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Nijnik, A; Hancock, REW (2009)
Publisher: CoAction Publishing
Journal: Emerging Health Threats Journal
Languages: English
Types: Article
Subjects: Review Articles
The rapidly increasing incidence of multidrug-resistant infections and the alarmingly low rate of discovery of conventional antibiotics create an urgent need for alternative strategies to treat bacterial infections. Host defence peptides are short cationic molecules produced by the immune systems of most multicellular organisms; they are a class of compounds being actively researched. In this review, we provide an overview of the antimicrobial and immunomodulatory activities of natural host defence peptides, and discuss strategies for creating artificial derivatives with improved biological and pharmacological properties, issues of microbial resistance, and challenges associated with their adaptation for clinical use. (Published: 24 February 2009) Citation: Emerging Health Threats Journal 2009, 2:e1. doi: 10.3134/ehtj.09.001
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    • 1 Zasloff M. Antimicrobial peptides of multicellular organisms. Nature 2002;415:389-95.
    • 2 Powers JP, Hancock RE. The relationship between peptide structure and antibacterial activity. Peptides 2003;24:1681-91.
    • 3 Hancock RE, Sahl HG. Antimicrobial and host-defense peptides as new anti-infective therapeutic strategies. Nat Biotechnol 2006;24:1551-7.
    • 4 Ganz T. Defensins: antimicrobial peptides of innate immunity. Nat Rev Immunol 2003;3:710-20.
    • 5 Agerberth B, Charo J, Werr J, Olsson B, Idali F, Lindbom L, et al. The human antimicrobial and chemotactic peptides LL-37 and alpha-defensins are expressed by specific lymphocyte and monocyte populations. Blood 2000;96:3086-93.
    • 6 Zeya HI, Spitznagel JK. Antibacterial and enzymic basic proteins from leukocyte lysosomes: separation and identification. Science 1963;142:1085-7.
    • 7 Ayabe T, Ashida T, Kohgo Y, Kono T. The role of Paneth cells and their antimicrobial peptides in innate host defense. Trends Microbiol 2004;12:394-8.
    • 8 Wehkamp J, Schauber J, Stange EF. Defensins and cathelicidins in gastrointestinal infections. Curr Opin Gastroenterol 2007;23:32-8.
    • 9 Ghosh D, Porter E, Shen B, Lee SK, Wilk D, Drazba J, et al. Paneth cell trypsin is the processing enzyme for human defensin-5. Nat Immunol 2002;3:583-90.
    • 10 Wilson CL, Ouellette AJ, Satchell DP, Ayabe T, Lo´ pez-Boado YS, Stratman JL, et al. Regulation of intestinal alpha-defensin activation by the metalloproteinase matrilysin in innate host defense. Science 1999;286:113-17.
    • 11 Ayabe T, Satchell DP, Wilson CL, Parks WC, Selsted ME, Ouellette AJ, et al. Secretion of microbicidal alpha-defensins by intestinal Paneth cells in response to bacteria. Nat Immunol 2000;1:113-18.
    • 12 Wehkamp J, Salzman NH, Porter E, Nuding S, Weichenthal M, Petras RE, et al. Reduced Paneth cell alpha-defensins in ileal Crohn's disease. Proc Natl Acad Sci USA 2005;102:18129-34.
    • 13 Bals R, Wang X, Wu Z, Freeman T, Bafna V, Zasloff M, et al. Human beta-defensin 2 is a salt-sensitive peptide antibiotic expressed in human lung. J Clin Invest 1998;102:874-80.
    • 14 Goldman MJ, Anderson GM, Stolzenberg ED, Kari UP, Zasloff M, Wilson JM, et al. Human beta-defensin-1 is a salt-sensitive antibiotic in lung that is inactivated in cystic fibrosis. Cell 1997;88:553-60.
    • 15 Harder J, Bartels J, Christophers E, Schro¨der JM. A peptide antibiotic from human skin. Nature 1997;387:861.
    • 16 Stolzenberg ED, Anderson GM, Ackermann MR, Whitlock RH, Zasloff M. Epithelial antibiotic induced in states of disease. Proc Natl Acad Sci USA 1997;94:8686-90.
    • 17 Tang YQ, Yuan J, Osapay G, Osapay K, Tran D, Miller CJ, et al. A cyclic antimicrobial peptide produced in primate leukocytes by the ligation of two truncated alpha-defensins. Science 1999;286: 498-502.
    • 18 Zanetti M. Cathelicidins, multifunctional peptides of the innate immunity. J Leukoc Biol 2004;75:39-48.
    • 19 Bowdish DM, Davidson DJ, Lau YE, Lee K, Scott MG, Hancock RE, et al. Impact of LL-37 on anti-infective immunity. J Leukoc Biol 2005;77:451-9.
    • 20 Braff MH, Hawkins MA, Di Nardo A, Lopez-Garcia B, Howell MD, Wong C, et al. Structure-function relationships among human cathelicidin peptides: dissociation of antimicrobial properties from host immunostimulatory activities. J Immunol 2005;174:4271-8.
    • 21 Gallo RL, Kim KJ, Bernfield M, Kozak CA, Zanetti M, Merluzzi L, et al. Identification of CRAMP, a cathelin-related antimicrobial peptide expressed in the embryonic and adult mouse. J Biol Chem 1997;272:13088-93.
    • 22 Sorensen O, Arnljots K, Cowland JB, Bainton DF, Borregaard N. The human antibacterial cathelicidin, hCAP-18, is synthesized in myelocytes and metamyelocytes and localized to specific granules in neutrophils. Blood 1997;90:2796-803.
    • 23 Bals R, Wang X, Zasloff M, Wilson JM. The peptide antibiotic LL37/hCAP-18 is expressed in epithelia of the human lung where it has broad antimicrobial activity at the airway surface. Proc Natl Acad Sci USA 1998;95:9541-6.
    • 24 Frohm M, Agerberth B, Ahangari G, Staˆhle-Ba¨ckdahl M, Lide´n S, Wigzell H, et al. The expression of the gene coding for the antibacterial peptide LL-37 is induced in human keratinocytes during inflammatory disorders. J Biol Chem 1997; 272:15258-63.
    • 25 Frohm Nilsson M, Sandstedt B, Sorensen O, Weber G, Borregaard N, Sta˚hle-Ba¨ckdahl M, et al. The human cationic antimicrobial protein (hCAP18), a peptide antibiotic, is widely expressed in human squamous epithelia and colocalizes with interleukin-6. Infect Immun 1999;67:2561-6.
    • 26 Liu PT, Stenger S, Li H, Wenzel L, Tan BH, Krutzik SR, et al. Tolllike receptor triggering of a vitamin D-mediated human antimicrobial response. Science 2006;311:1770-3.
    • 27 Peyssonnaux C, Boutin AT, Zinkernagel AS, Datta V, Nizet V, Johnson RS, et al. Critical role of HIF-1alpha in keratinocyte defense against bacterial infection. J Invest Dermatol 2008;128:1964-8.
    • 28 Peyssonnaux C, Datta V, Cramer T, Doedens A, Theodorakis EA, Gallo RL, et al. HIF-1alpha expression regulates the bactericidal capacity of phagocytes. J Clin Invest 2005;115:1806-15.
    • 29 Kavanagh K, Dowd S. Histatins: antimicrobial peptides with therapeutic potential. J Pharm Pharmacol 2004;56:285-9.
    • 30 Schittek B, Hipfel R, Sauer B, Bauer J, Kalbacher H, Stevanovic S, et al. Dermcidin: a novel human antibiotic peptide secreted by sweat glands. Nat Immunol 2001;2:1133-7.
    • 31 Farnaud S, Evans RW. LactoferrinFa multifunctional protein with antimicrobial properties. Mol Immunol 2003;40:395-405.
    • 32 Scott MG, Davidson DJ, Gold MR, Bowdish D, Hancock RE. The human antimicrobial peptide LL-37 is a multifunctional modulator of innate immune responses. J Immunol 2002;169:3883-91.
    • 33 Klotman ME, Chang TL. Defensins in innate antiviral immunity. Nat Rev Immunol 2006;6:447-56.
    • 34 Johansson J, Gudmundsson GH, Rottenberg ME, Berndt KD, Agerberth B. Conformation-dependent antibacterial activity of the naturally occurring human peptide LL-37. J Biol Chem 1998;273:3718-24.
    • 35 De Y, Chen Q, Schmidt AP, Anderson GM, Wang JM, Wooters J, et al. LL-37, the neutrophil granule- and epithelial cell-derived cathelicidin, utilizes formyl peptide receptor-like 1 (FPRL1) as a receptor to chemoattract human peripheral blood neutrophils, monocytes, and T cells. J Exp Med 2000;192:1069-74.
    • 36 Niyonsaba F, Iwabuchi K, Someya A, Hirata M, Matsuda H, Ogawa H, et al. A cathelicidin family of human antibacterial peptide LL-37 induces mast cell chemotaxis. Immunology 2002;106:20-6.
    • 37 Lee HY, Bae YS. The anti-infective peptide, innate defenseregulator peptide, stimulates neutrophil chemotaxis via a formyl peptide receptor. Biochem Biophys Res Commun 2008;369:573-8.
    • 38 Scott MG, Dullaghan E, Mookherjee N, Glavas N, Waldbrook M, Thompson A, et al. An anti-infective peptide that selectively modulates the innate immune response. Nat Biotechnol 2007; 25:465-72.
    • 39 Bowdish DM, Davidson DJ, Speert DP, Hancock RE. The human cationic peptide LL-37 induces activation of the extracellular signal-regulated kinase and p38 kinase pathways in primary human monocytes. J Immunol 2004;172:3758-65.
    • 40 Mookherjee N, Brown KL, Bowdish DM, Doria S, Falsafi R, Hokamp K, et al. Modulation of the TLR-mediated inflammatory response by the endogenous human host defense peptide LL-37. J Immunol 2006;176:2455-64.
    • 41 Kandler K, Shaykhiev R, Kleemann P, Klescz F, Lohoff M, Vogelmeier C, et al. The anti-microbial peptide LL-37 inhibits the activation of dendritic cells by TLR ligands. Int Immunol 2006;18:1729-36.
    • 42 Davidson DJ, Currie AJ, Reid GS, Bowdish DM, MacDonald KL, Ma RC, et al. The cationic antimicrobial peptide LL-37 modulates dendritic cell differentiation and dendritic cell-induced T cell polarization. J Immunol 2004;172:1146-56.
    • 43 Lande R, Gregorio J, Facchinetti V, Chatterjee B, Wang YH, Homey B, et al. Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide. Nature 2007;449:564-9.
    • 44 Zheng Y, Niyonsaba F, Ushio H, Nagaoka I, Ikeda S, Okumura K, et al. Cathelicidin LL-37 induces the generation of reactive oxygen species and release of human alpha-defensins from neutrophils. Br J Dermatol 2007;157:1124-31.
    • 45 Niyonsaba F, Someya A, Hirata M, Ogawa H, Nagaoka I. Evaluation of the effects of peptide antibiotics human betadefensins-1/-2 and LL-37 on histamine release and prostaglandin D(2) production from mast cells. Eur J Immunol 2001;31:1066-75.
    • 46 Elssner A, Duncan M, Gavrilin M, Wewers MD. A novel P2X7 receptor activator, the human cathelicidin-derived peptide LL37, induces IL-1 beta processing and release. J Immunol 2004; 172:4987-94.
    • 47 Barlow PG, Li Y, Wilkinson TS, Bowdish DM, Lau YE, Cosseau C, et al. The human cationic host defense peptide LL-37 mediates contrasting effects on apoptotic pathways in different primary cells of the innate immune system. J Leukoc Biol 2006;80:509-20.
    • 48 Nagaoka I, Tamura H, Hirata M. An antimicrobial cathelicidin peptide, human CAP18/LL-37, suppresses neutrophil apoptosis via the activation of formyl-peptide receptor-like 1 and P2X7. J Immunol 2006;176:3044-52.
    • 49 Zhang Z, Cherryholmes G, Shively JE. Neutrophil secondary necrosis is induced by LL-37 derived from cathelicidin. J Leukoc Biol 2008;84:780-8.
    • 50 Carretero M, Escamez MJ, Garcia M, Duarte B, Holgu´ın A, Retamosa L, et al. In vitro and in vivo wound healing-promoting activities of human cathelicidin LL-37. J Invest Dermatol 2008;128:223-36.
    • 51 Tokumaru S, Sayama K, Shirakata Y, Komatsuzawa H, Ouhara K, Hanakawa Y, et al. Induction of keratinocyte migration via transactivation of the epidermal growth factor receptor by the antimicrobial peptide LL-37. J Immunol 2005;175:4662-8.
    • 52 Lau YE, Rozek A, Scott MG, Goosney DL, Davidson DJ, Hancock RE, et al. Interaction and cellular localization of the human host defense peptide LL-37 with lung epithelial cells. Infect Immun 2005;73:583-91.
    • 53 Tjabringa GS, Aarbiou J, Ninaber DK, Drijfhout JW, Sørensen OE, Borregaard N, et al. The antimicrobial peptide LL-37 activates innate immunity at the airway epithelial surface by transactivation of the epidermal growth factor receptor. J Immunol 2003; 171:6690-6.
    • 54 Koczulla R, von Degenfeld G, Kupatt C, Kro¨tz F, Zahler S, Gloe T, et al. An angiogenic role for the human peptide antibiotic LL-37/ hCAP-18. J Clin Invest 2003;111:1665-72.
    • 55 Biragyn A, Ruffini PA, Leifer CA, Klyushnenkova E, Shakhov A, Chertov O, et al. Toll-like receptor 4-dependent activation of dendritic cells by beta-defensin 2. Science 2002;298:1025-9.
    • 56 Kobayashi KS, Chamaillard M, Ogura Y, Henegariu O, Inohara N, Nun˜ez G, et al. Nod2-dependent regulation of innate and adaptive immunity in the intestinal tract. Science 2005;307:731-4.
    • 57 Salzman NH, Ghosh D, Huttner KM, Paterson Y, Bevins CL. Protection against enteric salmonellosis in transgenic mice expressing a human intestinal defensin. Nature 2003;422:522-6.
    • 58 Nizet V, Ohtake T, Lauth X, Trowbridge J, Rudisill J, Dorschner RA, et al. Innate antimicrobial peptide protects the skin from invasive bacterial infection. Nature 2001;414:454-7.
    • 59 Chromek M, Slamova´ Z, Bergman P, Kova´cs L, Podracka´ L, Ehre´n I, et al. The antimicrobial peptide cathelicidin protects the urinary tract against invasive bacterial infection. Nat Med 2006;12:636-41.
    • 60 Ganz T, Metcalf JA, Gallin JI, Boxer LA, Lehrer RI, et al. Microbicidal/cytotoxic proteins of neutrophils are deficient in two disorders: Chediak-Higashi syndrome and 'specific' granule deficiency. J Clin Invest 1988;82:552-6.
    • 61 Putsep K, Carlsson G, Boman HG, Andersson M. Deficiency of antibacterial peptides in patients with morbus Kostmann: an observation study. Lancet 2002;360:1144-9.
    • 62 Ong PY, Ohtake T, Brandt C, Strickland I, Boguniewicz M, Ganz T, et al. Endogenous antimicrobial peptides and skin infections in atopic dermatitis. N Engl J Med 2002;347:1151-60.
    • 63 Yamasaki K, Di Nardo A, Bardan A, Murakami M, Ohtake T, Coda A, et al. Increased serine protease activity and cathelicidin promotes skin inflammation in rosacea. Nat Med 2007;13: 975-80.
    • 64 Bals R, Weiner DJ, Wilson JM. The innate immune system in cystic fibrosis lung disease. J Clin Invest 1999;103:303-7.
    • 65 Smith JJ, Travis SM, Greenberg EP, Welsh MJ. Cystic fibrosis airway epithelia fail to kill bacteria because of abnormal airway surface fluid. Cell 1996;85:229-36.
    • 66 Levy SB, Marshall B. Antibacterial resistance worldwide: causes, challenges and responses. Nat Med 2004;10 (12 Suppl): S122-9.
    • 67 Houghten RA, Pinilla C, Blondelle SE, Appel JR, Dooley CT, Cuervo JH, et al. Generation and use of synthetic peptide combinatorial libraries for basic research and drug discovery. Nature 1991;354:84-6.
    • 68 Watt PM. Screening for peptide drugs from the natural repertoire of biodiverse protein folds. Nat Biotechnol 2006;24:177-83.
    • 69 Hilpert K, Volkmer-Engert R, Walter T, Hancock RE. Highthroughput generation of small antibacterial peptides with improved activity. Nat Biotechnol 2005;23:1008-12.
    • 70 Jenssen H, Fjell CD, Cherkasov A, Hancock RE. QSAR modeling and computer-aided design of antimicrobial peptides. J Pept Sci 2008;14:110-14.
    • 71 Loose C, Jensen K, Rigoutsos I, Stephanopoulos G. A linguistic model for the rational design of antimicrobial peptides. Nature 2006;443:867-9.
    • 72 Mygind PH, Fischer RL, Schnorr KM, Hansen MT, So¨nksen CP, Ludvigsen S, et al. Plectasin is a peptide antibiotic with therapeutic potential from a saprophytic fungus. Nature 2005;437:975-80.
    • 73 Cotter PD, Hill C, Ross RP. Bacteriocins: developing innate immunity for food. Nat Rev Microbiol 2005;3:777-88.
    • 74 Nizet V. Antimicrobial peptide resistance mechanisms of human bacterial pathogens. Curr Issues Mol Biol 2006;8:11-26.
    • 75 Peschel A, Sahl HG. The co-evolution of host cationic antimicrobial peptides and microbial resistance. Nat Rev Microbiol 2006;4:529-36.
    • 76 Perron GG, Zasloff M, Bell G. Experimental evolution of resistance to an antimicrobial peptide. Proc Biol Sci 2006;273:251-6.
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