Antimicrobial Peptides

  • Srinjoy Chakraborti
  • Sanjay RamEmail author


Antimicrobial peptides (AMPs) are small proteins synthesized predominantly by leukocytes. Although discovered about a century ago, interest in AMPs has only recently burgeoned, largely fueled by the need for alternative therapeutics against drug-resistant infections. AMPs are widely distributed; they are found intracellularly, in body fluids and at mucosal surfaces. Although their primary physiological function is considered protection against infections, it is increasingly evident that the role of AMPs may also extend to wound healing and immunomodulation. Several studies have associated dysregulation of AMPs with predisposition to infectious diseases and immune disorders, although causality remains to be established. Naturally occurring and synthetic AMPs have been developed for treatment of infections. However, as with antibiotics, pathogens acquire resistance to AMPs, which have posed an obstacle to their clinical development. The current review provides a brief overview of this complex and evolving field.


Antimicrobial peptide Defensin 


  1. 1.
    Wang G, Li X, Wang Z. APD3: the antimicrobial peptide database as a tool for research and education. Nucleic Acids Res. 2016;44(D1):D1087–93.PubMedCrossRefGoogle Scholar
  2. 2.
    Zimmer J, Hobkirk J, Mohamed F, Browning M, Stover CM. On the functional overlap between complement and antimicrobial peptides. Front Immunol. 2015;5Google Scholar
  3. 3.
    Zasloff M. Antimicrobial peptides of multicellular organisms. Nature. 2002;415(6870):389–95.PubMedCrossRefGoogle Scholar
  4. 4.
    Park Y, Hahm KS. Antimicrobial peptides (AMPs): peptide structure and mode of action. J Biochem Mol Biol. 2005;38(5):507–16.PubMedGoogle Scholar
  5. 5.
    Tennessen JA. Molecular evolution of animal antimicrobial peptides: widespread moderate positive selection. J Evol Biol. 2005;18(6):1387–94.PubMedCrossRefGoogle Scholar
  6. 6.
    Zhang LJ, Gallo RL. Antimicrobial peptides. Curr Biol. 2016;26(1):R14–9.PubMedCrossRefGoogle Scholar
  7. 7.
    Hollox EJ, Armour JA, Barber JC. Extensive normal copy number variation of a beta-defensin antimicrobial-gene cluster. Am J Hum Genet. 2003;73(3):591–600.PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Coda AB, et al. Cathelicidin, kallikrein 5, and serine protease activity is inhibited during treatment of rosacea with azelaic acid 15% gel. J Am Acad Dermatol. 2013;69(4):570–7.PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Senyurek I, Klein G, Kalbacher H, Deeg M, Schittek B. Peptides derived from the human laminin alpha 4 and alpha 5 chains exhibit antimicrobial activity. Peptides. 2010;31(8):1468–72.PubMedCrossRefGoogle Scholar
  10. 10.
    Mansour SC, Pena OM, Hancock REW. Host defense peptides: front-line immunomodulators. Trends Immunol. 2014;35(9):443–50.PubMedCrossRefGoogle Scholar
  11. 11.
    Steinstraesser L, Kraneburg U, Jacobsen F, Al-Benna S. Host defense peptides and their antimicrobial-immunomodulatory duality. Immunobiology. 2011;216(3):322–33.PubMedCrossRefGoogle Scholar
  12. 12.
    Meisch JP, et al. Human beta-defensin 3 peptide is increased and redistributed in Crohn’s ileitis. Inflamm Bowel Dis. 2013;19(5):942–53.PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Lande R, et al. Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide. Nature. 2007;449(7162):564–9.PubMedCrossRefGoogle Scholar
  14. 14.
    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(7):3883–91.PubMedCrossRefGoogle Scholar
  15. 15.
    Rosenfeld Y, Papo N, Shai Y. Endotoxin (lipopolysaccharide) neutralization by innate immunity host-defense peptides. Peptide properties and plausible modes of action. J Biol Chem. 2006;281(3):1636–43.PubMedCrossRefGoogle Scholar
  16. 16.
    Yamasaki K, et al. Increased serine protease activity and cathelicidin promotes skin inflammation in rosacea. Nat Med. 2007;13(8):975–80.PubMedCrossRefGoogle Scholar
  17. 17.
    Courth LF, et al. Crohn's disease-derived monocytes fail to induce Paneth cell defensins. Proc Natl Acad Sci U S A. 2015;112(45):14000–5.PubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    Wang G. Improved methods for classification, prediction, and design of antimicrobial peptides. Methods Mol Biol. 2015;1268:43–66.PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Zanetti M. Cathelicidins, multifunctional peptides of the innate immunity. J Leukoc Biol. 2004;75(1):39–48.PubMedCrossRefGoogle Scholar
  20. 20.
    Bulet P, Stocklin R, Menin L. Anti-microbial peptides: from invertebrates to vertebrates. Immunol Rev. 2004;198:169–84.PubMedCrossRefGoogle Scholar
  21. 21.
    Brogden KA. Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria? Nat Rev Microbiol. 2005;3(3):238–50.PubMedCrossRefGoogle Scholar
  22. 22.
    Ahmad A, et al. Identification and design of antimicrobial peptides for therapeutic applications. Curr Protein Pept Sci. 2012;13(3):211–23.PubMedCrossRefGoogle Scholar
  23. 23.
    White SH, Wimley WC, Selsted ME. Structure, function, and membrane integration of defensins. Curr Opin Struct Biol. 1995;5(4):521–7.PubMedCrossRefGoogle Scholar
  24. 24.
    Lehrer RI, Cole AM, Selsted ME. θ-Defensins: cyclic peptides with endless potential. J Biol Chem. 2012;287(32):27014–9.PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Yount NY, Yeaman MR. Immunocontinuum: perspectives in antimicrobial peptide mechanisms of action and resistance. Protein Pept Lett. 2005;12(1):49–67.PubMedCrossRefGoogle Scholar
  26. 26.
    Shah P, Hsiao FS, Ho YH, Chen CS. The proteome targets of intracellular targeting antimicrobial peptides. Proteomics. 2015.Google Scholar
  27. 27.
    Nguyen LT, Haney EF, Vogel HJ. The expanding scope of antimicrobial peptide structures and their modes of action. Trends Biotechnol. 2011;29(9):464–72.PubMedCrossRefGoogle Scholar
  28. 28.
    Cho J, et al. The novel biological action of antimicrobial peptides via apoptosis induction. J Microbiol Biotechnol. 2012;22(11):1457–66.PubMedCrossRefGoogle Scholar
  29. 29.
    Burian M, Schittek B. The secrets of dermcidin action. Int J Med Microbiol. 2015;305(2):283–6.PubMedCrossRefGoogle Scholar
  30. 30.
    Sass V, et al. Human beta-defensin 3 inhibits cell wall biosynthesis in Staphylococci. Infect Immun. 2010;78(6):2793–800.PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    de Leeuw E, et al. Functional interaction of human neutrophil peptide-1 with the cell wall precursor lipid II. FEBS Lett. 2010;584(8):1543–8.PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Spencer JD, et al. Ribonuclease 7, an antimicrobial peptide upregulated during infection, contributes to microbial defense of the human urinary tract. Kidney Int. 2013;83(4):615–25.PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Lin YM, et al. Outer membrane protein I of Pseudomonas aeruginosa is a target of cationic antimicrobial peptide/protein. J Biol Chem. 2010;285(12):8985–94.PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Kim HS, et al. Endotoxin-neutralizing antimicrobial proteins of the human placenta. J Immunol. 2002;168(5):2356–64.PubMedCrossRefGoogle Scholar
  35. 35.
    Hazrati E, et al. Human α- and β-Defensins block multiple steps in herpes simplex virus infection. J Immunol. 2006;177(12):8658–66.PubMedCrossRefGoogle Scholar
  36. 36.
    Helmerhorst EJ, et al. The cellular target of histatin 5 on Candida albicans is the energized mitochondrion. J Biol Chem. 1999;274(11):7286–91.PubMedCrossRefGoogle Scholar
  37. 37.
    Luque-Ortega JR, van’t Hof W, Veerman EC, Saugar JM, Rivas L. Human antimicrobial peptide histatin 5 is a cell-penetrating peptide targeting mitochondrial ATP synthesis in Leishmania. FASEB J. 2008;22(6):1817–28.PubMedCrossRefGoogle Scholar
  38. 38.
    Mochon AB, Liu H. The antimicrobial peptide histatin-5 causes a spatially restricted disruption on the Candida albicans surface, allowing rapid entry of the peptide into the cytoplasm. PLoS Pathog. 2008;4(10):e1000190.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Barker HC, Kinsella N, Jaspe A, Friedrich T, O’Connor CD. Formate protects stationary-phase Escherichia coli and Salmonella cells from killing by a cationic antimicrobial peptide. Mol Microbiol. 2000;35(6):1518–29.PubMedCrossRefPubMedCentralGoogle Scholar
  40. 40.
    Backo M, Gaenger E, Burkart A, Chai YL, Bayer AS. Treatment of experimental staphylococcal endocarditis due to a strain with reduced susceptibility in vitro to vancomycin: efficacy of ampicillin-sulbactam. Antimicrob Agents Chemother. 1999;43(10):2565–8.PubMedPubMedCentralGoogle Scholar
  41. 41.
    Territo MC, Ganz T, Selsted ME, Lehrer R. Monocyte-chemotactic activity of defensins from human neutrophils. J Clin Invest. 1989;84(6):2017–20.PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Lai Y, Gallo RL. AMPed up immunity: how antimicrobial peptides have multiple roles in immune defense. Trends Immunol. 2009;30(3):131–41.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    De Y, 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(7):1069–74.CrossRefGoogle Scholar
  44. 44.
    Befus AD, et al. Neutrophil defensins induce histamine secretion from mast cells: mechanisms of action. J Immunol. 1999;163(2):947–53.PubMedGoogle Scholar
  45. 45.
    Yang D, Biragyn A, Kwak LW, Oppenheim JJ. Mammalian defensins in immunity: more than just microbicidal. Trends Immunol. 2002;23(6):291–6.PubMedCrossRefGoogle Scholar
  46. 46.
    Funderburg N, et al. Human -defensin-3 activates professional antigen-presenting cells via Toll-like receptors 1 and 2. Proc Natl Acad Sci U S A. 2007;104(47):18631–5.PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Niyonsaba F, Ushio H, Nagaoka I, Okumura K, Ogawa H. The human beta-defensins (-1, -2, -3, -4) and cathelicidin LL-37 induce IL-18 secretion through p38 and ERK MAPK activation in primary human keratinocytes. J Immunol. 2005;175(3):1776–84.PubMedCrossRefGoogle Scholar
  48. 48.
    Prohaszka Z, et al. Defensins purified from human granulocytes bind C1q and activate the classical complement pathway like the transmembrane glycoprotein gp41 of HIV-1. Mol Immunol. 1997;34(11):809–16.PubMedCrossRefGoogle Scholar
  49. 49.
    Groeneveld TW, et al. Human neutrophil peptide-1 inhibits both the classical and the lectin pathway of complement activation. Mol Immunol. 2007;44(14):3608–14.PubMedCrossRefGoogle Scholar
  50. 50.
    Nizet V. Antimicrobial peptide resistance mechanisms of human bacterial pathogens. Curr Issues Mol Biol. 2006;8:11–26.PubMedGoogle Scholar
  51. 51.
    Gruenheid S, Le Moual H. Resistance to antimicrobial peptides in Gram-negative bacteria. FEMS Microbiol Lett. 2012;330(2):81–9.PubMedCrossRefGoogle Scholar
  52. 52.
    Yeaman MR, Yount NY. Mechanisms of antimicrobial peptide action and resistance. Pharmacol Rev. 2003;55(1):27–55.PubMedCrossRefGoogle Scholar
  53. 53.
    Jin T, et al. Staphylococcus aureus resists human defensins by production of staphylokinase, a novel bacterial evasion mechanism. J Immunol. 2004;172(2):1169–76.PubMedCrossRefGoogle Scholar
  54. 54.
    Frick IM, Akesson P, Rasmussen M, Schmidtchen A, Bjorck L. SIC, a secreted protein of Streptococcus pyogenes that inactivates antibacterial peptides. J Biol Chem. 2003;278(19):16561–6.PubMedCrossRefGoogle Scholar
  55. 55.
    Paulsen IT, Brown MH, Skurray RA. Proton-dependent multidrug efflux systems. Microbiol Rev. 1996;60(4):575–608.PubMedPubMedCentralGoogle Scholar
  56. 56.
    Xu Z, O’Rourke BA, Skurray RA, Brown MH. Role of transmembrane segment 10 in efflux mediated by the staphylococcal multidrug transport protein QacA. J Biol Chem. 2006;281(2):792–9.PubMedCrossRefGoogle Scholar
  57. 57.
    Guilhelmelli F, et al. Antibiotic development challenges: the various mechanisms of action of antimicrobial peptides and of bacterial resistance. Front Microbiol. 2013;4:353.PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Bengoechea JA, Skurnik M. Temperature-regulated efflux pump/potassium antiporter system mediates resistance to cationic antimicrobial peptides in Yersinia. Mol Microbiol. 2000;37(1):67–80.PubMedCrossRefGoogle Scholar
  59. 59.
    Padilla E, et al. Klebsiella pneumoniae AcrAB efflux pump contributes to antimicrobial resistance and virulence. Antimicrob Agents Chemother. 2010;54(1):177–83.PubMedCrossRefGoogle Scholar
  60. 60.
    Nikaido H, Hall JA. Overview of bacterial ABC transporters. Methods Enzymol. 1998;292:3–20.PubMedCrossRefGoogle Scholar
  61. 61.
    Eswarappa SM, Panguluri KK, Hensel M, Chakravortty D. The yejABEF operon of Salmonella confers resistance to antimicrobial peptides and contributes to its virulence. Microbiology. 2008;154(Pt 2):666–78.PubMedCrossRefGoogle Scholar
  62. 62.
    Schmidtchen A, Frick IM, Andersson E, Tapper H, Bjorck L. Proteinases of common pathogenic bacteria degrade and inactivate the antibacterial peptide LL-37. Mol Microbiol. 2002;46(1):157–68.PubMedCrossRefGoogle Scholar
  63. 63.
    Kooi C, Sokol PA. Burkholderia cenocepacia zinc metalloproteases influence resistance to antimicrobial peptides. Microbiology. 2009;155(Pt 9):2818–25.PubMedCrossRefGoogle Scholar
  64. 64.
    Sieprawska-Lupa M, et al. Degradation of human antimicrobial peptide LL-37 by Staphylococcus aureus-derived proteinases. Antimicrob Agents Chemother. 2004;48(12):4673–9.PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Maisetta G, Brancatisano FL, Esin S, Campa M, Batoni G. Gingipains produced by Porphyromonas gingivalis ATCC49417 degrade human-beta-defensin 3 and affect peptide’s antibacterial activity in vitro. Peptides. 2011;32(5):1073–7.PubMedCrossRefGoogle Scholar
  66. 66.
    Thomassin JL, Brannon JR, Gibbs BF, Gruenheid S, Le Moual H. OmpT outer membrane proteases of enterohemorrhagic and enteropathogenic Escherichia coli contribute differently to the degradation of human LL-37. Infect Immun. 2012;80(2):483–92.PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Grodberg J, Dunn JJ. Comparison of Escherichia coli K-12 outer membrane protease OmpT and Salmonella typhimurium E protein. J Bacteriol. 1989;171(5):2903–5.PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Guina T, Yi EC, Wang H, Hackett M, Miller SI. A PhoP-regulated outer membrane protease of Salmonella enterica serovar typhimurium promotes resistance to alpha-helical antimicrobial peptides. J Bacteriol. 2000;182(14):4077–86.PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Dinulos JG, Mentele L, Fredericks LP, Dale BA, Darmstadt GL. Keratinocyte expression of human beta defensin 2 following bacterial infection: role in cutaneous host defense. Clin Diagn Lab Immunol. 2003;10(1):161–6.PubMedPubMedCentralGoogle Scholar
  70. 70.
    Islam D, et al. Downregulation of bactericidal peptides in enteric infections: a novel immune escape mechanism with bacterial DNA as a potential regulator. Nat Med. 2001;7(2):180–5.PubMedCrossRefGoogle Scholar
  71. 71.
    Chakraborty K, et al. Bacterial exotoxins downregulate cathelicidin (hCAP-18/LL-37) and human beta-defensin 1 (HBD-1) expression in the intestinal epithelial cells. Cell Microbiol. 2008;10(12):2520–37.PubMedCrossRefGoogle Scholar
  72. 72.
    Bergman P, et al. Neisseria gonorrhoeae downregulates expression of the human antimicrobial peptide LL-37. Cell Microbiol. 2005;7(7):1009–17.PubMedCrossRefGoogle Scholar
  73. 73.
    Taggart CC, et al. Inactivation of human beta-defensins 2 and 3 by elastolytic cathepsins. J Immunol. 2003;171(2):931–7.PubMedCrossRefGoogle Scholar
  74. 74.
    West AH, Stock AM. Histidine kinases and response regulator proteins in two-component signaling systems. Trends Biochem Sci. 2001;26(6):369–76.PubMedCrossRefGoogle Scholar
  75. 75.
    Beier D, Gross R. Regulation of bacterial virulence by two-component systems. Curr Opin Microbiol. 2006;9(2):143–52.PubMedCrossRefGoogle Scholar
  76. 76.
    Guo L, et al. Lipid A acylation and bacterial resistance against vertebrate antimicrobial peptides. Cell. 1998;95(2):189–98.PubMedCrossRefGoogle Scholar
  77. 77.
    Ernst RK, Guina T, Miller SI. Salmonella typhimurium outer membrane remodeling: role in resistance to host innate immunity. Microbes Infect. 2001;3(14–15):1327–34.PubMedCrossRefGoogle Scholar
  78. 78.
    Moskowitz SM, Ernst RK, Miller SI. PmrAB, a two-component regulatory system of Pseudomonas aeruginosa that modulates resistance to cationic antimicrobial peptides and addition of aminoarabinose to lipid A. J Bacteriol. 2004;186(2):575–9.PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Fernandez L, et al. The two-component system CprRS senses cationic peptides and triggers adaptive resistance in Pseudomonas aeruginosa independently of ParRS. Antimicrob Agents Chemother. 2012;56(12):6212–22.PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Domingues MM, Castanho MA, Santos NC. rBPI(21) promotes lipopolysaccharide aggregation and exerts its antimicrobial effects by (hemi)fusion of PG-containing membranes. PLoS One. 2009;4(12):e8385.PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    Domingues MM, Lopes SC, Santos NC, Quintas A, Castanho MA. Fold-unfold transitions in the selectivity and mechanism of action of the N-terminal fragment of the bactericidal/permeability-increasing protein (rBPI(21)). Biophys J. 2009;96(3):987–96.PubMedPubMedCentralCrossRefGoogle Scholar
  82. 82.
    Levin M, et al. Recombinant bactericidal/permeability-increasing protein (rBPI21) as adjunctive treatment for children with severe meningococcal sepsis: a randomised trial. rBPI21 Meningococcal Sepsis Study Group. Lancet. 2000;356(9234):961–7.PubMedCrossRefGoogle Scholar
  83. 83.
    Mackin WM. Neuprex XOMA Corp. IDrugs. 1998;1(6):715–23.PubMedGoogle Scholar
  84. 84.
    Gottler LM, Ramamoorthy A. Structure, membrane orientation, mechanism, and function of pexiganan – a highly potent antimicrobial peptide designed from magainin. Biochim Biophys Acta. 2009;1788(8):1680–6.PubMedCrossRefGoogle Scholar
  85. 85.
    Bolintineanu DS, Vivcharuk V, Kaznessis YN. Multiscale models of the antimicrobial peptide protegrin-1 on Gram-negative bacteria membranes. Int J Mol Sci. 2012;13(9):11000–11.PubMedPubMedCentralCrossRefGoogle Scholar
  86. 86.
    Jerse AE, et al. Multiple gonococcal opacity proteins are expressed during experimental urethral infection in the male. J Exp Med. 1994;179(3):911–20.PubMedCrossRefGoogle Scholar
  87. 87.
    Seo MD, Won HS, Kim JH, Mishig-Ochir T, Lee BJ. Antimicrobial peptides for therapeutic applications: a review. Molecules. 2012;17(10):12276–86.PubMedCrossRefGoogle Scholar
  88. 88.
    Nibbering PH, et al. Human lactoferrin and peptides derived from its N terminus are highly effective against infections with antibiotic-resistant bacteria. Infect Immun. 2001;69(3):1469–76.PubMedPubMedCentralCrossRefGoogle Scholar
  89. 89.
    Lupetti A, et al. Human lactoferrin-derived peptide’s antifungal activities against disseminated Candida albicans infection. J Infect Dis. 2007;196(9):1416–24.PubMedCrossRefGoogle Scholar
  90. 90.
    van der Does AM, et al. The human lactoferrin-derived peptide hLF1-11 primes monocytes for an enhanced TLR-mediated immune response. Biometals. 2010;23(3):493–505.PubMedCrossRefGoogle Scholar
  91. 91.
    van der Does AM, et al. Antimicrobial peptide hLF1-11 directs granulocyte-macrophage colony-stimulating factor-driven monocyte differentiation toward macrophages with enhanced recognition and clearance of pathogens. Antimicrob Agents Chemother. 2010;54(2):811–6.PubMedCrossRefGoogle Scholar
  92. 92.
    Hancock RE, Sahl HG. Antimicrobial and host-defense peptides as new anti-infective therapeutic strategies. Nat Biotechnol. 2006;24(12):1551–7.PubMedCrossRefGoogle Scholar
  93. 93.
    Fjell CD, Hiss JA, Hancock RE, Schneider G. Designing antimicrobial peptides: form follows function. Nat Rev Drug Discov. 2012;11(1):37–51.CrossRefGoogle Scholar
  94. 94.
    Mendez-Samperio P. Peptidomimetics as a new generation of antimicrobial agents: current progress. Infect Drug Resist. 2014;7:229–37.PubMedPubMedCentralCrossRefGoogle Scholar
  95. 95.
    Aoki W, Kuroda K, Ueda M. Next generation of antimicrobial peptides as molecular targeted medicines. J Biosci Bioeng. 2012;114(4):365–70.PubMedCrossRefGoogle Scholar
  96. 96.
    Mojsoska B, Jenssen H. Peptides and Peptidomimetics for antimicrobial drug design. Pharmaceuticals (Basel). 2015;8(3):366–415.CrossRefGoogle Scholar
  97. 97.
    Rieg S, et al. Deficiency of dermcidin-derived antimicrobial peptides in sweat of patients with atopic dermatitis correlates with an impaired innate defense of human skin in vivo. J Immunol. 2005;174(12):8003–10.PubMedCrossRefGoogle Scholar
  98. 98.
    Ong PY, et al. Endogenous antimicrobial peptides and skin infections in atopic dermatitis. N Engl J Med. 2002;347(15):1151–60.PubMedCrossRefGoogle Scholar
  99. 99.
    Rivas-Santiago B, Serrano CJ, Enciso-Moreno JA. Susceptibility to infectious diseases based on antimicrobial peptide production. Infect Immun. 2009;77(11):4690–5.PubMedPubMedCentralCrossRefGoogle Scholar
  100. 100.
    Fellermann K, et al. A chromosome 8 gene-cluster polymorphism with low human beta-defensin 2 gene copy number predisposes to Crohn disease of the colon. Am J Hum Genet. 2006;79(3):439–48.PubMedPubMedCentralCrossRefGoogle Scholar
  101. 101.
    Jurevic RJ, Bai M, Chadwick RB, White TC, Dale BA. Single-nucleotide polymorphisms (SNPs) in human beta-defensin 1: high-throughput SNP assays and association with Candida carriage in type I diabetics and nondiabetic controls. J Clin Microbiol. 2003;41(1):90–6.PubMedPubMedCentralCrossRefGoogle Scholar
  102. 102.
    Segat L, et al. DEFB-1 genetic polymorphism screening in HIV-1 positive pregnant women and their children. J Matern Fetal Neonatal Med. 2006;19(1):13–6.PubMedCrossRefGoogle Scholar
  103. 103.
    Milanese M, et al. DEFB1 gene polymorphisms and increased risk of HIV-1 infection in Brazilian children. AIDS. 2006;20(12):1673–5.PubMedCrossRefGoogle Scholar
  104. 104.
    Pütsep K, Carlsson G, Boman HG, Andersson M. Deficiency of antibacterial peptides in patients with morbus Kostmann: an observation study. Lancet. 2002;360(9340):1144–9.PubMedCrossRefGoogle Scholar
  105. 105.
    Limoli DH, et al. Cationic antimicrobial peptides promote microbial mutagenesis and pathoadaptation in chronic infections. PLoS Pathog. 2014;10(4):e1004083.PubMedPubMedCentralCrossRefGoogle Scholar
  106. 106.
    Ganz T, Metcalf JA, Gallin JI, Boxer LA, Lehrer RI. Microbicidal/cytotoxic proteins of neutrophils are deficient in two disorders: Chediak-Higashi syndrome and “specific” granule deficiency. J Clin Invest. 1988;82(2):552–6.PubMedPubMedCentralCrossRefGoogle Scholar
  107. 107.
    Kelly P, et al. Reduced gene expression of intestinal alpha-defensins predicts diarrhea in a cohort of African adults. J Infect Dis. 2006;193(10):1464–70.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Division of Infectious Diseases and Immunology, Department of MedicineUniversity of Massachusetts Medical SchoolWorcesterUSA

Personalised recommendations