How to Teach Old Antibiotics New Tricks

  • Stephanie Deshayes
  • Michelle W. Lee
  • Nathan W. Schmidt
  • Wujing Xian
  • Andrea Kasko
  • Gerard C. L. Wong


Antimicrobial peptides (AMPs), or more generally host defense peptides, have broad-spectrum antimicrobial activity and use nonspecific interactions to target generic features common to the membranes of many pathogens. As a result, development of resistance to such natural defenses is inhibited compared to conventional antibiotics. The disadvantage of AMPs, however, is that they are often not very potent. In contrast, traditional antibiotics typically have strong potency, but due to a broad range of bacterial defense mechanisms, there are many examples of resistance. Here, we explore the possibility of combining these two classes of molecules. In the first half of this chapter, we review the fundamentals of membrane curvature generation and the various strategies recently used to mimic this membrane activity of AMPs using different classes of synthetic molecules. In the second half, we show that it is possible to impart membrane activity to molecules with no previous membrane activity, and summarize some of our recent works which aim to combine advantages of traditional antibiotics and AMPs into a single molecule with multiple mechanisms of killing as well as multiple mechanisms of specificity.


Minimum Inhibitory Concentration Hemolytic Activity Bacterial Membrane Cationic Amino Acid Membrane Curvature 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Achermann Y, Goldstein EJ, Coenye T, Shirtliff ME (2014) Propionibacterium acnes: from commensal to opportunistic biofilm-associated implant pathogen. Clin Microbiol Rev 27(3):419–440PubMedPubMedCentralCrossRefGoogle Scholar
  2. Agerberth B, Lee J-Y, Bergman T, Carlquist M, Boman HG, Mutt V, Jörnvall H (1991) Amino acid sequence of pr-39. Eur J Biochem 202(3):849–854PubMedCrossRefGoogle Scholar
  3. Allison KR, Brynildsen MP, Collins JJ (2011) Metabolite-enabled eradication of bacterial persisters by aminoglycosides. Nature 473(7346):216–220PubMedPubMedCentralCrossRefGoogle Scholar
  4. Altay E, Yapaöz MA, Keskin B, Yucesan G, Eren T (2015) Influence of alkyl chain length on the surface activity of antibacterial polymers derived from romp. Colloids Surf B 127:73–78CrossRefGoogle Scholar
  5. Anguita-Alonso P, Hanssen A, Osmon D, Trampuz A, Steckelberg J, Patel R (2005) High rate of aminoglycoside resistance among staphylococci causing prosthetic joint infection. Clin Orthop Relat Res 439:43–47PubMedCrossRefGoogle Scholar
  6. Asensio JL, Hidalgo A, Bastida A, Torrado M, Corzana F, Chiara JL, Garcia-Junceda E, Canada J, Jimenez-Barbero J (2005) A simple structural-based approach to prevent aminoglycoside inactivation by bacterial defense proteins. Conformational restriction provides effective protection against neomycin-b nucleotidylation by ant4. J Am Chem Soc 127(23):8278–8279PubMedCrossRefGoogle Scholar
  7. Balaban NQ, Merrin J, Chait R, Kowalik L, Leibler S (2004) Bacterial persistence as a phenotypic switch. Science 305(5690):1622–1625PubMedCrossRefGoogle Scholar
  8. Baumgart T, Capraro BR, Zhu C, Das SL (2011) Thermodynamics and mechanics of membrane curvature generation and sensing by proteins and lipids. Annu Rev Phys Chem 62(1):483–506PubMedPubMedCentralCrossRefGoogle Scholar
  9. Bechinger B (2009) Rationalizing the membrane interactions of cationic amphipathic antimicrobial peptides by their molecular shape. Curr Opin Colloid Interface Sci 14(5):349–355CrossRefGoogle Scholar
  10. Bechinger B, Kim Y, Chirlian LE, Gesell J, Neumann JM, Montal M, Tomich J, Zasloff M, Opella SJ (1991) Orientations of amphipathic helical peptides in membrane bilayers determined by solid-state nmr spectroscopy. J Biomol NMR 1(2):167–173PubMedCrossRefGoogle Scholar
  11. Bigger J (1944) Treatment of staphylococcal infections with penicillin by intermittent sterilisation. Lancet 244(6320):497–500CrossRefGoogle Scholar
  12. Bowdish DME, Davidson DJ, Hancock REW (2005) A re-evaluation of the role of host defence peptides in mammalian immunity. Curr Protein Pept Sci 6(1):35–51PubMedCrossRefGoogle Scholar
  13. Brogden KA (2005a) Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria? Nat Rev Micro 3(3):238–250CrossRefGoogle Scholar
  14. Brogden KA (2005b) Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria? Nat Rev Microbiol 3(3):238–250PubMedCrossRefGoogle Scholar
  15. Brouwer CPJM, Rahman M, Welling MM (2011) Discovery and development of a synthetic peptide derived from lactoferrin for clinical use. Peptides 32(9):1953–1963PubMedCrossRefGoogle Scholar
  16. Bryan L, Kowand S, Van Den Elzen H (1979) Mechanism of aminoglycoside antibiotic resistance in anaerobic bacteria: clostridium perfringens and bacteroides fragilis. Antimicrob Agents Chemother 15(1):7–13PubMedPubMedCentralCrossRefGoogle Scholar
  17. Budhathoki-Uprety J, Peng L, Melander C, Novak BM (2012) Synthesis of guanidinium functionalized polycarbodiimides and their antibacterial activities. ACS Macro Lett 1(3):370–374CrossRefGoogle Scholar
  18. Campelo F, McMahon HT, Kozlov MM (2008) The hydrophobic insertion mechanism of membrane curvature generation by proteins. Biophys J 95(5):2325–2339PubMedPubMedCentralCrossRefGoogle Scholar
  19. Carmona-Ribeiro A, de Melo Carrasco L (2014) Novel formulations for antimicrobial peptides. Int J Mol Sci 15(10):18040PubMedPubMedCentralCrossRefGoogle Scholar
  20. Chakraborty S, Liu R, Hayouka Z, Chen X, Ehrhardt J, Lu Q, Burke E, Yang Y, Weisblum B, Wong GCL, Masters KS, Gellman SH (2014) Ternary nylon-3 copolymers as host-defense peptide mimics: beyond hydrophobic and cationic subunits. J Am Chem Soc 136(41):14530–14535PubMedPubMedCentralCrossRefGoogle Scholar
  21. Chan DI, Prenner EJ, Vogel HJ (2006) Tryptophan- and arginine-rich antimicrobial peptides: structures and mechanisms of action. Biochimica et Biophysica Acta (BBA)-Biomembranes 1758(9):1184–1202CrossRefGoogle Scholar
  22. Chen Y, Mant CT, Farmer SW, Hancock REW, Vasil ML, Hodges RS (2005) Rational design of α-helical antimicrobial peptides with enhanced activities and specificity/therapeutic index. J Biol Chem 280(13):12316–12329PubMedPubMedCentralCrossRefGoogle Scholar
  23. Chongsiriwatana NP, Patch JA, Czyzewski AM, Dohm MT, Ivankin A, Gidalevitz D, Zuckermann RN, Barron AE (2008) Peptoids that mimic the structure, function, and mechanism of helical antimicrobial peptides. Proc Natl Acad Sci USA 105(8):2794–2799PubMedPubMedCentralCrossRefGoogle Scholar
  24. Claudon P, Violette A, Lamour K, Decossas M, Fournel S, Heurtault B, Godet J, Mely Y, Jamart-Gregoire B, Averlant-Petit MC, Briand JP, Duportail G, Monteil H, Guichard G (2010) Consequences of isostructural main-chain modifications for the design of antimicrobial foldamers: helical mimics of host-defense peptides based on a heterogeneous amide/urea backbone. Angew Chem Int Ed 49(2):333–336CrossRefGoogle Scholar
  25. Cohen NR, Lobritz MA, Collins JJ (2013) Microbial persistence and the road to drug resistance. Cell Host Microbe 13(6):632–642PubMedPubMedCentralCrossRefGoogle Scholar
  26. Conlon BP, Nakayasu ES, Fleck LE, LaFleur MD, Isabella VM, Coleman K, Leonard SN, Smith RD, Adkins JN, Lewis K (2013) Activated clpp kills persisters and eradicates a chronic biofilm infection. Nature 503(7476):365–370PubMedPubMedCentralCrossRefGoogle Scholar
  27. Davis BD (1987) Mechanism of bactericidal action of aminoglycosides. Microbiol Rev 51(3):341PubMedPubMedCentralGoogle Scholar
  28. Davis BD, Chen L, Tai PC (1986) Misread protein creates membrane channels: an essential step in the bactericidal action of aminoglycosides. Proc Natl Acad Sci 83(16):6164–6168PubMedPubMedCentralCrossRefGoogle Scholar
  29. Derossi D, Joliot AH, Chassaing G, Prochiantz A (1994) The third helix of the antennapedia homeodomain translocates through biological membranes. J Biol Chem 269(14):10444–10450PubMedGoogle Scholar
  30. Derossi D, Chassaing G, Prochiantz A (1998) Trojan peptides: the penetratin system for intracellular delivery. Trends Cell Biol 8(2):84–87PubMedCrossRefGoogle Scholar
  31. Derzelle S, Turlin E, Duchaud E, Pages S, Kunst F, Givaudan A, Danchin A (2004) The phop-phoq two-component regulatory system of photorhabdus luminescens is essential for virulence in insects. J Bacteriol 186(5):1270–1279Google Scholar
  32. Deserno M (2009) Membrane elasticity and mediated interactions in continuum theory: a differential geometric approach. In: Faller R, Longo ML, Risbud SH, Jue T (eds) Biomembrane frontiers. Handbook of modern biophysics. Humana Press, pp 41–74Google Scholar
  33. Dohm MT, Mowery BP, Czyzewski AM, Stahl SS, Gellman SH, Barron AE (2010) Biophysical mimicry of lung surfactant protein b by random nylon-3 copolymers. J Am Chem Soc 132(23):7957–7967PubMedPubMedCentralCrossRefGoogle Scholar
  34. Döring G, Flume P, Heijerman H, Elborn JS, Group CS (2012) Treatment of lung infection in patients with cystic fibrosis: current and future strategies. J Cyst Fibros 11(6):461–479CrossRefGoogle Scholar
  35. Dorner F, Lienkamp K (2014) Polymer-based synthetic mimics of antimicrobial peptides (smamps)—a new class of nature-inspired antimicrobial agents with low bacterial resistance formation potential. In: Munoz-Bonilla A, Cerrada ML, Fernandez-Garcia M (eds) Polymeric materials with antimicrobial activity: from synthesis to applications, vol 10. R Soc Chem, pp 97–138Google Scholar
  36. Dréno B, Bettoli V, Ochsendorf F, Layton A, Mobacken H, Degreef H (2004) European recommendations on the use of oral antibiotics for acne. Eur J Dermatol 14(6):391–399PubMedGoogle Scholar
  37. Drin G, Antonny B (2010) Amphipathic helices and membrane curvature. FEBS Lett 584(9):1840–1847PubMedCrossRefGoogle Scholar
  38. Dürr UHN, Sudheendra US, Ramamoorthy A (2006) Ll-37, the only human member of the cathelicidin family of antimicrobial peptides. Biochimica et Biophysica Acta (BBA)-Biomembranes 1758(9):1408–1425CrossRefGoogle Scholar
  39. Ehrenstein G, Lecar H (1977) Electrically gated ionic channels in lipid bilayers. Q Rev Biophys 10(01):1–34PubMedCrossRefGoogle Scholar
  40. Eisenberg D, Weiss RM, Terwilliger TC, Wilcox W (1982) Hydrophobic moments and protein structure. Faraday Symp Chem Soc 17:109–120CrossRefGoogle Scholar
  41. Engler AC, Wiradharma N, Ong ZY, Coady DJ, Hedrick JL, Yang Y-Y (2012) Emerging trends in macromolecular antimicrobials to fight multi-drug-resistant infections. Nano Today 7(3):201–222CrossRefGoogle Scholar
  42. Engler AC, Tan JPK, Ong ZY, Coady DJ, Ng VWL, Yang YY, Hedrick JL (2013) Antimicrobial polycarbonates: investigating the impact of balancing charge and hydrophobicity using a same-centered polymer approach. Biomacromolecules 14(12):4331–4339PubMedCrossRefGoogle Scholar
  43. Epand RM, Epand RF (2011) Bacterial membrane lipids in the action of antimicrobial agents. J Pept Sci 17(5):298–305PubMedCrossRefGoogle Scholar
  44. Epand RF, Mowery BP, Lee SE, Stahl SS, Lehrer RI, Gellman SH, Epand RM (2008) Dual mechanism of bacterial lethality for a cationic sequence-random copolymer that mimics host-defense antimicrobial peptides. J Mol Biol 379(1):38–50PubMedCrossRefGoogle Scholar
  45. Falagas ME, Kasiakou SK, Saravolatz LD (2005) Colistin: The revival of polymyxins for the management of multidrug-resistant gram-negative bacterial infections. Clin Infect Dis 40(9):1333–1341PubMedCrossRefGoogle Scholar
  46. Farsad K, Camilli PD (2003) Mechanisms of membrane deformation. Curr Opin Cell Biol 15(4):372–381PubMedCrossRefGoogle Scholar
  47. Fjell CD, Hiss JA, Hancock RE, Schneider G (2012) Designing antimicrobial peptides: form follows function. Nat Rev Drug Discovery 11(1):37–51Google Scholar
  48. Fourmy D, Recht MI, Blanchard SC, Puglisi JD (1996) Structure of the ä site of escherichia coli 16 s ribosomal rna complexée! With an aminoglycoside antibiotic. Science 274:1367–1371PubMedCrossRefGoogle Scholar
  49. Fowler SA, Blackwell HE (2009) Structure-function relationships in peptoids: recent advances toward deciphering the structural requirements for biological function. Org Biomol Chem 7(8):1508–1524PubMedCrossRefGoogle Scholar
  50. Gabriel GJ, Madkour AE, Dabkowski JM, Nelson CF, Nüsslein K, Tew GN (2008) Synthetic mimic of antimicrobial peptide with nonmembrane-disrupting antibacterial properties. Biomacromolecules 9(11):2980–2983PubMedPubMedCentralCrossRefGoogle Scholar
  51. Gangloff N, Ulbricht J, Lorson T, Schlaad H, Luxenhofer R (2015) Peptoids and polypeptoids at the frontier of supra- and macromolecular engineering. Chem Rev (Washington, DC, US)Google Scholar
  52. Ganz T (2003) Defensins: antimicrobial peptides of innate immunity. Nat Rev Immunol 3(9):710–720PubMedCrossRefGoogle Scholar
  53. Gazit E, Lee W-J, Brey PT, Shai Y (1994) Mode of action of the antibacterial cecropin b2: a spectrofluorometric study. Biochemistry 33(35):10681–10692PubMedCrossRefGoogle Scholar
  54. Gefen O, Balaban NQ (2009) The importance of being persistent: heterogeneity of bacterial populations under antibiotic stress. FEMS Microbiol Rev 33(4):704–717PubMedCrossRefGoogle Scholar
  55. Gelbart WM, Ben-Shaul A, Roux D (eds) (1994) Micelles, membranes, microemulsions, and monolayers. Partially ordered systems. SpringerGoogle Scholar
  56. Gidalevitz D, Ishitsuka Y, Muresan AS, Konovalov O, Waring AJ, Lehrer RI, Lee KYC (2003) Interaction of antimicrobial peptide protegrin with biomembranes. Proc Natl Acad Sci 100(11):6302–6307PubMedPubMedCentralCrossRefGoogle Scholar
  57. Giuliani A, Rinaldi A (2011a) Beyond natural antimicrobial peptides: multimeric peptides and other peptidomimetic approaches. Cell Mol Life Sci 68(13):2255–2266PubMedCrossRefGoogle Scholar
  58. Giuliani A, Rinaldi AC (2011b) Beyond natural antimicrobial peptides: multimeric peptides and other peptidomimetic approaches. Cell Mol Life Sci 68(13):2255–2266PubMedCrossRefGoogle Scholar
  59. Gizdavic-Nikolaidis MR, Bennett JR, Swift S, Easteal AJ, Ambrose M (2011) Broad spectrum antimicrobial activity of functionalized polyanilines. Acta Biomater 7(12):4204–4209PubMedCrossRefGoogle Scholar
  60. Guo L, Lim KB, Gunn JS, Bainbridge B, Darveau RP, Hackett M, Miller SI (1997) Regulation of lipid a modifications by salmonella typhimurium virulence genes phop-phoq. Science 276(5310):250–253178Google Scholar
  61. Hancock R, Bell A (1988) Antibiotic uptake into gram-negative bacteria. Eur J Clin Microbiol Infect Dis 7(6):713–720PubMedCrossRefGoogle Scholar
  62. Hancock REW, Lehrer R (1998) Cationic peptides: a new source of antibiotics. Trends Biotechnol 16(2):82–88PubMedCrossRefGoogle Scholar
  63. Hancock REW, Sahl H-G (2006) Antimicrobial and host-defense peptides as new anti-infective therapeutic strategies. Nat Biotech 24(12):1551–1557CrossRefGoogle Scholar
  64. Hanessian S, Masse R, Capmeau M-L (1977) Aminoglycoside antibiotics: synthesis of 5”-amino-5”-deoxyneomycin and 5”-amino-5”-deoxyparomomycin. J Antibiot 30(10):893–896PubMedCrossRefGoogle Scholar
  65. Hansen T, Alst T, Havelkova M, Strom MB (2010) Antimicrobial activity of small beta-peptidomimetics based on the pharmacophore model of short cationic antimicrobial peptides. J Med Chem 53(2):595–606PubMedCrossRefGoogle Scholar
  66. Helfrich W (1973) Elastic properties of lipid bilayers: theory and possible experiments. Zeitschrift für Naturforschung C 28(11):693–703Google Scholar
  67. Henderson MJ, Lee KYC (2013) Promising antimicrobial agents designed from natural peptide templates. Curr Opin Solid State Mater Sci 17(4):175–192CrossRefGoogle Scholar
  68. Hessa T, Kim H, Bihlmaier K, Lundin C, Boekel J, Andersson H, Nilsson I, White SH, von Heijne G (2005) Recognition of transmembrane helices by the endoplasmic reticulum translocon. Nature 433(7024):377–381PubMedCrossRefGoogle Scholar
  69. Hong J, Oren Z, Shai Y (1999) Structure and organization of hemolytic and nonhemolytic diastereomers of antimicrobial peptides in membranes. Biochemistry 38(51):16963–16973PubMedCrossRefGoogle Scholar
  70. Hsu C-H, Chen C, Jou M-L, Lee AY-L, Lin Y-C, Yu Y-P, Huang W-T, Wu S-H (2005) Structural and DNA-binding studies on the bovine antimicrobial peptide, indolicidin: evidence for multiple conformations involved in binding to membranes and DNA. Nucleic Acids Res 33(13):4053–4064PubMedPubMedCentralCrossRefGoogle Scholar
  71. Hu YG, Li XL, Sebti SM, Chen JD, Cai JF (2011) Design and synthesis of aapeptides: a new class of peptide mimics. Bioorg Med Chem Lett 21(5):1469–1471PubMedCrossRefGoogle Scholar
  72. Hu K, Schmidt NW, Zhu R, Jiang Y, Lai GH, Wei G, Palermo EF, Kuroda K, Wong GCL, Yang L (2013) A critical evaluation of random copolymer mimesis of homogeneous antimicrobial peptides. Macromolecules 46(5):1908–1915PubMedPubMedCentralCrossRefGoogle Scholar
  73. Huang HW (2000) Action of antimicrobial peptides: two-state model. Biochemistry 39(29):8347–8352PubMedCrossRefGoogle Scholar
  74. Huang ML, Shin SBY, Benson MA, Torres VJ, Kirshenbaum K (2012) A comparison of linear and cyclic peptoid oligomers as potent antimicrobial agents. ChemMedChem 7(1):114–122PubMedCrossRefGoogle Scholar
  75. Hurdle JG, O’Neill AJ, Chopra I, Lee RE (2011) Targeting bacterial membrane function: an underexploited mechanism for treating persistent infections. Nat Rev Microbiol 9(1):62–75PubMedPubMedCentralCrossRefGoogle Scholar
  76. Ilker MF, Nüsslein K, Tew GN, Coughlin EB (2004) Tuning the hemolytic and antibacterial activities of amphiphilic polynorbornene derivatives. J Am Chem Soc 126(48):15870–15875PubMedCrossRefGoogle Scholar
  77. Ishitsuka Y, Arnt L, Majewski J, Frey SL, Ratajczak M, Kjaer K, Tew GN (2006) Lee KYC (2008) Amphiphilic poly(phenyleneethynylene)s can mimic antimicrobial peptide membrane disordering effect by membrane insertion (vol 128, p 13123). J Am Chem Soc 130(7):2372CrossRefGoogle Scholar
  78. Israelachvili JN, Marčelja S, Horn RG (1980) Physical principles of membrane organization. Q Rev Biophys 13(02):121–200PubMedCrossRefGoogle Scholar
  79. James WH, Buchanan EG, Muller CW, Dean JC, Kosenkov D, Slipchenko LV, Guo L, Reidenbach AG, Gellman SH, Zwier TS (2011) Evolution of amide stacking in larger gamma-peptides: triamide h-bonded cycles. J Phys Chem A 115(47):13783–13798PubMedCrossRefGoogle Scholar
  80. Jenssen H, Hamill P, Hancock REW (2006) Peptide antimicrobial agents. Clin Microbiol Rev 19(3):491–511PubMedPubMedCentralCrossRefGoogle Scholar
  81. Kalfa VC, Jia HP, Kunkle RA, McCray PB, Tack BF, Brogden KA (2001) Congeners of smap29 kill ovine pathogens and induce ultrastructural damage in bacterial cells. Antimicrob Agents Chemother 45(11):3256–3261PubMedPubMedCentralCrossRefGoogle Scholar
  82. Keren I, Kaldalu N, Spoering A, Wang Y, Lewis K (2004) Persister cells and tolerance to antimicrobials. FEMS Microbiol Lett 230(1):13–18PubMedCrossRefGoogle Scholar
  83. Kohanski MA, Dwyer DJ, Collins JJ (2010) How antibiotics kill bacteria: from targets to networks. Nat Rev Microbiol 8(6):423–435PubMedPubMedCentralCrossRefGoogle Scholar
  84. Kokryakov VN, Harwig SSL, Panyutich EA, Shevchenko AA, Aleshina GM, Shamova OV, Korneva HA, Lehrer RI (1993) Protegrins: leukocyte antimicrobial peptides that combine features of corticostatic defensins and tachyplesins. FEBS Lett 327(2):231–236PubMedCrossRefGoogle Scholar
  85. Kuroda K, Caputo GA (2013) Antimicrobial polymers as synthetic mimics of host-defense peptides. Wiley Interdiscip Rev Nanomed Nanobiotechnol 5(1):49–66PubMedCrossRefGoogle Scholar
  86. Kuroda K, DeGrado WF (2005) Amphiphilic polymethacrylate derivatives as antimicrobial agents. J Am Chem Soc 127(12):4128–4129PubMedCrossRefGoogle Scholar
  87. Kuroda K, Caputo GA, DeGrado WF (2009) The role of hydrophobicity in the antimicrobial and hemolytic activities of polymethacrylate derivatives. Chem Eur J 15(5):1123–1133PubMedCrossRefGoogle Scholar
  88. Kwon YU, Kodadek T (2007) Quantitative evaluation of the relative cell permeability of peptoids and peptides. J Am Chem Soc 129(6):1508-+Google Scholar
  89. Kyte J, Doolittle RF (1982) A simple method for displaying the hydropathic character of a protein. J Mol Biol 157(1):105–132PubMedCrossRefGoogle Scholar
  90. Lam KLH, Ishitsuka Y, Cheng Y, Chien K, Waring AJ, Lehrer RI, Lee KYC (2006) Mechanism of supported membrane disruption by antimicrobial peptide protegrin-1. J Phys Chem B 110(42):21282–21286PubMedCrossRefGoogle Scholar
  91. Lande R, Gregorio J, Facchinetti V, Chatterjee B, Wang Y-H, Homey B, Cao W, Wang Y-H, Su B, Nestle FO, Zal T, Mellman I, Schroder J-M, Liu Y-J, Gilliet M (2007) Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide. Nature 449(7162):564–569PubMedCrossRefGoogle Scholar
  92. Lande R, Ganguly D, Facchinetti V, Frasca L, Conrad C, Gregorio J, Meller S, Chamilos G, Sebasigari R, Riccieri V, Bassett R, Amuro H, Fukuhara S, Ito T, Liu Y-J, Gilliet M (2011) Neutrophils activate plasmacytoid dendritic cells by releasing self-DNA–peptide complexes in systemic lupus erythematosus. Sci Trans Med 3(73):73ra19–73ra19Google Scholar
  93. Lee MW, Chakraborty S, Schmidt NW, Murgai R, Gellman SH, Wong GCL (2014) Two interdependent mechanisms of antimicrobial activity allow for efficient killing in nylon-3-based polymeric mimics of innate immunity peptides. Biochimica et Biophysica Acta (BBA)-Biomembranes 1838(9):2269–2279CrossRefGoogle Scholar
  94. Lehrer RI (2004) Primate defensins. Nat Rev Micro 2(9):727–738CrossRefGoogle Scholar
  95. Lewis K (2007) Persister cells, dormancy and infectious disease. Nat Rev Microbiol 5(1):48–56PubMedCrossRefGoogle Scholar
  96. Lewis K (2010) Persister cells. Annu Rev Microbiol 64:357–372PubMedCrossRefGoogle Scholar
  97. Li M, Lai Y, Villaruz AE, Cha DJ, Sturdevant DE, Otto M (2007a) Gram-positive three-component antimicrobial peptide-sensing system. Proc Natl Acad Sci 104(22):9469–9474PubMedPubMedCentralCrossRefGoogle Scholar
  98. Li M, Cha DJ, Lai Y, Villaruz AE, Sturdevant DE, Otto M (2007b) The antimicrobial peptide-sensing system aps of staphylococcus aureus. Mol Microbiol 66(5):1136–1147PubMedCrossRefGoogle Scholar
  99. Li P, Li X, Saravanan R, Li CM, Leong SSJ (2012) Antimicrobial macromolecules: synthesis methods and future applications. RSC Adv 2(10):4031–4044CrossRefGoogle Scholar
  100. Li YQ, Smith C, Wu HF, Teng P, Shi Y, Padhee S, Jones T, Nguyen AM, Cao CH, Yin H, Cai JF (2014) Short antimicrobial lipo-alpha/gamma-aa hybrid peptides. ChemBioChem 15(15):2275–2280PubMedPubMedCentralCrossRefGoogle Scholar
  101. Liu DH, DeGrado WF (2001) De novo design, synthesis, and characterization of antimicrobial beta-peptides. J Am Chem Soc 123(31):7553–7559PubMedCrossRefGoogle Scholar
  102. Liu R, Masters KS, Gellman SH (2012a) Polymer chain length effects on fibroblast attachment on nylon-3-modified surfaces. Biomacromolecules 13(4):1100–1105PubMedPubMedCentralCrossRefGoogle Scholar
  103. Liu R, Vang KZ, Kreeger PK, Gellman SH, Masters KS (2012b) Experimental and computational analysis of cellular interactions with nylon-3-bearing substrates. J Biomed Mater Res Part A 100A(10):2750–2759CrossRefGoogle Scholar
  104. Liu R, Chen X, Chakraborty S, Lemke JJ, Hayouka Z, Chow C, Welch RA, Weisblum B, Masters KS, Gellman SH (2014) Tuning the biological activity profile of antibacterial polymers via subunit substitution pattern. J Am Chem Soc 136(11):4410–4418PubMedPubMedCentralCrossRefGoogle Scholar
  105. Liu R, Chen X, Falk SP, Masters KS, Weisblum B, Gellman SH (2015) Nylon-3 polymers active against drug-resistant candida albicans biofilms. J Am Chem Soc 137(6):2183–2186PubMedPubMedCentralCrossRefGoogle Scholar
  106. Ljunggren S, Eriksson JC (1992) Minimal surfaces and winsor iii microemulsions. Langmuir 8(5):1300–1306CrossRefGoogle Scholar
  107. Locock KES, Michl TD, Valentin JDP, Vasilev K, Hayball JD, Qu Y, Traven A, Griesser HJ, Meagher L, Haeussler M (2013) Guanylated polymethacrylates: a class of potent antimicrobial polymers with low hemolytic activity. Biomacromolecules 14(11):4021–4031PubMedCrossRefGoogle Scholar
  108. Locock KES, Michl TD, Stevens N, Hayball JD, Vasilev K, Postma A, Griesser HJ, Meagher L, Haeussler M (2014) Antimicrobial polymethacrylates synthesized as mimics of tryptophan-rich cationic peptides. ACS Macro Letters 3(4):319–323CrossRefGoogle Scholar
  109. Ludtke SJ, He K, Heller WT, Harroun TA, Yang L, Huang HW (1996) Membrane pores induced by magainin. Biochemistry 35(43):13723–13728PubMedCrossRefGoogle Scholar
  110. Magnet S, Blanchard JS (2005) Molecular insights into aminoglycoside action and resistance. Chem Rev (Washington, DC, US) 105(2):477–498Google Scholar
  111. Malanovic N, Leber R, Schmuck M, Kriechbaum M, Cordfunke RA, Drijfhout JW, de Breij A, Nibbering PH, Kolb D, Lohner K (2015) Phospholipid-driven differences determine the action of the synthetic antimicrobial peptide op-145 on gram-positive bacterial and mammalian membrane model systems. Biochimica et Biophysica Acta (BBA)-Biomembranes 1848(10, Part A):2437–2447Google Scholar
  112. Masip I, Perez-Paya E, Messeguer A (2005) Peptoids as source of compounds eliciting antibacterial activity. Comb Chem High Throughput Screening 8(3):235–239CrossRefGoogle Scholar
  113. Matsuzaki K (1999) Why and how are peptide–lipid interactions utilized for self-defense? Magainins and tachyplesins as archetypes. Biochimica et Biophysica Acta (BBA)-Biomembranes 1462(1–2):1–10CrossRefGoogle Scholar
  114. Matsuzaki K (2009) Control of cell selectivity of antimicrobial peptides. Biochimica Et Biophysica Acta-Biomembranes 1788(8):1687–1692CrossRefGoogle Scholar
  115. Matsuzaki K, Murase O, Tokuda H, Funakoshi S, Fujii N, Miyajima K (1994) Orientational and aggregational states of magainin 2 in phospholipid bilayers. Biochemistry 33(11):3342–3349PubMedCrossRefGoogle Scholar
  116. Matsuzaki K, Murase O, Fujii N, Miyajima K (1996) An antimicrobial peptide, magainin 2, induced rapid flip-flop of phospholipids coupled with pore formation and peptide translocation. Biochemistry 35(35):11361–11368PubMedCrossRefGoogle Scholar
  117. Matsuzaki K, Sugishita K, Harada M, Fujii N, Miyajima K (1997) Interactions of an antimicrobial peptide, magainin 2, with outer and inner membranes of gram-negative bacteria. Biochimica et Biophysica Acta (BBA)-Biomembranes 1327(1):119–130CrossRefGoogle Scholar
  118. Matsuzaki K, Sugishita K-I, Ishibe N, Ueha M, Nakata S, Miyajima K, Epand RM (1998) Relationship of membrane curvature to the formation of pores by magainin 2. Biochemistry 37(34):11856–11863PubMedCrossRefGoogle Scholar
  119. McInturff JE, Wang S-J, Machleidt T, Lin TR, Oren A, Hertz CJ, Krutzik SR, Hart S, Zeh K, Anderson DH, Gallo RL, Modlin RL, Kim J (2005) Granulysin-derived peptides demonstrate antimicrobial and anti-inflammatory effects against propionibacterium acnes. J Invest Dermatol 125(2):256–263PubMedPubMedCentralGoogle Scholar
  120. McMahon HT, Gallop JL (2005) Membrane curvature and mechanisms of dynamic cell membrane remodelling. Nature 438(7068):590–596PubMedCrossRefGoogle Scholar
  121. Mendez-Samperio P (2014) Peptidomimetics as a new generation of antimicrobial agents: current progress. Infect Drug Resist 7:229–237PubMedPubMedCentralCrossRefGoogle Scholar
  122. Mensa B, Kim YH, Choi S, Scott R, Caputo GA, DeGrado WF (2011) Antibacterial mechanism of action of arylamide foldamers. Antimicrob Agents Chemother 55(11):5043–5053PubMedPubMedCentralCrossRefGoogle Scholar
  123. Mingeot-Leclercq M-P, Glupczynski Y, Tulkens PM (1999) Aminoglycosides: Activity and resistance. Antimicrob Agents Chemother 43(4):727–737PubMedPubMedCentralGoogle Scholar
  124. Mishra A, Gordon VD, Yang L, Coridan R, Wong GCL (2008a) Hiv tat forms pores in membranes by inducing saddle-splay curvature: potential role of bidentate hydrogen bonding. Angew Chem Int Ed 47(16):2986–2989CrossRefGoogle Scholar
  125. Mishra A, Gordon VD, Yang L, Coridan R, Wong GC (2008b) Hiv tat forms pores in membranes by inducing saddle-splay curvature: potential role of bidentate hydrogen bonding. Angew Chem Int Ed 47(16):2986–2989CrossRefGoogle Scholar
  126. Mishra A, Tai KP, Schmidt NW, Ouellette AJ, Wong GCL (2011a) Chapter four—small-angle X-ray scattering studies of peptide–lipid interactions using the mouse paneth cell α-defensin cryptdin-4. In: Michael L, Johnson JMH, Gary KA (eds) Methods in enzymology, vol 492. Academic Press, pp 127–149Google Scholar
  127. Mishra A, Lai GH, Schmidt NW, Sun VZ, Rodriguez AR, Tong R, Tang L, Cheng J, Deming TJ, Kamei DT, Wong GCL (2011b) Translocation of hiv tat peptide and analogues induced by multiplexed membrane and cytoskeletal interactions. Proc Natl Acad Sci 108(41):16883–16888PubMedPubMedCentralCrossRefGoogle Scholar
  128. Mishra A, Lai GH, Schmidt NW, Sun VZ, Rodriguez AR, Tong R, Tang L, Cheng J, Deming TJ, Kamei DT (2011c) Translocation of hiv tat peptide and analogues induced by multiplexed membrane and cytoskeletal interactions. Proc Natl Acad Sci 108(41):16883–16888PubMedPubMedCentralCrossRefGoogle Scholar
  129. Mojsoska B, Jensses H (2015) Peptides and peptidomimetics for antimicrobial drug design. Pharmaceuticals 8:366–415PubMedPubMedCentralCrossRefGoogle Scholar
  130. Mowery BP, Lee SE, Kissounko DA, Epand RF, Epand RM, Weisblum B, Stahl SS, Gellman SH (2007) Mimicry of antimicrobial host-defense peptides by random copolymers. J Am Chem Soc 129(50):15474–15476PubMedCrossRefGoogle Scholar
  131. Mulcahy LR, Burns JL, Lory S, Lewis K (2010) Emergence of pseudomonas aeruginosa strains producing high levels of persister cells in patients with cystic fibrosis. J Bacteriol 192(23):6191–6199PubMedPubMedCentralCrossRefGoogle Scholar
  132. Muñoz-Bonilla A, Fernández-García M (2012) Polymeric materials with antimicrobial activity. Prog Polym Sci 37(2):281–339CrossRefGoogle Scholar
  133. Nandel FS, Saini A (2007) Conformational study of short peptoid models for future applications as potent antimicrobial compounds. Macromol Theory Simul 16(3):295–303CrossRefGoogle Scholar
  134. Nederberg F, Zhang Y, Tan JPK, Xu K, Wang H, Yang C, Gao S, Guo XD, Fukushima K, Li L, Hedrick JL, Yang Y-Y (2011) Biodegradable nanostructures with selective lysis of microbial membranes. Nat Chem 3(5):409–414PubMedCrossRefGoogle Scholar
  135. Ng VWL, Tan JPK, Leong J, Voo ZX, Hedrick JL, Yang YY (2014) Antimicrobial polycarbonates: investigating the impact of nitrogen-containing heterocycles as quaternizing agents. Macromolecules 47(4):1285–1291CrossRefGoogle Scholar
  136. Nikaido H (2003) Molecular basis of bacterial outer membrane permeability revisited. Microbiol Mol Biol Rev 67(4):593–656PubMedPubMedCentralCrossRefGoogle Scholar
  137. Nilsson AC, Janson H, Wold H, Fugelli A, Andersson K, Håkangård C, Olsson P, Olsen WM (2015) Ltx-109 is a novel agent for nasal decolonization of methicillin-resistant and-sensitive staphylococcus aureus. Antimicrob Agents Chemother 59(1):145–151PubMedPubMedCentralCrossRefGoogle Scholar
  138. Niu YH, Hu YG, Li XL, Chen JD, Cai JF (2011) Gamma-aapeptides: design, synthesis and evaluation. New J Chem 35(3):542–545CrossRefGoogle Scholar
  139. Oda Y, Kanaoka S, Sato T, Aoshima S, Kuroda K (2011) Block versus random amphiphilic copolymers as antibacterial agents. Biomacromolecules 12(10):3581–3591PubMedCrossRefGoogle Scholar
  140. Oren Z, Shai Y (1997) Selective lysis of bacteria but not mammalian cells by diastereomers of melittin: structure—function study. Biochemistry 36(7):1826–1835PubMedCrossRefGoogle Scholar
  141. Pagès J-M, James CE, Winterhalter M (2008) The porin and the permeating antibiotic: a selective diffusion barrier in gram-negative bacteria. Nat Rev Microbiol 6(12):893–903PubMedCrossRefGoogle Scholar
  142. Palermo EF, Kuroda K (2009) Chemical structure of cationic groups in amphiphilic polymethacrylates modulates the antimicrobial and hemolytic activities. Biomacromolecules 10(6):1416–1428PubMedCrossRefGoogle Scholar
  143. Palermo E, Kuroda K (2010) Structural determinants of antimicrobial activity in polymers which mimic host defense peptides. Appl Microbiol Biotechnol 87(5):1605–1615PubMedCrossRefGoogle Scholar
  144. Palermo EF, Sovadinova I, Kuroda K (2009) Structural determinants of antimicrobial activity and biocompatibility in membrane-disrupting methacrylamide random copolymers. Biomacromolecules 10(11):3098–3107PubMedCrossRefGoogle Scholar
  145. Palermo EF, Lee D-K, Ramamoorthy A, Kuroda K (2011) Role of cationic group structure in membrane binding and disruption by amphiphilic copolymers. J Phys Chem B 115(2):366–375PubMedPubMedCentralCrossRefGoogle Scholar
  146. Palermo EF, Vemparala S, Kuroda K (2013) Antimicrobial polymers: Molecular design as synthetic mimics of host-defense peptides. In: Scholz C, Kressler J (eds) Tailored polymer architectures for pharmaceutical and biomedical applications, vol 1135. Acs symposium series, vol 1135. Am Chem Soc, pp 319–330Google Scholar
  147. 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(1):253–257PubMedCrossRefGoogle Scholar
  148. Patch JA, Barron AE (2003) Helical peptoid mimics of magainin-2 amide. J Am Chem Soc 125(40):12092–12093PubMedCrossRefGoogle Scholar
  149. Peek F, Nell MJ, Brand R, Jansen-Werkhoven T, Van Hoogdalem E, Frijns J (2009) Double-blind placebo-controlled study of the novel peptide drug p60.4ac in cronic middle ear infection. ICAAC:L1–L337Google Scholar
  150. Perron GG, Zasloff M, Bell G (2006) Experimental evolution of resistance to an antimicrobial peptide. Proc R Soc Lond B Biol Sci 273(1583):251–256CrossRefGoogle Scholar
  151. Peschel A, Jack RW, Otto M, Collins LV, Staubitz P, Nicholson G, Kalbacher H, Nieuwenhuizen WF, Jung G, Tarkowski A (2001) 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(9):1067–1076PubMedPubMedCentralCrossRefGoogle Scholar
  152. Porter EA, Wang XF, Lee HS, Weisblum B, Gellman SH (2000) Antibiotics-non-haemolytic beta-amino-acid oligomers. Nature 404(6778):565PubMedCrossRefGoogle Scholar
  153. Porter EA, Weisblum B, Gellman SH (2005) Use of parallel synthesis to probe structure-activity relationships among 12-helical beta-peptides: evidence of a limit on antimicrobial activity. J Am Chem Soc 127(32):11516–11529PubMedCrossRefGoogle Scholar
  154. Pouny Y, Rapaport D, Mor A, Nicolas P, Shai Y (1992) Interaction of antimicrobial dermaseptin and its fluorescently labeled analogs with phospholipid membranes. Biochemistry 31(49):12416–12423PubMedCrossRefGoogle Scholar
  155. Punia A, Mancuso A, Banerjee P, Yang N-L (2015) Nonhemolytic and antibacterial acrylic copolymers with hexamethyleneamine and poly(ethylene glycol) side chains. ACS Macro Lett 4(4):426–430CrossRefGoogle Scholar
  156. 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(6):657–659PubMedCrossRefGoogle Scholar
  157. Rebeil R, Ernst RK, Gowen BB, Miller SI, Hinnebusch BJ (2004) Variation in lipid a structure in the pathogenic yersiniae. Mol Microbiol 52(5):1363–1373PubMedCrossRefGoogle Scholar
  158. Ross J, Snelling A, Carnegie E, Coates P, Cunliffe W, Bettoli V, Tosti G, Katsambas A, Pulgar Galvan Perez Del, Rollman O (2003) Antibiotic-resistant acne: lessons from europe. Brit J Dermatol 148(3):467–478CrossRefGoogle Scholar
  159. Rotem S, Mor A (2009) Antimicrobial peptide mimics for improved therapeutic properties. Biochimica et Biophysica Acta (BBA)-Biomembranes 1788(8):1582–1592CrossRefGoogle Scholar
  160. Saiman L, Tabibi S, Starner TD, San Gabriel P, Winokur PL, Jia HP, McCray PB, Tack BF (2001) Cathelicidin peptides inhibit multiply antibiotic-resistant pathogens from patients with cystic fibrosis. Antimicrob Agents Chemother 45(10):2838–2844PubMedPubMedCentralCrossRefGoogle Scholar
  161. Sambhy V, Peterson BR, Sen A (2008) Antibacterial and hemolytic activities of pyridinium polymers as a function of the spatial relationship between the positive charge and the pendant alkyl tail. Angew Chem Int Ed 47(7):1250–1254CrossRefGoogle Scholar
  162. 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(12):4308–4314PubMedPubMedCentralCrossRefGoogle Scholar
  163. Sato H, Feix JB (2006) Peptide–membrane interactions and mechanisms of membrane destruction by amphipathic α-helical antimicrobial peptides. Biochimica et Biophysica Acta (BBA)-Biomembranes 1758(9):1245–1256CrossRefGoogle Scholar
  164. Schauber J, Gallo RL (2008) Antimicrobial peptides and the skin immune defense system. J Allergy Clin Immunol 122(2):261–266PubMedPubMedCentralCrossRefGoogle Scholar
  165. Schmidt NW, Wong GCL (2013) Antimicrobial peptides and induced membrane curvature: geometry, coordination chemistry, and molecular engineering. Curr Opin Solid State Mater Sci 17(4):151–163PubMedPubMedCentralCrossRefGoogle Scholar
  166. Schmidt N, Mishra A, Lai GH, Wong GCL (2010) Arginine-rich cell-penetrating peptides. FEBS Lett 584(9):1806–1813PubMedCrossRefGoogle Scholar
  167. Schmidt NW, Mishra A, Lai GH, Davis M, Sanders LK, Tran D, Garcia A, Tai KP, McCray PB, Ouellette AJ, Selsted ME, Wong GCL (2011) Criterion for amino acid composition of defensins and antimicrobial peptides based on geometry of membrane destabilization. J Am Chem Soc 133(17):6720–6727PubMedPubMedCentralCrossRefGoogle Scholar
  168. Schmidt NW, Tai KP, Kamdar K, Mishra A, Lai GH, Zhao K, Ouellette AJ, Wong GCL (2012a) Arginine in α-defensins: differential effects on bactericidal activity correspond to geometry of membrane curvature generation and peptide-lipid phase behavior. J Biol Chem 287(26):21866–21872PubMedPubMedCentralCrossRefGoogle Scholar
  169. Schmidt NW, Lis M, Zhao K, Lai GH, Alexandrova AN, Tew GN, Wong GCL (2012b) Molecular basis for nanoscopic membrane curvature generation from quantum mechanical models and synthetic transporter sequences. J Am Chem Soc 134(46):19207–19216PubMedPubMedCentralCrossRefGoogle Scholar
  170. Schmidt NW, Deshayes S, Hawker S, Blacker A, Kasko AM, Wong GC (2014) Engineering persister-specific antibiotics with synergistic antimicrobial functions. ACS Nano 8(9):8786–8793PubMedPubMedCentralCrossRefGoogle Scholar
  171. Schmidt NW, Jin F, Lande R, Curk T, Xian W, Lee C, Frasca L, Frenkel D, Dobnikar J, Gilliet M, Wong GCL (2015a) Liquid-crystalline ordering of antimicrobial peptide-DNA complexes controls tlr9 activation. Nat Mater 14(7):696–700PubMedCrossRefGoogle Scholar
  172. Schmidt NW, Agak GW, Deshayes S, Yu Y, Blacker A, Champer J, Xian W, Kasko AM, Kim J, Wong GC (2015b) Pentobra: a potent antibiotic with multiple layers of selective antimicrobial mechanisms against propionibacterium acnes. J Invest Dermatol 135(6):1581–1589PubMedPubMedCentralCrossRefGoogle Scholar
  173. Schmitt MA, Weisblum B, Gellman SH (2004) Unexpected relationships between structure and function in alpha, beta-peptides: antimicrobial foldamers with heterogeneous backbones. J Am Chem Soc 126(22):6848–6849PubMedCrossRefGoogle Scholar
  174. Scott RW, DeGrado WF, Tew GN (2008) De novo designed synthetic mimics of antimicrobial peptides. Curr Opin Biotechnol 19(6):620–627PubMedPubMedCentralCrossRefGoogle Scholar
  175. Seddon JM, Templer RH (1993) Cubic phases of self-assembled amphiphilic aggregates. Philos Trans R Soc Lond A Math Phys Eng Sci 344(1672):377–401CrossRefGoogle Scholar
  176. Selsted ME, Ouellette AJ (2005) Mammalian defensins in the antimicrobial immune response. Nat Immunol 6(6):551–557PubMedCrossRefGoogle Scholar
  177. Selsted ME, Novotny MJ, Morris WL, Tang YQ, Smith W, Cullor JS (1992) Indolicidin, a novel bactericidal tridecapeptide amide from neutrophils. J Biol Chem 267(7):4292–4295PubMedGoogle Scholar
  178. Sens P, Johannes L, Bassereau P (2008) Biophysical approaches to protein-induced membrane deformations in trafficking. Curr Opin Cell Biol 20(4):476–482PubMedCrossRefGoogle Scholar
  179. Shai Y (1999) Mechanism of the binding, insertion and destabilization of phospholipid bilayer membranes by α-helical antimicrobial and cell non-selective membrane-lytic peptides. Biochimica et Biophysica Acta (BBA)-Biomembranes 1462(1–2):55–70CrossRefGoogle Scholar
  180. Shai Y, Oren Z (2001) From “carpet” mechanism to de-novo designed diastereomeric cell-selective antimicrobial peptides. Peptides 22(10):1629–1641PubMedCrossRefGoogle Scholar
  181. Shearman GC, Ces O, Templer RH, Seddon JM (2006) Inverse lyotropic phases of lipids and membrane curvature. J Phys Condens Matter 18(28):S1105PubMedCrossRefGoogle Scholar
  182. Siegel DP, Kozlov MM (2004) The gaussian curvature elastic modulus of n-monomethylated dioleoylphosphatidylethanolamine: relevance to membrane fusion and lipid phase behavior. Biophys J 87(1):366–374PubMedPubMedCentralCrossRefGoogle Scholar
  183. Som A, Vemparala S, Ivanov I, Tew GN (2008a) Synthetic mimics of antimicrobial peptides. Pept Sci 90(2):83–93CrossRefGoogle Scholar
  184. Som A, Vemparala S, Ivanov I, Tew GN (2008b) Synthetic mimics of antimicrobial peptides. Biopolymers 90(2):83–93PubMedCrossRefGoogle Scholar
  185. Song A, Walker SG, Parker KA, Sampson NS (2011) Antibacterial studies of cationic polymers with alternating, random, and uniform backbones. ACS Chem Biol 6(6):590–599PubMedPubMedCentralCrossRefGoogle Scholar
  186. Sovadinova I, Palermo EF, Huang R, Thoma LM, Kuroda K (2011a) Mechanism of polymer-induced hemolysis: nanosized pore formation and osmotic lysis. Biomacromolecules 12(1):260–268PubMedCrossRefGoogle Scholar
  187. Sovadinova I, Palermo EF, Urban M, Mpiga P, Caputo GA, Kuroda K (2011b) Activity and mechanism of antimicrobial peptide-mimetic amphiphilic polymethacrylate derivatives. Polymers 3(3):1512–1532CrossRefGoogle Scholar
  188. Spaar A, Münster C, Salditt T (2004) Conformation of peptides in lipid membranes studied by X-ray grazing incidence scattering. Biophys J 87(1):396–407PubMedPubMedCentralCrossRefGoogle Scholar
  189. Stachowiak JC, Hayden CC, Sasaki DY (2010) Steric confinement of proteins on lipid membranes can drive curvature and tubulation. Proc Natl Acad Sci 107(17):7781–7786PubMedPubMedCentralCrossRefGoogle Scholar
  190. Stachowiak JC, Schmid EM, Ryan CJ, Ann HS, Sasaki DY, Sherman MB, Geissler PL, Fletcher DA, Hayden CC (2012) Membrane bending by protein–protein crowding. Nat Cell Biol 14(9):944–949PubMedCrossRefGoogle Scholar
  191. Taber HW, Mueller J, Miller P, Arrow A (1987) Bacterial uptake of aminoglycoside antibiotics. Microbiol Rev 51(4):439PubMedPubMedCentralGoogle Scholar
  192. Tang M, Waring AJ, Hong M (2007) Phosphate-mediated arginine insertion into lipid membranes and pore formation by a cationic membrane peptide from solid-state nmr. J Am Chem Soc 129(37):11438–11446PubMedCrossRefGoogle Scholar
  193. Tew GN, Liu DH, Chen B, Doerksen RJ, Kaplan J, Carroll PJ, Klein ML, DeGrado WF (2002) De novo design of biomimetic antimicrobial polymers. Proc Natl Acad Sci USA 99(8):5110–5114PubMedPubMedCentralCrossRefGoogle Scholar
  194. Vaara M (2009) New approaches in peptide antibiotics. Curr Opin Pharmacol 9(5):571–576PubMedCrossRefGoogle Scholar
  195. Vakulenko SB, Mobashery S (2003) Versatility of aminoglycosides and prospects for their future. Clin Microbiol Rev 16(3):430–450PubMedPubMedCentralCrossRefGoogle Scholar
  196. van der Does AM, Bogaards SJP, Ravensbergen B, Beekhuizen H, van Dissel JT, Nibbering PH (2010) Antimicrobial peptide hlf1-11 directs granulocyte-macrophage colony-stimulating factor-driven monocyte differentiation toward macrophages with enhanced recognition and clearance of pathogens. Antimicrob Agents Chemother 54(2):811–816PubMedPubMedCentralCrossRefGoogle Scholar
  197. van Meer G, Voelker DR, Feigenson GW (2008) Membrane lipids: where they are and how they behave. Nat Rev Mol Cell Biol 9(2):112–124PubMedPubMedCentralCrossRefGoogle Scholar
  198. Vicens Q, Westhof E (2002) Crystal structure of a complex between the aminoglycoside tobramycin and an oligonucleotide containing the ribosomal decoding a site. Chem Biol 9(6):747–755PubMedCrossRefGoogle Scholar
  199. Walsh PS, Kusaka R, Buchanan EG, James WH, Fisher BF, Gellman SH, Zwier TS (2013) Cyclic constraints on conformational flexibility in gamma-peptides: conformation specific ir and uv spectroscopy. J Phys Chem A 117(47):12350–12362PubMedCrossRefGoogle Scholar
  200. Wang Z, Wang G (2004) Apd: The antimicrobial peptide database. Nucleic Acids Res 32(suppl 1):D590–D592PubMedPubMedCentralCrossRefGoogle Scholar
  201. Wang WLL, Everett ED, Johnson M, Dean E (1977) Susceptibility of propionibacterium acnes to seventeen antibiotics. Antimicrob Agents Chemother 11(1):171–173PubMedPubMedCentralCrossRefGoogle Scholar
  202. Wu CW, Sanborn TJ, Huang K, Zuckermann RN, Barron AE (2001) Peptoid oligomers with alpha-chiral, aromatic side chains: sequence requirements for the formation of stable peptoid helices. J Am Chem Soc 123(28):6778–6784PubMedCrossRefGoogle Scholar
  203. Wu Z, Cui Q, Yethiraj A (2013) Why do arginine and lysine organize lipids differently? Insights from coarse-grained and atomistic simulations. J Phys Chem B 117(40):12145–12156PubMedCrossRefGoogle Scholar
  204. Yang L, Harroun TA, Weiss TM, Ding L, Huang HW (2001) Barrel-stave model or toroidal model? a case study on melittin pores. Biophys J 81(3):1475–1485PubMedPubMedCentralCrossRefGoogle Scholar
  205. Yeaman MR, Yount NY (2003) Mechanisms of antimicrobial peptide action and resistance. Pharmacol Rev 55(1):27–55PubMedCrossRefGoogle Scholar
  206. Yeung AY, Gellatly S, Hancock RW (2011) Multifunctional cationic host defence peptides and their clinical applications. Cell Mol Life Sci 68(13):2161–2176PubMedCrossRefGoogle Scholar
  207. Yonezawa A, Kuwahara J, Fujii N, Sugiura Y (1992) 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(11):2998–3004PubMedCrossRefGoogle Scholar
  208. Yu Y, Vroman JA, Bae SC, Granick S (2010) Vesicle budding induced by a pore-forming peptide. J Am Chem Soc 132(1):195–201PubMedCrossRefGoogle Scholar
  209. Zachowski A (1993) Phospholipids in animal eukaryotic membranes: transverse asymmetry and movement. Biochem J 294(1):1–14PubMedPubMedCentralCrossRefGoogle Scholar
  210. 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 84(15):5449–5453PubMedPubMedCentralCrossRefGoogle Scholar
  211. Zasloff M (2002) Antimicrobial peptides of multicellular organisms. Nature 415(6870):389–395PubMedCrossRefGoogle Scholar
  212. Zhang J, Markiewicz MJ, Mowery BP, Weisblum B, Stahl SS, Gellman SH (2012) C-terminal functionalization of nylon-3 polymers: effects of c-terminal groups on antibacterial and hemolytic activities. Biomacromolecules 13(2):323–331PubMedPubMedCentralCrossRefGoogle Scholar
  213. Zhao K, Choe U-J, Kamei DT, Wong GCL (2012a) Enhanced activity of cyclic transporter sequences driven by phase behavior of peptide-lipid complexes. Soft Matter 8(24):6430–6433PubMedPubMedCentralCrossRefGoogle Scholar
  214. Zhao K, Choe U-J, Kamei DT, Wong GCL (2012b) Enhanced activity of cyclic transporter sequences driven by phase behavior of peptide-lipid complexes. Soft Matter 8:6430–6433PubMedPubMedCentralCrossRefGoogle Scholar
  215. Zimmerberg J, Kozlov MM (2006) How proteins produce cellular membrane curvature. Nat Rev Mol Cell Biol 7(1):9–19PubMedCrossRefGoogle Scholar
  216. Zimmerli W, Trampuz A, Ochsner PE (2004) Prosthetic-joint infections. N Engl J Med 351(16):1645–1654PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Stephanie Deshayes
    • 1
  • Michelle W. Lee
    • 1
    • 2
  • Nathan W. Schmidt
    • 4
  • Wujing Xian
    • 1
    • 2
  • Andrea Kasko
    • 1
    • 3
  • Gerard C. L. Wong
    • 1
    • 2
    • 3
  1. 1.Department of BioengineeringUniversity of CaliforniaLos AngelesUSA
  2. 2.Department of Chemistry & BiochemistryUniversity of CaliforniaLos AngelesUSA
  3. 3.California Nano Systems InstituteUniversity of CaliforniaLos AngelesUSA
  4. 4.Department of Pharmaceutical ChemistryUniversity of CaliforniaSan FranciscoUSA

Personalised recommendations