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Short native antimicrobial peptides and engineered ultrashort lipopeptides: similarities and differences in cell specificities and modes of action

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Abstract

Due to the rapid emergence of resistant microbes to the currently available antibiotics, cationic antimicrobial peptides have attracted considerable interest as a possible new generation of anti-infective compounds. However, low cost development for therapeutic or industrial purposes requires, among other properties, that the peptides will be small and with simple structure. Therefore, considerable research has been devoted to optimizing peptide length combined with a simple design. This review focuses on the similarities and differences in the mode of action and target cell specificity of two families of small peptides: the naturally occurring temporins from the skin of amphibia and the engineered ultrashort lipopeptides. We will also discuss the finding that acylation of cationic peptides results in molecules with a more potent spectrum of activity and a higher resistance to proteolytic degradation. Conjugation of fatty acids to linear native peptide sequences is a powerful strategy to engineer novel successful anti-infective drugs.

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Abbreviations

AMP:

Antimicrobial peptide

GFP:

Green fluorescent protein

LiPs:

Lipopeptides

LPS:

Lipopolysaccharide

LPG:

Lipophosphoglycan

LTA:

Lipoteichoic acid

IM:

Inner membrane

MIC:

Minimum inhibitory concentration

OM:

Outer membrane

TNFα:

Tumor necrosis factor alpha

USLiPs:

Ultrashort lipopeptides

References

  1. Boman HG (2003) Antibacterial peptides: basic facts and emerging concepts. J Intern Med 254:197–215

    PubMed  CAS  Google Scholar 

  2. Boman HG (1995) Peptide antibiotics and their role in innate immunity. Annu Rev Immunol 13:61–92

    PubMed  CAS  Google Scholar 

  3. Ganz T, Lehrer RI (1998) Antimicrobial peptides of vertebrates. Curr Opin Immunol 10:41–44

    PubMed  CAS  Google Scholar 

  4. Hancock REW, Brown KL, Mookherjee N (2006) Host defence peptides from invertebrates—emerging antimicrobial strategies. Immunobiology 211:315–322

    PubMed  CAS  Google Scholar 

  5. Zasloff M (2002) Antimicrobial peptides of multicellular organisms. Nature 415:389–395

    PubMed  CAS  Google Scholar 

  6. Selsted ME, Ouellette AJ (2005) Mammalian defensins in the antimicrobial immune response. Nat Immunol 6:551–557

    PubMed  CAS  Google Scholar 

  7. Peters BM, Shirtliff ME, Jabra-Rizk MA (2010) Antimicrobial peptides: primeval molecules or future drugs? PLoS Pathog 6:e1001067

    PubMed  Google Scholar 

  8. Steinstraesser L, Kraneburg U, Jacobsen F, Al-Benna S (2011) Host defense peptides and their antimicrobial-immunomodulatory duality. Immunobiology 216:322–333

    PubMed  CAS  Google Scholar 

  9. Wilson CL, Ouellette AJ, Satchell DP, Ayabe T, Lopez-Boado YS, Stratman JL, Hultgren SJ, Matrisian LM, Parks WC (1999) Regulation of intestinal alpha-defensin activation by the metalloproteinase matrilysin in innate host defense. Science 286:113–117

    PubMed  CAS  Google Scholar 

  10. Lehrer RI, Ganz T (2002) Cathelicidins: a family of endogenous antimicrobial peptides. Curr Opin Hematol 9:18–22

    PubMed  Google Scholar 

  11. Ganz T (2005) Defensins and other antimicrobial peptides: a historical perspective and an update. Comb Chem High Throughput Screen 8:209–217

    PubMed  CAS  Google Scholar 

  12. Steiner H, Hultmark D, Engstrom A, Bennich H, Boman HG (1981) Sequence and specificity of two antibacterial proteins involved in insect immunity. Nature 292:246–248

    PubMed  CAS  Google Scholar 

  13. Zasloff M (1987) 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

    PubMed  CAS  Google Scholar 

  14. Hancock REW (2001) Cationic peptides: effectors in innate immunity and novel antimicrobials. Lancet Infect Dis 1:156–164

    PubMed  CAS  Google Scholar 

  15. Sahl HG, Pag U, Bonness S, Wagner S, Antcheva N, Tossi A (2005) Mammalian defensins: structures and mechanism of antibiotic activity. J Leukoc Biol 77:466–475

    PubMed  CAS  Google Scholar 

  16. Osterholm MT (1996) Emerging infectious diseases. A real public health crisis? Postgrad Med 100:15–16, 21, 25–26

    PubMed  CAS  Google Scholar 

  17. Maviglia R, Nestorini R, Pennisi M (2009) Role of old antibiotics in multidrug resistant bacterial infections. Curr Drug Targets 10:895–905

    PubMed  CAS  Google Scholar 

  18. Denning DW (1997) Echinocandins and pneumocandins—a new antifungal class with a novel mode of action. J Antimicrob Chemother 40:611–614

    PubMed  CAS  Google Scholar 

  19. Denning DW (2002) Echinocandins: a new class of antifungal. J Antimicrob Chemother 49:889–891

    PubMed  CAS  Google Scholar 

  20. Straus SK, Hancock REW (2006) Mode of action of the new antibiotic for Gram-positive pathogens daptomycin: comparison with cationic antimicrobial peptides and lipopeptides. Biochim Biophys Acta 1758:1215–1223

    PubMed  CAS  Google Scholar 

  21. Balkovec JM (1994) Anti-infectives: lipopeptide antifungal agents. Expert Opin Invest Drugs 3:65–82

    Google Scholar 

  22. De Lucca AJ, Walsh TJ (1999) Antifungal peptides: novel therapeutic compounds against emerging pathogens. Antimicrob Agents Chemother 43:1–11

    PubMed  Google Scholar 

  23. Bassarello C, Lazzaroni S, Bifulco G, Lo Cantore P, Iacobellis NS, Riccio R, Gomez-Paloma L, Evidente A (2004) Tolaasins A–E, five new lipodepsipeptides produced by Pseudomonas tolaasii. J Nat Prod 67:811–816

    PubMed  CAS  Google Scholar 

  24. Peggion C, Formaggio F, Crisma M, Epand RF, Epand RM, Toniolo C (2003) Trichogin: a paradigm for lipopeptaibols. J Pept Sci 9:679–689

    PubMed  CAS  Google Scholar 

  25. Tsubery H, Ofek I, Cohen S, Fridkin M (2001) N-terminal modifications of polymyxin B nonapeptide and their effect on antibacterial activity. Peptides 22:1675–1681

    PubMed  CAS  Google Scholar 

  26. Fiechter A (1992) Biosurfactants: moving towards industrial application. Trends Biotechnol 10:208–217

    PubMed  CAS  Google Scholar 

  27. Raaijmakers JM, de Bruijn I, de Kock MJ (2006) Cyclic lipopeptide production by plant-associated Pseudomonas spp.: diversity, activity, biosynthesis, and regulation. Mol Plant Microbe Interact 19:699–710

    PubMed  CAS  Google Scholar 

  28. Jeu L, Fung HB (2004) Daptomycin: a cyclic lipopeptide antimicrobial agent. Clin Ther 26:1728–1757

    PubMed  CAS  Google Scholar 

  29. Sauermann R, Rothenburger M, Graninger W, Joukhadar C (2008) Daptomycin: a review 4 years after first approval. Pharmacology 81:79–91

    PubMed  CAS  Google Scholar 

  30. Moudgal V, Little T, Boikov D, Vazquez JA (2005) Multiechinocandin- and multiazole-resistant Candida parapsilosis isolates serially obtained during therapy for prosthetic valve endocarditis. Antimicrob Agents Chemother 49:767–769

    PubMed  CAS  Google Scholar 

  31. Avrahami D, Shai Y (2002) Conjugation of a magainin analogue with lipophilic acids controls hydrophobicity, solution assembly, and cell selectivity. Biochemistry 41:2254–2263

    PubMed  CAS  Google Scholar 

  32. Chicharro C, Granata C, Lozano R, Andreu D, Rivas L (2001) N-terminal fatty acid substitution increases the leishmanicidal activity of CA(1–7)M(2–9), a cecropin-melittin hybrid peptide. Antimicrob Agents Chemother 45:2441–2449

    PubMed  CAS  Google Scholar 

  33. Lockwood NA, Haseman JR, Tirrell MV, Mayo KH (2004) Acylation of SC4 dodecapeptide increases bactericidal potency against Gram-positive bacteria, including drug-resistant strains. Biochem J 378:93–103

    PubMed  CAS  Google Scholar 

  34. Majerle A, Kidric J, Jerala R (2003) Enhancement of antibacterial and lipopolysaccharide binding activities of a human lactoferrin peptide fragment by the addition of acyl chain. J Antimicrob Chemother 51:1159–1165

    PubMed  CAS  Google Scholar 

  35. Mak P, Pohl J, Dubin A, Reed MS, Bowers SE, Fallon MT, Shafer WM (2003) The increased bactericidal activity of a fatty acid-modified synthetic antimicrobial peptide of human cathepsin G correlates with its enhanced capacity to interact with model membranes. Int J Antimicrob Agents 21:13–19

    PubMed  CAS  Google Scholar 

  36. Radzishevsky IS, Rotem S, Zaknoon F, Gaidukov L, Dagan A, Mor A (2005) Effects of acyl versus aminoacyl conjugation on the properties of antimicrobial peptides. Antimicrob Agents Chemother 49:2412–2420

    PubMed  CAS  Google Scholar 

  37. Wakabayashi H, Matsumoto H, Hashimoto K, Teraguchi S, Takase M, Hayasawa H (1999) N-Acylated and D enantiomer derivatives of a nonamer core peptide of lactoferricin B showing improved antimicrobial activity. Antimicrob Agents Chemother 43:1267–1269

    PubMed  CAS  Google Scholar 

  38. Avrahami D, Shai Y (2003) Bestowing antifungal and antibacterial activities by lipophilic acid conjugation to d, l-amino acid-containing antimicrobial peptides: a plausible mode of action. Biochemistry 42:14946–14956

    PubMed  CAS  Google Scholar 

  39. Avrahami D, Shai Y (2004) A new group of antifungal and antibacterial lipopeptides derived from non-membrane active peptides conjugated to palmitic acid. J Biol Chem 279:12277–12285

    PubMed  CAS  Google Scholar 

  40. Malina A, Shai Y (2005) Conjugation of fatty acids with different lengths modulates the antibacterial and antifungal activity of a cationic biologically inactive peptide. Biochem J 390:695–702

    PubMed  CAS  Google Scholar 

  41. Mookherjee N, Hancock REW (2007) Cationic host defence peptides: innate immune regulatory peptides as a novel approach for treating infections. Cell Mol Life Sci 64:922–933

    PubMed  CAS  Google Scholar 

  42. Maget-Dana R, Peypoux F (1994) Iturins, a special class of pore-forming lipopeptides: biological and physicochemical properties. Toxicology 87:151–174

    PubMed  CAS  Google Scholar 

  43. Maget-Dana R, Ptak M (1995) Interactions of surfactin with membrane models. Biophys J 68:1937–1943

    PubMed  CAS  Google Scholar 

  44. Peypoux F, Bonmatin JM, Wallach J (1999) Recent trends in the biochemistry of surfactin. Appl Microbiol Biotechnol 51:553–563

    PubMed  CAS  Google Scholar 

  45. Steenbergen JN, Alder J, Thorne GM, Tally FP (2005) Daptomycin: a lipopeptide antibiotic for the treatment of serious Gram-positive infections. J Antimicrob Chemother 55:283–288

    PubMed  CAS  Google Scholar 

  46. Simmaco M, Mignogna G, Barra D (1998) Antimicrobial peptides from amphibian skin: what do they tell us? Biopolymers 47:435–450

    PubMed  CAS  Google Scholar 

  47. Rinaldi AC (2002) Antimicrobial peptides from amphibian skin: an expanding scenario. Curr Opin Chem Biol 6:799–804

    PubMed  CAS  Google Scholar 

  48. Conlon JM, Iwamuro S, King JD (2009) Dermal cytolytic peptides and the system of innate immunity in anurans. Ann NY Acad Sci 1163:75–82

    PubMed  CAS  Google Scholar 

  49. Miele R, Ponti D, Boman HG, Barra D, Simmaco M (1998) Molecular cloning of a bombinin gene from Bombina orientalis: detection of NF-kappaB and NF-IL6 binding sites in its promoter. FEBS Lett 431:23–28

    PubMed  CAS  Google Scholar 

  50. Simmaco M, Mignogna G, Canofeni S, Miele R, Mangoni ML, Barra D (1996) Temporins, antimicrobial peptides from the European red frog Rana temporaria. Eur J Biochem 242:788–792

    PubMed  CAS  Google Scholar 

  51. Mangoni ML (2006) Temporins, anti-infective peptides with expanding properties. Cell Mol Life Sci 63:1060–1069

    PubMed  CAS  Google Scholar 

  52. Mangoni ML, Shai Y (2009) Temporins and their synergism against Gram-negative bacteria and in lipopolysaccharide detoxification. Biochim Biophys Acta 1788:1610–1619

    PubMed  CAS  Google Scholar 

  53. Rinaldi AC, Mangoni ML, Rufo A, Luzi C, Barra D, Zhao H, Kinnunen PK, Bozzi A, Di Giulio A, Simmaco M (2002) Temporin L: antimicrobial, haemolytic and cytotoxic activities, and effects on membrane permeabilization in lipid vesicles. Biochem J 368:91–100

    PubMed  CAS  Google Scholar 

  54. Zhao H, Kinnunen PK (2003) Modulation of the activity of secretory phospholipase A2 by antimicrobial peptides. Antimicrob Agents Chemother 47:965–971

    PubMed  CAS  Google Scholar 

  55. Abbassi F, Lequin O, Piesse C, Goasdoue N, Foulon T, Nicolas P, Ladram A (2010) Temporin-SHf, a new type of phe-rich and hydrophobic ultrashort antimicrobial peptide. J Biol Chem 285:16880–16892

    PubMed  CAS  Google Scholar 

  56. Makovitzki A, Avrahami D, Shai Y (2006) Ultrashort antibacterial and antifungal lipopeptides. Proc Natl Acad Sci USA 103:15997–16002

    PubMed  CAS  Google Scholar 

  57. Makovitzki A, Baram J, Shai Y (2008) Antimicrobial lipopolypeptides composed of palmitoyl di- and tricationic peptides: in vitro and in vivo activities, self-assembly to nanostructures, and a plausible mode of action. Biochemistry 47:10630–10636

    PubMed  CAS  Google Scholar 

  58. Shai Y, Makovitzky A, Avrahami D (2006) Host defense peptides and lipopeptides: modes of action and potential candidates for the treatment of bacterial and fungal infections. Curr Protein Pept Sci 7:479–486

    PubMed  CAS  Google Scholar 

  59. Oren Z, Lerman JC, Gudmundsson GH, Agerberth B, Shai Y (1999) Structure and organization of the human antimicrobial peptide LL-37 in phospholipid membranes: relevance to the molecular basis for its non-cell-selective activity. Biochem J 341:501–513

    PubMed  CAS  Google Scholar 

  60. Papo N, Braunstein A, Eshhar Z, Shai Y (2004) Suppression of human prostate tumor growth in mice by a cytolytic d-, l-amino acid peptide: membrane lysis, increased necrosis, and inhibition of prostate-specific antigen secretion. Cancer Res 64:5779–5786

    PubMed  CAS  Google Scholar 

  61. Papo N, Oren Z, Pag U, Sahl HG, Shai Y (2002) The consequence of sequence alteration of an amphipathic alpha-helical antimicrobial peptide and its diastereomers. J Biol Chem 277:33913–33921

    PubMed  CAS  Google Scholar 

  62. Papo N, Seger D, Makovitzki A, Kalchenko V, Eshhar Z, Degani H, Shai Y (2006) Inhibition of tumor growth and elimination of multiple metastases in human prostate and breast xenografts by systemic inoculation of a host defense-like lytic peptide. Cancer Res 66:5371–5378

    PubMed  CAS  Google Scholar 

  63. Radzishevsky IS, Rotem S, Bourdetsky D, Navon-Venezia S, Carmeli Y, Mor A (2007) Improved antimicrobial peptides based on acyl-lysine oligomers. Nat Biotechnol 25:657–659

    PubMed  CAS  Google Scholar 

  64. Rotem S, Radzishevsky IS, Bourdetsky D, Navon-Venezia S, Carmeli Y, Mor A (2008) Analogous oligo-acyl-lysines with distinct antibacterial mechanisms. FASEB J 22:2652–2661

    PubMed  CAS  Google Scholar 

  65. Sarig H, Rotem S, Ziserman L, Danino D, Mor A (2008) Impact of self-assembly properties on antibacterial activity of short acyl-lysine oligomers. Antimicrob Agents Chemother 52:4308–4314

    PubMed  CAS  Google Scholar 

  66. Lehrer RI, Ganz T (1999) Antimicrobial peptides in mammalian and insect host defence. Curr Opin Immunol 11:23–27

    PubMed  CAS  Google Scholar 

  67. Shai Y (2002) From innate immunity to de novo designed antimicrobial peptides. Curr Pharm Des 8:715–725

    PubMed  CAS  Google Scholar 

  68. Marcellini L, Borro M, Gentile G, Rinaldi AC, Stella L, Aimola P, Barra D, Mangoni ML (2009) Esculentin-1b(1–18)-a membrane-active antimicrobial peptide that synergizes with antibiotics and modifies the expression level of a limited number of proteins in Escherichia coli. FEBS J 276:5647–5664

    PubMed  CAS  Google Scholar 

  69. Coccia C, Rinaldi AC, Luca V, Barra D, Bozzi A, Di Giulio A, Veerman EC, Mangoni ML (2011) Membrane interaction and antibacterial properties of two mildly cationic peptide diastereomers, bombinins H2 and H4, isolated from Bombina skin. Eur Biophys J 40(4):577–588

    Google Scholar 

  70. Hancock REW, Diamond G (2000) The role of cationic antimicrobial peptides in innate host defences. Trends Microbiol 8:402–410

    PubMed  CAS  Google Scholar 

  71. Patrzykat A, Friedrich CL, Zhang L, Mendoza V, Hancock REW (2002) Sublethal concentrations of pleurocidin-derived antimicrobial peptides inhibit macromolecular synthesis in Escherichia coli. Antimicrob Agents Chemother 46:605–614

    PubMed  CAS  Google Scholar 

  72. Subbalakshmi C, Sitaram N (1998) Mechanism of antimicrobial action of indolicidin. FEMS Microbiol Lett 160:91–96

    PubMed  CAS  Google Scholar 

  73. Chen W, Wang J, An H, Zhou J, Zhang L, Cao X (2005) Heat shock up-regulates TLR9 expression in human B cells through activation of ERK and NF-kappaB signal pathways. Immunol Lett 98:153–159

    PubMed  CAS  Google Scholar 

  74. Funderburg N, Lederman MM, Feng Z, Drage MG, Jadlowsky J, Harding CV, Weinberg A, Sieg SF (2007) Human-defensin-3 activates professional antigen-presenting cells via Toll-like receptors 1 and 2. Proc Natl Acad Sci USA 104:18631–18635

    PubMed  CAS  Google Scholar 

  75. Wu H, Arron JR (2003) TRAF6, a molecular bridge spanning adaptive immunity, innate immunity and osteoimmunology. Bioessays 25:1096–1105

    PubMed  CAS  Google Scholar 

  76. Brogden KA (2005) Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria? Nat Rev Microbiol 3:238–250

    PubMed  CAS  Google Scholar 

  77. Nicholls EF, Madera L, Hancock RE (2010) Immunomodulators as adjuvants for vaccines and antimicrobial therapy. Ann NY Acad Sci 1213:46–61

    PubMed  CAS  Google Scholar 

  78. Rosenfeld Y, Sahl HG, Shai Y (2008) Parameters involved in antimicrobial and endotoxin detoxification activities of antimicrobial peptides. Biochemistry 47:6468–6478

    PubMed  CAS  Google Scholar 

  79. Bechinger B, Lohner K (2006) Detergent-like actions of linear amphipathic cationic antimicrobial peptides. Biochim Biophys Acta 1758:1529–1539

    PubMed  CAS  Google Scholar 

  80. Lohner K (2009) New strategies for novel antibiotics: peptides targeting bacterial cell membranes. Gen Physiol Biophys 28:105–116

    PubMed  CAS  Google Scholar 

  81. Wassef MK, Fioretti TB, Dwyer DM (1985) Lipid analyses of isolated surface membranes of Leishmania donovani promastigotes. Lipids 20:108–115

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  83. Shai Y (2002) Mode of action of membrane active antimicrobial peptides. Biopolymers 66:236–248

    PubMed  CAS  Google Scholar 

  84. Ludtke SJ, He K, Heller WT, Harroun TA, Yang L, Huang HW (1996) Membrane pores induced by magainin. Biochemistry 35:13723–13728

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  86. Hancock REW, Rozek A (2002) Role of membranes in the activities of antimicrobial cationic peptides. FEMS Microbiol Lett 206:143–149

    PubMed  CAS  Google Scholar 

  87. Mangoni ML, Papo N, Barra D, Simmaco M, Bozzi A, Di Giulio A, Rinaldi AC (2004) Effects of the antimicrobial peptide temporin L on cell morphology, membrane permeability and viability of Escherichia coli. Biochem J 380:859–865

    PubMed  CAS  Google Scholar 

  88. Steffen H, Rieg S, Wiedemann I, Kalbacher H, Deeg M, Sahl HG, Peschel A, Gotz F, Garbe C, Schittek B (2006) Naturally processed dermcidin-derived peptides do not permeabilize bacterial membranes and kill microorganisms irrespective of their charge. Antimicrob Agents Chemother 50:2608–2620

    PubMed  CAS  Google Scholar 

  89. Bera A, Singh S, Nagaraj R, Vaidya T (2003) Induction of autophagic cell death in Leishmania donovani by antimicrobial peptides. Mol Biochem Parasitol 127:23–35

    PubMed  CAS  Google Scholar 

  90. Georgopapadakou NH, Tkacz JS (1995) The fungal cell wall as a drug target. Trends Microbiol 3:98–104

    PubMed  CAS  Google Scholar 

  91. Kartsonis NA, Nielsen J, Douglas CM (2003) Caspofungin: the first in a new class of antifungal agents. Drug Resist Updat 6:197–218

    PubMed  CAS  Google Scholar 

  92. Ullmann AJ (2003) Review of the safety, tolerability, and drug interactions of the new antifungal agents caspofungin and voriconazole. Curr Med Res Opin 19:263–271

    PubMed  CAS  Google Scholar 

  93. Debono M, Gordee RS (1994) Antibiotics that inhibit fungal cell wall development. Annu Rev Microbiol 48:471–497

    PubMed  CAS  Google Scholar 

  94. Evans ME, Feola DJ, Rapp RP (1999) Polymyxin B sulfate and colistin: old antibiotics for emerging multiresistant gram-negative bacteria. Ann Pharmacother 33:960–967

    PubMed  CAS  Google Scholar 

  95. Toniolo C, Crisma M, Formaggio F, Peggion C, Epand RF, Epand RM (2001) Lipopeptaibols, a novel family of membrane active, antimicrobial peptides. Cell Mol Life Sci 58:1179–1188

    PubMed  CAS  Google Scholar 

  96. Alexander C, Rietschel ET (2001) Bacterial lipopolysaccharides and innate immunity. J Endotoxin Res 7:167–202

    PubMed  CAS  Google Scholar 

  97. Raetz CR, Whitfield C (2002) Lipopolysaccharide endotoxins. Annu Rev Biochem 71:635–700

    PubMed  CAS  Google Scholar 

  98. Nikaido H (1994) Prevention of drug access to bacterial targets: permeability barriers and active efflux. Science 264:382–388

    PubMed  CAS  Google Scholar 

  99. Nikaido H, Vaara M (1985) Molecular basis of bacterial outer membrane permeability. Microbiol Rev 49:1–32

    PubMed  CAS  Google Scholar 

  100. Rosenfeld Y, Barra D, Simmaco M, Shai Y, Mangoni ML (2006) A synergism between temporins toward Gram-negative bacteria overcomes resistance imposed by the lipopolysaccharide protective layer. J Biol Chem 281:28565–28574

    PubMed  CAS  Google Scholar 

  101. Papo N, Shai Y (2005) A molecular mechanism for lipopolysaccharide protection of Gram-negative bacteria from antimicrobial peptides. J Biol Chem 280:10378–10387

    PubMed  CAS  Google Scholar 

  102. Sal-Man N, Oren Z, Shai Y (2002) Preassembly of membrane-active peptides is an important factor in their selectivity toward target cells. Biochemistry 41:11921–11930

    PubMed  CAS  Google Scholar 

  103. Trent MS, Stead CM, Tran AX, Hankins JV (2006) Diversity of endotoxin and its impact on pathogenesis. J Endotoxin Res 12:205–223

    PubMed  CAS  Google Scholar 

  104. Rietschel ET, Kirikae T, Schade FU, Mamat U, Schmidt G, Loppnow H, Ulmer AJ, Zahringer U, Seydel U, Di Padova F, Schreier M, Brade H (1994) Bacterial endotoxin: molecular relationships of structure to activity and function. FASEB J 8:217–225

    PubMed  CAS  Google Scholar 

  105. Nikaido H (1989) Outer membrane barrier as a mechanism of antimicrobial resistance. Antimicrob Agents Chemother 33:1831–1836

    PubMed  CAS  Google Scholar 

  106. Friedrich CL, Moyles D, Beveridge TJ, Hancock REW (2000) Antibacterial action of structurally diverse cationic peptides on gram-positive bacteria. Antimicrob Agents Chemother 44:2086–2092

    PubMed  CAS  Google Scholar 

  107. Papo N, Shai Y (2005) Host defense peptides as new weapons in cancer treatment. Cell Mol Life Sci 62:784–790

    PubMed  CAS  Google Scholar 

  108. Allende D, McIntosh TJ (2003) Lipopolysaccharides in bacterial membranes act like cholesterol in eukaryotic plasma membranes in providing protection against melittin-induced bilayer lysis. Biochemistry 42:1101–1108

    PubMed  CAS  Google Scholar 

  109. Andra J, Koch MH, Bartels R, Brandenburg K (2004) Biophysical characterization of endotoxin inactivation by NK-2, an antimicrobial peptide derived from mammalian NK-lysin. Antimicrob Agents Chemother 48:1593–1599

    PubMed  Google Scholar 

  110. Mangoni ML, Rinaldi AC, Di Giulio A, Mignogna G, Bozzi A, Barra D, Simmaco M (2000) Structure-function relationships of temporins, small antimicrobial peptides from amphibian skin. Eur J Biochem 267:1447–1454

    PubMed  CAS  Google Scholar 

  111. Makovitzki A, Shai Y (2005) pH-dependent antifungal lipopeptides and their plausible mode of action. Biochemistry 44:9775–9784

    PubMed  CAS  Google Scholar 

  112. Domanov YA, Kinnunen PK (2006) Antimicrobial peptides temporins B and L induce formation of tubular lipid protrusions from supported phospholipid bilayers. Biophys J 91:4427–4439

    PubMed  CAS  Google Scholar 

  113. Mahalka AK, Kinnunen PK (2009) Binding of amphipathic alpha-helical antimicrobial peptides to lipid membranes: lessons from temporins B and L. Biochim Biophys Acta 1788:1600–1609

    PubMed  CAS  Google Scholar 

  114. Turco SJ, Hull SR, Orlandi PA, Shepherd SD, Homans SW, Dwek RA, Rademacher TW (1987) Structure of the major carbohydrate fragment of the Leishmania donovani lipophosphoglycan. Biochemistry 26:6233–6238

    PubMed  CAS  Google Scholar 

  115. McConville MJ, Mullin KA, Ilgoutz SC, Teasdale RD (2002) Secretory pathway of trypanosomatid parasites. Microbiol Mol Biol Rev 66:122–154

    PubMed  CAS  Google Scholar 

  116. Mangoni ML, Saugar JM, Dellisanti M, Barra D, Simmaco M, Rivas L (2005) Temporins, small antimicrobial peptides with leishmanicidal activity. J Biol Chem 280:984–990

    PubMed  CAS  Google Scholar 

  117. Mor A, Hani K, Nicolas P (1994) The vertebrate peptide antibiotics dermaseptins have overlapping structural features but target specific microorganisms. J Biol Chem 269:31635–31641

    PubMed  CAS  Google Scholar 

  118. Mangoni ML, Epand RF, Rosenfeld Y, Peleg A, Barra D, Epand RM, Shai Y (2008) Lipopolysaccharide, a key molecule involved in the synergism between temporins in inhibiting bacterial growth and in endotoxin neutralization. J Biol Chem 283:22907–22917

    PubMed  CAS  Google Scholar 

  119. Giacometti A, Cirioni O, Ghiselli R, Mocchegiani F, Orlando F, Silvestri C, Bozzi A, Di Giulio A, Luzi C, Mangoni ML, Barra D, Saba V, Scalise G, Rinaldi AC (2006) Interaction of antimicrobial peptide temporin L with lipopolysaccharide in vitro and in experimental rat models of septic shock caused by gram-negative bacteria. Antimicrob Agents Chemother 50:2478–2486

    PubMed  CAS  Google Scholar 

  120. Kubo Y, Fukuishi N, Yoshioka M, Kawasoe Y, Iriguchi S, Imajo N, Yasui Y, Matsui N, Akagi M (2007) Bacterial components regulate the expression of Toll-like receptor 4 on human mast cells. Inflamm Res 56:70–75

    PubMed  CAS  Google Scholar 

  121. Gee K, Kozlowski M, Kumar A (2003) Tumor necrosis factor-alpha induces functionally active hyaluronan-adhesive CD44 by activating sialidase through p38 mitogen-activated protein kinase in lipopolysaccharide-stimulated human monocytic cells. J Biol Chem 278:37275–37287

    PubMed  CAS  Google Scholar 

  122. Mukhopadhyay S, Herre J, Brown GD, Gordon S (2004) The potential for Toll-like receptors to collaborate with other innate immune receptors. Immunology 112:521–530

    PubMed  CAS  Google Scholar 

  123. Prins JM, Kuijper EJ, Mevissen ML, Speelman P, van Deventer SJ (1995) Release of tumor necrosis factor alpha and interleukin 6 during antibiotic killing of Escherichia coli in whole blood: influence of antibiotic class, antibiotic concentration, and presence of septic serum. Infect Immun 63:2236–2242

    PubMed  CAS  Google Scholar 

  124. Byl B, Clevenbergh P, Kentos A, Jacobs F, Marchant A, Vincent JL, Thys JP (2001) Ceftazidime and imipenem-induced endotoxin release during treatment of gram-negative infections. Eur J Clin Microbiol Infect Dis 20:804–807

    PubMed  CAS  Google Scholar 

  125. Cohen J (2002) The immunopathogenesis of sepsis. Nature 420:885–891

    PubMed  CAS  Google Scholar 

  126. Angus DC, Wax RS (2001) Epidemiology of sepsis: an update. Crit Care Med 29:S109–S116

    PubMed  CAS  Google Scholar 

  127. Scott MG, Davidson DJ, Gold MR, Bowdish D, Hancock REW (2002) The human antimicrobial peptide LL-37 is a multifunctional modulator of innate immune responses. J Immunol 169:3883–3891

    PubMed  CAS  Google Scholar 

  128. Bommineni YR, Dai H, Gong YX, Soulages JL, Fernando SC, Desilva U, Prakash O, Zhang G (2007) Fowlicidin-3 is an alpha-helical cationic host defense peptide with potent antibacterial and lipopolysaccharide-neutralizing activities. FEBS J 274:418–428

    PubMed  CAS  Google Scholar 

  129. Mookherjee N, Rehaume LM, Hancock RE (2007) Cathelicidins and functional analogues as antisepsis molecules. Expert Opin Ther Targets 11:993–1004

    PubMed  CAS  Google Scholar 

  130. Wright SD, Ramos RA, Tobias PS, Ulevitch RJ, Mathison JC (1990) CD14, a receptor for complexes of lipopolysaccharide (LPS) and LPS binding protein. Science 249:1431–1433

    PubMed  CAS  Google Scholar 

  131. Schumann RR, Leong SR, Flaggs GW, Gray PW, Wright SD, Mathison JC, Tobias PS, Ulevitch RJ (1990) Structure and function of lipopolysaccharide binding protein. Science 249:1429–1431

    PubMed  CAS  Google Scholar 

  132. Tobias PS, Ulevitch RJ (1993) Lipopolysaccharide binding protein and CD14 in LPS dependent macrophage activation. Immunobiology 187:227–232

    PubMed  CAS  Google Scholar 

  133. Poltorak A, He X, Smirnova I, Liu MY, Van Huffel C, Du X, Birdwell D, Alejos E, Silva M, Galanos C, Freudenberg M, Ricciardi-Castagnoli P, Layton B, Beutler B (1998) Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science 282:2085–2088

    PubMed  CAS  Google Scholar 

  134. Chow JC, Young DW, Golenbock DT, Christ WJ, Gusovsky F (1999) Toll-like receptor-4 mediates lipopolysaccharide-induced signal transduction. J Biol Chem 274:10689–10692

    PubMed  CAS  Google Scholar 

  135. Jiang Q, Akashi S, Miyake K, Petty HR (2000) Lipopolysaccharide induces physical proximity between CD14 and toll-like receptor 4 (TLR4) prior to nuclear translocation of NF-kappa B. J Immunol 165:3541–3544

    PubMed  CAS  Google Scholar 

  136. Rosenfeld Y, Lev N, Shai Y (2010) Effect of the hydrophobicity to net positive charge ratio on antibacterial and anti-endotoxin activities of structurally similar antimicrobial peptides. Biochemistry 49:361–853

    Google Scholar 

  137. Uccelletti D, Zanni E, Marcellini L, Palleschi C, Barra D, Mangoni ML (2010) Anti-Pseudomonas activity of frog skin antimicrobial peptides in a Caenorhabditis elegans infection model: a plausible mode of action in vitro and in vivo. Antimicrob Agents Chemother 54:3853–3860

    PubMed  CAS  Google Scholar 

  138. Vallon-Eberhard A, Landsman L, Yogev N, Verrier B, Jung S (2006) Transepithelial pathogen uptake into the small intestinal lamina propria. J Immunol 176:2465–2469

    PubMed  CAS  Google Scholar 

  139. Lopez-Garcia B, Lee PH, Yamasaki K, Gallo RL (2005) Anti-fungal activity of cathelicidins and their potential role in Candida albicans skin infection. J Invest Dermatol 125:108–115

    PubMed  CAS  Google Scholar 

  140. Buentke E, Scheynius A (2003) Dendritic cells and fungi. APMIS 111:789–796

    PubMed  CAS  Google Scholar 

  141. Van Burik JA, Magee PT (2001) Aspects of fungal pathogenesis in humans. Annu Rev Microbiol 55:743–772

    PubMed  Google Scholar 

  142. Netea MG, Brown GD, Kullberg BJ, Gow NA (2008) An integrated model of the recognition of Candida albicans by the innate immune system. Nat Rev Microbiol 6:67–78

    PubMed  CAS  Google Scholar 

  143. Filler SG, Sheppard DC (2006) Fungal invasion of normally non-phagocytic host cells. PLoS Pathog 2:e129

    PubMed  Google Scholar 

  144. Lu Y, Li J, Yu H, Xu X, Liang J, Tian Y, Ma D, Lin G, Huang G, Lai R (2006) Two families of antimicrobial peptides with multiple functions from skin of rufous-spotted torrent frog, Amolops loloensis. Peptides 27:3085–3091

    PubMed  CAS  Google Scholar 

  145. Ali MF, Lips KR, Knoop FC, Fritzsch B, Miller C, Conlon JM (2002) Antimicrobial peptides and protease inhibitors in the skin secretions of the crawfish frog, Rana areolata. Biochim Biophys Acta 1601:55–63

    PubMed  CAS  Google Scholar 

  146. Conlon J (2006) The temporins. In: Kastin AJ (ed) Handbook of biologically active peptides. Elsevier, San Diego, pp 305–309

    Google Scholar 

  147. Conlon JM, Sonnevend A, Patel M, Davidson C, Nielsen PF, Pal T, Rollins-Smith LA (2003) Isolation of peptides of the brevinin-1 family with potent candidacidal activity from the skin secretions of the frog Rana boylii. J Pept Res 62:207–213

    PubMed  CAS  Google Scholar 

  148. Halverson T, Basir YJ, Knoop FC, Conlon JM (2000) Purification and characterization of antimicrobial peptides from the skin of the North American green frog Rana clamitans. Peptides 21:469–476

    PubMed  CAS  Google Scholar 

  149. Ali MF, Knoop FC, Vaudry H, Conlon JM (2003) Characterization of novel antimicrobial peptides from the skins of frogs of the Rana esculenta complex. Peptides 24:955–961

    PubMed  CAS  Google Scholar 

  150. Conlon JM, Al-Kharrge R, Ahmed E, Raza H, Galadari S, Condamine E (2007) Effect of aminoisobutyric acid (Aib) substitutions on the antimicrobial and cytolytic activities of the frog skin peptide, temporin-1DRa. Peptides 28:2075–2080

    PubMed  CAS  Google Scholar 

  151. Kim JB, Halverson T, Basir YJ, Dulka J, Knoop FC, Abel PW, Conlon JM (2000) Purification and characterization of antimicrobial and vasorelaxant peptides from skin extracts and skin secretions of the North American pig frog Rana grylio. Regul Pept 90:53–60

    PubMed  CAS  Google Scholar 

  152. Zhou J, McClean S, Thompson A, Zhang Y, Shaw C, Rao P, Bjourson AJ (2006) Purification and characterization of novel antimicrobial peptides from the skin secretion of Hylarana guentheri. Peptides 27:3077–3084

    PubMed  CAS  Google Scholar 

  153. Conlon JM, Coquet L, Leprince J, Jouenne T, Vaudry H, Kolodziejek J, Nowotny N, Bevier CR, Moler PE (2007) Peptidomic analysis of skin secretions from Rana heckscheri and Rana okaloosae provides insight into phylogenetic relationships among frogs of the Aquarana species group. Regul Pept 138:87–93

    PubMed  CAS  Google Scholar 

  154. Goraya J, Wang Y, Li Z, O’Flaherty M, Knoop FC, Platz JE, Conlon JM (2000) Peptides with antimicrobial activity from four different families isolated from the skins of the North American frogs Rana luteiventris, Rana berlandieri and Rana pipiens. Eur J Biochem 267:894–900

    PubMed  CAS  Google Scholar 

  155. Rollins-Smith LA, Doersam JK, Longcore JE, Taylor SK, Shamblin JC, Carey C, Zasloff M (2002) Antimicrobial peptide defenses against pathogens associated with global amphibian declines. Dev Comp Immunol 26:63–72

    PubMed  CAS  Google Scholar 

  156. Kim JB, Iwamuro S, Knoop FC, Conlon JM (2001) Antimicrobial peptides from the skin of the Japanese mountain brown frog, Rana ornativentris. J Pept Res 58:349–356

    PubMed  CAS  Google Scholar 

  157. Bevier CR, Sonnevend A, Kolodziejek J, Nowotny N, Nielsen PF, Conlon JM (2004) Purification and characterization of antimicrobial peptides from the skin secretions of the mink frog (Rana septentrionalis). Comp Biochem Physiol C Toxicol Pharmacol 139:31–38

    PubMed  Google Scholar 

  158. Conlon JM, Sonnevend A, Patel M, Camasamudram V, Nowotny N, Zilahi E, Iwamuro S, Nielsen PF, Pal T (2003) A melittin-related peptide from the skin of the Japanese frog, Rana tagoi, with antimicrobial and cytolytic properties. Biochem Biophys Res Commun 306:496–500

    PubMed  CAS  Google Scholar 

  159. Conlon JM, Abraham B, Sonnevend A, Jouenne T, Cosette P, Leprince J, Vaudry H, Bevier CR (2005) Purification and characterization of antimicrobial peptides from the skin secretions of the carpenter frog Rana virgatipes (Ranidae, Aquarana). Regul Pept 131:38–45

    PubMed  CAS  Google Scholar 

  160. Chen T, Zhou M, Rao P, Walker B, Shaw C (2006) The Chinese bamboo leaf odorous frog (Rana (Odorrana) versabilis) and North American Rana frogs share the same families of skin antimicrobial peptides. Peptides 27:1738–1744

    PubMed  CAS  Google Scholar 

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Acknowledgments

This study was supported by grants from La Sapienza University of Rome and the Italian Ministero dell’Istruzione, Università e Ricerca (PRIN 2008) and partially by the German Israel Foudation to Y.S. We thank Christopher Angusch for his comments and editing the manuscript.

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  1. Istituto Pasteur-Fondazione Cenci Bolognetti, La Sapienza University of Rome, 00185, Rome, Italy

    Maria Luisa Mangoni

  2. Department of Biological Chemistry, The Weizmann Institute of Science, 76100, Rehovot, Israel

    Yechiel Shai

  3. Dipartimento di Scienze Biochimiche “A. Rossi Fanelli”, Università La Sapienza, Piazzale Aldo Moro 5, 00185, Rome, Italy

    Maria Luisa Mangoni

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  1. Maria Luisa Mangoni
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  2. Yechiel Shai
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Correspondence to Maria Luisa Mangoni.

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Mangoni, M.L., Shai, Y. Short native antimicrobial peptides and engineered ultrashort lipopeptides: similarities and differences in cell specificities and modes of action. Cell. Mol. Life Sci. 68, 2267–2280 (2011). https://doi.org/10.1007/s00018-011-0718-2

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  • DOI: https://doi.org/10.1007/s00018-011-0718-2

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