Antimicrobial kinocidin compositions and methods of use
View Patent ↗The present invention provides novel kinocidin peptides comprising a C-terminal portion of a kinocidin, wherein the C-terminal portion encompasses an α-helical secondary structure and further displays antimicrobial activity. The kinocidin peptides of the invention are derived from and correspond to a C-terminal portion of a kinocidin that includes a γ KO core and that can be a CXC, CC, or C class chemokine. Structural, physicochemical and functional properties of this novel class of antimicrobial peptides and amino acid sequences of particular kinocidin peptides are also disclosed. The invention also provides related antimicrobial methods.
1. A method for treating an infectious disease or condition in a subject in need of such treatment, comprising administering to the subject an effective amount of a peptide which (a) is 15 to 50 amino acid residues in length, (b) comprises a fragment of a C-terminal alpha-helical motif of a kinocidin protein selected from the group consisting of human CXCL1, CXCL2, CXCL3, CXCL4, CXCL5, CXCL6, CXCL7, CXCL8, CXCL9, CXCL10, CXCL11, CXCL12, CXCL13, CXCL14, CCL1, CCL2, CCL3, CCL4, CCL5, CCL7, CCL8, CCL11, CCL13, CCL14, CCL15, CCL16, CCL17, CCL18, CCL19, CCL20, CCL21, CCL22, CCL23, CCL24, CCL25, CCL26, CCL27, CCL28 and CL1, and (c) has microbicidal activity.
2. The method of claim 1 , wherein the fragment is 14 to 32 amino acid residues in length.
3. The method of claim 2 , wherein the kinocidin protein is human CXCL8.
4. The method of claim 3 , wherein the fragment consists of the amino acid sequence of KENWVQRVVEKFLKRAENS (SEQ ID NO: 1).
5. The method of claim 2 , wherein the kinocidin protein is human CXCL4.
6. The method of claim 5 , wherein the fragment consists of the amino acid sequence of QAPLYKKIIKKLLES (SEQ ID NO: 2).
7. The method of claim 2 , wherein the kinocidin protein is human CXCL1.
8. The method of claim 7 , wherein the fragment consists of the amino acid sequence of ASPIVKKIIEKMLNSDKSN (SEQ ID NO: 3).
9. The method of claim 2 , wherein the infectious disease or condition is caused by a fungal species, a Gram-negative bacterial species, a Gram-positive bacterial species, a protozoa, or a parasite.
10. The method of claim 9 , wherein the infectious disease or condition is caused by a fungal species selected from the group consisting of a Candida species, an Aspergillus species, a Cryptococcus species, a Histoplasma species, a Coccidioides species, a Paracoccidioides species, a Blastomyces species, a Basidiobolus species, a Conidiobolus species, a Rhizopus species, a Rhizomucor species, a Mucor species, an Absidia species, a Mortierella species, a Cunninghamella species, a Saksenaea species, a Pseudallescheria species, a Paecilomyces species, a Fusarium species, a Trichophyton species, a Trichosporon species, a Microsporum species, an Epidermophyton species, a Scytalidium species, a Malassezia species, an Actinomycetes species, a Sporothrix species, a Penicillium species, a Saccharomyces species, and a Pneumocystis species.
11. The method of claim 9 , wherein the infectious disease or condition is caused by a Gram-negative bacterial species selected from the group consisting of an Acidaminococcus species, an Acinetobacter species, an Aeromonas species, an Alcaligenes species, a Bacteroides species, a Bordetella species, a Branhamella species, a Brucella species, a Burkholderia species, a Calymmatobacterium species, a Campylobacter species, a Cardiobacterium species, a Chromobacterium species, a Citrobacter species, an Edwardsiella species, an Enterobacter species, an Escherichia species, a Flavobacterium species, a Francisella species, a Fusobacterium species, a Haemophilus species, a Klebsiella species, a Legionella species, a Moraxella species, a Morganella species, a Neisseria species, a Pasteurella species, a Plesiomonas species, a Porphyromonas species, a Prevotella species, a Proteus species, a Providencia species, a Pseudomonas species, a Salmonella species, a Serratia species, a Shigella species, a Stentrophomonas species, a Streptobacillus species, a Treponema species, a Veillonella species, a Vibrio species, an Yersinia species, and a Chlamydia species.
12. The method of claim 9 , wherein the infectious disease or condition is caused by a Gram-positive bacterial species selected from the group consisting of a Staphylococcus species, a Streptococcus species, a Micrococcus species, a Peptococcus species, a Peptostreptococcus species, an Enterococcus species, a Bacillus species, a Clostridium species, a Lactobacillus species, a Listeria species, an Erysipelothrix species, a Propionibacterium species, an Eubacterium species, a Nocardia species, an Actinomyces species, a Corynebacterium species, a Mycoplasma species, an Ureaplasma species, and a Mycobacteria species.
13. The method of claim 9 , wherein the infectious disease or condition is caused by a protozoa selected from the group consisting of a Plasmodia species, a Toxoplasma species, a Leishmania species, a Trypanosoma species, a Giardia species, a Entamoeba species, a Acanthamoeba species, a Nagleria species, a Hartmanella species, a Balantidium species, a Babesia species, a Cryptosporidium species, a Isospora species, a Microsporidium species, a Trichomonas species, and a Pneumocystis species.
14. The method of claim 9 , wherein the infectious disease or condition is caused by a helminth parasite.
15. The method of claim 1 , wherein the subject is a mammal.
16. The method of claim 1 , wherein the subject is a human.
17. The method of claim 1 , wherein the subject is immunocompromised or immunosuppressed.