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Antimicrobial Peptides: An Introduction

  • Evan F. Haney
  • Sarah C. Mansour
  • Robert E. W. Hancock
Part of the Methods in Molecular Biology book series (MIMB, volume 1548)

Abstract

The “golden era” of antibiotic discovery has long passed, but the need for new antibiotics has never been greater due to the emerging threat of antibiotic resistance. This urgency to develop new antibiotics has motivated researchers to find new methods to combat pathogenic microorganisms resulting in a surge of research focused around antimicrobial peptides (AMPs; also termed host defense peptides) and their potential as therapeutics. During the past few decades, more than 2000 AMPs have been identified from a diverse range of organisms (animals, fungi, plants, and bacteria). While these AMPs share a number of common features and a limited number of structural motifs; their sequences, activities, and targets differ considerably. In addition to their antimicrobial effects, AMPs can also exhibit immunomodulatory, anti-biofilm, and anticancer activities. These diverse functions have spurred tremendous interest in research aimed at understanding the activity of AMPs, and various protocols have been described to assess different aspects of AMP function including screening and evaluating the activities of natural and synthetic AMPs, measuring interactions with membranes, optimizing peptide function, and scaling up peptide production. Here, we provide a general overview of AMPs and introduce some of the methodologies that have been used to advance AMP research.

Key words

Antimicrobial peptides Host defense peptides Immunomodulatory function Antibiofilm activity 

Notes

Acknowledgments

The authors acknowledge all the members of the Hancock Lab (both past and present) for their valuable input and discussions regarding antimicrobial, antibiofilm, and immunomodulatory peptides. This work was supported by the Canadian Institutes of Health Research [funding reference number MOP-74493]. REWH holds a Canada Research Chair.

References

  1. 1.
    Steiner H, Hultmark D, Engström Å et al (1981) Sequence and specificity of two antibacterial proteins involved in insect immunity. Nature 292:246–248PubMedCrossRefGoogle Scholar
  2. 2.
    Zasloff M (1987) Magainins, A class of antimicrobial peptides from xenopus skin - isolation, characterization of 2 active forms, and partial cDNA sequence of a precursor. Proc Natl Acad Sci 84:5449–5453PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Zasloff M (2002) Antimicrobial peptides of multicellular organisms. Nature 415:389–395PubMedCrossRefGoogle Scholar
  4. 4.
    Mookherjee N, Hancock REW (2007) Cationic host defence peptides: innate immune regulatory peptides as a novel approach for treating infections. Cell Mol Life Sci 64:922–933PubMedCrossRefGoogle Scholar
  5. 5.
    Hancock REW, Scott MG (2000) The role of antimicrobial peptides in animal defenses. Proc Natl Acad Sci 97:8856–8861PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Lai JR, Huck BR, Weisblum B, Gellman SH (2002) Design of non-cysteine-containing antimicrobial β-hairpins: structure–activity relationship studies with linear protegrin-1 analogues. Biochemistry 41:12835–12842PubMedCrossRefGoogle Scholar
  7. 7.
    Gallo RL, Hooper LV (2012) Epithelial antimicrobial defence of the skin and intestine. Nat Rev Immunol 12:503–516PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Faurschou M, Borregaard N (2003) Neutrophil granules and secretory vesicles in inflammation. Microbes Infect 5:1317–1327PubMedCrossRefGoogle Scholar
  9. 9.
    Jenssen H, Hamill P, Hancock REW (2006) Peptide antimicrobial agents. Clin Microbiol Rev 19:491–511PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Phoenix DA, Dennison SR, Harris F (2013) Anionic antimicrobial peptides. In: Antimicrobial peptides. Wiley-VCH, GmbH & Co. KGaA, pp 83–113CrossRefGoogle Scholar
  11. 11.
    Hancock REW, Sahl HG (2006) Antimicrobial and host-defense peptides as new anti-infective therapeutic strategies. Nat Biotechnol 24:1551–1557PubMedCrossRefGoogle Scholar
  12. 12.
    Nguyen LT, Haney EF, Vogel HJ (2011) The expanding scope of antimicrobial peptide structures and their modes of action. Trends Biotechnol 29:464–472PubMedCrossRefGoogle Scholar
  13. 13.
    Waghu FH, Barai RS, Gurung P, Idicula-Thomas S (2015) CAMPR3: a database on sequences, structures and signatures of antimicrobial peptides. Nucleic Acids Res 44:D1094–D1097PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Piotto SP, Sessa L, Concilio S, Iannelli P (2012) YADAMP: yet another database of antimicrobial peptides. Int J Antimicrob Agents 39:346–351PubMedCrossRefGoogle Scholar
  15. 15.
    Hammami R, Hamida JB, Vergoten G, Fliss I (2009) PhytAMP: a database dedicated to antimicrobial plant peptides. Nucleic Acids Res 37:D963–D968PubMedCrossRefGoogle Scholar
  16. 16.
    Wang Z, Wang G (2004) APD: the antimicrobial peptide database. Nucleic Acids Res 32:D590–D592PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Wang G, Li X, Wang Z (2015) APD3: the antimicrobial peptide database as a tool for research and education. Nucleic Acids Res 44:D1087–D1093PubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    Skalickova S, Heger Z, Krejcova L et al (2015) Perspective of use of antiviral peptides against influenza virus. Viruses 7:5428–5442PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Hoskin DW, Ramamoorthy A (2008) Studies on anticancer activities of antimicrobial peptides. Biochim Biophys Acta 1778:357–375PubMedCrossRefGoogle Scholar
  20. 20.
    de la Fuente-Núñez C, Cardoso MH, de Souza Cândido E et al (2016) Synthetic antibiofilm peptides. Biochim Biophys Acta 1858:1061–1069PubMedCrossRefGoogle Scholar
  21. 21.
    Mansour SC, Pena OM, Hancock REW (2014) Host defense peptides: front-line immunomodulators. Trends Immunol 35:443–450PubMedCrossRefGoogle Scholar
  22. 22.
    Hilchie AL, Wuerth K, Hancock REW (2013) Immune modulation by multifaceted cationic host defense (antimicrobial) peptides. Nat Chem Biol 9:761–768PubMedCrossRefGoogle Scholar
  23. 23.
    Mor A, Nguyen VH, Delfour A et al (1991) Isolation, amino acid sequence and synthesis of dermaseptin, a novel antimicrobial peptide of amphibian skin. Biochemistry (Mosc) 30:8824–8830CrossRefGoogle Scholar
  24. 24.
    Durr UHN, Sudheendra US, Ramamoorthy A (2006) LL-37, the only human member of the cathelicidin family of antimicrobial peptides. Biochim Biophys Acta 1758:1408–1425PubMedCrossRefGoogle Scholar
  25. 25.
    Sørensen OE, Follin P, Johnsen AH et al (2001) Human cathelicidin, hCAP-18, is processed to the antimicrobial peptide LL-37 by extracellular cleavage with proteinase 3. Blood 97:3951–3959PubMedCrossRefGoogle Scholar
  26. 26.
    Sørensen OE, Gram L, Johnsen AH et al (2003) Processing of seminal plasma hCAP-18 to ALL-38 by gastricsin: a novel mechanism of generating antimicrobial peptides in vagina. J Biol Chem 278:28540–28546PubMedCrossRefGoogle Scholar
  27. 27.
    Murakami M, Lopez-Garcia B, Braff M et al (2004) Postsecretory processing generates multiple cathelicidins for enhanced topical antimicrobial defense. J Immunol 172:3070–3077PubMedCrossRefGoogle Scholar
  28. 28.
    Behrendt R, White P, Offer J (2016) Advances in Fmoc solid-phase peptide synthesis. J Pept Sci 22:4–27PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Knappe D, Piantavigna S, Hansen A et al (2010) Oncocin (VDKPPYLPRPRPPRRIYNR-NH2): a novel antibacterial peptide optimized against gram-negative human pathogens. J Med Chem 53:5240–5247PubMedCrossRefGoogle Scholar
  30. 30.
    de la Fuente-Núñez C, Reffuveille F, Mansour SC et al (2015) D-enantiomeric peptides that eradicate wild-type and multidrug-resistant biofilms and protect against lethal Pseudomonas aeruginosa infections. Chem Biol 22:196–205PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Jahnsen RD, Frimodt-Moller N, Franzyk H (2012) Antimicrobial activity of peptidomimetics against multidrug-resistant Escherichia coli: a comparative study of different backbones. J Med Chem 55:7253–7261PubMedCrossRefGoogle Scholar
  32. 32.
    Hilchie AL, Haney EF, Pinto DM et al (2015) Enhanced killing of breast cancer cells by a d-amino acid analog of the winter flounder-derived pleurocidin NRC-03. Exp Mol Pathol 99:426–434PubMedCrossRefGoogle Scholar
  33. 33.
    Bommarius B, Jenssen H, Elliott M et al (2010) Cost-effective expression and purification of antimicrobial and host defense peptides in Escherichia coli. Peptides 31:1957–1965PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Arias M, Hoffarth ER, Ishida H et al (2016) Recombinant expression, antimicrobial activity and mechanism of action of tritrpticin analogs containing fluoro-tryptophan residues. Biochim Biophys Acta 1858:1012PubMedCrossRefGoogle Scholar
  35. 35.
    Panteleev PV, Ovchinnikova TV (2015) Improved strategy for recombinant production and purification of antimicrobial peptide tachyplesin I and its analogs with high cell selectivity. Biotechnol Appl Biochem. doi:  10.1002/bab.1456
  36. 36.
    Li Y, Wang J, Yang J et al (2014) Recombinant expression, purification and characterization of antimicrobial peptide ORBK in Escherichia coli. Protein Expr Purif 95:182–187PubMedCrossRefGoogle Scholar
  37. 37.
    Mulder KC, de Lima LA, Aguiar PS et al (2015) Production of a modified peptide clavanin in Pichia pastoris: cloning, expression, purification and in vitro activities. AMB Express 5:46PubMedCentralCrossRefGoogle Scholar
  38. 38.
    Bellamy W, Takase M, Yamauchi K et al (1992) Identification of the bactericidal domain of lactoferrin. Biochim Biophys Acta 1121:130–136PubMedCrossRefGoogle Scholar
  39. 39.
    Théolier J, Hammami R, Labelle P et al (2013) Isolation and identification of antimicrobial peptides derived by peptic cleavage of whey protein isolate. J Funct Foods 5:706–714CrossRefGoogle Scholar
  40. 40.
    van der Kraan MIA, Nazmi K, Teeken A et al (2005) Lactoferrampin, an antimicrobial peptide of bovine lactoferrin, exerts its candidacidal activity by a cluster of positively charged residues at the C-terminus in combination with a helix-facilitating N-terminal part. Biol Chem 386:137–142PubMedGoogle Scholar
  41. 41.
    Jing W, Demcoe AR, Vogel HJ (2003) Conformation of a bactericidal domain of puroindoline a: structure and mechanism of action of a 13-residue antimicrobial peptide. J Bacteriol 185:4938–4947PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Ibrahim HR, Thomas U, Pellegrini A (2001) A helix-loop-helix peptide at the upper lip of the active site cleft of lysozyme confers potent antimicrobial activity with membrane permeabilization action. J Biol Chem 276:43767–43774PubMedCrossRefGoogle Scholar
  43. 43.
    Haney EF, Nguyen LT, Schibli DJ, Vogel HJ (2012) Design of a novel tryptophan-rich membrane-active antimicrobial peptide from the membrane-proximal region of the HIV glycoprotein, gp41. Beilstein J Org Chem 8:1172–1184PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    Haney EF, Hancock REW (2013) Peptide design for antimicrobial and immunomodulatory applications. Biopolymers 100:572–583PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Fjell CD, Hiss JA, Hancock REW, Schneider G (2012) Designing antimicrobial peptides: form follows function. Nat Rev Drug Discov 11:37–51Google Scholar
  46. 46.
    Xu L, Chou S, Wang J et al (2015) Antimicrobial activity and membrane-active mechanism of tryptophan zipper-like β-hairpin antimicrobial peptides. Amino Acids 47:2385–2397PubMedCrossRefGoogle Scholar
  47. 47.
    Henriksen JR, Etzerodt T, Gjetting T, Andresen TL (2014) Side chain hydrophobicity modulates therapeutic activity and membrane selectivity of antimicrobial peptide mastoparan-X. PLoS One 9:e91007PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Hilpert K, Winkler DF, Hancock REW (2007) Peptide arrays on cellulose support: SPOT synthesis, a time and cost efficient method for synthesis of large numbers of peptides in a parallel and addressable fashion. Nat Protoc 2:1333–1349PubMedCrossRefGoogle Scholar
  49. 49.
    Winkler DF, Hilpert K, Brandt O, Hancock REW (2009) Synthesis of peptide arrays using SPOT-technology and the CelluSpots-method. Methods Mol Biol 570:157–174PubMedCrossRefGoogle Scholar
  50. 50.
    Hilpert K, Volkmer-Engert R, Walter T, Hancock REW (2005) High-throughput generation of small antibacterial peptides with improved activity. Nat Biotechnol 23:1008–1012PubMedCrossRefGoogle Scholar
  51. 51.
    Cherkasov A, Hilpert K, Jenssen H et al (2009) Use of artificial intelligence in the design of small peptide antibiotics effective against a broad spectrum of highly antibiotic-resistant superbugs. ACS Chem Biol 4:65–74PubMedCrossRefGoogle Scholar
  52. 52.
    Powers JPS, Hancock REW (2003) The relationship between peptide structure and antibacterial activity. Peptides 24:1681–1691PubMedCrossRefGoogle Scholar
  53. 53.
    Taylor K, Barran PE, Dorin JR (2008) Structure–activity relationships in β-defensin peptides. J Pept Sci 90:1–7CrossRefGoogle Scholar
  54. 54.
    Avitabile C, D’Andrea LD, Romanelli A (2014) Circular Dichroism studies on the interactions of antimicrobial peptides with bacterial cells. Sci Rep 4:4293PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Bürck J, Wadhwani P, Fanghänel S, Ulrich AS (2016) Oriented circular dichroism: a method to characterize membrane-active peptides in oriented lipid bilayers. Acc Chem Res 49:184–192PubMedCrossRefGoogle Scholar
  56. 56.
    Haney EF, Vogel HJ (2009) NMR of antimicrobial peptides. Ann Rep NMR Spectrosc 65:1–51CrossRefGoogle Scholar
  57. 57.
    Bhunia A, Domadia PN, Torres J et al (2010) NMR structure of pardaxin, a pore-forming antimicrobial peptide, in lipopolysaccharide micelles: mechanism of outer membrane permeabilization. J Biol Chem 285:3883–3895PubMedCrossRefGoogle Scholar
  58. 58.
    Peschel A, Sahl H-G (2006) The co-evolution of host cationic antimicrobial peptides and microbial resistance. Nat Rev Microbiol 4:529–536PubMedCrossRefGoogle Scholar
  59. 59.
    Brogden KA (2005) Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria? Nat Rev Microbiol 3:238–250PubMedCrossRefGoogle Scholar
  60. 60.
    Yang L, Harroun TA, Weiss TM et al (2001) Barrel-Stave model or Toroidal model? A case study on melittin pores. Biophys J 81:1475–1485PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Laver DR (1994) The barrel-stave model as applied to alamethicin and its analogs reevaluated. Biophys J 66:355–359PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Leontiadou H, Mark AE, Marrink SJ (2006) Antimicrobial peptides in action. J Am Chem Soc 128:12156–12161PubMedCrossRefGoogle Scholar
  63. 63.
    Sengupta D, Leontiadou H, Mark AE, Marrink S-J (2008) Toroidal pores formed by antimicrobial peptides show significant disorder. Biochim Biophys Acta 1778:2308–2317PubMedCrossRefGoogle Scholar
  64. 64.
    Wu M, Maier E, Benz R, Hancock REW (1999) Mechanism of interaction of different classes of cationic antimicrobial peptides with planar bilayers and with the cytoplasmic membrane of Escherichia coli. Biochemistry 38:7235–7242PubMedCrossRefGoogle Scholar
  65. 65.
    Oren Z, Shai Y (1997) Selective lysis of bacteria but not mammalian cells by diastereomers of melittin: structure-function study. Biochemistry (Mosc) 36:1826–1835CrossRefGoogle Scholar
  66. 66.
    Gaspar D, Veiga AS, Castanho MARB (2013) From antimicrobial to anticancer peptides. A review. Antimicrob Resist Chemother 4:294Google Scholar
  67. 67.
    Gazit E, Miller IR, Biggin PC et al (1996) Structure and orientation of the mammalian antibacterial peptide cecropin P1 within phospholipid membranes. J Mol Biol 258:860–870PubMedCrossRefGoogle Scholar
  68. 68.
    Hong RW, Shchepetov M, Weiser JN, Axelsen PH (2003) Transcriptional profile of the Escherichia coli response to the antimicrobial insect peptide cecropin A. Antimicrob Agents Chemother 47:1–6PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Park CB, Yi KS, Matsuzaki K et al (2000) 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 97:8245–8250PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Zhang X, Wang Y, Liu L et al (2016) Two-peptide bacteriocin PlnEF causes cell membrane damage to Lactobacillus plantarum. Biochim Biophys Acta 1858:274–280PubMedCrossRefGoogle Scholar
  71. 71.
    Mularski A, Wilksch JJ, Wang H et al (2015) Atomic force microscopy reveals the mechanobiology of lytic peptide action on bacteria. Langmuir ACS J Surf Colloids 31:6164–6171CrossRefGoogle Scholar
  72. 72.
    Martin NI, Breukink E (2007) Expanding role of lipid II as a target for lantibiotics. Future Microbiol 2:513–525PubMedCrossRefGoogle Scholar
  73. 73.
    Bierbaum G, Sahl HG (1985) Induction of autolysis of staphylococci by the basic peptide antibiotics Pep 5 and nisin and their influence on the activity of autolytic enzymes. Arch Microbiol 141:249–254PubMedCrossRefGoogle Scholar
  74. 74.
    Milletti F (2012) Cell-penetrating peptides: classes, origin, and current landscape. Drug Discov Today 17:850–860PubMedCrossRefGoogle Scholar
  75. 75.
    Guilhelmelli F, Vilela N, Albuquerque P et al (2013) Antibiotic development challenges: the various mechanisms of action of antimicrobial peptides and of bacterial resistance. Front Microbiol 4:353PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Patrzykat A, Friedrich CL, Zhang L et al (2002) Sublethal concentrations of pleurocidin-derived antimicrobial peptides inhibit macromolecular synthesis in Escherichia coli. Antimicrob Agents Chemother 46:605–614PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Park CB, Kim HS, Kim SC (1998) 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 244:253–257PubMedCrossRefGoogle Scholar
  78. 78.
    Haney EF, Petersen AP, Lau CK et al (2013) Mechanism of action of puroindoline derived tryptophan-rich antimicrobial peptides. Biochim Biophys Acta 1828:1802–1813PubMedCrossRefGoogle Scholar
  79. 79.
    Friedrich CL, Moyles D, Beveridge TJ, Hancock REW (2000) Antibacterial action of structurally diverse cationic peptides on gram-positive bacteria. Antimicrob Agents Chemother 44:2086–2092PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Wiegand I, Hilpert K, Hancock RE (2008) Agar and broth dilution methods to determine the minimal inhibitory concentration (MIC) of antimicrobial substances. Nat Protoc 3:163–175PubMedCrossRefGoogle Scholar
  81. 81.
    Balouiri M, Sadiki M, Ibnsouda SK (2016) Methods for in vitro evaluating antimicrobial activity: a review. J Pharm Anal 6:71–79CrossRefGoogle Scholar
  82. 82.
    Vojtek L, Dobes P, Büyükgüzel E et al (2014) Bioluminescent assay for evaluating antimicrobial activity in insect haemolymph. Eur J Entomol 111:335–340CrossRefGoogle Scholar
  83. 83.
    Riccardi C, Nicoletti I (2006) Analysis of apoptosis by propidium iodide staining and flow cytometry. Nat Protoc 1:1458–1461PubMedCrossRefGoogle Scholar
  84. 84.
    Bowdish DM, Davidson DJ, Lau YE et al (2005) Impact of LL-37 on anti-infective immunity. J Leukoc Biol 77:451–459PubMedCrossRefGoogle Scholar
  85. 85.
    Lopez D, Vlamakis H, Kolter R (2010) Biofilms. Cold Spring Harb Perspect Biol 2:a000398PubMedPubMedCentralCrossRefGoogle Scholar
  86. 86.
    de la Fuente-Núñez C, Reffuveille F, Fernández L, Hancock RE (2013) Bacterial biofilm development as a multicellular adaptation: antibiotic resistance and new therapeutic strategies. Curr Opin Microbiol 16:580–589PubMedCrossRefGoogle Scholar
  87. 87.
    Overhage J, Campisano A, Bains M et al (2008) Human host defense peptide LL-37 prevents bacterial biofilm formation. Infect Immun 76:4176–4182PubMedPubMedCentralCrossRefGoogle Scholar
  88. 88.
    Haney EF, Mansour SC, Hilchie AL et al (2015) High throughput screening methods for assessing antibiofilm and immunomodulatory activities of synthetic peptides. Peptides 71:276–285PubMedPubMedCentralCrossRefGoogle Scholar
  89. 89.
    de la Fuente-Núñez C, Reffuveille F, Haney EF et al (2014) Broad-spectrum anti-biofilm peptide that targets a cellular stress response. PLoS Pathog 10:e1004152PubMedPubMedCentralCrossRefGoogle Scholar
  90. 90.
    Wang G, Hanke ML, Mishra B et al (2014) Transformation of human cathelicidin LL-37 into selective, stable, and potent antimicrobial compounds. ACS Chem Biol 9:1997–2002PubMedPubMedCentralCrossRefGoogle Scholar
  91. 91.
    Reffuveille F, de la Fuente-Núñez C, Mansour S, Hancock REW (2014) A broad-spectrum anti-biofilm peptide enhances antibiotic action against bacterial biofilms. Antimicrob Agents Chemother 58:5363–5371PubMedPubMedCentralCrossRefGoogle Scholar
  92. 92.
    Lebeaux D, Chauhan A, Rendueles O, Beloin C (2013) From in vitro to in vivo models of bacterial biofilm-related infections. Pathogens 2:288–356PubMedPubMedCentralCrossRefGoogle Scholar
  93. 93.
    Ceri H, Olson ME, Stremick C et al (1999) The calgary biofilm device: new technology for rapid determination of antibiotic susceptibilities of bacterial biofilms. J Clin Microbiol 37:1771–1776PubMedPubMedCentralGoogle Scholar
  94. 94.
    Olivares E, Badel-Berchoux S, Provot C et al (2016) The Biofilm Ring Test®: a rapid method for the routine analysis of P. aeruginosa biofilm formation kinetics. J Clin Microbiol 54:657PubMedPubMedCentralCrossRefGoogle Scholar
  95. 95.
    Merritt JH, Kadouri DE, O’Toole GA (2005) Growing and analyzing static biofilms. Curr Protoc Microbiol 22:1B11–1B118Google Scholar
  96. 96.
    Scott MG, Dullaghan E, Mookherjee N et al (2007) An anti-infective peptide that selectively modulates the innate immune response. Nat Biotechnol 25:465–472PubMedCrossRefGoogle Scholar
  97. 97.
    Yang D, Chertov O, Oppenheim JJ (2001) Participation of mammalian defensins and cathelicidins in anti-microbial immunity: receptors and activities of human defensins and cathelicidin (LL-37). J Leukoc Biol 69:691–697PubMedGoogle Scholar
  98. 98.
    Tjabringa GS, Ninaber DK, Drijfhout JW et al (2006) Human cathelicidin LL-37 is a chemoattractant for eosinophils and neutrophils that acts via formyl-peptide receptors. Int Arch Allergy Immunol 140:103–111PubMedCrossRefGoogle Scholar
  99. 99.
    Scott MG, Vreugdenhil ACE, Buurman WA et al (2000) Cutting edge: cationic antimicrobial peptides block the binding of lipopolysaccharide (LPS) to LPS binding protein. J Immunol 164:549–553PubMedCrossRefGoogle Scholar
  100. 100.
    Steinstraesser L, Hirsch T, Schulte M et al (2012) Innate defense regulator peptide 1018 in wound healing and wound infection. PLoS One 7:e39373PubMedPubMedCentralCrossRefGoogle Scholar
  101. 101.
    Heilborn JD, Nilsson MF, Kratz G et al (2003) The cathelicidin anti-microbial peptide LL-37 is involved in re-epithelialization of human skin wounds and is lacking in chronic ulcer epithelium. J Invest Dermatol 120:379–389PubMedCrossRefGoogle Scholar
  102. 102.
    van der Does AM, Joosten SA, Vroomans E et al (2012) The antimicrobial peptide hLF1-11 drives monocyte-dendritic cell differentiation toward dendritic cells that promote antifungal responses and enhance Th17 polarization. J Innate Immun 4:284–292PubMedCrossRefGoogle Scholar
  103. 103.
    Davidson DJ, Currie AJ, Reid GS et al (2004) The cationic antimicrobial peptide LL-37 modulates dendritic cell differentiation and dendritic cell-induced T cell polarization. J Immunol 172:1146–1156PubMedCrossRefGoogle Scholar
  104. 104.
    Mansour SC, de la Fuente-Núñez C, Hancock REW (2015) Peptide IDR-1018: modulating the immune system and targeting bacterial biofilms to treat antibiotic-resistant bacterial infections. J Pept Sci 21:323–329PubMedCrossRefGoogle Scholar
  105. 105.
    Chen H-C (2005) Boyden chamber assay. Methods Mol Biol 294:15–22PubMedGoogle Scholar
  106. 106.
    Bowdish DME, Davidson DJ, Scott MG, Hancock REW (2005) Immunomodulatory activities of small host defense peptides. Antimicrob Agents Chemother 49:1727–1732PubMedPubMedCentralCrossRefGoogle Scholar
  107. 107.
    Hancock REW (2016) Bioinformatics: novel insights from genomic information. Nestlé Nutr Inst Workshop Ser 84:35–46PubMedGoogle Scholar
  108. 108.
    Kozłowska K, Nowak J, Kwiatkowski B, Cichorek M (1999) ESR study of plasmatic membrane of the transplantable melanoma cells in relation to their biological properties. Exp Toxicol Pathol 51:89–92PubMedCrossRefGoogle Scholar
  109. 109.
    Eisenberg D, Terwilliger TC, Tsui F (1980) Structural studies of bee melittin. Biophys J 32:252–254PubMedPubMedCentralCrossRefGoogle Scholar
  110. 110.
    Lichtenstein A, Ganz T, Selsted ME, Lehrer RI (1986) In vitro tumor cell cytolysis mediated by peptide defensins of human and rabbit granulocytes. Blood 68:1407–1410PubMedGoogle Scholar
  111. 111.
    Riss TL, Moravec RA, Niles AL et al (2004) Cell viability assays. Assay Guidance Manual. Available from http://www.ncbi.nlm.nih.gov/books/NBK144065/
  112. 112.
    Smith SM, Wunder MB, Norris DA, Shellman YG (2011) A simple protocol for using a LDH-based cytotoxicity assay to assess the effects of death and growth inhibition at the same time. PLoS One 6:e26908PubMedPubMedCentralCrossRefGoogle Scholar
  113. 113.
    Mai JC, Mi Z, Kim S-H et al (2001) A proapoptotic peptide for the treatment of solid tumors. Cancer Res 61:7709–7712PubMedGoogle Scholar
  114. 114.
    Wang G (2008) Structures of human host defense cathelicidin LL-37 and its smallest antimicrobial peptide KR-12 in lipid micelles. J Biol Chem 283:32637–32643PubMedCrossRefGoogle Scholar
  115. 115.
    Hwang PM, Zhou N, Shan X et al (1998) Three-dimensional solution structure of lactoferricin B, an antimicrobial peptide derived from bovine lactoferrin. Biochemistry 37:4288–4298PubMedCrossRefGoogle Scholar
  116. 116.
    Rozek A, Friedrich CL, Hancock REW (2000) Structure of the bovine antimicrobial peptide indolicidin bound to dodecylphosphocholine and sodium dodecyl sulfate micelles. Biochemistry 39:15765–15774PubMedCrossRefGoogle Scholar
  117. 117.
    Sawai MV, Jia HP, Liu LD et al (2001) The NMR structure of human beta-defensin-2 reveals a novel alpha-helical segment. Biochemistry 40:3810–3816PubMedCrossRefGoogle Scholar
  118. 118.
    Pettersen EF, Goddard TD, Huang CC et al (2004) UCSF Chimera--a visualization system for exploratory research and analysis. J Comput Chem 25:1605–1612PubMedCrossRefGoogle Scholar
  119. 119.
    Gesell J, Zasloff M, Opella SJ (1997) Two-dimensional H-1 NMR experiments show that the 23-residue magainin antibiotic peptide is an alpha-helix in dodecylphosphocholine micelles, sodium dodecylsulfate micelles, and trifluoroethanol/water solution. J Biomol NMR 9:127–135PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media LLC 2017

Authors and Affiliations

  • Evan F. Haney
    • 1
  • Sarah C. Mansour
    • 1
  • Robert E. W. Hancock
    • 1
  1. 1.Department of Microbiology and Immunology, Center for Microbial Diseases and Immunity ResearchUniversity of British ColumbiaVancouverCanada

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