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  • Review Article
  • Published:

Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria?

Nature Reviews Microbiology volume 3, pages 238–250 (2005)Cite this article

Abstract

Antimicrobial peptides are an abundant and diverse group of molecules that are produced by many tissues and cell types in a variety of invertebrate, plant and animal species. Their amino acid composition, amphipathicity, cationic charge and size allow them to attach to and insert into membrane bilayers to form pores by 'barrel-stave', 'carpet' or 'toroidal-pore' mechanisms. Although these models are helpful for defining mechanisms of antimicrobial peptide activity, their relevance to how peptides damage and kill microorganisms still need to be clarified. Recently, there has been speculation that transmembrane pore formation is not the only mechanism of microbial killing. In fact several observations suggest that translocated peptides can alter cytoplasmic membrane septum formation, inhibit cell-wall synthesis, inhibit nucleic-acid synthesis, inhibit protein synthesis or inhibit enzymatic activity. In this review the different models of antimicrobial-peptide-induced pore formation and cell killing are presented.

Key Points

  • Antimicrobial peptides are abundant and produced by many tissues and cell types in a variety of invertebrate, plant and animal species. So far, more than 880 different antimicrobial peptides have been identified or predicted from their nucleic acid sequences.

  • These peptides are often divided into families on the basis of their unique amino acid compositions and structures. The families include anionic peptides, helical cationic peptides (which are short, lack cysteine residues and sometimes have a hinge or 'kink' in the middle), peptides rich in amino acids such as proline, arginine, phenylalanine or tryptophan, and anionic and cationic peptides, which contain cysteine, have disulphide bonds and form stable β-sheets.

  • Assessing the interaction of antimicrobial peptides with phospholipids in model membranes provides some insight into their mechanisms of activity. The attraction, attachment, insertion and orientation of the peptide in the lipid bilayer can be determined by X-ray crystallography, NMR spectroscopy in solution and in the presence of lipid bilayers, and FTIR, Raman, fluorescence and CD optical spectroscopies. They insert into well-defined membrane bilayers, forming pores by 'barrel-stave', 'carpet' or 'toroidal-pore' mechanisms.

  • Although the formation of transmembrane pores eventually leads to the lysis of microbial cells, there is a growing speculation that this is not the sole mechanism of microbial killing. In fact, translocated antimicrobial peptides can alter the cytoplasmic membrane septum formation, inhibit cell-wall synthesis, inhibit nucleic-acid synthesis, inhibit protein synthesis or inhibit enzymatic activity, all of which can rapidly kill microorganisms.

  • Microorganisms also use a number of resistance strategies to circumvent antimicrobial peptide killing, and these mechanisms have relevance to the concepts presented in this review. These bacterial strategies counter mechanisms of antimicrobial peptide attachment, peptide insertion and membrane permeability.

  • Recognition that antimicrobial peptides induce transmembrane pores and have other intracellular targets that are capable of rapidly killing microorganisms will facilitate the development, design and synthesis of more efficient, broad-spectrum therapeutic antimicrobial peptides.

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Figure 1: Antimicrobial peptides.
Figure 2: Pseudomonas aeruginosa PAO1 (108 cfu ml−1) incubated with the ovine cathelicidin SMAP29 (10 μg ml−1) for 1. 5 and 3 hours.
Figure 3: The barrel-stave model of antimicrobial-peptide-induced killing.
Figure 4: The carpet model of antimicrobial-induced killing.
Figure 5: The toroidal model of antimicrobial peptide-induced killing.
Figure 6: Mode of action for intracellular antimicrobial peptide activity.

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References

  1. Skarnes, R. C. & Watson, D. W. Antimicrobial factors of normal tissues and fluids. Bacteriol. Rev. 21, 273?294 (1957). An excellent description of the observations of early investigators, who not only demonstrated the existence of antimicrobial substances in normal tissues and fluids, but proposed that they aid allied mechanisms of natural and adaptive immunity.

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Fleming, A. On a remarkable bacteriolytic element found in tissues and secretions. Proc. R. Soc. London. B Biol. Sci. 93, 306?317 (1922).

    Article  CAS  Google Scholar 

  3. Hirsch, J. G. Phagocytin: a bactericidal substance from polymorphonuclear leucocytes. J. Exp. Med. 103, 589?611 (1956).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Zeya, H. I. & Spitznagel, J. K. Antibacterial and enzymic basic proteins from leukocyte lysosomes: separation and identification. Science 142, 1085?1087 (1963).

    Article  CAS  PubMed  Google Scholar 

  5. Friedberg, D., Friedberg, I. & Shilo, M. Interaction of Gram-negative bacteria with the lysosomal fraction of polymorphonuclear leukocytes. II. Changes in the cell envelope of Escherichia coli. Infect. Immun. 1, 311?331 (1970).

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Friedberg, D. & Shilo, M. Interaction of Gram-negative bacteria with the lysosomal fraction of polymorphonuclear leukocytes. I. Role of cell wall composition of Salmonella typhimurium. Infect. Immun. 1, 305?318 (1970).

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Weiss, J., Franson, R. C., Beckerdite, S., Schmeidler, K. & Elsbach, P. Partial characterization and purification of a rabbit granulocyte factor that increases permeability of Escherichia coli. J. Clin. Invest. 55, 33?42 (1975).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Steiner, H., Hultmark, D., Engstrom, A., Bennich, H. & Boman, H. G. Sequence and specificity of two antibacterial proteins involved in insect immunity. Nature 292, 246?248 (1981).

    Article  CAS  PubMed  Google Scholar 

  9. Ganz, T., Selsted, M. E. & Lehrer, R. I. Defensins. Eur. J. Haematol. 44, 1?8 (1990).

    Article  CAS  PubMed  Google Scholar 

  10. Zasloff, M. Magainins, a class of antimicrobial peptides from Xenopus skin: isolation, characterization of two active forms, and partial cDNA sequence of a precursor. Proc. Natl Acad. Sci. USA 84, 5449?5453 (1987).

    Article  CAS  PubMed  Google Scholar 

  11. Ganz, T. Defensins: antimicrobial peptides of innate immunity. Nature Rev. Immunol. 3, 710?720 (2003). A comprehensive overview of the definition, structure, distribution, synthesis, regulation and activity of neutrophil defensins, Paneth cell defensins and epithelial cell defensins.

    Article  CAS  Google Scholar 

  12. Lehrer, R. I. Primate defensins. Nature Rev. Microbiol. 2, 727?738 (2004). A detailed and specific review on the characteristics of defensins from primates.

    Article  CAS  Google Scholar 

  13. Zasloff, M. Antimicrobial peptides of multicellular organisms. Nature 415, 389?395 (2002). A broad overview of antimicrobial peptides, highlighting their diversity, mechanisms of activity, regulation in insects, vertebrates and plants, and their roles in health and disease.

    Article  CAS  PubMed  Google Scholar 

  14. Brogden, K. A., Ackermann, M., McCray, P. B. & Tack, B. F. Antimicrobial peptides in animals and their role in host defences. Int. J. Antimicrob. Agents 22, 465?478 (2003). A detailed review of antimicrobial peptides in livestock and poultry.

    Article  CAS  PubMed  Google Scholar 

  15. Vizioli, J. & Salzet, M. Antimicrobial peptides from animals: focus on invertebrates. Trends Pharmacol. Sci. 23, 494?496 (2002).

    Article  CAS  PubMed  Google Scholar 

  16. Cole, A. M. et al. Cutting edge: IFN-inducible ELR-CXC chemokines display defensin-like antimicrobial activity. J. Immunol. 167, 623?627 (2001).

    Article  CAS  PubMed  Google Scholar 

  17. Tang, Y. Q., Yeaman, M. R. & Selsted, M. E. Antimicrobial peptides from human platelets. Infect. Immun. 70, 6524?6533 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Yang, D. et al. Many chemokines including CCL20/MIP-3α display antimicrobial activity. J. Leukoc. Biol. 74, 448?455 (2003).

    Article  CAS  PubMed  Google Scholar 

  19. Kowalska, K., Carr, D. B. & Lipkowski, A. W. Direct antimicrobial properties of substance P. Life Sci. 71, 747?750 (2002).

    Article  CAS  PubMed  Google Scholar 

  20. Allaker, R. P. & Kapas, S. Adrenomedullin and mucosal defence: interaction between host and microorganism. Regul. Pept. 112, 147?152 (2003).

    Article  CAS  PubMed  Google Scholar 

  21. Kuwata, H., Yip, T. T., Yip, C. L., Tomita, M. & Hutchens, T. W. Bactericidal domain of lactoferrin: detection, quantitation, and characterization of lactoferricin in serum by SELDI affinity mass spectrometry. Biochem. Biophys. Res. Commun. 245, 764?773 (1998).

    Article  CAS  PubMed  Google Scholar 

  22. Pellegrini, A., Thomas, U., Bramaz, N., Hunziker, P. & von Fellenberg, R. Isolation and identification of three bactericidal domains in the bovine α-lactalbumin molecule. Biochim. Biophys. Acta 1426, 439?448 (1999).

    Article  CAS  PubMed  Google Scholar 

  23. Liepke, C. et al. Human hemoglobin-derived peptides exhibit antimicrobial activity: a class of host defense peptides. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 791, 345?356 (2003).

    Article  CAS  PubMed  Google Scholar 

  24. Finlay, B. B. & Hancock, R. E. Can innate immunity be enhanced to treat microbial infections? Nature Rev. Microbiol. 2, 497?504 (2004).

    Article  CAS  Google Scholar 

  25. Hancock, R. E. & Patrzykat, A. Clinical development of cationic antimicrobial peptides: from natural to novel antibiotics. Curr. Drug Targets Infect. Disord. 2, 79?83 (2002).

    Article  CAS  PubMed  Google Scholar 

  26. Gennaro, R. & Zanetti, M. Structural features and biological activities of the cathelicidin-derived antimicrobial peptides. Biopolymers 55, 31?49 (2000).

    Article  CAS  PubMed  Google Scholar 

  27. Hancock, R. E. W. Peptide antibiotics. Lancet 349, 418?422 (1997).

    Article  CAS  PubMed  Google Scholar 

  28. Boman, H. G. Peptide antibiotics and their role in innate immunity. Annu. Rev. Immunol. 13, 61?92 (1995). A comprehensive review describing the chemical and biochemical characteristics of antimicrobial peptides, their gene structures and biosynthesis, their mechanisms of action and their future role as therapeutic agents.

    Article  CAS  PubMed  Google Scholar 

  29. Brogden, K. A., Ackermann, M. & Huttner, K. M. Detection of anionic antimicrobial peptides in ovine bronchoalveolar lavage fluid and respiratory epithelium. Infect. Immun. 66, 5948?5954 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Brogden, K. A., De Lucca, A. J., Bland, J. & Elliott, S. Isolation of an ovine pulmonary surfactant-associated anionic peptide bactericidal for Pasteurella haemolytica. Proc. Natl Acad. Sci. USA 93, 412?416 (1996).

    Article  CAS  PubMed  Google Scholar 

  31. Brogden, K. A., Ackermann, M. R., McCray, P. B. Jr & Huttner, K. M. Differences in the concentrations of small, anionic, antimicrobial peptides in bronchoalveolar lavage fluid and in respiratory epithelia of patients with and without cystic fibrosis. Infect. Immun. 67, 4256?4259 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Brogden, K. A., Ackermann, M. & Huttner, K. M. Small, anionic, and charge-neutralizing propeptide fragments of zymogens are antimicrobial. Antimicrob. Agents Chem. 41, 1615?1617 (1997).

    Article  CAS  Google Scholar 

  33. Tossi, A., Sandri, L. & Giangaspero, A. Amphipathic, α-helical antimicrobial peptides. Biopolymers 55, 4?30 (2000). A broad overview of the α-helical antimicrobial peptides from invertebrates, fish, amphibians and mammals, including the structural and physicochemical parameters that modulate their activity and specificity.

    Article  CAS  PubMed  Google Scholar 

  34. Johansson, J., Gudmundsson, G. H., Rottenberg, M. E., Berndt, K. D. & Agerberth, B. Conformation-dependent antibacterial activity of the naturally occurring human peptide LL-37. J. Biol. Chem. 273, 3718?3724 (1998).

    Article  CAS  PubMed  Google Scholar 

  35. Park, C. B., Yi, K. S., Matsuzaki, K., Kim, M. S. & Kim, S. C. Structure?activity analysis of buforin II, a histone H2A-derived antimicrobial peptide: the proline hinge is responsible for the cell-penetrating ability of buforin II. Proc. Natl Acad. Sci. USA 97, 8245?8250 (2000).

    Article  CAS  PubMed  Google Scholar 

  36. Otvos, L., Jr. The short proline-rich antibacterial peptide family. Cell. Mol. Life Sci. 59, 1138?1150 (2002). A specific overview of the short proline-rich antimicrobial peptides from insects.

    Article  CAS  PubMed  Google Scholar 

  37. Lehrer, R. I., Lichtenstein, A. K. & Ganz, T. Defensins: antimicrobial and cytotoxic peptides of mammalian cells. Annu. Rev. Immunol. 11, 105?128 (1993).

    Article  CAS  PubMed  Google Scholar 

  38. Schutte, B. C. & McCray, P. B. Jr. β-defensins in lung host defense. Annu. Rev. Physiol. 64, 709?748 (2002).

    Article  CAS  PubMed  Google Scholar 

  39. Ganz, T. Immunology. Versatile defensins. Science 298, 977?979 (2002).

    Article  CAS  PubMed  Google Scholar 

  40. 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).

    Article  CAS  PubMed  Google Scholar 

  41. Weiss, T. M. et al. Two states of cyclic antimicrobial peptide RTD-1 in lipid bilayers. Biochemistry 41, 10070?10076 (2002).

    Article  CAS  PubMed  Google Scholar 

  42. von Horsten, H. H., Schafer, B. & Kirchhoff, C. SPAG11/isoform HE2C, an atypical anionic β-defensin-like peptide. Peptides 25, 1223?1233 (2004).

    Article  CAS  PubMed  Google Scholar 

  43. Kalfa, V. C. et al. Congeners of SMAP29 kill ovine pathogens and induce ultrastructural damage in bacterial cells. Antimicrob. Agents Chemother. 45, 3256?3261 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Lehrer, R. I. et al. Interaction of human defensins with Escherichia coli Mechanism of bactericidal activity. J. Clin. Invest. 84, 553?561 (1989).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Yenugu, S., Hamil, K. G., Radhakrishnan, Y., French, F. S. & Hall, S. H. The androgen-regulated epididymal sperm-binding protein, human β-defensin 118 (DEFB118) (formerly ESC42), is an antimicrobial β-defensin. Endocrinology 145, 3165?3173 (2004).

    Article  CAS  PubMed  Google Scholar 

  46. Ladokhin, A. S., Selsted, M. E. & White, S. H. Sizing membrane pores in lipid vesicles by leakage of co-encapsulated markers: pore formation by melittin. Biophys. J. 72, 1762?1766 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Matsuzaki, K., Yoneyama, S. & Miyajima, K. Pore formation and translocation of melittin. Biophys. J. 73, 831?838 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Kang, J. H., Shin, S. Y., Jang, S. Y., Lee, M. K. & Hahm, K. S. Release of aqueous contents from phospholipid vesicles induced by cecropin A (1?8) magainin 2 (1?12) hybrid and its analogues. J. Peptide Res. 52, 45?50 (1998).

    Article  CAS  Google Scholar 

  49. Hristova, K., Selsted, M. E. & White, S. H. Critical role of lipid composition in membrane permeabilization by rabbit neutrophil defensins. J. Biol. Chem. 272, 24224?24233 (1997).

    Article  CAS  PubMed  Google Scholar 

  50. Zhao, H., Mattila, J. P., Holopainen, J. M. & Kinnunen, P. K. Comparison of the membrane association of two antimicrobial peptides, magainin 2 and indolicidin. Biophys. J. 81, 2979?2991 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Matsuzaki, K., Murase, O. & Miyajima, K. Kinetics of pore formation by an antimicrobial peptide, magainin 2, in phospholipid bilayers. Biochemistry 34, 12553?12559 (1995).

    Article  CAS  PubMed  Google Scholar 

  52. Christensen, B., Fink, J., Merrifield, R. B. & Mauzerall, D. Channel-forming properties of cecropins and related model compounds incorporated into planar lipid membranes. Proc. Natl Acad. Sci. USA 85, 5072?5076 (1988). An early report suggesting that the broad antibacterial activity of cecropins is due to formation of large time-variant and voltage-dependent ion channels in planar lipid membranes.

    Article  CAS  PubMed  Google Scholar 

  53. Lockey, T. D. & Ourth, D. D. Formation of pores in Escherichia coli cell membranes by a cecropin isolated from hemolymph of Heliothis virescens larvae. Eur. J. Biochem. 236, 263?271 (1996).

    Article  CAS  PubMed  Google Scholar 

  54. Kagan, B. L., Selsted, M. E., Ganz, T. & Lehrer, R. I. Antimicrobial defensin peptides form voltage-dependent ion-permeable channels in planar lipid bilayer membranes. Proc. Natl Acad. Sci. USA 87, 210?214 (1990).

    Article  CAS  PubMed  Google Scholar 

  55. Lee, M. T., Chen, F. Y. & Huang, H. W. Energetics of pore formation induced by membrane active peptides. Biochemistry 43, 3590?3599 (2004). Describes how variations in the peptide-to-lipid ratio might be closely related to the efficacy of antimicrobial peptides against different cell types.

    Article  CAS  PubMed  Google Scholar 

  56. Wu, Y., Huang, H. W. & Olah, G. A. Method of oriented circular dichroism. Biophys. J. 57, 797?806 (1990).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Ladokhin, A. S., Selsted, M. E. & White, S. H. Bilayer interactions of indolicidin, a small antimicrobial peptide rich in tryptophan, proline, and basic amino acids. Biophys. J. 72, 794?805 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Oishi, O. et al. Conformations and orientations of aromatic amino acid residues of tachyplesin I in phospholipid membranes. Biochemistry 36, 4352?4359 (1997).

    Article  CAS  PubMed  Google Scholar 

  59. Turner, J., Cho, Y., Dinh, N. N., Waring, A. J. & Lehrer, R. I. Activities of LL-37, a cathelin-associated antimicrobial peptide of human neutrophils. Antimicrob. Agents Chemother. 42, 2206?2214 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Mor, A., Amiche, M. & Nicolas, P. Structure, synthesis, and activity of dermaseptin b, a novel vertebrate defensive peptide from frog skin: relationship with adenoregulin. Biochemistry 33, 6642?6650 (1994).

    Article  CAS  PubMed  Google Scholar 

  61. Bechinger, B. The structure, dynamics and orientation of antimicrobial peptides in membranes by multidimensional solid-state NMR spectroscopy. Biochim. Biophys. Acta 1462, 157?183 (1999). Reviews the solid-state NMR structural studies of membrane-active peptides, showing that many have amphipathic α-helical conformations and alignments of the helical axis parallel to the membrane surface.

    Article  CAS  PubMed  Google Scholar 

  62. Yamaguchi, S., Hong, T., Waring, A., Lehrer, R. I. & Hong, M. Solid-state NMR investigations of peptide?lipid interaction and orientation of a β-sheet antimicrobial peptide, protegrin. Biochemistry 41, 9852?9862 (2002). Describes the use of solid-state NMR to determine the orientation of protegrin-1.

    Article  CAS  PubMed  Google Scholar 

  63. Bechinger, B., Zasloff, M. & Opella, S. J. Structure and orientation of the antibiotic peptide magainin in membranes by solid-state nuclear magnetic resonance spectroscopy. Protein Sci. 2, 2077?2084 (1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Yamaguchi, S. et al. Orientation and dynamics of an antimicrobial peptide in the lipid bilayer by solid-state NMR spectroscopy. Biophys. J. 81, 2203?2214 (2001). Describes the use of solid-state NMR to determine the orientation of ovispirin in synthetic phospholipids.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Henzler Wildman, K. A., Lee, D. K. & Ramamoorthy, A. Mechanism of lipid bilayer disruption by the human antimicrobial peptide, LL-37. Biochemistry 42, 6545?6558 (2003).

    Article  CAS  PubMed  Google Scholar 

  66. Buffy, J. J. et al. Solid-state NMR investigation of the selective perturbation of lipid bilayers by the cyclic antimicrobial peptide RTD-1. Biochemistry 43, 9800?9812 (2004).

    Article  CAS  PubMed  Google Scholar 

  67. Spaar, A., Munster, C. & Salditt, T. Conformation of peptides in lipid membranes studied by X-ray grazing incidence scattering. Biophys. J. 87, 396?407 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. He, K., Ludtke, S. J., Huang, H. W. & Worcester, D. L. Antimicrobial peptide pores in membranes detected by neutron in-plane scattering. Biochemistry 34, 15614?15618 (1995).

    Article  CAS  PubMed  Google Scholar 

  69. Ludtke, S. J. et al. Membrane pores induced by magainin. Biochemistry 35, 13723?13728 (1996).

    Article  CAS  PubMed  Google Scholar 

  70. Yang, L., Harroun, T. A., Heller, W. T., Weiss, T. M. & Huang, H. W. Neutron off-plane scattering of aligned membranes. I. Method of measurement. Biophys. J. 75, 641?645 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Yang, L., Weiss, T. M., Harroun, T. A., Heller, W. T. & Huang, H. W. Supramolecular structures of peptide assemblies in membranes by neutron off-plane scattering: method of analysis. Biophys. J. 77, 2648?2656 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Chen, F. Y., Lee, M. T. & Huang, H. W. Evidence for membrane thinning effect as the mechanism for peptide-induced pore formation. Biophys. J. 84, 3751?3758 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Boman, H. G., Agerberth, B. & Boman, A. Mechanisms of action on Escherichia coli of cecropin P1 and PR-39, two antibacterial peptides from pig intestine. Infect. Immun. 61, 2978?2984 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Silvestro, L., Gupta, K., Weiser, J. N. & Axelsen, P. H. The concentration-dependent membrane activity of cecropin A. Biochemistry. 36, 11452?11460 (1997).

    Article  CAS  PubMed  Google Scholar 

  75. Scott, M. G., Yan, H. & Hancock, R. E. Biological properties of structurally related α-helical cationic antimicrobial peptides. Infect. Immun. 67, 2005?2009 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  76. Scott, M. G., Gold, M. R. & Hancock, R. E. Interaction of cationic peptides with lipoteichoic acid and gram- positive bacteria. Infect. Immun. 67, 6445?6453 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  77. Huang, H. W. Action of antimicrobial peptides: two-state model. Biochemistry 39, 8347?8352 (2000). Discusses the two-state model for the action of helical and β-sheet antimicrobial peptides. .

    Article  CAS  PubMed  Google Scholar 

  78. Ludtke, S., He, K. & Huang, H. Membrane thinning caused by magainin 2. Biochemistry 34, 16764?16769 (1995).

    Article  CAS  PubMed  Google Scholar 

  79. Heller, W. T. et al. Membrane thinning effect of the β-sheet antimicrobial protegrin. Biochemistry 39, 139?145 (2000).

    Article  CAS  PubMed  Google Scholar 

  80. Wu, Y., He, K., Ludtke, S. J. & Huang, H. W. X-ray diffraction study of lipid bilayer membranes interacting with amphiphilic helical peptides: diphytanoyl phosphatidylcholine with alamethicin at low concentrations. Biophys. J. 68, 2361?2369 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Yang, L., Harroun, T. A., Weiss, T. M., Ding, L. & Huang, H. W. Barrel-stave model or toroidal model? A case study on melittin pores. Biophys. J. 81, 1475?1485 (2001).

    Article  PubMed  PubMed Central  Google Scholar 

  82. Ehrenstein, G. & Lecar, H. Electrically gated ionic channels in lipid bilayers. Q. Rev. Biophys. 10, 1?34 (1977).

    Article  CAS  PubMed  Google Scholar 

  83. He, K., Ludtke, S. J., Worcester, D. L. & Huang, H. W. Neutron scattering in the plane of membranes: structure of alamethicin pores. Biophys. J. 70, 2659?2666 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Cantor, R. S. Size distribution of barrel-stave aggregates of membrane peptides: influence of the bilayer lateral pressure profile. Biophys. J. 82, 2520?2525 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Pouny, Y., Rapaport, D., Mor, A., Nicolas, P. & Shai, Y. Interaction of antimicrobial dermaseptin and its fluorescently labeled analogues with phospholipid membranes. Biochemistry 31, 12416?12423 (1992).

    Article  CAS  PubMed  Google Scholar 

  86. Shai, Y. Mechanism of the binding, insertion and destabilization of phospholipid bilayer membranes by alpha-helical antimicrobial and cell non-selective membrane-lytic peptides. Biochim. Biophys. Acta 1462, 55?70 (1999).

    Article  CAS  PubMed  Google Scholar 

  87. Ladokhin, A. S. & White, S. H. 'Detergent-like' permeabilization of anionic lipid vesicles by melittin. Biochim. Biophys. Acta 1514, 253?260 (2001).

    Article  CAS  PubMed  Google Scholar 

  88. Oren, Z. & Shai, Y. Mode of action of linear amphipathic α-helical antimicrobial peptides. Biopolymers 47, 451?463 (1998). An overview with good illustrations that presents the barrel-stave and carpet-like mechanisms of membrane permeation by amphipathic α-helical peptides.

    Article  CAS  PubMed  Google Scholar 

  89. Matsuzaki, K., Murase, O., Fujii, N. & Miyajima, K. An antimicrobial peptide, magainin 2, induced rapid flip-flop of phospholipids coupled with pore formation and peptide translocation. Biochemistry 35, 11361?11368 (1996).

    Article  CAS  PubMed  Google Scholar 

  90. Hallock, K. J., Lee, D. K. & Ramamoorthy, A. MSI-78, an analogue of the magainin antimicrobial peptides, disrupts lipid bilayer structure via positive curvature strain. Biophys. J. 84, 3052?3060 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Matsuzaki, K. et al. Relationship of membrane curvature to the formation of pores by magainin 2. Biochemistry 37, 11856?11863 (1998).

    Article  CAS  PubMed  Google Scholar 

  92. Matsuzaki, K., Sugishita, K., Harada, M., Fujii, N. & Miyajima, K. Interactions of an antimicrobial peptide, magainin 2, with outer and inner membranes of Gram-negative bacteria. Biochim. Biophys. Acta 1327, 119?130 (1997).

    Article  CAS  PubMed  Google Scholar 

  93. Fujii, G., Selsted, M. E. & Eisenberg, D. Defensins promote fusion and lysis of negatively charged membranes. Protein Sci. 2, 1301?1312 (1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Wimley, W. C., Selsted, M. E. & White, S. H. Interactions between human defensins and lipid bilayers: evidence for formation of multimeric pores. Protein Sci. 3, 1362?1373 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Cociancich, S., Ghazi, A., Hetru, C., Hoffmann, J. A. & Letellier, L. Insect defensin, an inducible antibacterial peptide, forms voltage-dependent channels in Micrococcus luteus. J. Biol. Chem. 268, 19239?19245 (1993).

    CAS  PubMed  Google Scholar 

  96. Takeuchi, K. et al. Channel-forming membrane permeabilization by an antibacterial protein, sapecin: determination of membrane-buried and oligomerization surfaces by NMR. J. Biol. Chem. 279, 4981?4987 (2004).

    Article  CAS  PubMed  Google Scholar 

  97. Dathe, M. & Wieprecht, T. Structural features of helical antimicrobial peptides: their potential to modulate activity on model membranes and biological cells. Biochim. Biophys. Acta 1462, 71?87 (1999).

    Article  CAS  PubMed  Google Scholar 

  98. Dathe, M. et al. General aspects of peptide selectivity towards lipid bilayers and cell membranes studied by variation of the structural parameters of amphipathic helical model peptides. Biochim. Biophys. Acta 1558, 171?186 (2002).

    Article  CAS  PubMed  Google Scholar 

  99. Duclohier, H. Anion pores from magainins and related defensive peptides. Toxicology 87, 175?188 (1994).

    Article  CAS  PubMed  Google Scholar 

  100. Juretic, D. et al. Magainin 2 amide and analogues. Antimicrobial activity, membrane depolarization and susceptibility to proteolysis. FEBS Lett. 249, 219?223 (1989).

    Article  CAS  PubMed  Google Scholar 

  101. Westerhoff, H. V., Juretic, D., Hendler, R. W. & Zasloff, M. Magainins and the disruption of membrane-linked free-energy transduction. Proc. Natl Acad. Sci. USA 86, 6597?6601 (1989).

    Article  CAS  PubMed  Google Scholar 

  102. Bierbaum, G. & Sahl, H. G. Autolytic system of Staphylococcus simulans 22: influence of cationic peptides on activity of N-acetylmuramoyl-L-alanine amidase. J. Bacteriol. 169, 5452?5458 (1987).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Zhao, H. & Kinnunen, P. K. Modulation of the activity of secretory phospholipase A2 by antimicrobial peptides. Antimicrob. Agents Chemother. 47, 965?971 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Scheller, A. et al. Structural requirements for cellular uptake of α-helical amphipathic peptides. J. Pept. Sci. 5, 185?194 (1999).

    Article  CAS  PubMed  Google Scholar 

  105. Futaki, S. et al. Arginine-rich peptides. An abundant source of membrane-permeable peptides having potential as carriers for intracellular protein delivery. J. Biol. Chem. 276, 5836?5840 (2001).

    Article  CAS  PubMed  Google Scholar 

  106. Richard, J. P. et al. Cell-penetrating peptides. A re-evaluation of the mechanism of cellular uptake. J. Biol. Chem. 278, 585?590 (2003).

    Article  CAS  PubMed  Google Scholar 

  107. Wadia, J. S., Stan, R. V. & Dowdy, S. F. Transducible TAT-HA fusogenic peptide enhances escape of TAT-fusion proteins after lipid raft macropinocytosis. Nature Med. 10, 310?315 (2004).

    Article  CAS  PubMed  Google Scholar 

  108. Casteels, P., Ampe, C., Jacobs, F. & Tempst, P. Functional and chemical characterization of hymenoptaecin, an antibacterial polypeptide that is infection-inducible in the honeybee (Apis mellifera). J. Biol. Chem. 268, 7044?7054 (1993).

    CAS  PubMed  Google Scholar 

  109. Shi, J. et al. Antibacterial activity of a synthetic peptide (PR-26) derived from PR-39, a proline?arginine-rich neutrophil antimicrobial peptide. Antimicrob. Agents Chemother. 40, 115?121 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Subbalakshmi, C. & Sitaram, N. Mechanism of antimicrobial action of indolicidin. FEMS Microbiol. Lett. 160, 91?96 (1998).

    Article  CAS  PubMed  Google Scholar 

  111. Salomon, R. A. & Farias, R. N. Microcin 25, a novel antimicrobial peptide produced by Escherichia coli. J. Bacteriol. 174, 7428?7435 (1992).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Brotz, H., Bierbaum, G., Leopold, K., Reynolds, P. E. & Sahl, H. G. The lantibiotic mersacidin inhibits peptidoglycan synthesis by targeting lipid II. Antimicrob. Agents Chemother. 42, 154?160 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Park, C. B., Kim, H. S. & Kim, S. C. Mechanism of action of the antimicrobial peptide buforin II: buforin II kills microorganisms by penetrating the cell membrane and inhibiting cellular functions. Biochem. Biophys. Res. Commun. 244, 253?257 (1998).

    Article  CAS  PubMed  Google Scholar 

  114. Yonezawa, A., Kuwahara, J., Fujii, N. & Sugiura, Y. Binding of tachyplesin I to DNA revealed by footprinting analysis: significant contribution of secondary structure to DNA binding and implication for biological action. Biochemistry 31, 2998?3004 (1992).

    Article  CAS  PubMed  Google Scholar 

  115. Patrzykat, A., Friedrich, C. L., Zhang, L., Mendoza, V. & Hancock, R. E. Sublethal concentrations of pleurocidin-derived antimicrobial peptides inhibit macromolecular synthesis in Escherichia coli. Antimicrob. Agents Chemother. 46, 605?614 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Kavanagh, K. & Dowd, S. Histatins: antimicrobial peptides with therapeutic potential. J. Pharm. Pharmacol. 56, 285?289 (2004).

    Article  CAS  PubMed  Google Scholar 

  117. Andreu, D. & Rivas, L. Animal antimicrobial peptides: an overview. Biopolymers 47, 415?433 (1998).

    Article  CAS  PubMed  Google Scholar 

  118. Otvos, L. Jr. et al. Interaction between heat shock proteins and antimicrobial peptides. Biochemistry 39, 14150?14159 (2000).

    Article  CAS  PubMed  Google Scholar 

  119. Kragol, G. et al. The antibacterial peptide pyrrhocoricin inhibits the ATPase actions of DnaK and prevents chaperone-assisted protein folding. Biochemistry 40, 3016?3026 (2001).

    Article  CAS  PubMed  Google Scholar 

  120. 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).

    Article  CAS  PubMed  Google Scholar 

  121. Kristian, S. A., Durr, 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. 71, 546?549 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Campos, M. A. et al. Capsule polysaccharide mediates bacterial resistance to antimicrobial peptides. Infect. Immun. 72, 7107?7114 (2004). Describes a novel mechanism of resistance in which K. pneumoniae capsule polysaccharide limits the interaction of antimicrobial peptides and proteins with the bacterial membrane targets.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Luderitz, O. et al. Lipopolysaccharides of Gram-negative Bacteria (Academic Press, 1982).

    Book  Google Scholar 

  125. Groisman, E. A., Parra-Lopez, C., Salcedo, M., Lipps, C. J. & Heffron, F. Resistance to host antimicrobial peptides is necessary for Salmonella virulence. Proc. Natl Acad. Sci. USA 89, 11939?11943 (1992).

    Article  CAS  PubMed  Google Scholar 

  126. McPhee, J. B., Lewenza, S. & Hancock, R. E. Cationic antimicrobial peptides activate a two-component regulatory system, PmrA?PmrB, that regulates resistance to polymyxin B and cationic antimicrobial peptides in Pseudomonas aeruginosa. Mol. Microbiol. 50, 205?217 (2003). Describes how antimicrobial peptides can induce the pmrA?pmrB genes and the putative LPS modification operon.

    Article  CAS  PubMed  Google Scholar 

  127. Guo, L. et al. Regulation of lipid A modifications by Salmonella typhimurium virulence genes phoP?phoQ. Science 276, 250?253 (1997).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  129. Baker, S. J., Gunn, J. S. & Morona, R. The Salmonella typhi melittin resistance gene pqaB affects intracellular growth in PMA-differentiated U937 cells, polymyxin B resistance and lipopolysaccharide. Microbiology 145, 367?378 (1999).

    Article  CAS  PubMed  Google Scholar 

  130. Visser, L. G., Hiemstra, P. S., Van Den Barselaar, M. T., Ballieux, P. A. & Van Furth, R. Role of yadA in resistance to killing of Yersinia enterocolitica by antimicrobial polypeptides of human granulocytes. Infect. Immun. 64, 1653?1658 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  131. Parra-Lopez, C., Baer, M. T. & Groisman, E., A. Molecular genetic analysis of a locus required for resistance to antimicrobial peptides in Salmonella typhimurium. EMBO J. 12, 4053?4062 (1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Groisman, E. A. How bacteria resist killing by host-defense peptides. Trends Microbiol. 2, 444?448 (1994).

    Article  CAS  PubMed  Google Scholar 

  133. Nikaido, H. Multidrug efflux pumps of Gram-negative bacteria. J. Bacteriol. 178, 5853?5859 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Shafer, W. M., Qu, X., 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).

    Article  CAS  PubMed  Google Scholar 

  135. Resnick, N. M., Maloy, W. L., Guy, H. R. & Zasloff, M. A novel endopeptidase from Xenopus that recognizes α-helical secondary structure. Cell 66, 541?554 (1991).

    Article  CAS  PubMed  Google Scholar 

  136. Roland, K. L., Esther, C. R. & Spitznagel, J. K. Isolation and characterization of a gene, pmrD, from Salmonella typhimurium that confers resistance to polymyxin when expressed in multiple copies. J. Bacteriol. 176, 3589?3597 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Belas, R., Manos, J. & Suvanasuthi, R. Proteus mirabilis ZapA metalloprotease degrades a broad spectrum of substrates, including antimicrobial peptides. Infect. Immun. 72, 5159?5167 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Sieprawska-Lupa, M. et al. Degradation of human antimicrobial peptide LL-37 by Staphylococcus aureus-derived proteinases. Antimicrob. Agents Chemother. 48, 4673?4679 (2004). Describes how staphylococcal proteases can degrade the human cathelicidin LL-37, which is thought to be a novel mechanism of bacterial resistance.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Ramanathan, B., Davis, E. G., Ross, C. R. & Blecha, F. Cathelicidins: microbicidal activity, mechanisms of action, and roles in innate immunity. Microbes Infect. 4, 361?372 (2002).

    Article  CAS  PubMed  Google Scholar 

  140. Powers, J. P. & Hancock, R. E. The relationship between peptide structure and antibacterial activity. Peptides 24, 1681?1691 (2003). A good overview examining the structure?activity relationships of antimicrobial peptides, particularly β-sheet peptides, α-helical peptides, extended peptides and loop peptides.

    Article  CAS  PubMed  Google Scholar 

  141. Boman, H. G. & Hultmark, D. Cell-free immunity in insects. Annu. Rev. Microbiol. 41, 103?126 (1987).

    Article  CAS  PubMed  Google Scholar 

  142. Yount, N. Y. & Yeaman, M. R. Multidimensional signatures in antimicrobial peptides. Proc. Natl Acad. Sci. USA 101, 7363?7368 (2004).

    Article  CAS  PubMed  Google Scholar 

  143. Matsuzaki, K., Sugishita, K., Fujii, N. & Miyajima, K. Molecular basis for membrane selectivity of an antimicrobial peptide, magainin 2. Biochemistry 34, 3423?3429 (1995).

    Article  CAS  PubMed  Google Scholar 

  144. Costerton, J. W., Stewart, P. S. & Greenberg, E. P. Bacterial biofilms: a common cause of persistent infections. Science 284, 1318?1322 (1999).

    Article  CAS  PubMed  Google Scholar 

  145. Singh, P. K., Parsek, M. R., Greenberg, E. P. & Welsh, M. J. A component of innate immunity prevents bacterial biofilm development. Nature 417, 552?555 (2002).

    Article  CAS  PubMed  Google Scholar 

  146. Lai, R., Liu, H., Hui Lee, W. & Zhang, Y. An anionic antimicrobial peptide from toad Bombina maxima. Biochem. Biophys. Res. Commun. 295, 796?799 (2002).

    Article  CAS  PubMed  Google Scholar 

  147. Schittek, B. et al. Dermcidin: a novel human antibiotic peptide secreted by sweat glands. Nature Immunol. 2, 1133?1137 (2001).

    Article  CAS  Google Scholar 

  148. Andersson, M., Boman, A. & Boman, H. G. Ascaris nematodes from pig and human make three antibacterial peptides: isolation of cecropin P1 and two ASABF peptides. Cell. Mol. Life Sci. 60, 599?606 (2003).

    Article  CAS  PubMed  Google Scholar 

  149. Shamova, O. et al. Purification and properties of proline-rich antimicrobial peptides from sheep and goat leukocytes. Infect. Immun. 67, 4106?4111 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  150. Zhao, C., Ganz, T. & Lehrer, R. I. Structures of genes for two cathelin-associated antimicrobial peptides: prophenin-2 and PR-39. FEBS Lett. 376, 130?134 (1995).

    Article  CAS  PubMed  Google Scholar 

  151. Selsted, M. E. et al. Indolicidin, a novel bactericidal tridecapeptide amide from neutrophils. J. Biol. Chem. 267, 4292?4295 (1992).

    CAS  PubMed  Google Scholar 

  152. Basir, Y. J., Knoop, F. C., Dulka, J. & Conlon, J. M. Multiple antimicrobial peptides and peptides related to bradykinin and neuromedin N isolated from skin secretions of the pickerel frog, Rana palustris. Biochim. Biophys. Acta 1543, 95?105 (2000).

    Article  CAS  PubMed  Google Scholar 

  153. Kokryakov, V. N. et al. Protegrins: leukocyte antimicrobial peptides that combine features of corticostatic defensins and tachyplesins. FEBS Lett. 327, 231?236 (1993).

    Article  CAS  PubMed  Google Scholar 

  154. Ganz, T. & Lehrer, R. I. Defensins. Pharmacol. Ther. 66, 191?205 (1995).

    Article  CAS  PubMed  Google Scholar 

  155. Fehlbaum, P. et al. Insect immunity. Septic injury of Drosophila induces the synthesis of a potent antifungal peptide with sequence homology to plant antifungal peptides. J. Biol. Chem. 269, 33159?33163 (1994).

    CAS  PubMed  Google Scholar 

  156. Gazit, E., Boman, A., Boman, H. G. & Shai, Y. Interaction of the mammalian antibacterial peptide cecropin P1 with phospholipid vesicles. Biochemistry 34, 11479?11488 (1995).

    Article  CAS  PubMed  Google Scholar 

  157. Shai, Y. Molecular recognition between membrane-spanning polypeptides. Trends Biochem. Sci. 20, 460?464 (1995).

    Article  CAS  PubMed  Google Scholar 

  158. Naito, A. et al. Conformation and dynamics of melittin bound to magnetically oriented lipid bilayers by solid-state 31P and 13C NMR spectroscopy. Biophys. J. 78, 2405?2417 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  159. Wong, H., Bowie, J. H. & Carver, J. A. The solution structure and activity of caerin 1.1, an antimicrobial peptide from the Australian green tree frog, Litoria splendida. Eur. J. Biochem. 247, 545?557 (1997).

    Article  CAS  PubMed  Google Scholar 

  160. Kraulis, P. J. MolScript: a program to produce both detailed and schematic plots of protein structures. J. Appl. Crystallogr. 24, 946?950 (1991).

    Article  Google Scholar 

  161. Merritt, E. A. & Bacon, D. J. Raster3D: photorealistic molecular graphics. Methods Enzymol. 277, 505?524 (1997).

    Article  CAS  PubMed  Google Scholar 

  162. Huang, H. W. Molecular mechanism of peptide induced pores in membranes. Phys. Rev. Lett. 92, 198304-1?198304-4 (2004).

    Google Scholar 

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Acknowledgements

Kim Brogden's laboratory is supported by the National Institute of Dental and Craniofacial Research, National Institutes of Health (NIH).

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Authors and Affiliations

  1. Department of Periodontics and Dows Institute for Dental Research, College of Dentistry, The University of Iowa, Iowa City, 52242, Iowa, USA

    Kim A. Brogden

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  1. Kim A. Brogden
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DATABASES

Entrez

DEFB118

Escherichia coli

HNP-1

Klebsiella pneumoniae

LL-37

PhoP

PhoQ

Pseudomonas aeruginosa

Salmonella enterica serovar Typhimurium

Staphylococcus aureus

YadA

Yersinia enterocolitica

YlpA

SwissProt

CAP18

FURTHER INFORMATION

Anti-infective peptides

Kim A. Brogden's laboratory

Glossary

AMPHIPATHIC

Here, used to describe peptides containing both hydrophilic and hydrophobic amino acid residues, where spatial separation of these residues facilitates their attachment and insertion into membranes.

LIQUID-CRYSTALLINE STATE

The state and temperature at which hydrocarbon tails of the lipid bilayers are fluid and can move. In most biomembranes, the lipids are in the liquid-crystalline state under physiological conditions.

NEUTRON IN-PLANE SCATTERING

A neutron-diffraction pattern of a peptide and membrane sample with the multilayer sample oriented normal to the incident neutron beam.

NEUTRON OFF-PLANE SCATTERING

A neutron-diffraction pattern of a peptide and membrane sample in a sandwiched multilayer sample oriented at an oblique angle with respect to the incident neutron beam, so that the entire low-angle diffraction pattern can be recorded by the area detector at one sample-to-detector distance.

COULOMB ENERGY

The energy that one stationary, electrically charged substance of small volume exerts on another. For example, in pores formed from numerous cationic peptides, the Coulomb energy would be so high that pore formation would not be possible unless the positive charges are effectively screened when the peptides insert into the membrane containing anionic phospholipids.

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Brogden, K. Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria?. Nat Rev Microbiol 3, 238–250 (2005). https://doi.org/10.1038/nrmicro1098

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