrane damage mediated by the killing region.

A number of anti-S. mutans STAMPs (see Table 21) and anti-C. jeikeium STAMPs have been designed and tested, some in formulations. All show potent selective activity against their bacterial targets in vitro, including against biofilm forms. When tested, STAMPs have little cytotoxicity against cell lines in vitro.

TABLE 21

Illustrative anti-S. mutans STAMPs.

SEQ ID

STAMP
Amino Acid Sequence
NO

2_1G2

FIKHFIHRFGGGKNLRIIRKGIHIIKKY*
3230

C16AF5

TFFRLFNRSFTQALGKGGGFLKFLKKFFKKLKY*
3231

1845L621

KFINGVLSQFVLERKPYPKLFKFLRKHLL*
3232

1903-21

NIFEYFLEGGGKLFKFLRKHLL*
3233

Single underline is binding peptide.

Double underline is antimicrobial peptide (AMP).

No underline is linker.

*indicates optionally protected (e.g., amidated) C terminal.

TABLE 22

Illustrative anti-C. jeikeium STAMPs.

STAMP
Amino Acid Sequence
SEQ ID NO

2038L6CAM135

GKAKPYQVRQVLRAVDKLETRRKKGGR

3234

PYPGWRLIKKILRVFKGL*

1619-

SKRGRKRKDRRKKKANHGKRPNSGGGG
3235

CAM135

WRLIKKILRVFKGL*

1599-BD2.16
YSKTLHFADGGGKILKFLFKKVF*
3236

1619-BD2.16

SKRGRKRKDRRKKKANHGKRPNSGGG
3237

KILKFLFKKVF*

1904-BD2.16
GSVIKKRRKRMSKKKHRKMLRRTRVQR
3238

RKLGKGGGKILKFLFKKVF*

Single underline is binding peptide.

Double underline is antimicrobial peptide (AMP).

No underline is linker.

*indicates optionally protected (e.g., amidated) C terminal.

It was a surprising discovery that certain anti-S. mutans STAMPs required a salt in the formulation (e.g., PBS) for optimum activity. Thus, for example, the anti-S. mutans STAMP C16G2 (TFFRLFNRSFTQALGKGGGKNLRIIRKGIHIIKKY*, SEQ ID NO:2) comprising the TFFRLFNRSFTQALGK (SEQ ID NO:1) attached to the antimicrobial peptide (AMP) KNLRIIRKGIHIIKKY (SEQ ID NO: 3080) by a peptide linker (GGG) was substantially inactive in water-based salt-free buffers and nanoemulsions, but was active in a phosphate buffered saline (PBS) formulation. Suitable PBS formulations ranged from 0.5×PBS to about 2.5×PBS with an activity optimum at about 1×PBS. Similar results are believed to obtain for other anti-S. mutans STAMPS as well as a number of other STAMPs. In certain embodiments STAMP stability in solution was improved by inclusion of fluoride in mouthrinse.

Example 5
Photodynamic Therapy Targeted Against Streptococcus mutans

Dental caries (tooth decay) is one of the most prevalent and costly infectious diseases in the United States. Currently, the annual expenditures on dental services exceed $85 billion, with the majority of these costs attributable to dental caries and its sequelae (www.ada.org/). The oral cavity harbors a complex microbial community consisting of over 600 different non-harmful/commensal microbial species together with a limited number of pathogenic bacteria, including the major etiological agent of dental caries, Streptococcus mutans. Once established, S. mutans generates acid during the fermentation of dietary sugars, which causes the demineralization of tooth structure and inhibits the growth of non-pathogenic commensal bacteria within the same microbial niche. Despite diligent use of broad-spectrum antimicrobial compounds and tooth brushing, S. mutans persists within the oral cavity and causes repeated cycles of cariogenesis. Current “remove all, kill-all” approaches have shown limited efficacy, since a “cleaned” tooth surface provides an equal opportunity for commensal as well as pathogenic bacteria to re-colonize in the non-sterile environment of the oral cavity. To address this shortcoming, we have constructed and evaluated a light-activated S. mutans-selective antimicrobial agent. C16-RB, constructed via conjugation of the S. mutans competence-stimulating peptide to the photodynamic dye rose bengal, displays robust anti-S. mutans activity in vitro under blue exposure from a handheld dental curing light. C16-RB has reduced activity against other oral streptococci under mixed biofilm conditions and has limited cytotoxicity in vitro.

To develop a method of selectively eliminating S. mutans from a dental biofilm so that beneficial species exert a protective colonization effect and long-term protection from S. mutans re-colonization can be attained we created a novel class of targeted antimicrobials, known as specifically-targeted antimicrobial peptides, or STAMPs. STAMPs consist of functionally independent, yet conjoined, domains within a linear peptide sequence; a targeting region and an antimicrobial region. The targeting region, which binds specifically to a bacterial species of interest, delivers the killing portion of the molecule that consists of a normally wide-spectrum antimicrobial peptide. Previously, we successfully designed STAMPs against S. mutans by taking advantage of the competence stimulating pheromone (CSP) peptide produced by this organism that has demonstrated S. mutans-specific recognition. STAMPs synthesized with portions of CSP as targeting domains were capable of specific antimicrobial activity against S. mutans, and not other oral streptococci or non-cariogenic organisms in biofilms.

We hypothesized that targeted killing might be achieved through the use of non-peptide antimicrobial molecules, such as porphyrins or dyes utilized in PDT. Here we present the proof-of-principle construction and in vitro efficacy of the targeted, peptide-guided, photodynamic molecule C16-RB. C16-RB displays S. mutans selective antimicrobial activity upon blue light activation with limited activity against non-cariogenic oral streptococci and epithelial cells.

Materials and Methods
Synthesis of C16-RB

All amino acids, synthesis resins and reagents were peptide synthesis grade

(Anaspec, San Jose, Calif.; Fisher Scientific). To construct our C16-RB conjugate, conventional 9-fluorenylmethoxy carbonyl (Fmoc) solid-phase methodology was employed to synthesize the CSP_c16peptide and attach the succinate and PEG linkers, utilizing double coupling cycles in N-hdroxybenzotrazole, HBTU (O-benzotriazole-N,N, N,N-tetramethyl-uronium hexafluoro-phosphate) and diisopropyl ethylamine (DIEA), with dimethylformamide (DMF) and N-methylpyrrolidone (NMP) as solvents, as described previously. The peptide resin (1 molar equivalent, 15 mg) was then swollen in DMF for 30 min prior to attachment of the PEG terminal amide group to the carboxyl lactone in RB (FIG. 19B). This reaction was carried out in a mixture of 2-(7-Aza-1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU, 5-molar excess) in dichloromethane (DCM):DMF:dimethylsulphoxide (DMSO) (1:1:1 (v/v)). Ten molar equivalents of DIEA were added to the reaction flask to initiate the reaction, which was protected with argon and stirred at room temperature for 5 h. After completion, the reaction mixture was passed down sintered glass filtered vial and extensively washed with DMF and DCM to remove all waste reagents. The resin was then dried overnight in vacuum, and cleaved with 1 mL of trifluoroacetic acid (TFA)/thioanisole/water/EDT (10/0.5/0.5/025) for 2 hr at room temperature. The cleavage solution was precipitated with 10 mL methyl-tert butyl ether, and the precipitate was washed twice with the same amount of ether. The crude product was purified via preparative-level HPLC (Source 15RPC column, ACTA purifier, Amersham) and eluted with gradient acetonitrile/water from 10 to 35% in 10 min, which was increased to 90% over 8 min before finally being washed 15 min with 95% acetonitrile.

C16-RB was purified further to >90% and the molecular mass confirmed via LC/MS, utilizing increasing hydrophobicity gradient of acetonitrile in water with 0.01% TFA as described above (Waters X-bridge BEH 130 C18 column, 4.6×100 mm, particle size 5 μm, Waters 3100 system). LC spectra were analyzed with MassLynx Softward v. 4.1 (Waters). C16-RB mass (3118.0) was confirmed by electrospray ionization (ESI) mass spectroscopy in linear, positive ion mode. The final product was lyophilized and protected from light at all times. C16-RB was soluble in 50% methanol.

Bacterial and Cellular Growth

Streptococcus oralis ATCC10557, Streptococcus gordonii (Challis), Streptococcus sanguinis (NY101), Streptococcus mitis ATCC903, Streptococcus salivarius ATCC13419 and S. mutans wild-type UA140 and JM11 (spectinomycin-resistant) strains were grown in Todd-Hewitt (TH) broth 37° C. in an anaerobic atmosphere of 80% N₂, 10% CO₂, and 10% H₂. BHK-21 (ATCC CRL-10) fibroblasts were propagated in DMEM with 10% FBS, 1 mM sodium pyruvate, 100 units/mL penicillin G, and 100 μg/mL streptomycin at 37° C. with 5% CO₂. Cells were detached with 0.25% trypsin and subcultured as recommended by the supplier.

Photodynamic Antimicrobial Assays Against Biofilms

To evaluate C16-RB against monoculture biofilms, S. mutans UA140 was grown overnight in TH prior to inoculation for biofilm formation. For biofilms, 1:5000 dilution of overnight culture was made into TH with 1% sucrose in 2 mL centrifuge tubes (200 μL volume) and grown 24 h under anaerobic conditions. After incubation, biofilms were treated for 5 min with 5 or 25 μM C16-RB or 5 μM RB in 1×PBS, or PBS alone, followed by removal of supernatant and exposure to 5 min blue light (emission 400-550 nm, power 400 mW/cm²) from an Astralis 7 (Ivoclar Vivodent, Austria) handheld LED commonly used as a dental curing light. The light source was suspended 4 cm from the tube bottom (even with the mouth of the tube). A duplicate set of samples were left covered to serve as dark controls. After treatment, biofilms were mechanically disrupted and plated to determine cfu/mL.

To gauge C16-RB selectivity for S. mutans, similar assays were conducted against multispecies biofilms. Mixed biofilms were seeded by diluting (1:5000) a mixture of equal parts S. oralis, S. gordonii, S. mitis, S. sanguinis, S. salivarius, and S. mutans JM11 (made from overnight cultures) into TH with 1% sucrose, 1% glucose, and 1% mannose. Biofilms were incubated and treated as described above with the addition of vitamin C or potassium gluconate. After the addition of agent and 5 min incubation, biofilms were washed 1× with 1×PBS prior to light exposure. After PDT and biofilm disruption, survivors were plated on TH, and TH supplemented with 800 μg/mL spectinomycin, which allowed for quantitation of surviving total oral streptococci and surviving S. mutans, respectively.

Evaluation of C16-RB Cytotoxicity

The effect of RB and C16-RB on human fibroblasts was ascertained by utilizing the Promega CellTiterGlo assay, as described by the manufacturer. Briefly, fibroblasts were grown to confluence, detached, and seeded to 5,000 cells per well in a 96-well opaque walled, clear bottom 96-well plate (Nunc International). For long-term dark toxicity, cells were allowed to attach to for 18 h before the culture medium was replaced with medium plus serially-diluted RB or C16-RB (200 μM to 390 nM) or medium alone. After 18-24 h, equal volume Cell Titer Glo reagent was added to each well and mixed. Luciferace activity was then quantified to measure cell viability (Varian Fluorometer in Biolumenescence mode). To measure cytotoxicity after RB or C16-RB light exposure, cells were seeded at ˜10,000 cells per well and allowed to attach for 4 h. Cell growth medium was then replaced with RB or C16-RB containing medium, prior to exposure (a single well at a time) with blue light (400 mW/cm²) suspended ˜3 cm from the well bottom. After exposure, cultures were disrupted with Cell Titer Glo and luciferase activity quantitated as above.

Results

Design of Photodynamic Peptide-Dye Conjugate

For the targeting peptide component of the chimeric molecule, we selected a shortened derivative of S. mutans CSP, CSP_c16(sequence: TFFRLFNRSFTQALGK). CSP_C16has been utilized successfully as a STAMP targeting peptide in several constructs, and demonstrates selective binding to S. mutans and not other non-cariogenic bacteria. For the photodynamic dye, we selected rose bengal (RB, FIG. 19A), a xanthene dye with a demonstrated record of safety as a diagnostic tool in optometry. Unlike TBO or methylene blue, RB is not recognized by efflux pumps, and has shown robust activity against a variety of bacteria in vitro in the presence of green or blue light (max absorption ˜549 nm), and can be activated by a handheld dental curing LED.

C16-RB Synthesis

As shown in FIG. 19B, RB was attached to the N-terminus of CSP_c16through a succinate/PEG linker to construct the C16-RB molecule. Conventional solid-phase peptide methods were utilized to synthesize CSPC₁₆, followed by linker and RB coupling prior to cleavage from the resin. After cleavage, C16-RB was repeatedly purified by LC/MS prior to evaluation. As shown in FIG. 20, over 95% purity was achieved with the expected mass species observed. The lactone ring in RB was opened as a result of CSP_C16attachment. However, we hypothesized that the conjugate would retain enough singlet-oxygen generating activity for a proof-of-principle demonstration, as other xanthene dyes with activity lack this ring.

C16-RB Efficacy Against Single-Species S. mutans Biofilms

After synthesis, the basic photosensitization potential of C16-RB was assessed by challenging mature single-species S. mutans biofilms (grown 24 h) with C16-RB or unmodified RB, followed by blue emission from a dental curing light. As shown in FIG. 21, potent antimicrobial activity was observed in cultures exposed to C16-RB or RB and blue light: a reduction in over 3 log₁₀from input cfu/mL at 5 or 25 μM. In contrast, appreciable decreases in cfu/mL were not observed in S. mutans treated with blue light alone, or 5 μM RB or C16-RB dark controls. Modest dark toxicity was observed in samples treated with 25 μM C16—RB. Overall, these results indicate that the peptide-dye conjugate is active against S. mutans and at roughly similar levels to the parental RB molecule.

Selective PDT Against Multi-Species Biofilms

C16-RB was next evaluated for selectivity in mixed cultures containing S. mutans and non-cariogenic oral streptococci that compete for the same niche on the tooth surface. We utilized mixed biofilms of S. mutans transformed with spectinomycin resistance (strain JM11, Merritt, et al., 2005), plus S. oralis, S. gordonii, S. mitis, S. sanguinis, and S. salivarius. The mixed cultures were grown 24 and then treated with RB or C16-RB as indicated, plus potassium gluconate to minimize killing of untargeted bacteria by reducing the superoxide-producing activity of the free C16-RB not bound to S. mutans. Ethanol treatment served as an indiscriminant killing control. As shown in FIG. 21, RB alone exhibited strong indiscriminant photodynamic antimicrobial effects against S. mutans and non-S. mutans in the mixed biofilm system (ratio of surviving S. mutans:non-cariogenic streptococci cfu ˜1). In contrast, C16-RB displayed specific photodynamic activity towards S. mutans, and not the other oral streptococci examined, as reflected in the low ratio of recovered S. mutans to other streptococci. These results suggest C16-RB has antimicrobial activity in the presence of blue light that is specific for S. mutans and dependent on the CSP_c16targeting peptide.

Cytotoxicity Against Eukaryotic Cells

Given the demonstrated PDT potential of RB-C16, experiments were conducted to examine the cytotoxicity for this conjugate and RB alone. IC₅₀s were obtained for BHK cells exposed C16—RB, RB, or Melittin B (positive control for cytotoxicity), with and without blue light exposure. As shown in Table 23, cytotoxicity was noted for cells exposed to Melittin B at the lowest peptide dilution tested at either 5 min or 24 h, with or without light (IC₅₀<1.56 μM), while light-dependent toxicity was observed only for RB-treated samples. No photo-associated toxicity was noted in BHK cells treated with C16-RB, though modest light-independent cytotoxicity (IC₅₀=90 μM) was detected after 24 h of exposure. These results suggest that C16-RB is not toxic to BHK cells after illumination, and displays mild toxic effects (when compared to Melittin B) after 24 h exposure.

TABLE 23

Cytotoxicity of RB and C16-RB compounds.

IC₅₀(μM)

BHK

5 min dark:

RB-C16
>100

RB
>100

Melittin B
<1.56

5 min w/blue light:

RB-C16
>100

RB
40

Melittin B
<1.56

24 h dark

RB-C16
55

RB
90

Melittin B
<1.56

It is understood that the examples and embodiments described herein are for illustrative purposes only and that various modifications or changes in light thereof will be suggested to persons skilled in the art and are to be included within the spirit and purview of this application and scope of the appended claims. All publications, patents, and patent applications cited herein are hereby incorporated by reference in their entirety for all purposes.

Number	Date	Country
61142830	Jan 2009	US
61151445	Feb 2009	US
61243905	Sep 2009	US
61243930	Sep 2009	US

TARGETED ANTIMICROBIAL MOIETIES

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