Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

The co-evolution of host cationic antimicrobial peptides and microbial resistance

Nature Reviews Microbiology volume 4, pages 529–536 (2006)Cite this article

Key Points

  • Host–pathogen interactions are a result of long-term co-evolution and adaptation processes. Endogenous cationic antimicrobial peptides (CAMPs) such as defensins, cathelicidins and kinocidins are produced by virtually all classes of organisms and belong to the oldest and most effective components of antimicrobial host defence. Host CAMPs and bacterial CAMP-resistance mechanisms represent an intriguing example of host–pathogen co-evolution.

  • CAMP genes are subject to positive selection and CAMPs belong to the most rapidly evolving group of mammalian proteins, with major differences even between primate species. Some CAMPs are conserved throughout the various mammalian lineages, whereas others seem to have appeared, disappeared or expanded by gene multiplication in a subset of mammalian families.

  • Several bacterial pathogens can resist certain CAMPs to some extent by, for example, proteolytic cleavage, CAMP-specific binding or extrusion mechanisms, or by modifications to the bacterial surface that reduce the affinity for CAMPs. However, it is still unclear how the emergence and adaptation of microbial CAMP-resistance mechanisms has affected the evolution of CAMPs.

  • It is proposed that the emergence of bacterial CAMP resistance has had a profound effect on the evolution of CAMP variants. The introduction of stabilizing disulphide bridges into CAMPs, extensive variation of peptide sequences and adaptation of the electrostatic properties of CAMPs might contribute to the ongoing development of host strategies to circumvent microbial CAMP resistance, leading to continuously effective antimicrobial peptides.

  • Drawing the correct conclusions from the ongoing effectiveness of CAMPs might help to avoid the rapid loss of efficacy of therapeutic antibiotics and to design new, 'smarter' antibiotics. In addition to the proposed host-adaptation strategies, conceptual differences between the mode of action of CAMPs and antibiotics might have played key roles in the extraordinary success of CAMPs during evolution.

  • The combination of two or more antimicrobial mechanisms in one molecule, the targeting of essential, non-protein bacterial structures such as the cytoplasmic membrane, and the availability of CAMPs in high concentrations at sites of infection, could have been major obstacles for bacteria to develop highly effective CAMP resistance. Incorporating such properties into novel therapeutic antibiotics represents a major challenge for future antimicrobial drug design.

Abstract

Endogenous cationic antimicrobial peptides (CAMPs) are among the most ancient and efficient components of host defence. It is somewhat of an enigma that bacteria have not developed highly effective CAMP-resistance mechanisms, such as those that inhibit many therapeutic antibiotics. Here, we propose that CAMPs and CAMP-resistance mechanisms have co-evolved, leading to a transient host–pathogen balance that has shaped the existing CAMP repertoire. Elucidating the underlying principles of this process could help in the development of more sustainable antibiotics.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Diversity of human cationic antimicrobial peptides.
Figure 2: Bacterial cationic antimicrobial peptide (CAMP)-resistance mechanisms.
Figure 3: Co-evolution of cationic antimicrobial peptides (CAMPs) and bacterial CAMP-resistance mechanisms.
Figure 4: Nisin and its various modes of antimicrobial action.

Similar content being viewed by others

References

  1. Woolhouse, M. E., Webster, J. P., Domingo, E., Charlesworth, B. & Levin, B. R. Biological and biomedical implications of the co-evolution of pathogens and their hosts. Nature Genet. 32, 569–577 (2002).

    CAS  PubMed  Google Scholar 

  2. Grenfell, B. T. et al. Unifying the epidemiological and evolutionary dynamics of pathogens. Science 303, 327–332 (2004).

    CAS  PubMed  Google Scholar 

  3. Brubaker, R. R. The recent emergence of plague: a process of felonious evolution. Microb. Ecol. 47, 293–299 (2004).

    CAS  PubMed  Google Scholar 

  4. Waldvogel, F. A. Infectious diseases in the 21st century: old challenges and new opportunities. Int. J. Infect. Dis. 8, 5–12 (2004).

    PubMed  Google Scholar 

  5. Zasloff, M. Antimicrobial peptides of multicellular organisms. Nature 415, 389–395 (2002). This is a comprehensive review on the diversity, structure, activity and possible applications of endogenous antimicrobial peptides from higher organisms.

    CAS  PubMed  Google Scholar 

  6. Hancock, R. E. W. & Diamond, G. The role of cationic antimicrobial peptides in innate host defences. Trends Microbiol. 8, 402–410 (2000).

    CAS  PubMed  Google Scholar 

  7. Ganz, T. Defensins: antimicrobial peptides of innate immunity. Nature Rev. Immunol. 3, 710–720 (2003).

    CAS  Google Scholar 

  8. Lehrer, R. I. Primate defensins. Nature Rev. Microbiol. 2, 727–738 (2004).

    CAS  Google Scholar 

  9. Brogden, K. A. Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria? Nature Rev. Microbiol. 3, 238–250 (2005).

    CAS  Google Scholar 

  10. Selsted, M. E. & Ouellette, A. J. Mammalian defensins in the antimicrobial immune response. Nature Immunol. 6, 551–557 (2005).

    CAS  Google Scholar 

  11. Dorschner, R. A. et al. The mammalian ionic environment dictates microbial susceptibility to antimicrobial defense peptides. FASEB J. 20, 35–42 (2006).

    CAS  PubMed  Google Scholar 

  12. Sahl, H. G. et al. Mammalian defensins: structures and mechanism of antibiotic activity. J. Leukoc. Biol. 77, 466–475 (2005). This article compares the antibacterial and membrane-disrupting properties of mammalian defensins.

    CAS  PubMed  Google Scholar 

  13. Yang, D., Biragyn, A., Kwak, L. W. & Oppenheim, J. J. Mammalian defensins in immunity: more than just microbicidal. Trends Immunol. 23, 291–296 (2002).

    CAS  PubMed  Google Scholar 

  14. Bals, R. & Wilson, J. M. Cathelicidins — a family of multifunctional antimicrobial peptides. Cell. Mol. Life Sci. 60, 711–720 (2003).

    CAS  PubMed  Google Scholar 

  15. Bowdish, D. M. et al. Impact of LL-37 on anti-infective immunity. J. Leukoc. Biol. 77, 451–459 (2005).

    CAS  PubMed  Google Scholar 

  16. Dürr, M. & Peschel, A. Chemokines meet defensins — the merging concepts of chemoattractants and antimicrobial peptides in host defense. Infect. Immun. 70, 6515–6517 (2002).

    PubMed  PubMed Central  Google Scholar 

  17. Rosenfeld, Y., Papo, N. & Shai, Y. Endotoxin (LPS) neutralization by innate immunity host-defense peptides: peptides' properties and plausible modes of action. J. Biol. Chem. 281, 1636–1643 (2006).

    CAS  PubMed  Google Scholar 

  18. Vallender, E. J. & Lahn, B. T. Positive selection on the human genome. Hum. Mol. Genet. 13,R245–R254 (2004).

  19. Patil, A., Hughes, A. L. & Zhang, G. Rapid evolution and diversification of mammalian α-defensins as revealed by comparative analysis of rodent and primate genes. Physiol. Genomics 20, 1–11 (2004).

    CAS  PubMed  Google Scholar 

  20. Nusbaum, C. et al. DNA sequence and analysis of human chromosome 8. Nature 439, 331–335 (2006).

    CAS  PubMed  Google Scholar 

  21. Crovella, S. et al. Primate β-defensins — structure, function and evolution. Curr. Protein Pept. Sci. 6, 7–21 (2005). This article describes the diversity of defensin structures in primate species.

    CAS  PubMed  Google Scholar 

  22. Nizet, V. in Antimicrobial Peptides in Human Health and Disease (ed. Gallo, R. L.) 277–304 (Horizon Bioscience, Norfolk, 2005).

    Google Scholar 

  23. Peschel, A. How do bacteria resist human antimicrobial peptides? Trends Microbiol. 10, 179–186 (2002).

    CAS  PubMed  Google Scholar 

  24. Kraus, D. & Peschel, A. Molecular mechanisms of bacterial resistance to antimicrobial peptides. Curr. Top. Microbiol. Immunol. 306, 231–250 (2006).

    CAS  PubMed  Google Scholar 

  25. Kristian, S. A. et al. Alanylation of teichoic acids protects Staphylococcus aureus against Toll-like receptor 2-dependent host defense in a mouse tissue cage infection model. J. Infect. Dis. 188, 414–423 (2003).

    CAS  PubMed  Google Scholar 

  26. Nizet, V. et al. Innate antimicrobial peptide protects the skin from invasive bacterial infection. Nature 414, 454–457 (2001). This article demonstrates the important role of CAMPs in host defence using transgenic mice lacking the murine homologue of LL-37.

    CAS  PubMed  Google Scholar 

  27. Gunn, J. S., Ryan, S. S., Van Velkinburgh, J. C., Ernst, R. K. & Miller, S. I. Genetic and functional analysis of a PmrA–PmrB-regulated locus necessary for lipopolysaccharide modification, antimicrobial peptide resistance, and oral virulence of Salmonella enterica serovar Typhimurium. Infect. Immun. 68, 6139–6146 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Weidenmaier, C. et al. DltABCD- and MprF-mediated cell envelope modifications of Staphylococcus aureus confer resistance to platelet microbicidal proteins and contribute to virulence in a rabbit endocarditis model. Infect. Immun. 73, 8033–8038 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Kramer, N. E., van Hijum, S. A. F. T., Knol, J., Kok, J. & Kuipers, O. Transcriptome analysis reveals mechanisms by which Lactococcus lactis acquires nisin resistance. Antimicrob. Agents Chemother. 50, 1753–1761 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Perron, G. G., Zasloff, M. & Bell, G. Experimental evolution of resistance to an antimicrobial peptide. Proc. Biol. Sci. 273, 251–256 (2006). This article demonstrates that bacteria can become spontaneously resistant to endogenous antimicrobial peptides on in vitro exposure to slowly increasing peptide concentrations.

    CAS  PubMed  Google Scholar 

  31. Levy, S. B. & Marshall, B. Antibacterial resistance worldwide: causes, challenges and responses. Nature Med. 10, S122–S129 (2004).

    CAS  PubMed  Google Scholar 

  32. Chambers, H. F. Community-associated MRSA — resistance and virulence converge. N. Engl. J. Med. 352, 1485–1487 (2005).

    CAS  PubMed  Google Scholar 

  33. Foster, T. J. The Staphylococcus aureus 'superbug'. J. Clin. Invest. 114, 1693–1696 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Andres, E. & Dimarcq, J. L. Cationic antimicrobial peptides: update of clinical development. J. Intern. Med. 255, 519–520 (2004).

    CAS  PubMed  Google Scholar 

  35. Mygind, P. H. et al. Plectasin is a peptide antibiotic with therapeutic potential from a saprophytic fungus. Nature 437, 975–980 (2005).

    CAS  PubMed  Google Scholar 

  36. Sieprawska-Lupa, M. et al. Degradation of human antimicrobial peptide LL-37 by Staphylococcus aureus-derived proteinases. Antimicrob. Agents Chemother. 48, 4673–4679 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Guina, T., Yi, E. C., Wang, H., Hackett, M. & Miller, S. I. A PhoP-regulated outer membrane protease of Salmonella enterica serovar Typhimurium promotes resistance to α-helical antimicrobial peptides. J. Bacteriol. 182, 4077–4086 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Nyberg, P., Rasmussen, M. & Bjorck, L. α2-Macroglobulin-proteinase complexes protect Streptococcus pyogenes from killing by the antimicrobial peptide LL-37. J. Biol. Chem. 279, 52820–52823 (2004).

    CAS  PubMed  Google Scholar 

  39. Schmidtchen, A., Frick, I. M., Andersson, E., Tapper, H. & Bjorck, L. Proteinases of common pathogenic bacteria degrade and inactivate the antibacterial peptide LL-37. Mol. Microbiol. 46, 157–168 (2002).

    CAS  PubMed  Google Scholar 

  40. Wu, Z. et al. Engineering disulfide bridges to dissect antimicrobial and chemotactic activities of human β-defensin 3. Proc. Natl Acad. Sci. USA 100, 8880–8885 (2003). This article analyses different structural requirements for antimicrobial or chemotactic activity of CAMPs.

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Maemoto, A. et al. Functional analysis of the α-defensin disulfide array in mouse cryptdin-4. J. Biol. Chem. 279, 44188–44196 (2004).

    CAS  PubMed  Google Scholar 

  42. Campopiano, D. J. et al. Structure–activity relationships in defensin dimers: a novel link between β-defensin tertiary structure and antimicrobial activity. J. Biol. Chem. 279, 48671–48679 (2004).

    CAS  PubMed  Google Scholar 

  43. Rozek, A., Powers, J. P., Friedrich, C. L. & Hancock, R. E. Structure-based design of an indolicidin peptide analogue with increased protease stability. Biochemistry 42, 14130–14138 (2003).

    CAS  PubMed  Google Scholar 

  44. Harwig, S. S. et al. Intramolecular disulfide bonds enhance the antimicrobial and lytic activities of protegrins at physiological sodium chloride concentrations. Eur. J. Biochem. 240, 352–357 (1996).

    CAS  PubMed  Google Scholar 

  45. Hornef, M. W., Putsep, K., Karlsson, J., Refai, E. & Andersson, M. Increased diversity of intestinal antimicrobial peptides by covalent dimer formation. Nature Immunol. 5, 836–843 (2004). This article describes how the formation of heterodimers by murine CRS peptides leads to multiple antimicrobial molecules with different activity spectra.

    CAS  Google Scholar 

  46. Tang, Y. Q. et al. A cyclic antimicrobial peptide produced in primate leukocytes by the ligation of two truncated α-defensins. Science 286, 498–502 (1999).

    CAS  PubMed  Google Scholar 

  47. Jack, R. W., Bierbaum, G. & Sahl, H.-G. Lantibiotics and Related Peptides (Springer, Berlin, 1998).

    Google Scholar 

  48. Cotter, P. D., Hill, C. & Ross, R. P. Bacteriocins: developing innate immunity for food. Nature Rev. Microbiol. 3, 777–788 (2005).

    CAS  Google Scholar 

  49. Tjabringa, G. S. et al. Host defense effector molecules in mucosal secretions. FEMS Immunol. Med. Microbiol. 45, 151–158 (2005).

    CAS  PubMed  Google Scholar 

  50. Jin, T. et al. Staphylococcus aureus resists human defensins by production of staphylokinase, a novel bacterial evasion mechanism. J. Immunol. 172, 1169–1176 (2004).

    CAS  PubMed  Google Scholar 

  51. Frick, I. M., Akesson, P., Rasmussen, M., Schmidtchen, A. & Bjorck, L. SIC, a secreted protein of Streptococcus pyogenes that inactivates antibacterial peptides. J. Biol. Chem. 278, 16561–16566 (2003).

    CAS  PubMed  Google Scholar 

  52. Shafer, W. M., Qu, X.-D., Waring, A. J. & Lehrer, R. I. Modulation of Neisseria gonorrhoeae susceptibility to vertebrate antibacterial peptides due to a member of the resistance/nodulation/division efflux pump family. Proc. Natl Acad. Sci. USA 95, 1829–1833 (1998). This article describes the first multiple drug resistance protein involved in CAMP resistance.

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Tzeng, Y. L. et al. Cationic antimicrobial peptide resistance in Neisseria meningitidis. J. Bacteriol. 187, 5387–5396 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Fernie-King, B. A., Seilly, D. J. & Lachmann, P. J. The interaction of streptococcal inhibitor of complement (SIC) and its proteolytic fragments with the human β-defensins. Immunology 111, 444–452 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Douglas, S. E., Gallant, J. W., Liebscher, R. S., Dacanay, A. & Tsoi, S. C. Identification and expression analysis of hepcidin-like antimicrobial peptides in bony fish. Dev. Comp. Immunol. 27, 589–601 (2003).

    CAS  PubMed  Google Scholar 

  56. Park, C. H., Valore, E. V., Waring, A. J. & Ganz, T. Hepcidin, a urinary antimicrobial peptide synthesized in the liver. J. Biol. Chem. 276, 7806–7810 (2001).

    CAS  PubMed  Google Scholar 

  57. Ouellette, A. J. & Selsted, M. E. Paneth cell defensins: endogenous peptide components of intestinal host defense. FASEB J. 10, 1280–1289 (1996).

    CAS  PubMed  Google Scholar 

  58. Eckmann, L. Defence molecules in intestinal innate immunity against bacterial infections. Curr. Opin. Gastroenterol. 21, 147–151 (2005).

    CAS  PubMed  Google Scholar 

  59. Taudien, S. et al. Polymorphic segmental duplications at 8p23.1 challenge the determination of individual defensin gene repertoires and the assembly of a contiguous human reference sequence. BMC Genomics 5, 92 (2004).

    PubMed  PubMed Central  Google Scholar 

  60. Ernst, R. K., Guina, T. & Miller, S. I. Salmonella typhimurium outer membrane remodeling: role in resistance to host innate immunity. Microbes Infect. 3, 1327–1334 (2001).

    CAS  PubMed  Google Scholar 

  61. Neuhaus, F. C. & Baddiley, J. A continuum of anionic charge: structures and functions of D-alanyl-teichoic acids in Gram-positive bacteria. Microbiol. Mol. Biol. Rev. 67, 686–723 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Peschel, A. et al. Inactivation of the dlt operon in Staphylococcus aureus confers sensitivity to defensins, protegrins and other antimicrobial peptides. J. Biol. Chem. 274, 8405–8410 (1999). This article describes CAMP resistance by alterations of the Gram-positive cell envelope, paralleling lipid A modifications in Gram-negative bacteria.

    CAS  PubMed  Google Scholar 

  63. Abachin, E. et al. Formation of D-alanyl-lipoteichoic acid is required for adhesion and virulence of Listeria monocytogenes. Mol. Microbiol. 43, 1–14 (2002).

    CAS  PubMed  Google Scholar 

  64. Poyart, C. et al. Attenuated virulence of Streptococcus agalactiae deficient in D-alanyl-lipoteichoic acid is due to an increased susceptibility to defensins and phagocytic cells. Mol. Microbiol. 49, 1615–1625 (2003).

    CAS  PubMed  Google Scholar 

  65. Kristian, S. A. et al. D-alanylation of teichoic acid promotes group A Streptococcus antimicrobial peptide resistance, neutrophil survival, and epithelial cell invasion. J. Bacteriol. 187, 6719–6725 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Peschel, A. et al. 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. 193, 1067–1076 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Weidenmaier, C., Kristian, S. A. & Peschel, A. Bacterial resistance to antimicrobial host defenses — an emerging target for novel antiinfective strategies? Curr. Drug Targets 4, 643–649 (2003).

    CAS  PubMed  Google Scholar 

  68. Miller, S. I., Ernst, R. K. & Bader, M. W. LPS, TLR4 and infectious disease diversity. Nature Rev. Microbiol. 3, 36–46 (2005).

    CAS  Google Scholar 

  69. Koprivnjak, T., Peschel, A., Gelb, M. H., Liang, N. S. & Weiss, J. P. Role of charge properties of bacterial envelope in bactericidal action of human Group IIA phospholipase A2 against Staphylococcus aureus. J. Biol. Chem. 277, 47636–47644 (2002).

    CAS  PubMed  Google Scholar 

  70. Collins, L. V. et al. Staphylococcus aureus strains lacking D-alanine modifications of teichoic acids are highly susceptible to human neutrophil killing and are virulence attenuated in mice. J. Infect. Dis. 186, 214–219 (2002).

    CAS  PubMed  Google Scholar 

  71. Midorikawa, K. et al. Staphylococcus aureus susceptibility to innate antimicrobial peptides, β-defensins and CAP18, expressed by human keratinocytes. Infect. Immun. 71, 3730–3739 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Weidenmaier, C. et al. Role of teichoic acids in Staphylococcus aureus nasal colonization, a major risk factor in nosocomial infections. Nature Med. 10, 243–245 (2004).

    CAS  PubMed  Google Scholar 

  73. Harder, J., Bartels, J., Christophers, E. & Schroder, J. M. Isolation and characterization of human β-defensin-3, a novel human inducible peptide antibiotic. J. Biol. Chem. 276, 5707–5713 (2001).

    CAS  PubMed  Google Scholar 

  74. Shafer, W. M., Casey, S. G. & Spitznagel, J. K. Lipid A and resistance of Salmonella typhimurium to antimicrobial granule proteins of human neutrophil granulocytes. Infect. Immun. 43, 834–838 (1984).

    CAS  PubMed  PubMed Central  Google Scholar 

  75. Guo, L. et al. Lipid A acylation and bacterial resistance against vertebrate antimicrobial peptides. Cell 95, 189–198 (1998).

    CAS  PubMed  Google Scholar 

  76. Vuong, C. et al. Polysaccharide intercellular adhesin (PIA) protects Staphylococcus epidermidis against major components of the human innate immune system. Cell. Microbiol. 6, 269–275 (2004).

    CAS  PubMed  Google Scholar 

  77. Otto, M. Bacterial evasion of antimicrobial peptides by biofilm formation. Curr. Top. Microbiol. Immunol. 306, 251–258 (2006).

    CAS  PubMed  Google Scholar 

  78. Ginsburg, I. The role of bacteriolysis in the pathophysiology of inflammation, infection and post-infectious sequelae. APMIS 110, 753–770 (2002).

    PubMed  Google Scholar 

  79. Breukink, E. et al. Use of the cell wall precursor lipid II by a pore-forming peptide antibiotic. Science 286, 2361–2364 (1999).

    CAS  PubMed  Google Scholar 

  80. Wiedemann, I. et al. Specific binding of nisin to the peptidoglycan precursor lipid II combines pore formation and inhibition of cell wall biosynthesis for potent antibiotic activity. J. Biol. Chem. 276, 1772–1779 (2001). This article demonstrates the combination of several antimicrobial mechanisms in the antimicrobial peptide nisin.

    CAS  PubMed  Google Scholar 

  81. Bierbaum, G. & Sahl, H. G. Induction of autolysis of staphylococci by the basic peptide antibiotic pep5 and nisin and their influence on the activity of autolytic enzymes. Arch. Microbiol. 141, 249–254 (1985).

    CAS  PubMed  Google Scholar 

  82. Pag, U. & Sahl, H. G. Multiple activities in lantibiotics — models for the design of novel antibiotics? Curr. Pharm. Des. 8, 815–833 (2002).

    CAS  PubMed  Google Scholar 

  83. Gravesen, A., Jydegaard Axelsen, A. M., Mendes, d. S., Hansen, T. B. & Knochel, S. Frequency of bacteriocin resistance development and associated fitness costs in Listeria monocytogenes. Appl. Environ. Microbiol. 68, 756–764 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Ganz, T. Hepcidin in iron metabolism. Curr. Opin. Hematol. 11, 251–254 (2004).

    CAS  PubMed  Google Scholar 

  85. Nguyen, T. X., Cole, A. M. & Lehrer, R. I. Evolution of primate θ-defensins: a serpentine path to a sweet tooth. Peptides 24, 1647–1654 (2003).

    CAS  PubMed  Google Scholar 

  86. Fowler, V. G. Jr et al. Persistent bacteremia due to methicillin-resistant Staphylococcus aureus infection is associated with agr dysfunction and low-level in vitro resistance to thrombin-induced platelet microbicidal protein. J. Infect. Dis. 190, 1140–1149 (2004).

    CAS  PubMed  Google Scholar 

  87. Fowler, V. G. Jr et al. In vitro resistance to thrombin-induced platelet microbicidal protein in isolates of Staphylococcus aureus from endocarditis patients correlates with an intravascular device source. J. Infect. Dis. 182, 1251–1254 (2000).

    CAS  PubMed  Google Scholar 

  88. Frantz, S. Drug discovery: playing dirty. Nature 437, 942–943 (2005).

    CAS  PubMed  Google Scholar 

  89. Arthur, M., Reynolds, P. & Courvalin, P. Glycopeptide resistance in enterococci. Trends Microbiol. 4, 401–407 (1996).

    CAS  PubMed  Google Scholar 

  90. Allen, N. E. & Nicas, T. I. Mechanism of action of oritavancin and related glycopeptide antibiotics. FEMS Microbiol. Rev. 26, 511–532 (2003).

    CAS  PubMed  Google Scholar 

  91. Zhang, H. Z., Hackbarth, C. J., Chansky, K. M. & Chambers, H. F. A proteolytic transmembrane signaling pathway and resistance to β-lactams in staphylococci. Science 291, 1962–1965 (2001).

    CAS  PubMed  Google Scholar 

  92. Bader, M. W. et al. Recognition of antimicrobial peptides by a bacterial sensor kinase. Cell 122, 461–472 (2005). This article characterizes the first bacterial CAMP-sensing regulation system.

    CAS  PubMed  Google Scholar 

  93. Jacoby, G. A. & Munoz-Price, L. S. The new β-lactamases. N. Engl. J. Med. 352, 380–391 (2005).

    CAS  PubMed  Google Scholar 

  94. Hiramatsu, K. Vancomycin-resistant Staphylococcus aureus: a new model of antibiotic resistance. Lancet Infect. Dis. 1, 147–155 (2001).

    CAS  PubMed  Google Scholar 

  95. van Veen, H. W. & Konings, W. N. Drug efflux proteins in multidrug resistant bacteria. Biol. Chem. 378, 769–777 (1997).

    CAS  PubMed  Google Scholar 

  96. Fux, C. A., Costerton, J. W., Stewart, P. S. & Stoodley, P. Survival strategies of infectious biofilms. Trends Microbiol. 13, 34–40 (2005).

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We would like to thank our co-workers and collaborators for help and support. Our research is supported by grants from the German Research Foundation, the European Union, the German Ministry of Education and Research, the IZKF program of the Medical Faculty, University of Tübingen, and the BONFOR program of the Medical Faculty, University of Bonn.

Author information

Authors and Affiliations

  1. Cellular and Molecular Microbiology Division, Medical Microbiology and Hygiene Department, University of Tbingen, Tbingen, 72076, Germany

    Andreas Peschel

  2. Department of Medical Microbiology, Immunology and Parasitology, Pharmaceutical Microbiology Unit, University of Bonn, Bonn, 53115, Germany

    Hans-Georg Sahl

Authors
  1. Andreas Peschel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hans-Georg Sahl
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Andreas Peschel.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Related links

Related links

DATABASES

Entrez Genome Project

Enterococcus faecalis

Lactococcus lactis

Listeria monocytogenes

Neisseria gonorrhoeae

Neisseria meningitidis

Porphyromonas gingivalis

Proteus mirabilis

Pseudomonas aeurginosa

Salmonella enterica

Streptococcus agalactiae

Staphylococcus aureus

Streptococcus pyogenes

FURTHER INFORMATION

Andreas Peschel's homepage

Hans-Georg Sahl's homepage

Glossary

LL-37

A linear peptide that is also known as human cationic protein 18 (hCAP18). It is the only member of the cathelicidin family of antimicrobial peptides in humans.

Magainin

A linear antimicrobial peptide produced by amphibians.

Cecropin

A linear antimicrobial peptide produced by insects and other invertebrates.

Defenin

An antimicrobial peptide of diverse origin, usually adopting a sheet structure with three intramolecular disulphide bridges.

Protegrin

A porcine antimicrobial peptide with a sheet structure and two intramolecular disulphide bridges.

Cryptdin-related sequence (CRS) peptide

An antimicrobial peptide produced in the mouse intestine that forms disulphide-bridge-linked homo- or heterodimers.

Lantibiotic

An antimicrobial peptide produced by Gram-positive bacteria (bacteriocin), which contains lanthionine and/or methyllanthionine amino acids with thioether bridges.

Hepcidin-related CAMP

A vertebrate peptide with antimicrobial and iron-metabolism-regulating hormone-like activities.

Cryptdin

An α-defensin produced by Paneth cells in the small intestine of mice.

Kinocidin

An antimicrobial chemokine or chemokine-derived peptide from mammalian platelets.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Peschel, A., Sahl, HG. The co-evolution of host cationic antimicrobial peptides and microbial resistance. Nat Rev Microbiol 4, 529–536 (2006). https://doi.org/10.1038/nrmicro1441

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrmicro1441

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing