Natural roles of antimicrobial peptides in microbes, plants and animals

Research in Microbiology

Volumn 162, Issue 4, 2011, Pages 363-374

  Maroti Gergely G ^a,b   Kereszt, Attila ^a,b   Kondorosi, Éva ^a,c   Mergaert, Peter ^c  

^a BAY ZOLTÁN NONPROFIT LTD FOR APPLIED RESEARCH   (Hungary)

^b SZENT ISTVÁN UNIVERSITY   (Hungary)

^c CNRS   (France)

Author keywords

Antimicrobial peptides; Defensin; Innate immunity; Pathogen; Resistance; Symbiosis

Indexed keywords

BACTERIOCIN; POLYPEPTIDE ANTIBIOTIC AGENT;

ARTICLE; BACTERIUM; BIODIVERSITY; DROSOPHILA; DRUG MECHANISM; IN VIVO STUDY; INNATE IMMUNITY; INSECT; MAMMAL; NONHUMAN; PLANT; PRIORITY JOURNAL; SYMBIONT;

ANIMALS; ANTIMICROBIAL CATIONIC PEPTIDES; BACTERIA; HUMANS; INSECTS; MAMMALS; PLANTS;

ANIMALIA; HEXAPODA; MAMMALIA;

EID: 79955164524     PISSN: 09232508     EISSN: 17697123     Source Type: Journal    
DOI: 10.1016/j.resmic.2011.02.005     Document Type: Article

References (89)

1. Alunni B., Kevei Z., Redondo-Nieto M., Kondorosi A., Mergaert P., Kondorosi E. Genomic organization and evolutionary insights on GRP and NCR genes, two large nodule-specific gene families in Medicago truncatula. Mol. Plant Microbe Interact. 2007, 20:1138-1148.
2. Amid C., Rehaume L.M., Brown K.L., Gilbert J.G., Dougan G., Hancock R.E., Harrow J.L. Manual annotation and analysis of the defensin gene cluster in the C57BL/6J mouse reference genome. BMC Genomics 2009, 10:606.
3. Amien S., Kliwer I., Márton M.L., Debener T., Geiger D., Becker D., Dresselhaus T. Defensin-like ZmES4 mediates pollen tube burst in maize via opening of the potassium channel KZM1. PLoS Biol. 2010, 8:e1000388.
4. Ausubel F.M. Are innate immune signaling pathways in plants and animals conserved?. Nat. Immunol. 2005, 6:973-979.
5. Bader M.W., Sanowar S., Daley M.E., Schneider A.R., Cho U., Xu W., Klevit R.E., Le Moual H., Miller S.I. Recognition of antimicrobial peptides by a bacterial sensor kinase. Cell 2005, 122:461-472.
6. Bals R., Weiner D.J., Moscioni A.D., Meegalla R.L., Wilson J.M. Augmentation of innate host defense by expression of a cathelicidin antimicrobial peptide. Infect. Immun. 1999, 67:6084-6089.
7. Bell G., Gouyon P.H. Arming the enemy: the evolution of resistance to self-proteins. Microbiology 2003, 149:1367-1375.
8. Brogden K.A. Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria?. Nat. Rev. Microbiol. 2005, 3:238-250.
9. Buckling A., Brockhurst M. RAMP resistance. Nature 2005, 438:170-171.
10. Cadwell K., Liu J.Y., Brown S.L., Miyoshi H., Loh J., Lennerz J.K., Kishi C., Kc W., Carrero J.A., Hunt S., Stone C.D., Brunt E.M., Xavier R.J., Sleckman B.P., Li E., Mizushima N., Stappenbeck T.S., Virgin H.W. A key role for autophagy and the autophagy gene Atg16l1 in mouse and human intestinal Paneth cells. Nature 2008, 456:259-263.
11. Chauhan A., Madiraju M.V., Fol M., Lofton H., Maloney E., Reynolds R., Rajagopalan M. Mycobacterium tuberculosis cells growing in macrophages are filamentous and deficient in FtsZ rings. J. Bacteriol. 2006, 188:1856-1865.
12. Chromek M., Slamová Z., Bergman P., Kovács L., Podracká L., Ehrén I., Hökfelt T., Gudmundsson G.H., Gallo R.L., Agerberth B., Brauner A. The antimicrobial peptide cathelicidin protects the urinary tract against invasive bacterial infection. Nat. Med. 2006, 12:636-641.
13. Cole J.N., Pence M.A., von Köckritz-Blickwede M., Hollands A., Gallo R.L., Walker M.J., Nizet V. M protein and hyaluronic acid capsule are essential for in vivo selection of covRS mutations characteristic of invasive serotype M1T1 group A Streptococcus. mBio 2010, 1:e00191-10.
14. Czárán T.L., Hoekstra R.F., Pagie L. Chemical warfare between microbes promotes biodiversity. Proc. Natl. Acad. Sci. U S A 2002, 99:786-790.
15. De Coninck B.M., Sels J., Venmans E., Thys W., Goderis I.J., Carron D., Delauré S.L., Cammue B.P., De Bolle M.F., Mathys J. Arabidopsis thaliana plant defensin AtPDF1.1 is involved in the plant response to biotic stress. New Phytol. 2010, 187:1075-1088.
16. Derzelle S., Turlin E., Duchaud E., Pages S., Kunst F., Givaudan A., Danchin A. The PhoP-PhoQ two-component regulatory system of Photorhabdus luminescens is essential for virulence in insects. J. Bacteriol. 2004, 186:1270-1279.
17. Fields P.I., Groisman E.A., Heffron F. A Salmonella locus that controls resistance to microbicidal proteins from phagocytic cells. Science 1989, 243:1059-1062.
18. Fierer N., Breitbart M., Nulton J., Salamon P., Lozupone C., Jones R., Robeson M., Edwards R.A., Felts B., Rayhawk S., Knight R., Rohwer F., Jackson R.B. Metagenomic and small-subunit rRNA analyses reveal the genetic diversity of bacteria, archaea, fungi, and viruses in soil. Appl. Environ. Microbiol. 2007, 73:7059-7066.
19. Froehlich B.J., Bates C., Scott J.R. Streptococcus pyogenes CovRS mediates growth in iron starvation and in the presence of the human cationic antimicrobial peptide LL-37. J. Bacteriol. 2009, 191:673-677.
20. Ganz T. Paneth cells - guardians of the gut cell hatchery. Nat. Immunol. 2000, 1:99-100.
21. Ganz T. Defensins: antimicrobial peptides of innate immunity. Nat. Rev. Immunol. 2003, 3:710-720.
22. Gao A.G., Hakimi S.M., Mittanck C.A., Wu Y., Woerner B.M., Stark D.M., Shah D.M., Liang J., Rommens C.M. Fungal pathogen protection in potato by expression of a plant defensin peptide. Nat. Biotechnol. 2000, 18:1307-1310.
23. Gordon D.M., Riley M.A., Pinou T. Temporal changes in the frequency of colicinogeny in Escherichia coli from house mice. Microbiology 1998, 144:2233-2240.
24. Gryllos I., Tran-Winkler H.J., Cheng M.F., Chung H., Bolcome R., Lu W., Lehrer R.I., Wessels M.R. Induction of group A Streptococcus virulence by a human antimicrobial peptide. Proc. Natl. Acad. Sci. U S A 2008, 105:16755-16760.
25. Ha E.M., Oh C.T., Bae Y.S., Lee W.J. A direct role for dual oxidase in drosophila gut immunity. Science 2005, 310:847-850.
26. Haine E.R., Moret Y., Siva-Jothy M.T., Rolff J. Antimicrobial defense and persistent infection in insects. Science 2008, 322:1257-1259.
27. Hale J.D., Hancock R.E. Alternative mechanisms of action of cationic antimicrobial peptides on bacteria. Expert Rev. Anti. Infect. Ther. 2007, 5:951-959.
28. Hancock R.E., Sahl H.G. Antimicrobial and host-defense peptides as new anti-infective therapeutic strategies. Nat. Biotechnol. 2006, 24:1551-1557.
29. Handler A.A., Lim J.E., Losick R. Peptide inhibitor of cytokinesis during sporulation in Bacillus subtilis. Mol. Microbiol. 2008, 68:588-599.
30. Hasper H.E., Kramer N.E., Smith J.L., Hillman J.D., Zachariah C., Kuipers O.P., de Kruijff B., Breukink E. An alternative bactericidal mechanism of action for lantibiotic peptides that target lipid II. Science 2006, 313:1636-1637.
31. Hedengren M., Asling B., Dushay M.S., Ando I., Ekengren S., Wihlborg M., Hultmark D. Relish, a central factor in the control of humoral but not cellular immunity in Drosophila. Mol. Cell. 1999, 4:827-837.
32. Higashiyama T. Peptide signaling in pollen-pistil interactions. Plant Cell Physiol. 2010, 51:177-189.
33. Hilpert K., McLeod B., Yu J., Elliott M.R., Rautenbach M., Ruden S., Bürck J., Muhle-Gol C., Ulrich A.S., Keller S., Hancock R.E. Short cationic antimicrobial peptides interact with ATP. Antimicrob. Agents Chemother. 2010, 54:4480-4483.
34. Hooper L.V., Macpherson A.J. Immune adaptations that maintain homeostasis with the intestinal microbiota. Nat. Rev. Immunol. 2010, 10:159-169.
35. Huber J.A., Mark Welch D.B., Morrison H.G., Huse S.M., Neal P.R., Butterfield D.A., Sogin M.L. Microbial population structures in the deep marine biosphere. Science 2007, 318:97-100.
36. Kerr B., Riley M.A., Feldman M.W., Bohannan B.J. Local dispersal promotes biodiversity in a real-life game of rock-paper-scissors. Nature 2002, 418:171-174.
37. Kirkup B.C., Riley M.A. Antibiotic-mediated antagonism leads to a bacterial game of rock-paper-scissors in vivo. Nature 2004, 428:412-414.
38. Kobayashi K.S., Chamaillard M., Ogura Y., Henegariu O., Inohara N., Nuñez G., Flavell R.A. Nod2-dependent regulation of innate and adaptive immunity in the intestinal tract. Science 2005, 307:731-734.
39. Kristian S.A., Dürr M., Van Strijp J.A., Neumeister B., Peschel A. MprF-mediated lysinylation of phospholipids in Staphylococcus aureus leads to protection against oxygen-independent neutrophil killing. Infect. Immun. 2003, 71:546-549.
40. Lauth X., von Köckritz-Blickwede M., McNamara C.W., Myskowski S., Zinkernagel A.S., Beall B., Ghosh P., Gallo R.L., Nizet V. M1 protein allows Group A streptococcal survival in phagocyte extracellular traps through cathelicidin inhibition. J. Innate Immun. 2009, 1:202-214.
41. Lemaitre B., Hoffmann J. The host defense of Drosophila melanogaster. Annu. Rev. Immunol. 2007, 25:697-743.
42. Lemaitre B., Nicolas E., Michaut L., Reichhart J.M., Hoffmann J.A. The dorsoventral regulatory gene cassette spätzle/Toll/cactus controls the potent antifungal response in drosophila adults. Cell 1996, 86:973-983.
43. Li M., Lai Y., Villaruz A.E., Cha D.J., Sturdevant D.E., Otto M. Gram-positive three-component antimicrobial peptide-sensing system. Proc. Natl. Acad. Sci. U S A 2007, 104:9469-9474.
44. Liehl P., Blight M., Vodovar N., Boccard F., Lemaitre B. Prevalence of local immune response against oral infection in a Drosophila/Pseudomonas infection model. PLoS Pathog. 2006, 2:e56.
45. Liu P.T., Stenger S., Li H., Wenzel L., Tan B.H., Krutzik S.R., Ochoa M.T., Schauber J., Wu K., Meinken C., Kamen D.L., Wagner M., Bals R., Steinmeyer A., Zügel U., Gallo R.L., Eisenberg D., Hewison M., Hollis B.W., Adams J.S., Bloom B.R., Modlin R.L. Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science 2006, 311:1770-1773.
46. Llama-Palacios A., López-Solanilla E., Poza-Carrión C., García-Olmedo F., Rodríguez-Palenzuela P. The Erwinia chrysanthemi phoP-phoQ operon plays an important role in growth at low pH, virulence and bacterial survival in plant tissue. Mol. Microbiol. 2003, 49:347-357.
47. Lobo D.S., Pereira I.B., Fragel-Madeira L., Medeiros L.N., Cabral L.M., Faria J., Bellio M., Campos R.C., Linden R., Kurtenbach E. Antifungal Pisum sativum defensin 1 interacts with Neurospora crassa cyclin F related to the cell cycle. Biochemistry 2007, 46:987-996.
48. Marlow V.L., Haag A.F., Kobayashi H., Fletcher V., Scocchi M., Walker G.C., Ferguson G.P. Essential role for the BacA protein in the uptake of a truncated eukaryotic peptide in Sinorhizobium meliloti. J. Bacteriol. 2009, 191:1519-1527.
49. Mattiuzzo M., Bandiera A., Gennaro R., Benincasa M., Pacor S., Antcheva N., Scocchi M. Role of the Escherichia coli SbmA in the antimicrobial activity of proline-rich peptides. Mol. Microbiol. 2007, 66:151-163.
50. Mergaert P., Nikovics K., Kelemen Z., Maunoury N., Vaubert D., Kondorosi A., Kondorosi E. A novel family in Medicago truncatula consisting of more than 300 nodule-specific genes coding for small, secreted polypeptides with conserved cysteine motifs. Plant Physiol. 2003, 132:161-173.
51. Mergaert P., Uchiumi T., Alunni B., Evanno G., Cheron A., Catrice O., Mausset A.E., Barloy-Hubler F., Galibert F., Kondorosi A., Kondorosi E. Eukaryotic control on bacterial cell cycle and differentiation in the Rhizobium-legume symbiosis. Proc. Natl. Acad. Sci. U S A 2006, 103:5230-5235.
52. Morrison G., Kilanowski F., Davidson D., Dorin J. Characterization of the mouse beta defensin 1, Defb1, mutant mouse model. Infect. Immun. 2002, 70:3053-3060.
53. Moser C., Weiner D.J., Lysenko E., Bals R., Weiser J.N., Wilson J.M. β-Defensin 1 contributes to pulmonary innate immunity in mice. Infect. Immun. 2002, 70:3068-3072.
54. Nizet V., Ohtake T., Lauth X., Trowbridge J., Rudisill J., Dorschner R.A., Pestonjamasp V., Piraino J., Huttner K., Gallo R.L. Innate antimicrobial peptide protects the skin from invasive bacterial infection. Nature 2001, 414:454-457.
55. Okuda S., Tsutsui H., Shiina K., Sprunck S., Takeuchi H., Yui R., Kasahara R.D., Hamamura Y., Mizukami A., Susaki D., Kawano N., Sakakibara T., Namiki S., Itoh K., Otsuka K., Matsuzaki M., Nozaki H., Kuroiwa T., Nakano A., Kanaoka M.M., Dresselhaus T., Sasaki N., Higashiyama T. Defensin-like polypeptide LUREs are pollen tube attractants secreted from synergid cells. Nature 2009, 458:357-361.
56. Oono R., Denison R.F. Comparing symbiotic efficiency between swollen versus nonswollen rhizobial bacteroids. Plant Physiol. 2010, 154:1541-1548.
57. Perron G.G., Zasloff M., Bell G. Experimental evolution of resistance to an antimicrobial peptide. Proc. Biol. Sci. 2006, 273:251-256.
58. Peschel A., Jack R.W., Otto M., Collins L.V., Staubitz P., Nicholson G., Kalbacher H., Nieuwenhuizen W.F., Jung G., Tarkowski A., van Kessel K.P., van Strijp J.A. Staphylococcus aureus resistance to human defensins and evasion of neutrophil killing via the novel virulence factor MprF is based on modification of membrane lipids with L-lysine. J. Exp. Med. 2001, 193:1067-1076.
59. Peschel A., Sahl H.G. The co-evolution of host cationic antimicrobial peptides and microbial resistance. Nat. Rev. Microbiol. 2006, 4:529-536.
60. Peyrin-Biroulet L., Beisner J., Wang G., Nuding S., Oommen S.T., Kelly D., Parmentier-Decrucq E., Dessein R., Merour E., Chavatte P., Grandjean T., Bressenot A., Desreumaux P., Colombel J.F., Desvergne B., Stange E.F., Wehkamp J., Chamaillard M. Peroxisome proliferator-activated receptor gamma activation is required for maintenance of innate antimicrobial immunity in the colon. Proc. Natl. Acad. Sci. U S A 2010, 107:8772-8777.
61. Qin J., Li R., Raes J., Arumugam M., Burgdorf K.S., Manichanh C., Nielsen T., Pons N., Levenez F., Yamada T., Mende D.R., Li J., Xu J., Li S., Li D., Cao J., Wang B., Liang H., Zheng H., Xie Y., Tap J., Lepage P., Bertalan M., Batto J.M., Hansen T., Le Paslier D., Linneberg A., Nielsen H.B., Pelletier E., Renault P., Sicheritz-Ponten T., Turner K., Zhu H., Yu C., Li S., Jian M., Zhou Y., Li Y., Zhang X., Li S., Qin N., Yang H., Wang J., Brunak S., Doré J., Guarner F., Kristiansen K., Pedersen O., Parkhill J., Weissenbach J., MetaHIT Consortium, Bork P., Ehrlich S.D., Wang J. A human gut microbial gene catalogue established by metagenomic sequencing. Nature 2010, 464:59-65.
62. Radek K.A., Elias P.M., Taupenot L., Mahata S.K., O'Connor D.T., Gallo R.L. Neuroendocrine nicotinic receptor activation increases susceptibility to bacterial infections by suppressing antimicrobial peptide production. Cell Host Microbe 2010, 7:277-289.
63. Raqib R., Sarker P., Bergman P., Ara G., Lindh M., Sack D.A., Nasirul Islam K.M., Gudmundsson G.H., Andersson J., Agerberth B. Improved outcome in shigellosis associated with butyrate induction of an endogenous peptide antibiotic. Proc. Natl. Acad. Sci. U S A 2006, 103:9178-9183.
64. Reichenbach T., Mobilia M., Frey E. Mobility promotes and jeopardizes biodiversity in rock-paper-scissors games. Nature 2007, 448:1046-1049.
65. Riley M.A., Gordon D.M. The ecological role of bacteriocins in bacterial competition. Trends Microbiol. 1999, 7:129-133.
66. Rosenberger C.M., Gallo R.L., Finlay B.B. Interplay between antibacterial effectors: a macrophage antimicrobial peptide impairs intracellular Salmonella replication. Proc. Natl. Acad. Sci. U S A 2004, 101:2422-2427.
67. Ryu J.H., Ha E.M., Oh C.T., Seol J.H., Brey P.T., Jin I., Lee D.G., Kim J., Lee D., Lee W.J. An essential complementary role of NF-kappaB pathway to microbicidal oxidants in Drosophila gut immunity. EMBO J. 2006, 25:3693-3701.
68. Ryu J.H., Kim S.H., Lee H.Y., Bai J.Y., Nam Y.D., Bae J.W., Lee D.G., Shin S.C., Ha E.M., Lee W.J. Innate immune homeostasis by the homeobox gene caudal and commensal-gut mutualism in Drosophila. Science 2008, 319:777-782.
69. Salzman N.H., Ghosh D., Huttner K.M., Paterson Y., Bevins C.L. Protection against enteric salmonellosis in transgenic mice expressing a human intestinal defensin. Nature 2003, 422:522-526.
70. Salzman N.H., Hung K., Haribhai D., Chu H., Karlsson-Sjöberg J., Amir E., Teggatz P., Barman M., Hayward M., Eastwood D., Stoel M., Zhou Y., Sodergren E., Weinstock G.M., Bevins C.L., Williams C.B., Bos N.A. Enteric defensins are essential regulators of intestinal microbial ecology. Nat. Immunol. 2010, 11:76-83.
71. Sass V., Schneider T., Wilmes M., Körner C., Tossi A., Novikova N., Shamova O., Sahl H.G. Human β-defensin 3 inhibits cell wall biosynthesis in Staphylococci. Infect. Immun. 2010, 78:2793-2800.
72. Schneider T., Kruse T., Wimmer R., Wiedemann I., Sass V., Pag U., Jansen A., Nielsen A.K., Mygind P.H., Raventós D.S., Neve S., Ravn B., Bonvin A.M., De Maria L., Andersen A.S., Gammelgaard L.K., Sahl H.G., Kristensen H.H. Plectasin, a fungal defensin, targets the bacterial cell wall precursor lipid II. Science 2010, 328:1168-1172.
73. Schopfer C.R., Nasrallah M.E., Nasrallah J.B. The male determinant of self-incompatibility in Brassica. Science 1999, 286:1697-1700.
74. Schutte B.C., Mitros J.P., Bartlett J.A., Walters J.D., Jia H.P., Welsh M.J., Casavant T.L., McCray P.B. Discovery of five conserved β-defensin gene clusters using a computational search strategy. Proc. Natl. Acad. Sci. U S A 2002, 99:2129-2133.
75. Sels J., Mathys J., De Coninck B.M., Cammue B.P., De Bolle M.F. Plant pathogenesis-related (PR) proteins: a focus on PR peptides. Plant Physiol. Biochem. 2008, 46:941-950.
76. Silverstein K.A., Moskal W.A., Wu H.C., Underwood B.A., Graham M.A., Town C.D., VandenBosch K.A. Small cysteine-rich peptides resembling antimicrobial peptides have been under-predicted in plants. Plant J. 2007, 51:262-280.
77. Stotz H.U., Spence B., Wang Y. A defensin from tomato with dual function in defense and development. Plant Mol. Biol. 2009, 71:131-143.
78. Sugano S.S., Shimada T., Imai Y., Okawa K., Tamai A., Mori M., Hara-Nishimura I. Stomagen positively regulates stomatal density in Arabidopsis. Nature 2010, 463:241-244.
79. Tait K., Sutherland I.W. Antagonistic interactions amongst bacteriocin-producing enteric bacteria in dual species biofilms. J. Appl. Microbiol. 2002, 93:345-352.
80. Torsvik V., Øvreås L., Thingstad T.F. Prokaryotic diversity-magnitude, dynamics, and controlling factors. Science 2002, 296:1064-1066.
81. Tringe S.G., von Mering C., Kobayashi A., Salamov A.A., Chen K., Chang H.W., Podar M., Short J.M., Mathur E.J., Detter J.C., Bork P., Hugenholtz P., Rubin E.M. Comparative metagenomics of microbial communities. Science 2005, 308:554-557.
82. Tzou P., Ohresser S., Ferrandon D., Capovilla M., Reichhart J.M., Lemaitre B., Jules A., Hoffmann J.A., Imler J.-L. Tissue-specific inducible expression of antimicrobial peptide genes in Drosophila surface epithelia. Immunity 2000, 13:737-748.
83. Tzou P., Reichhart J.M., Lemaitre B. Constitutive expression of a single antimicrobial peptide can restore wild-type resistance to infection in immunodeficient Drosophila mutants. Proc. Natl. Acad. Sci. U S A 2002, 99:2152-2157.
84. Vaishnava S., Behrendt C.L., Ismail A.S., Eckmann L., Hooper L.V. Paneth cells directly sense gut commensals and maintain homeostasis at the intestinal host-microbial interface. Proc. Natl. Acad. Sci. U S A 2008, 105:20858-20863.
85. Van de Velde W., Zehirov G., Szatmari A., Debreczeny M., Ishihara H., Kevei Z., Farkas A., Mikulass K., Nagy A., Tiricz H., Satiat-Jeunemaître B., Alunni B., Bourge M., Kucho K., Abe M., Kereszt A., Maroti G., Uchiumi T., Kondorosi E., Mergaert P. Plant peptides govern terminal differentiation of bacteria in symbiosis. Science 2010, 327:1122-1126.
86. Wehkamp J., Salzman N.H., Porter E., Nuding S., Weichenthal M., Petras R.E., Shen B., Schaeffeler E., Schwab M., Linzmeier R., Feathers R.W., Chu H., Lima H., Fellermann K., Ganz T., Stange E.F., Bevins C.L. Reduced Paneth cell α-defensins in ileal Crohn's disease. Proc. Natl. Acad. Sci. U S A 2005, 102:18129-18134.
87. Wehkamp J., Wang G., Kübler I., Nuding S., Gregorieff A., Schnabel A., Kays R.J., Fellermann K., Burk O., Schwab M., Clevers H., Bevins C.L., Stange E.F. The Paneth cell α-defensin deficiency of ileal Crohn's disease is linked to Wnt/Tcf-4. J. Immunol. 2007, 179:3109-3118.
88. Wilson C.L., Ouellette A.J., Satchell D.P., Ayabe T., López-Boado Y.S., Stratman J.L., Hultgren S.J., Matrisian L.M., Parks W.C. Regulation of intestinal α-defensin activation by the metalloproteinase matrilysin in innate host defense. Science 1999, 286:113-117.
89. Zasloff M. Antimicrobial peptides of multicellular organisms. Nature 2002, 415:389-395.