AMPs as Anti-biofilm Agents for Human Therapy and Prophylaxis

  • Hawraa Shahrour
  • Raquel Ferrer-Espada
  • Israa Dandache
  • Sergio Bárcena-Varela
  • Susana Sánchez-Gómez
  • Ali Chokr
  • Guillermo Martinez-de-TejadaEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1117)


Microbial cells show a strong natural tendency to adhere to surfaces and to colonize them by forming complex communities called biofilms. In this growth mode, biofilm-forming cells encase themselves inside a dense matrix which efficiently protects them against antimicrobial agents and effectors of the immune system. Moreover, at the physiological level, biofilms contain a very heterogeneous cell population including metabolically inactive organisms and persisters, which are highly tolerant to antibiotics. The majority of human infectious diseases are caused by biofilm-forming microorganisms which are responsible for pathologies such as cystic fibrosis, infective endocarditis, pneumonia, wound infections, dental caries, infections of indwelling devices, etc. AMPs are well suited to combat biofilms because of their potent bactericidal activity of broad spectrum (including resting cells and persisters) and their ability to first penetrate and then to disorganize these structures. In addition, AMPs frequently synergize with antimicrobial compounds and were recently reported to repress the molecular pathways leading to biofilm formation. Finally, there is a very active research to develop AMP-containing coatings that can prevent biofilm formation by killing microbial cells on contact or by locally releasing their active principle. In this chapter we will describe these strategies and discuss the perspectives of the use of AMPs as anti-biofilm agents for human therapy and prophylaxis.


Biofilm Antimicrobial peptide Host-defense peptide Antibiotic lock therapy Medical implant 



This work was supported by the Proyectos de Investigación Universidad de Navarra, Spain (PIUNA-P2011-17 and P2015-14 to G. M. T.). R. F. E and S.B.V. are recipients of doctoral fellowships granted by Gobierno Vasco, Spain (BFI-2011-9) and Asociación de Amigos de la Universidad de Navarra (Spain), respectively.

H.S. is grateful to financial support received from the Lebanese National Council for Scientific Research (CNRS) and by the Lebanese University.


  1. Ahire JJ, Dicks LMT (2014) Nisin incorporated with 2,3-Dihydroxybenzoic acid in nanofibers inhibits biofilm formation by a methicillin-resistant strain of Staphylococcus aureus. Probiotics Antimicrob Proteins 7:52–59. CrossRefGoogle Scholar
  2. Ahn KB, Kim AR, Kum KY et al (2017) The synthetic human beta-defensin-3 C15 peptide exhibits antimicrobial activity against Streptococcus mutans, both alone and in combination with dental disinfectants. J Microbiol 55:830–836. CrossRefPubMedGoogle Scholar
  3. Akyıldız I, Take G, Uygur K et al (2013) Bacterial biofilm formation in the middle-ear mucosa of chronic otitis media patients. Indian J Otolaryngol Head Neck Surg 65:557–561. CrossRefPubMedGoogle Scholar
  4. Alabdullatif M, Atreya CD, Ramirez-Arcos S (2018) Antimicrobial peptides: an effective approach to prevent bacterial biofilm formation in platelet concentrates. Transfusion 00:1–9. CrossRefGoogle Scholar
  5. Almaaytah A, Qaoud MT, Mohammed GK et al (2018) Antimicrobial and antibiofilm activity of UP-5, an ultrashort antimicrobial peptide designed using only arginine and biphenylalanine. Pharmaceuticals 11:1–18. CrossRefGoogle Scholar
  6. Alt V, Bitschnau A, Böhner F et al (2011) Effects of gentamicin and gentamicin–RGD coatings on bone ingrowth and biocompatibility of cementless joint prostheses: an experimental study in rabbits. Acta Biomater 7:1274–1280. CrossRefPubMedGoogle Scholar
  7. Ammons MC, Copié V (2013) Mini-review: lactoferrin: a bioinspired, anti-biofilm therapeutic. Biofouling 29:443–455. CrossRefPubMedPubMedCentralGoogle Scholar
  8. Anunthawan T, De La Fuente-Núñez C, Hancock REW, Klaynongsruang S (2015) Cationic amphipathic peptides KT2 and RT2 are taken up into bacterial cells and kill planktonic and biofilm bacteria. CrossRefGoogle Scholar
  9. Bahar AA, Liu Z, Garafalo M et al (2015) Controlling persister and biofilm cells of gram-negative bacteria with a new 1,3,5-triazine derivative. Pharmaceuticals 8:696–710. CrossRefPubMedPubMedCentralGoogle Scholar
  10. Balaban N, Gov Y, Giacometti A et al (2004) A chimeric peptide composed of a dermaseptin derivative and an RNA III-inhibiting peptide prevents graft-associated infections by antibiotic-resistant staphylococci. Antimicrob Agents Chemother 48:2544–2550.–2550.2004 CrossRefPubMedPubMedCentralGoogle Scholar
  11. Banerjee I, Pangule RC, Kane RS (2011) Antifouling coatings: recent developments in the design of surfaces that prevent fouling by proteins, bacteria, and marine organisms. Adv Mater 23:690–718. CrossRefPubMedGoogle Scholar
  12. Batoni G, Maisetta G, Lisa Brancatisano F et al (2011) Use of antimicrobial peptides against microbial biofilms: advantages and limits. Curr Med Chem 18:256–279. CrossRefPubMedGoogle Scholar
  13. Beckloff N, Laube D, Castro T et al (2007) Activity of an antimicrobial peptide mimetic against planktonic and biofilm cultures of oral pathogens. Antimicrob Agents Chemother 51:4125–4132. CrossRefPubMedPubMedCentralGoogle Scholar
  14. Belley A, Neesham-Grenon E, McKay G et al (2009) Oritavancin kills stationary-phase and biofilm Staphylococcus aureus cells in vitro. Antimicrob Agents Chemother 53:918–925. CrossRefPubMedGoogle Scholar
  15. Berditsch M, Jäger T, Strempel N et al (2015) Synergistic effect of membrane-active peptides polymyxin B and gramicidin s on multidrug-resistant strains and biofilms of Pseudomonas aeruginosa. Antimicrob Agents Chemother 59:5288–5296. CrossRefPubMedPubMedCentralGoogle Scholar
  16. Bispo P, Haas W, Gilmore M (2015) Biofilms in infections of the eye. Pathogens 4:111–136. CrossRefPubMedPubMedCentralGoogle Scholar
  17. Blower RJ, Barksdale SM, van Hoek ML (2015) Snake cathelicidin NA-CATH and smaller helical antimicrobial peptides are effective against Burkholderia thailandensis. PLoS Negl Trop Dis 9:e0003862. CrossRefPubMedPubMedCentralGoogle Scholar
  18. Brancatisano FL, Maisetta G, Di Luca M et al (2014) Inhibitory effect of the human liver-derived antimicrobial peptide hepcidin 20 on biofilms of polysaccharide intercellular adhesin (PIA)-positive and PIA-negative strains of Staphylococcus epidermidis. Biofouling 30:435–446. CrossRefPubMedGoogle Scholar
  19. Bray BL (2003) Large-scale manufacture of peptide therapeutics by chemical synthesis. Nat Rev Drug Discov 2:587–593. CrossRefPubMedGoogle Scholar
  20. Bryers JD, Ratner BD (2004) Bioinspired implant materials befuddle bacteria. ASM News 70:232–237. Scholar
  21. Busscher HJ, van der Mei HC, Subbiahdoss G et al (2012) Biomaterial-associated infection: locating the finish line in the race for the surface. Sci Transl Med 4:153rv10. CrossRefPubMedGoogle Scholar
  22. Cao J, De La Fuente-Nunez C, Ou RW et al (2018) Yeast-based synthetic biology platform for antimicrobial peptide production. ACS Synth Biol 7:896–902. CrossRefPubMedGoogle Scholar
  23. Carmona-Ribeiro (2000) Interactions between cationic liposomes and drugs or biomolecules. An Acad Bras Cienc. 72(1):39–43. CrossRefGoogle Scholar
  24. CDC (2013) Antibiotic resistance threats in the United States, 2013.
  25. Chen Y, Mant CT, Farmer SW et al (2005) Rational design of alpha-helical antimicrobial peptides with enhanced activities and specificity/therapeutic index. J Biol Chem 280:12316–12329. CrossRefPubMedPubMedCentralGoogle Scholar
  26. Chen X, Hirt H, Li Y et al (2014) Antimicrobial GL13K peptide coatings killed and ruptured the wall of Streptococcus gordonii and prevented formation and growth of biofilms. PLoS One 9:e111579. CrossRefPubMedPubMedCentralGoogle Scholar
  27. Cheng H, Yue K, Kazemzadeh-Narbat M et al (2017) Mussel-inspired multifunctional hydrogel coating for prevention of infections and enhanced osteogenesis. ACS Appl Mater Interfaces 9:11428–11439. CrossRefPubMedPubMedCentralGoogle Scholar
  28. Chernysh S, Gordya N, Tulin D, Yakovlev A (2018) Biofilm infections between Scylla and Charybdis: interplay of host antimicrobial peptides and antibiotics. Infect Drug Resist 11:501–514. CrossRefPubMedPubMedCentralGoogle Scholar
  29. Cirioni O, Giacometti A, Ghiselli R et al (2006) RNAIII-inhibiting peptide significantly reduces bacterial load and enhances the effect of antibiotics in the treatment of central venous catheter-associated Staphylococcus aureus infections. J Infect Dis 193:180–186. CrossRefPubMedGoogle Scholar
  30. Cleophas RTC, Riool M, Quarles van Ufford H, Linda C et al (2014) Convenient preparation of bactericidal hydrogels by covalent attachment of stabilized antimicrobial peptides using thiol–ene click chemistry. ACS Macro Lett 3:477–480. CrossRefGoogle Scholar
  31. Cools TL, Struyfs C, Drijfhout JW et al (2017) A linear 19-mer plant defensin-derived peptide acts synergistically with caspofungin against Candida albicans biofilms. Front Microbiol 8:1–14. CrossRefGoogle Scholar
  32. Costa F, Carvalho IF, Montelaro RC et al (2011) Covalent immobilization of antimicrobial peptides (AMPs) onto biomaterial surfaces. Acta Biomater 7:1431–1440. CrossRefPubMedGoogle Scholar
  33. d’Angelo I, Casciaro B, Miro A et al (2015) Overcoming barriers in Pseudomonas aeruginosa lung infections: engineered nanoparticles for local delivery of a cationic antimicrobial peptide. Colloids Surf B Biointerfaces 135:717–725. CrossRefPubMedGoogle Scholar
  34. Davey ME, O’Toole GA (2000) Microbial biofilms: from ecology to molecular genetics. Microbiol Mol Biol Rev 64:847–867. CrossRefGoogle Scholar
  35. De la Fuente-Núñez C, Korolik V, Bains M et al (2012) Inhibition of bacterial biofilm formation and swarming motility by a small synthetic cationic peptide. Antimicrob Agents Chemother 56:2696–2704. CrossRefGoogle Scholar
  36. 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:e1004152. CrossRefGoogle Scholar
  37. 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 22:196–205. CrossRefPubMedPubMedCentralGoogle Scholar
  38. De Zoysa GH, Sarojini V (2017) Feasibility study exploring the potential of novel Battacin Lipopeptides as antimicrobial coatings. ACS Appl Mater Interfaces 9:1373–1383. CrossRefPubMedGoogle Scholar
  39. Dean SN, Bishop BM, van Hoek ML (2011) Natural and synthetic cathelicidin peptides with anti-microbial and anti-biofilm activity against Staphylococcus aureus. BMC Microbiol 11. CrossRefGoogle Scholar
  40. Dutta D, Kumar N, Willcox MDP (2016) Antimicrobial activity of four cationic peptides immobilised to poly-hydroxyethylmethacrylate. Biofouling 32(4):429–438CrossRefGoogle Scholar
  41. Di Luca M, Maccari G, Nifosì R (2014) Treatment of microbial biofilms in the post-antibiotic era: prophylactic and therapeutic use of antimicrobial peptides and their design by bioinformatics tools. Pathog Dis 70:257–270. CrossRefPubMedGoogle Scholar
  42. Di Luca M, Maccari G, Maisetta G, Batoni G (2015) BaAMPs: the database of biofilm-active antimicrobial peptides. Biofouling 31:193–199. CrossRefPubMedGoogle Scholar
  43. Domenico P, Gurzenda E, Giacometti A et al (2004) BisEDT and RIP act in synergy to prevent graft infections by resistant staphylococci. Peptides 25:2047–2053. CrossRefPubMedGoogle Scholar
  44. Donlan RM (2002) Biofilms: microbial life on surfaces. Emerg Infect Dis 8:881–890. CrossRefPubMedPubMedCentralGoogle Scholar
  45. Dudeck MA, Weiner LM, Allen-Bridson K et al (2013) National Healthcare Safety Network (NHSN) report, data summary for 2012, device-associated module. Am J Infect Control 41:1148–1166. CrossRefPubMedPubMedCentralGoogle Scholar
  46. ECDC (2009) The bacterial challenge: time to react. A call to narrow the gap between multidrug-resistant bacteria in the EU and the development of new antibacterial agents. Scholar
  47. Eckert R, Brady KM, Greenberg EP et al (2006) Enhan-cement of antimicrobial activity against Pseudomonas aeruginosa by coadministration of G10KHc and tobramycin. Antimicrob Agents Chemother 50:3833–3838. CrossRefGoogle Scholar
  48. Eilers H, Alexeyev OA (2016) Effect of GT-peptide 10 and triethyl citrate on P. acnes biofilm formation, viability, and dispersion. J Drugs Dermatol 15:778–781.
  49. Fernández-Hidalgo N, Almirante B (2014) Antibiotic-lock therapy: a clinical viewpoint. Expert Rev Anti-Infect Ther 12:117–129. CrossRefGoogle Scholar
  50. Field D, O’Connor R, Cotter PD et al (2016a) In vitro activities of nisin and nisin derivatives alone and in combination with antibiotics against staphylococcus biofilms. Front Microbiol 7:1–11. CrossRefGoogle Scholar
  51. Field D, Seisling N, Cotter PD et al (2016b) Synergistic nisin-polymyxin combinations for the control of pseudomonas biofilm formation. Front Microbiol 7:1–7. CrossRefGoogle Scholar
  52. Fjell CD, Hiss JA, Hancock REW, Schneider G (2011) Designing antimicrobial peptides: form follows function. Nat Rev Drug Discov 11:37–51. CrossRefPubMedGoogle Scholar
  53. Flemming H-C, Wingender J (2010) The biofilm matrix. Nat Rev Microbiol 8:623–633. CrossRefPubMedGoogle Scholar
  54. Forbes S, McBain AJ, Felton-Smith S et al (2013) Comparative surface antimicrobial properties of synthetic biocides and novel human apolipoprotein E derived antimicrobial peptides. Biomaterials 34:5453–5464. CrossRefPubMedGoogle Scholar
  55. Gabriel M, Nazmi K, Veerman EC et al (2006) Preparation of LL-37-grafted titanium surfaces with bactericidal activity. Bioconjug Chem 17:548–550. CrossRefGoogle Scholar
  56. Gaglione R, Dell’Olmo E, Bosso A et al (2017) Novel human bioactive peptides identified in apolipoprotein B: evaluation of their therapeutic potential. Biochem Pharmacol 130:34–50. CrossRefPubMedGoogle Scholar
  57. Gawande PV, Leung KP, Madhyastha S (2014) Antibiofilm and antimicrobial efficacy of Dispersinb®-KSL-w peptide-based wound gel against chronic wound infection associated bacteria. Curr Microbiol 68:635–641. CrossRefPubMedGoogle Scholar
  58. Gbejuade HO, Lovering AM, Webb JC (2014) The role of microbial biofilms in prosthetic joint infections. Acta Orthop 86:1–12. CrossRefGoogle Scholar
  59. Giamarellou H (2002) Nosocomial cardiac infections. J Hosp Infect 50:91–105. CrossRefGoogle Scholar
  60. Godoy-Gallardo M, Mas-Moruno C, Fernández-Calderón MC et al (2014) Covalent immobilization of hLf1-11 peptide on a titanium surface reduces bacterial adhesion and biofilm formation. Acta Biomater 10:3522–3534. CrossRefPubMedGoogle Scholar
  61. Gopal R, Kim YG, Lee JH et al (2014) Synergistic effects and antibiofilm properties of chimeric peptides against multidrug-resistant Acinetobacter baumannii strains. Antimicrob Agents Chemother 58:1622–1629. CrossRefPubMedPubMedCentralGoogle Scholar
  62. Grassi L, Maisetta G, Esin S, Batoni G (2017a) Combination strategies to enhance the efficacy of antimicrobial peptides against bacterial biofilms. Front Microbiol 8:2409. CrossRefPubMedPubMedCentralGoogle Scholar
  63. Grassi L, Maisetta G, Maccari G et al (2017b) Analogs of the frog-skin antimicrobial peptide temporin 1Tb exhibit a wider spectrum of activity and a stronger antibiofilm potential as compared to the parental peptide. Front Chem 5:1–13. CrossRefGoogle Scholar
  64. Gristina AG (1987) Biomaterial-centered infection: microbial adhesion versus tissue integration. Science 237:1588–1595. CrossRefPubMedGoogle Scholar
  65. Guggenbichler JP, Assadian O, Boeswald M, Kramer A (2011) Incidence and clinical implication of nosocomial infections associated with implantable biomaterials – catheters, ventilator-associated pneumonia, urinary tract infections. GMS Krankenhhyg Interdiszip 6:Doc18. CrossRefPubMedPubMedCentralGoogle Scholar
  66. Gupta S, Kapoor P, Chaudhary K et al (2013) In silico approach for predicting toxicity of peptides and proteins. PLoS One 8:e73957. CrossRefPubMedPubMedCentralGoogle Scholar
  67. Hall CW, Mah T-F (2017) Molecular mechanisms of biofilm-based antibiotic resistance and tolerance in pathogenic bacteria. FEMS Microbiol Rev 41:276–301. CrossRefPubMedGoogle Scholar
  68. Hancock REW (2015) Rethinking the antibiotic discovery paradigm. EBIOM 2:629–630. CrossRefGoogle Scholar
  69. Harms A, Maisonneuve E, Gerdes K (2016) Mechanisms of bacterial persistence during stress and antibiotic exposure. Science 354:aaf4268. CrossRefPubMedGoogle Scholar
  70. Heinbockel L, de Tejada G, Sánchez-Gómez S, et al (2014) Anti-infective polypeptides for combating bacterial and viral infections. In: Frontiers in clinical drug research: anti-infectives. Bentham Science Publishers, p 3–31.
  71. Herrmann G, Yang L, Wu H et al (2010) Colistin-tobramycin combinations are superior to monotherapy concerning the killing of biofilm Pseudomonas aeruginosa. J Infect Dis 202:1585–1592. CrossRefPubMedGoogle Scholar
  72. Hill D, Hill D, Rose B et al (2005) Antibiotic susceptibility of Pseudomonas aeruginosa isolates derived from patients with cystic fibrosis under aerobic, anaerobic, and biofilm conditions. J Clin Microbiol 43:5085–5090. CrossRefPubMedPubMedCentralGoogle Scholar
  73. Hirt H, Gorr SU (2013) Antimicrobial peptide GL13K is effective in reducing biofilms of Pseudomonas aeruginosa. Antimicrob Agents Chemother 57:4903–4910. CrossRefPubMedPubMedCentralGoogle Scholar
  74. Hobby CR, Herndon JL, Morrow CA et al (2018) Exogenous fatty acids alter phospholipid composition, membrane permeability, capacity for biofilm formation, and antimicrobial peptide susceptibility in Klebsiella pneumoniae. Microbiology 635:1–11. CrossRefGoogle Scholar
  75. Høiby N, Ciofu O, Bjarnsholt T (2010) Pseudomonas aeruginosa biofilms in cystic fibrosis. Future Microbiol 5:1663–1674. CrossRefPubMedGoogle Scholar
  76. Howard JJ, Sturge CR, Moustafa DA et al (2017) Inhibition of Pseudomonas aeruginosa by peptide-conjugated phosphorodiamidate morpholino oligomers. Antimicrob Agents Chemother 61:e01938–e01916. CrossRefPubMedPubMedCentralGoogle Scholar
  77. Hoyos-Nogués M, Velasco F, Ginebra M-P et al (2017) Regenerating bone via multifunctional coatings: the blending of cell integration and bacterial inhibition properties on the surface of biomaterials. ACS Appl Mater Interfaces 9:21618–21630. CrossRefPubMedGoogle Scholar
  78. Hwang IS, Hwang JS, Hwang JH et al (2013) Synergistic effect and antibiofilm activity between the antimicrobial peptide coprisin and conventional antibiotics against opportunistic bacteria. Curr Microbiol 66:56–60. CrossRefPubMedGoogle Scholar
  79. Jamal M, Ahmad W, Andleeb S et al (2018) Bacterial biofilm and associated infections. J Chin Med Assoc 81:7–11. CrossRefPubMedGoogle Scholar
  80. Jefferson KK (2004) What drives bacteria to produce a biofilm? FEMS Microbiol Lett 236:163–173. CrossRefPubMedGoogle Scholar
  81. Jones EA, McGillivary G, Bakaletz LO (2013) Extracellular DNA within a nontypeable haemophilus influenzae-induced biofilm binds human beta defensin-3 and reduces its antimicrobial activity. J Innate Immun 5:24–38. CrossRefPubMedGoogle Scholar
  82. Jorge P, Lourenço A, Pereira MO (2012) New trends in peptide-based anti-biofilm strategies: a review of recent achievements and bioinformatic approaches. Biofouling 28:1033–1061. CrossRefPubMedGoogle Scholar
  83. Jorge P, Grzywacz D, Kamysz W et al (2017) Searching for new strategies against biofilm infections: colistin-AMP combinations against pseudomonas aeruginosa and staphylococcus aureus single- and double-species biofilms. PLoS One 12:1–21. CrossRefGoogle Scholar
  84. Justo JA, Bookstaver PB (2014) Antibiotic lock therapy: review of technique and logistical challenges. Infect Drug Resist 7:343–363. CrossRefPubMedPubMedCentralGoogle Scholar
  85. Kanthawong S, Bolscher JGM, Veerman ECI et al (2012) Antimicrobial and antibiofilm activity of LL-37 and its truncated variants against Burkholderia pseudomallei. Int J Antimicrob Agents 39:39–44. CrossRefPubMedGoogle Scholar
  86. Karygianni L, Al-Ahmad A, Argyropoulou A et al (2016) Natural antimicrobials and oral microorganisms: a systematic review on herbal interventions for the eradication of multispecies oral biofilms. Front Microbiol 6:1–17. CrossRefGoogle Scholar
  87. Kazemzadeh-Narbat M, Kindrachuk J, Duan K et al (2010) Antimicrobial peptides on calcium phosphate-coated titanium for the prevention of implant-associated infections. Biomaterials 31:9519–9526. CrossRefPubMedGoogle Scholar
  88. Kostakioti M, Hadjifrangiskou M, Hultgren SJ (2013) Bacterial biofilms: development, dispersal, and therapeutic strategies in the dawn of the postantibiotic era. Cold Spring Harb Perspect Med 3:1–23. CrossRefGoogle Scholar
  89. Lai Y, Gallo RL (2009) AMPed up immunity: how antimicrobial peptides have multiple roles in immune defense. Trends Immunol 30:131–141. CrossRefPubMedPubMedCentralGoogle Scholar
  90. Landini P, Antoniani D, Burgess JG, Nijland R (2010) Molecular mechanisms of compounds affecting bacterial biofilm formation and dispersal. Appl Microbiol Biotechnol 86:813–823. CrossRefPubMedGoogle Scholar
  91. Lashua LP, Melvin JA, Deslouches B et al (2016) Engineered cationic antimicrobial peptide (eCAP) prevents Pseudomonas aeruginosa biofilm growth on airway epithelial cells. J Antimicrob Chemother 71:2200–2207. CrossRefPubMedPubMedCentralGoogle Scholar
  92. Lebeaux D, Ghigo J-M, Beloin C (2014) Biofilm-related infections: bridging the gap between clinical management and fundamental aspects of recalcitrance toward antibiotics. Microbiol Mol Biol Rev 78:510–543. CrossRefPubMedPubMedCentralGoogle Scholar
  93. Lehner A, Riedel K, Eberl L et al (2005) Biofilm formation, extracellular polysaccharide production, and cell-to-cell signaling in various Enterobacter sakazakii strains: aspects promoting environmental persistence. J Food Prot 68:2287–2294. Scholar
  94. Li Y, Wei S, Wu J et al (2015a) Effects of peptide immobilization sites on the structure and activity of surface-tethered antimicrobial peptides. J Phys Chem C 119:7146–7155. CrossRefGoogle Scholar
  95. Li S, Zhu C, Fang S et al (2015b) Ultrasound microbubbles enhance human β-defensin 3 against biofilms. J Surg Res 199:458–469. CrossRefPubMedGoogle Scholar
  96. Lim K, Chua RRY, Saravanan R et al (2013) Immobilization studies of an engineered arginine–tryptophan-rich peptide on a silicone surface with antimicrobial and antibiofilm activity. ACS Appl Mater Interfaces 5:6412–6422. CrossRefPubMedGoogle Scholar
  97. Lim K, Chua RRY, Ho B et al (2015) Development of a catheter functionalized by a polydopamine peptide coating with antimicrobial and antibiofilm properties. Acta Biomater 15:127–138. CrossRefPubMedGoogle Scholar
  98. Liu X, Yin H, Weng CX, Cai Y (2016) Low-frequency ultrasound enhances antimicrobial activity of colistin-vancomycin combination against pan-resistant biofilm of acinetobacter baumannii. Ultrasound Med Biol 42:1968–1975. CrossRefPubMedGoogle Scholar
  99. Lora-Tamayo J, Murillo O, Bergen PJ et al (2014) Activity of colistin combined with doripenem at clinically relevant concentrations against multidrug-resistant pseudomonas aeruginosa in an in vitro dynamic biofilm model. J Antimicrob Chemother 69:2434–2442. CrossRefPubMedGoogle Scholar
  100. Luo Y, McLean DTF, Linden GJ et al (2017) The naturally occurring host defense peptide, LL-37, and its truncated mimetics KE-18 and KR-12 have selected biocidal and antibiofilm activities against Candida albicans, Staphylococcus aureus, and Escherichia coli in vitro. Front Microbiol 8:544. CrossRefPubMedPubMedCentralGoogle Scholar
  101. Mah TFC, O’Toole GA (2001) Mechanisms of biofilm resistance to antimicrobial agents. Trends Microbiol 9:34–39. CrossRefPubMedGoogle Scholar
  102. Maisetta G, Grassi L, Di Luca M et al (2016) Anti-biofilm properties of the antimicrobial peptide temporin 1Tb and its ability, in combination with EDTA, to eradicate Staphylococcus epidermidis biofilms on silicone catheters. Biofouling 32:787–800. CrossRefPubMedGoogle Scholar
  103. Maisetta G, Grassi L, Esin S et al (2017) The semi-synthetic peptide Lin-SB056-1 in combination with EDTA exerts strong antimicrobial and antibiofilm activity against pseudomonas aeruginosa in conditions mimicking cystic fibrosis sputum. Int J Mol Sci 18:1–18. CrossRefGoogle Scholar
  104. Malmsten M, Kasetty G, Pasupuleti M et al (2011) Highly selective end-tagged antimicrobial peptides derived from PRELP. PLoS One 6:e16400. CrossRefPubMedPubMedCentralGoogle Scholar
  105. 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 21:323–329. CrossRefPubMedGoogle Scholar
  106. Mataraci Kara E, Ozbek Celik B (2018) Investigation of the effects of various antibiotics against Klebsiella pneumoniae biofilms on in vitro catheter model. J Chemother 30:82–88. CrossRefPubMedGoogle Scholar
  107. Messing B, Peitra-Cohen S, Debure A et al (1988) Antibiotic-lock technique: a new approach to optimal therapy for catheter-related sepsis in home-parenteral nutrition patients. J Parenter Enter Nutr 12:185–189. CrossRefGoogle Scholar
  108. Mielich-Süss B, Lopez D (2015) Molecular mechanisms involved in Bacillus subtilis biofilm formation. Environ Microbiol 17:555–565. CrossRefPubMedGoogle Scholar
  109. Miller SM, Simon RJ, Ng S et al (1994) Proteolytic studies of homologous peptide and N-substituted glycine peptoid oligomers. Bioorg Med Chem Lett 4:2657–2662. CrossRefGoogle Scholar
  110. Minardi D, Ghiselli R, Cirioni O et al (2007) The antimicrobial peptide Tachyplesin III coated alone and in combination with intraperitoneal piperacillin-tazobactam prevents ureteral stent pseudomonas infection in a rat subcutaneous pouch model. Peptides 28:2293–2298. CrossRefPubMedGoogle Scholar
  111. Mishra B, Wang G (2017) Individual and combined effects of engineered peptides and antibiotics on Pseudomonas aeruginosa biofilms. Pharmaceuticals 10.
  112. Mishra NM, Briers Y, Lamberigts C et al (2015) Evaluation of the antibacterial and antibiofilm activities of novel CRAMP–vancomycin conjugates with diverse linkers. Org Biomol Chem 13:7477–7486. CrossRefPubMedGoogle Scholar
  113. Mokkaphan J, Banlunara W, Palaga T et al (2014) Silicone surface with drug nanodepots for medical devices. ACS Appl Mater Interfaces 6:20188–20196. CrossRefPubMedGoogle Scholar
  114. Mora-Navarro C, Caraballo-Leõn J, Torres-Lugo M, Ortiz-Bermúdez P (2015) Synthetic antimicrobial β-peptide in dual-treatment with fluconazole or ketoconazole enhances the in vitro inhibition of planktonic and biofilm Candida albicans. J Pept Sci 21:853–861. CrossRefPubMedGoogle Scholar
  115. Mygind PH, Fischer RL, Schnorr KM et al (2005) Plectasin is a peptide antibiotic with therapeutic potential from a saprophytic fungus. Nature 437:975–980. CrossRefPubMedGoogle Scholar
  116. Nguyen LT, Chau JK, Perry NA et al (2010) Serum stabilities of short tryptophan- and arginine-rich antimicrobial peptide analogs. PLoS One 5:e12684. CrossRefPubMedPubMedCentralGoogle Scholar
  117. Nie B, Ao H, Long T et al (2017) Immobilizing bacitracin on titanium for prophylaxis of infections and for improving osteoinductivity: an in vivo study. Colloids Surf B Biointerfaces 150:183–191. CrossRefPubMedGoogle Scholar
  118. Niemirowicz K, Piktel E, Wilczewska AZ et al (2016) Core–shell magnetic nanoparticles display synergistic antibacterial effects against Pseudomonas aeruginosa and Staphylococcus aureus when combined with cathelicidin LL-37 or selected ceragenins. Int J Nanomedicine 11:5443–5455. CrossRefPubMedPubMedCentralGoogle Scholar
  119. Oh E, Bae J, Kumar A et al (2018) Antioxidant-based synergistic eradication of methicillin-resistant Staphylococcus aureus (MRSA) biofilms with bacitracin. Int J Antimicrob Agents. CrossRefGoogle Scholar
  120. Orlando F, Ghiselli R, Cirioni O et al (2008) BMAP-28 improves the efficacy of vancomycin in rat models of gram-positive cocci ureteral stent infection. Peptides 29:1118–1123. CrossRefPubMedGoogle Scholar
  121. Overhage J, Campisano A, Bains M et al (2008) Human host defense peptide LL-37 prevents bacterial biofilm formation. Infect Immun 76:4176–4182. CrossRefPubMedPubMedCentralGoogle Scholar
  122. Ozbek B, Mataraci E (2013) In vitro effectiveness of colistin, tigecycline and levofloxacin alone and combined with clarithromycin and/or heparin as lock solutions against embedded Acinetobacter baumannii strains. J Antimicrob Chemother 68:827–830. CrossRefPubMedGoogle Scholar
  123. Ozbek B, Mataraci-Kara E (2016) Comparative in vitro efficacies of various antipseudomonal antibiotics based catheter lock solutions on eradication of Pseudomonas aeruginosa biofilms. J Chemother 28:20–24. CrossRefPubMedGoogle Scholar
  124. Palmer J, Flint S, Brooks J (2007) Bacterial cell attachment, the beginning of a biofilm. J Ind Microbiol Biotechnol 34:577–588. CrossRefPubMedGoogle Scholar
  125. Pletzer D, Hancock REW (2016) Antibiofilm peptides: potential as broad-spectrum agents. J Bacteriol 198:2572–2578. CrossRefPubMedPubMedCentralGoogle Scholar
  126. Pletzer D, Coleman SR, Hancock REW (2016) Anti-biofilm peptides as a new weapon in antimicrobial warfare. Curr Opin Microbiol 33:35–40. CrossRefPubMedPubMedCentralGoogle Scholar
  127. Rabin N, Zheng Y, Opoku-Temeng C et al (2008) Biofilm formation mechanisms and targets for developing antibiofilm agents. Future Med Chem 7:493–512. CrossRefGoogle Scholar
  128. Rajasekaran G, Kim EY, Shin SY (2017) LL-37-derived membrane-active FK-13 analogs possessing cell selectivity, anti-biofilm activity and synergy with chloramphenicol and anti-inflammatory activity. Biochim Biophys Acta Biomembr 1859:722–733. CrossRefPubMedGoogle Scholar
  129. Reffuveille F, de la Fuente-Núñez C, Mansour S, Hancock REW (2014) A broad-spectrum antibiofilm peptide enhances antibiotic action against bacterial biofilms. Antimicrob Agents Chemother 58:5363–5371. CrossRefPubMedPubMedCentralGoogle Scholar
  130. Ren H, Wu J, Colletta A et al (2016) Efficient eradication of mature Pseudomonas aeruginosa biofilm via controlled delivery of nitric oxide combined with antimicrobial peptide and antibiotics. Front Microbiol 7:1–8. CrossRefGoogle Scholar
  131. Riool M, de Breij A, Drijfhout JW et al (2017) Antimicrobial peptides in biomedical device manufacturing. Front Chem 5:63. CrossRefPubMedPubMedCentralGoogle Scholar
  132. Roilides E, Simitsopoulou M, Katragkou A, Walsh TJ (2015) How biofilms evade host defenses. Microbiol Spectr 3:287–300. CrossRefGoogle Scholar
  133. Rudilla H, Fusté E, Cajal Y et al (2016) Synergistic antipseudomonal effects of synthetic peptide AMP38 and carbapenems. Molecules 21:1–12. CrossRefGoogle Scholar
  134. Sánchez-Gómez S, Martínez-de-Tejada G (2017) Antimicrobial peptides as anti-biofilm agents in medical implants. Curr Top Med Chem 17:590–603. CrossRefGoogle Scholar
  135. Sánchez-Gómez S, Ferrer-Espada R, Stewart PS et al (2015) Antimicrobial activity of synthetic cationic peptides and lipopeptides derived from human lactoferricin against Pseudomonas aeruginosa planktonic cultures and biofilms. BMC Microbiol 15:137. CrossRefPubMedPubMedCentralGoogle Scholar
  136. Scarsini M, Tomasinsig L, Arzese A et al (2015) Antifungal activity of cathelicidin peptides against planktonic and biofilm cultures of Candida species isolated from vaginal infections. Peptides 71:211–221. CrossRefPubMedGoogle Scholar
  137. Sharma A, Gupta P, Kumar R, Bhardwaj A (2016) dPABBs: a novel in silico approach for predicting and designing anti-biofilm peptides. Sci Rep 6:21839. CrossRefPubMedPubMedCentralGoogle Scholar
  138. Shire SJ, Shahrokh Z, Liu J (2004) Challenges in the development of high protein concentration formulations. J Pharm Sci 93:1390–1402. CrossRefPubMedGoogle Scholar
  139. Silva RR, Avelino KYPS, Ribeiro KL et al (2016) Chemical immobilization of antimicrobial peptides on biomaterial surfaces. Front Biosci (Schol Ed) 8:129–142. CrossRefGoogle Scholar
  140. Simonetti O, Cirioni O, Cacciatore I et al (2016) Efficacy of the quorum sensing inhibitor FS10 alone and in combination with tigecycline in an animal model of staphylococcal infected wound. PLoS One 11:1–12. CrossRefGoogle Scholar
  141. Singh PK, Parsek MR, Greenberg EP, Welsh MJ (2002) A component of innate immunity prevents bacterial biofilm development. Nature 417:552–555. CrossRefPubMedGoogle Scholar
  142. Singh K, Shekhar S, Yadav Y et al (2017) DS6: anticandidal, antibiofilm peptide against Candida tropicalis and exhibit synergy with commercial drug. J Pept Sci 23:228–235. CrossRefPubMedGoogle Scholar
  143. Singha P, Locklin J, Handa H (2017) A review of the recent advances in antimicrobial coatings for urinary catheters. Acta Biomater 50:20–40. CrossRefPubMedGoogle Scholar
  144. Stanley NR, Lazazzera BA (2004) Environmental signals and regulatory pathways that influence biofilm formation. Mol Microbiol 52:917–924. CrossRefPubMedGoogle Scholar
  145. Stewart PS, Costerton JW (2001) Antibiotic resistance of bacteria in biofilms. Lancet 358:135–138. CrossRefGoogle Scholar
  146. Strömstedt AA, Pasupuleti M, Schmidtchen A, Malmsten M (2009) Evaluation of strategies for improving proteolytic resistance of antimicrobial peptides by using variants of EFK17, an internal segment of LL-37. Antimicrob Agents Chemother 53:593–602. CrossRefPubMedGoogle Scholar
  147. Tan XW, Lakshminarayanan R, Liu SP et al (2012) Dual functionalization of titanium with vascular endothelial growth factor and β-defensin analog for potential application in keratoprosthesis. J Biomed Mater Res B Appl Biomater 100B:2090–2100. CrossRefGoogle Scholar
  148. Tong Z, Ling J, Lin Z et al (2013) The effect of MTADN on 10 enterococcus faecalis isolates and biofilm: an in vitro study. J Endod 39:674–678. CrossRefPubMedGoogle Scholar
  149. Tong Z, Zhang Y, Ling J, et al (2014a) An in vitro study on the effects of nisin on the antibacterial activities of 18 antibiotics against enterococcus faecalis. PLoS One 9. CrossRefGoogle Scholar
  150. Tong Z, Zhang L, Ling J et al (2014b) An in vitro study on the effect of free amino acids alone or in combination with nisin on biofilms as well as on planktonic bacteria of Streptococcus mutans. PLoS One 9:3–10. CrossRefGoogle Scholar
  151. Venkatesh M, Rong L, Raad I, Versalovic J (2009) Novel synergistic antibiofilm combinations for salvage of infected catheters. J Med Microbiol 58:936–944. CrossRefPubMedGoogle Scholar
  152. Vincentelli J, Braguer D, Guillet P et al (1997) Formulation of a flush solution of heparin, vancomycin, and colistin for implantable access systems in oncology. J Oncol Pharm Pract 3:18–23. Scholar
  153. Wakabayashi H, Yamauchi K, Kobayashi T et al (2009) Inhibitory effects of lactoferrin on growth and biofilm formation of Porphyromonas gingivalis and Prevotella intermedia. Antimicrob Agents Chemother 53:3308–3316. CrossRefPubMedPubMedCentralGoogle Scholar
  154. Wang Z, De La Fuente-Núñez C, Shen Y et al (2015) Treatment of oral multispecies biofilms by an anti-biofilm peptide. PLoS One 10:1–16. CrossRefGoogle Scholar
  155. Willcox MDP, Hume EBH, Aliwarga Y et al (2008) A novel cationic-peptide coating for the prevention of microbial colonization on contact lenses. J Appl Microbiol 105:1817–1825. CrossRefPubMedGoogle Scholar
  156. Wu H, Moser C, Wang H-Z et al (2015) Strategies for combating bacterial biofilm infections. Int J Oral Sci 7:1–7. CrossRefPubMedGoogle Scholar
  157. Xu W, Zhu X, Tan T et al (2014) Design of embedded-hybrid antimicrobial peptides with enhanced cell selectivity and anti-biofilm activity. PLoS One 9:e98935. CrossRefPubMedPubMedCentralGoogle Scholar
  158. Yazici H, O’Neill MB, Kacar T et al (2016) Engineered chimeric peptides as antimicrobial surface coating agents toward infection-free implants. ACS Appl Mater Interfaces 8:5070–5081. CrossRefPubMedPubMedCentralGoogle Scholar
  159. Yoshinari M, Kato T, Matsuzaka K et al (2010) Prevention of biofilm formation on titanium surfaces modified with conjugated molecules comprised of antimicrobial and titanium-binding peptides. Biofouling 26:103–110. CrossRefPubMedGoogle Scholar
  160. Yu L, Hou Y, Cheng C et al (2017a) High-antifouling polymer brush coatings on nonpolar surfaces via adsorption-cross-linking strategy. ACS Appl Mater Interfaces 9:44281–44292. CrossRefPubMedGoogle Scholar
  161. Yu K, Lo JCY, Yan M et al (2017b) Anti-adhesive antimicrobial peptide coating prevents catheter associated infection in a mouse urinary infection model. Biomaterials 116:69–81. CrossRefPubMedGoogle Scholar
  162. Zhang T, Wang Z, Hancock REW et al (2016) Treatment of oral biofilms by a D-enantiomeric peptide. PLoS One 11:1–16. CrossRefGoogle Scholar
  163. Zhu C, Tan H, Cheng T et al (2013) Human β-defensin 3 inhibits antibiotic-resistant staphylococcus biofilm formation. J Surg Res 183:204–213. CrossRefPubMedGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Hawraa Shahrour
    • 1
    • 2
    • 3
  • Raquel Ferrer-Espada
    • 1
    • 4
  • Israa Dandache
    • 2
    • 3
  • Sergio Bárcena-Varela
    • 1
  • Susana Sánchez-Gómez
    • 5
  • Ali Chokr
    • 2
    • 3
  • Guillermo Martinez-de-Tejada
    • 1
    Email author
  1. 1.Department of Microbiology and ParasitologyUniversity of NavarraPamplonaSpain
  2. 2.Laboratory of Microbiology, Department of Life & Earth Sciences, Faculty of Sciences ILebanese University, Hadat campusBeirutLebanon
  3. 3.Platform of Research and Analysis in Environmental Sciences (PRASE), Doctoral School of Sciences and TechnologiesLebanese University, Hadat CampusBeirutLebanon
  4. 4.Wellman Center for PhotomedicineMassachusetts General Hospital, Harvard Medical SchoolBostonUSA
  5. 5.Bionanoplus S.L. Polígono MocholíNoainSpain

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