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Novel Treatment Strategies for Biofilm-Based Infections

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Abstract

Biofilm-growing cells show an enhanced antimicrobial tolerance with respect to the same cells growing in a free-floating way. This is due to physical or chemical diffusion barriers and increased transfer of resistance markers. Thus, tissue- and medical device-related biofilms can be considered among the leading sources of antibiotic treatment failure, causing many of the deadliest chronic infections afflicting humans nowadays. To find a satisfying way to counteract this major health threat, a great effort has been made in recent years to develop safe, effective and fast-acting anti-biofilm strategies. In this review, we summarise and evaluate the most promising tools and molecules that have demonstrated their ability to modulate steps involved in biofilm formation or to disperse pre-formed biofilms, without conferring evolutionary pressure to microorganisms.

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References

  1. Costerton JW, Geesey GG, Cheng KJ. How bacteria stick. Sci Am. 1978;238:86–95.

    Article  CAS  PubMed  Google Scholar 

  2. Akers KS, Cardile AP, Wenke JC, Murray CK. Biofilm formation by clinical isolates and its relevance to clinical infections. Adv Exp Med Biol. 2015;830:1–28.

    Article  PubMed  Google Scholar 

  3. Stoodley P, Sauer K, Davies DG, Costerton JW. Biofilms as complex differentiated communities. Annu Rev Microbiol. 2002;56:187–209.

    Article  CAS  PubMed  Google Scholar 

  4. Watnick PI, Kolter R. Steps in the development of a Vibrio cholerae El Tor biofilm. Mol Microbiol. 1999;34:586–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Prigent-Combaret C, Vidal O, Dorel C, Lejeune P. Abiotic surface sensing and biofilm-dependent regulation of gene expression in Escherichia coli. J Bacteriol. 1999;181:5993–6002.

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Davies DG, Parsek MR, Pearson JP, Iglewski BH, Costerton JW, Greenberg EP. The involvement of cell-to-cell signals in the development of a bacterial biofilm. Science. 1998;280:295–8.

    Article  CAS  PubMed  Google Scholar 

  7. Rumbaugh KP, Diggle SP, Watters CM, Ross-Gillespie A, Griffin AS, West SA. Quorum sensing and the social evolution of bacterial virulence. Curr Biol. 2009;19:341–5.

    Article  CAS  PubMed  Google Scholar 

  8. Høiby N, Bjarnsholt T, Givskov M, Molin S, Ciofu O. Antibiotic resistance of bacterial biofilms. Int J Antimicrob Agents. 2010;35:322–3.

    Article  PubMed  CAS  Google Scholar 

  9. Mack D, Becker P, Chatterjee I, Dobinsky S, Knobloch JK, Peters G, Rohde H, Herrmann M. Mechanisms of biofilm formation in Staphylococcus epidermidis and Staphylococcus aureus: functional molecules, regulatory circuits, and adaptive responses. Int J Med Microbiol. 2004;294:203–12.

    Article  CAS  PubMed  Google Scholar 

  10. Stewart PS, Davison WM, Steenbergen JN. Daptomycin rapidly penetrates a Staphylococcus epidermidis biofilm. Antimicrob Agents Chemother. 2009;53:3505–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Doroshenko N, Tseng BS, Howlin RP, Deacon J, Wharton JA, Thurner PJ, Gilmore BF, Parsek MR, Stoodley P. Extracellular DNA impedes the transport of vancomycin in Staphylococcus epidermidis biofilms preexposed to subinhibitory concentrations of vancomycin. Antimicrob Agents Chemother. 2014;58:7273–82.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Siala W, Mingeot-Leclercq MP, Tulkens PM, Hallin M, Denis O, Van Bambeke F. Comparison of the antibiotic activities of Daptomycin, Vancomycin, and the investigational Fluoroquinolone Delafloxacin against biofilms from Staphylococcus aureus clinical isolates. Antimicrob Agents Chemother. 2014;58:6385–97.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Hoffman LR, D’Argenio DA, MacCoss MJ, Zhang Z, Jones RA, Miller SI. Aminoglycoside antibiotics induce bacterial biofilm formation. Nature. 2005;436:1171–5.

    Article  CAS  PubMed  Google Scholar 

  14. Cargill JS, Upton M. Low concentrations of vancomycin stimulate biofilm formation in some clinical isolates of Staphylococcus epidermidis. J Clin Pathol. 2009;62:1112–6.

    Article  CAS  PubMed  Google Scholar 

  15. Vuotto C, Moura I, Barbanti F, Donelli G, Spigaglia P. Subinhibitory concentrations of metronidazole increase biofilm formation in Clostridium difficile strains. Pathog Dis. 2016;74:ftv114.

    Article  PubMed  CAS  Google Scholar 

  16. Pasquaroli S, Citterio B, Cesare AD, Amiri M, Manti A, Vuotto C, Biavasco F. Role of daptomycin in the induction and persistence of the viable but non-culturable state of Staphylococcus aureus biofilms. Pathogens. 2014;3:759–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Pasquaroli S, Zandri G, Vignaroli C, Vuotto C, Donelli G, Biavasco F. Antibiotic pressure can induce the viable but non-culturable state in Staphylococcus aureus growing in biofilms. J Antimicrob Chemother. 2013;68:1812–7.

    Article  CAS  PubMed  Google Scholar 

  18. Bragg RR, Meyburgh CM, Lee JY, Coetzee M. Potential treatment options in a post-antibiotic era. Adv Exp Med Biol. 2018;1052:51–61.

    Article  CAS  PubMed  Google Scholar 

  19. Römling U, Balsalobre C. Biofilm infections, their resilience to therapy and innovative treatment strategies. J Intern Med. 2012;272:541–61.

    Article  PubMed  CAS  Google Scholar 

  20. Günther F, Wabnitz GH, Stroh P, Prior B, Obst U, Samstag Y, Wagner C, Hänsch GM. Host defence against Staphylococcus aureus biofilms infection: phagocytosis of biofilms by polymorphonuclear neutrophils (PMN). Mol Immunol. 2009;46:1805–13.

    Article  PubMed  CAS  Google Scholar 

  21. Rodney MD. Biofilm formation; a clinically relevant microbiological process. Clin Infect Dis. 2001;33:1387–92.

    Article  Google Scholar 

  22. Percival SL, Suleman L, Vuotto C, Donelli G. Healthcare-associated infections, medical devices and biofilms: risk, tolerance and control. Med Microbiol. 2015;64:323–41.

    Article  Google Scholar 

  23. Donelli G, Vuotto C. Biofilm-based infections in long-term care facilities. Future Microbiol. 2014;9:175–88.

    Article  CAS  PubMed  Google Scholar 

  24. Høiby N, Bjarnsholt T, Moser C, Bassi GL, Coenye T, Donelli G, Hall-Stoodley L, Holá V, Imbert C, Kirketerp-Møller K, Lebeaux D, Oliver A, Ullmann AJ, Williams C, ESCMID Study Group for Biofilms and Consulting External Expert Werner Zimmerli. ESCMID guideline for the diagnosis and treatment of biofilm infections 2014. Clin Microbiol Infect. 2015;21:S1–25.

    Article  PubMed  Google Scholar 

  25. Vuotto C, Donelli G, Buckley A, Chilton C. Clostridium difficile biofilm. Adv Exp Med Biol. 2018;1050:97–115.

    Article  PubMed  Google Scholar 

  26. Percival SL, Vuotto C, Donelli G, Lipsky BA. Biofilms and wounds: an identification algorithm and potential treatment options. Adv Wound Care (New Rochelle). 2015;4:389–97.

    Article  Google Scholar 

  27. Fabbri S, Johnston DA, Rmaile A, Gottenbos B, De Jager M, Aspiras M, Starke EM, Ward MT, Stoodley P. Streptococcus mutans biofilm transient viscoelastic fluid behaviour during high-velocity microsprays. J Mech Behav Biomed Mater. 2016;59:197–206.

    Article  CAS  PubMed  Google Scholar 

  28. Urish KL, DeMuth PW, Craft DW, Haider H, Davis CM 3rd. Pulse lavage is inadequate at removal of biofilm from the surface of total knee arthroplasty materials. J Arthroplasty. 2014;29:1128–32.

    Article  PubMed  Google Scholar 

  29. Raad I, Chaftari AM, Zakhour R, Jordan M, Al Hamal Z, Jiang Y, Yousif A, Garoge K, Mulanovich V, Viola GM, Kanj S, Pravinkumar E, Rosenblatt J, Hachem R. Successful salvage of central venous catheters in patients with catheter-related or central line-associated bloodstream infections by using a catheter lock solution consisting of minocycline, edta, and 25% ethanol. Antimicrob Agents Chemother. 2016;60:3426–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Walder B, Pittet D, Tramèr MR. Prevention of bloodstream infections with central venous catheters treated with anti-infective agents depends on catheter type and insertion time: evidence from a meta-analysis. Infect Control Hosp Epidemiol. 2002;23:748–56.

    Article  PubMed  Google Scholar 

  31. Darouiche RO, Berger DH, Khardori N, Robertson CS, Wall MJ Jr, Metzler MH, Shah S, Mansouri MD, Cerra-Stewart C, Versalovic J, Reardon MJ, Raad II. Comparison of antimicrobial impregnation with tunneling of long-term central venous catheters: a randomized controlled trial. Ann Surg. 2005;242:193–200.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Boelch SP, Rueckl K, Fuchs C, Jordan M, Knauer M, Steinert A, Rudert M, Luedemann M. Comparison of elution characteristics and compressive strength of biantibiotic-loaded PMMA bone cement for spacers: copal® spacem with gentamicin and vancomycin versus Palacos® R+G with vancomycin. Biomed Res Int. 2018;2018:4323518.

    PubMed  PubMed Central  Google Scholar 

  33. Kalfon P, de Vaumas C, Samba D, Boulet E, Lefrant JY, Eyraud D, Lherm T, Santoli F, Naija W, Riou B. Comparison of silver-impregnated with standard multi-lumen central venous catheters in critically ill patients. Crit Care Med. 2007;35:1032–9.

    Article  PubMed  Google Scholar 

  34. Ramos ER, Reitzel R, Jiang Y, Hachem RY, Chaftari AM, Chemaly RF, Hackett B, Pravinkumar SE, Nates J, Tarrand JJ, Raad II. Clinical effectiveness and risk of emerging resistance associated with prolonged use of antibiotic-impregnated catheters: more than 0.5 million catheter days and 7 years of clinical experience. Crit Care Med. 2011;39:245–51.

    Article  PubMed  Google Scholar 

  35. Bianchi T, Wolcott RD, Peghetti A, Leaper D, Cutting K, Polignano R, Rosa Rita Z, Moscatelli A, Greco A, Romanelli M, Pancani S, Bellingeri A, Ruggeri V, Postacchini L, Tedesco S, Manfredi L, Camerlingo M, Rowan S, Gabrielli A, Pomponio G. Recommendations for the management of biofilm: a consensus document. J Wound Care. 2016;25:305–17.

    Article  CAS  PubMed  Google Scholar 

  36. Bjerkan G, Witso E, Bergh K. Sonication is superior to scraping for retrieval of bacteria in biofilm on titanium and steel surfaces in vitro. Acta Orthop. 2009;80:245–50.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Bos R, van der Mei HC, Busscher HJ. Physico-chemistry of initial microbial adhesive interactions—its mechanisms and methods for study. FEMS Microbiol Rev. 1999;23:179–230.

    Article  CAS  PubMed  Google Scholar 

  38. Kolenbrander PE, Palmer RJ Jr, Periasamy S, Jakubovics NS. Oral multispecies biofilm development and the key role of cell–cell distance. Nat Rev Microbiol. 2010;8:471–80.

    Article  CAS  PubMed  Google Scholar 

  39. Flemming HC, Wingender J. The biofilm matrix. Nat Rev Microbiol. 2010;8:623–33.

    Article  CAS  PubMed  Google Scholar 

  40. Peterson BW, He Y, Ren Y, Zerdoum A, Libera MR, Sharma PK, van Winkelhoff AJ, Neut D, Stoodley P, van der Mei HC, Busscher HJ. Viscoelasticity of biofilms and their recalcitrance to mechanical and chemical challenges. FEMS Microbiol Rev. 2015;39:234–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Yan J, Moreau A, Khodaparast S, Perazzo A, Feng J, Fei C, Mao S, Mukherjee S, Košmrlj A, Wingreen NS, Bassler BL, Stone HA. Bacterial biofilm material properties enable removal and transfer by capillary peeling. Adv Mater. 2019;31:e1807586.

    Article  PubMed  CAS  Google Scholar 

  42. Wu J, Nyborg WL. Ultrasound, cavitation bubbles and their interaction with cells. Adv Drug Deliv Rev. 2008;60:1103–16.

    Article  CAS  PubMed  Google Scholar 

  43. Cai Y, Wang J, Liu X, Wang R, Xia L. A review of the combination therapy of low frequency ultrasound with antibiotics. Biomed Res Int. 2017;2017:2317846.

    PubMed  PubMed Central  Google Scholar 

  44. Qian Z, Stoodley P, Pitt WG. Effect of low-intensity ultrasound upon biofilm structure from confocal scanning laser microscopy observation. Biomaterials. 1996;17:1975–80.

    Article  CAS  PubMed  Google Scholar 

  45. Peterson RV, Pitt WG. The effect of frequency and power density on the ultrasonically-enhanced killing of biofilm-sequestered Escherichia coli. Colloids Surf B. 2000;17:219–27.

    Article  CAS  Google Scholar 

  46. Hou Y, Yang M, Jiang H, Li D, Du Y. Effects of low-intensity and low-frequency ultrasound combined with tobramycin on biofilms of extended-spectrum beta-lactamases (ESBLs) Escherichia coli. FEMS Microbiol Lett. 2019;366:fnz026.

    Article  PubMed  Google Scholar 

  47. Yang M, Du K, Hou Y, Xie S, Dong Y, Li D, Du Y. Synergistic antifungal effect of amphotericin B-loaded PLGA nanoparticle with ultrasound against C. albicans biofilms. Antimicrob Agents Chemother. 2019;63:e02022-18.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Liu X, Yin H, Weng CX, Cai Y. Low-frequency ultrasound enhances antimicrobial activity of colistin-vancomycin combination against pan-resistant biofilm of Acinetobacter baumannii. Ultrasound Med Biol. 2016;42:1968–75.

    Article  PubMed  Google Scholar 

  49. Karosi T, Sziklai I, Csomor P. Low-frequency ultrasound for biofilm disruption in chronic rhinosinusitis with nasal polyposis: in vitro pilot study. Laryngoscope. 2013;123:17–23.

    Article  PubMed  Google Scholar 

  50. Carmen JC, Roeder BL, Nelson JL, Ogilvie RL, Robison RA, Schaalje GB, Pitt WG. Treatment of biofilm infections on implants with low-frequency ultrasound and antibiotics. Am J Infect Control. 2005;33:78–82.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Seth AK, Nguyen KT, Geringer MR, Hong SJ, Leung KP, Mustoe TA, Galiano RD. Noncontact, low-frequency ultrasound as an effective therapy against Pseudomonas aeruginosa-infected biofilm wounds. Wound Repair Regen. 2013;21:266–74.

    Article  PubMed  Google Scholar 

  52. Hazan Z, Zumeris J, Jacob H, Raskin H, Kratysh G, Vishnia M, Dror N, Barliya T, Mandel M, Lavie G. Effective prevention of microbial biofilm formation on medical devices by low-energy surface acoustic waves. Antimicrob Agents Chemother. 2006;50:4144–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Carmen JC, Nelson JL, Beckstead BL, Runyan CM, Robison RA, Schaalje GB, Pitt WG. Ultrasonic-enhanced gentamicin transport through colony biofilms of Pseudomonas aeruginosa and Escherichia coli. J Infect Chemother. 2004;10:193–9.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Rapoport N, Smirnov AI, Timoshin A, Pratt AM, Pitt WG. Factors affecting the permeability of Pseudomonas aeruginosa cell walls toward lipophilic compounds: effects of ultrasound and cell age. Arch Biochem Biophys. 1997;344:114–24.

    Article  CAS  PubMed  Google Scholar 

  55. Pitt WG, Ross SA. Ultrasound increases the rate of bacterial cell growth. Biotechnol Prog. 2003;19:1038–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Pitt WG, McBride MO, Lunceford JK, Roper RJ, Sagers RD. Ultrasonic enhancement of antibiotic action on gram-negative bacteria. Antimicrob Agents Chemother. 1994;38:2577–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Vyas N, Manmi K, Wang Q, Jadhav AJ, Barigou M, Sammons RL, Kuehne SA, Walmsley AD. Which parameters affect biofilm removal with acoustic cavitation? A review. Ultrasound Med Biol. 2019;45:1044–55.

    Article  PubMed  Google Scholar 

  58. Brinkman CL, Schmidt-Malan SM, Karau MJ, Greenwood-Quaintance K, Hassett DJ, Mandrekar JN, Patel R. Exposure of bacterial biofilms to electrical current leads to cell death mediated in part by reactive oxygen species. PLoS One. 2016;11:e0168595.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  59. Schmidt-Malan SM, Karau MJ, Cede J, Greenwood-Quaintance KE, Brinkman CL, Mandrekar JN, Patel R. Antibiofilm activity of low-amperage continuous and intermittent direct electrical current. Antimicrob Agents Chemother. 2015;59:4610–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Sahrmann P, Zehnder M, Mohn D, Meier A, Imfeld T, Thurnheer T. Effect of low direct current on anaerobic multispecies biofilm adhering to a titanium implant surface. Clin Implant Dent Relat Res. 2014;16:552–6.

    Article  PubMed  Google Scholar 

  61. Lasserre JF, Leprince JG, Toma S, Brecx MC. Electrical enhancement of chlorhexidine efficacy against the periodontal pathogen Porphyromonas gingivalis within a biofilm. New Microbiol. 2015;38:511–9.

    CAS  PubMed  Google Scholar 

  62. Wattanakaroon W, Stewart PS. Electrical enhancement of Streptococcus gordonii biofilm killing by gentamicin. Arch Oral Biol. 2000;45:167–71.

    Article  CAS  PubMed  Google Scholar 

  63. Lasserre JF, Toma S, Bourgeois T, El Khatmaoui H, Marichal E, Brecx MC. Influence of low direct electric currents and chlorhexidine upon human dental biofilms. Clin Exp Dent Res. 2016;2:146–54.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Voegele P, Badiola J, Schmidt-Malan SM, Karau MJ, Greenwood-Quaintance KE, Mandrekar JN, Patel R. Antibiofilm activity of electrical current in a catheter model. Antimicrob Agents Chemother. 2016;60:1476–80.

    Article  CAS  PubMed Central  Google Scholar 

  65. Alshawabkeh AN, Maillacheruvu K. Electrochemical and biogeochemical interactions under DC electric fields. In: Smith JA, Burns SE, editors. Physicochemical groundwater remediation. New York: Kluwer Academic/Plenum Publishers; 2001. p. 73–90.

    Google Scholar 

  66. Levering V, Wang Q, Shivapooja P, Zhao X, López GP. Soft robotic concepts in catheter design: an on-demand fouling-release urinary catheter. Adv Healthc Mater. 2014;3:1588–96.

    Article  CAS  PubMed  Google Scholar 

  67. Levering V, Cao C, Shivapooja P, Levinson H, Zhao X, López GP. Urinary catheter capable of repeated on-demand removal of infectious biofilms via active deformation. Biomaterials. 2016;77:77–86.

    Article  CAS  PubMed  Google Scholar 

  68. Maskarinec SA, Parlak Z, Tu Q, Levering V, Zauscher S, López GP, Fowler VG Jr, Perfect JR. On-demand release of Candida albicans biofilms from urinary catheters by mechanical surface deformation. Biofouling. 2018;34:595–604.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Teirlinck E, Xiong R, Brans T, Forier K, Fraire J, Van Acker H, Matthijs N, De Rycke R, De Smedt SC, Coenye T, Braeckmans K. Laser-induced vapour nanobubbles improve drug diffusion and efficiency in bacterial biofilms. Nat Commun. 2018;9:4518.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  70. Vuotto C, Longo F, Donelli G. Probiotics to counteract biofilm-associated infections: promising and conflicting data. Int J Oral Sci. 2014;6:189–94.

    Article  PubMed  PubMed Central  Google Scholar 

  71. Vuotto C, Barbanti F, Mastrantonio P, Donelli G. Lactobacillus brevis CD2 inhibits Prevotella melaninogenica biofilm. Oral Dis. 2014;20:668–74.

    Article  CAS  PubMed  Google Scholar 

  72. Rossoni RD, Velloso MDS, de Barros PP, de Alvarenga JA, Santos JDD, Santos Prado ACCD, Ribeiro FC, Anbinder AL, Junqueira JC. Inhibitory effect of probiotic Lactobacillus supernatants from the oral cavity on Streptococcus mutans biofilms. Microb Pathog. 2018;123:361–7.

    Article  PubMed  Google Scholar 

  73. Bidossi A, De Grandi R, Toscano M, Bottagisio M, De Vecchi E, Gelardi M, Drago L. Probiotics Streptococcus salivarius 24SMB and Streptococcus oralis 89a interfere with biofilm formation of pathogens of the upper respiratory tract. BMC Infect Dis. 2018;18:653.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Humphreys GJ, McBain AJ. Antagonistic effects of Streptococcus and Lactobacillus probiotics in pharyngeal biofilms. Lett Appl Microbiol. 2019;68:303–12.

    Article  CAS  PubMed  Google Scholar 

  75. Collado MC, Jalonen L, Meriluoto, Salminen S. Protection mechanism of probiotic combination against human pathogens: in vitro adhesion to human intestinal mucus. Asia Pac J Clin Nutr. 2006;15:570–5.

    PubMed  Google Scholar 

  76. Candela M, Perna F, Carnevali P, Vitali B, Ciati R, Gionchetti P, Rizzello F, Campieri M, Brigidi P. Interaction of probiotic Lactobacillus and Bifidobacterium strains with human intestinal epithelial cells: adhesion properties, competition against enteropathogens and modulation of IL-8 production. Int J Food Microbiol. 2008;125:286–92.

    Article  CAS  PubMed  Google Scholar 

  77. Saunders S, Bocking A, Challis J, Reid G. Effect of Lactobacillus challenge on Gardnerella vaginalis biofilms. Colloids Surf B Biointerfaces. 2007;55:138–42.

    Article  CAS  PubMed  Google Scholar 

  78. McMillan A, Dell M, Zellar MP, Cribby S, Martz S, Hong E, Fu J, Abbas A, Dang T, Miller W, Reid G. Disruption of urogenital biofilms by lactobacilli. Colloids Surf B Biointerfaces. 2011;86:58–64.

    Article  CAS  PubMed  Google Scholar 

  79. Valdez JC, Peral MC, Rachid M, Santana M, Perdigón G. Interference of Lactobacillus plantarum with Pseudomonas aeruginosa in vitro and in infected burns: the potential use of probiotics in wound treatment. Clin Microbiol Infect. 2005;1:472–9.

    Article  Google Scholar 

  80. Ong JS, Taylor TD, Yong CC, Khoo BY, Sasidharan S, Choi SB, Ohno H, Liong MT. Lactobacillus plantarum USM8613 aids in wound healing and suppresses Staphylococcus aureus infection at wound sites. Probiotics Antimicrob Proteins. 2019. https://doi.org/10.1007/s12602-018-9505-9.

    Article  Google Scholar 

  81. Onbas T, Osmanagaoglu O, Kiran F. Potential properties of Lactobacillus plantarum F-10 as a bio-control strategy for wound infections. Probiotics Antimicrob Proteins. 2018. https://doi.org/10.1007/s12602-018-9486-8.

    Article  Google Scholar 

  82. Samot J, Lebreton J, Badet C. Adherence capacities of oral lactobacilli for potential probiotic purposes. Anaerobe. 2011;17:69–72.

    Article  CAS  PubMed  Google Scholar 

  83. Caselli E, Brusaferro S, Coccagna M, Arnoldo L, Berloco F, Antonioli P, Tarricone R, Pelissero G, Nola S, La Fauci V, Conte A, Tognon L, Villone G, Trua N, Mazzacane S, SAN-ICA Study Group. Reducing healthcare-associated infections incidence by a probiotic-based sanitation system: a multicentre, prospective, intervention study. PLoS One. 2018;13:e0199616.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  84. Li Z, Behrens AM, Ginat N, Tzeng SY, Lu X, Sivan S, Langer R, Jaklenec A. Biofilm-inspired encapsulation of probiotics for the treatment of complex infections. Adv Mater. 2018;30:e1803925.

    Article  PubMed  CAS  Google Scholar 

  85. Hallstrom H, Lindgren S, Yucel-Lindberg T, Dahlén G, Renvert S, Twetman S. Effect of probiotic lozenges on inflammatory reactions and oral biofilm during experimental gingivitis. Acta Odontol Scand. 2013;71:828–33.

    Article  PubMed  CAS  Google Scholar 

  86. Miyazaki Y, Kamiya S, Hanawa T, Fukuda M, Kawakami H, Takahashi H, Yokota H. Effect of probiotic bacterial strains of Lactobacillus, Bifidobacterium, and Enterococcus on enteroaggregative Escherichia coli. J Infect Chemother. 2010;16:10–8.

    Article  PubMed  Google Scholar 

  87. Francolini I, Vuotto C, Piozzi A, Donelli G. Antifouling and antimicrobial biomaterials: an overview. APMIS. 2017;125:392–417.

    Article  PubMed  Google Scholar 

  88. Francolini I, Donelli G, Vuotto C, Baroncini FA, Stoodley P, Taresco V, Martinelli A, D’Ilario L, Piozzi A. Antifouling polyurethanes to fight device-related staphylococcal infections: synthesis, characterization, and antibiofilm efficacy. Pathog Dis. 2014;70:401–7.

    Article  CAS  PubMed  Google Scholar 

  89. Bertesteanu S, Chifiriuc MC, Grumezescu AM, Printza AG, Marie-Paule T, Grumezescu V, Mihaela V, Lazar V, Grigore R. Biomedical applications of synthetic, biodegradable polymers for the development of anti-infective strategies. Curr Med Chem. 2014;21:3383–90.

    Article  CAS  PubMed  Google Scholar 

  90. Skovdal SM, Jørgensen NP, Petersen E, Jensen-Fangel S, Ogaki R, Zeng G, Johansen M, Wang M, Rohde H, Meyer RL. Ultra-dense polymer brush coating reduces Staphylococcus epidermidis biofilms on medical implants and improves antibiotic treatment outcome. Acta Biomater. 2018;76:46–55.

    Article  CAS  PubMed  Google Scholar 

  91. Hoyos-Nogués M, Buxadera-Palomero J, Ginebra MP, Manero JM, Gil FJ, Mas-Moruno C. All-in-one trifunctional strategy: a cell adhesive, bacteriostatic and bactericidal coating for titanium implants. Colloids Surf B Biointerfaces. 2018;169:30–40.

    Article  PubMed  CAS  Google Scholar 

  92. Zeng G, Ogaki R, Meyer RL. Non-proteinaceous bacterial adhesins challenge the antifouling properties of polymer brush coatings. Acta Biomater. 2015;24:64–73.

    Article  CAS  PubMed  Google Scholar 

  93. Wen L, Tian Y, Jiang L. Bioinspired super-wettability from fundamental research to practical applications. Angew Chem Int Ed Engl. 2015;54:3387–99.

    Article  CAS  PubMed  Google Scholar 

  94. Banat IM, De Rienzo MAD, Quinn GA. Microbial biofilms: biosurfactants as antibiofilm agents. Appl Microbiol Biotechnol. 2014;98:9915–29.

    Article  CAS  PubMed  Google Scholar 

  95. Ueda Y, Mashima K, Miyazaki M, Hara S, Takata T, Kamimura H, Takagi S, Jimi S. Inhibitory effects of polysorbate 80 on MRSA biofilm formed on different substrates including dermal tissue. Sci Rep. 2019;9:3128.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  96. Sloup RE, Cieza RJ, Needle DB, Abramovitch RB, Torres AG, Waters CM. Polysorbates prevent biofilm formation and pathogenesis of Escherichia coli O104:H4. Biofouling. 2016;32:1131–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Toutain-Kidd CM, Kadivar SC, Bramante CT, Bobin SA, Zegans ME. Polysorbate 80 inhibition of Pseudomonas aeruginosa biofilm formation and its cleavage by the secreted lipase LipA. Antimicrob Agents Chemother. 2009;53:136–45.

    Article  CAS  PubMed  Google Scholar 

  98. Naughton PJ, Marchant R, Naughton V, Banat IM. Microbial biosurfactants: current trends and applications in agricultural and biomedical industries. J Appl Microbiol. 2019;127:12–28.

    Article  CAS  PubMed  Google Scholar 

  99. Rodrigues L, van der Mei H, Banat IM, Teixeira J, Oliveira R. Inhibition of microbial adhesion to silicone rubber treated with biosurfactant from Streptococcus thermophilus A. FEMS Immunol Med Microbiol. 2006;46:107–12.

    Article  CAS  PubMed  Google Scholar 

  100. Ciandrini E, Campana R, Casettari L, Perinelli DR, Fagioli L, Manti A, Palmieri GF, Papa S, Baffone W. Characterization of biosurfactants produced by Lactobacillus spp. and their activity against oral streptococci biofilm. ApplMicrobiol Biotechnol. 2016;100:6767–77.

    CAS  Google Scholar 

  101. Satpute SK, Mone NS, Das P, Banat IM, Banpurkar AG. Inhibition of pathogenic bacterial biofilms on PDMS based implants by L. acidophilus derived biosurfactant. BMC Microbiol. 2019;19:39.

    Article  PubMed  PubMed Central  Google Scholar 

  102. Gómez NC, Ramiro JM, Quecan BX, de Melo Franco BD. Use of potential probiotic lactic acid bacteria (LAB) biofilms for the control of listeria monocytogenes, salmonella typhimurium, and Escherichia coli O157:H7 biofilms formation. Front Microbiol. 2016;7:863.

    Article  PubMed  PubMed Central  Google Scholar 

  103. Tahmourespour A, Kasra-Kermanshahi R, Salehi R. Lactobacillus rhamnosus biosurfactant inhibits biofilm formation and gene expression of caries-inducing Streptococcus mutans. Dent Res J (Isfahan). 2019;16:87–94.

    Article  Google Scholar 

  104. Ceresa C, Tessarolo F, Maniglio D, Caola I, Nollo G, Rinaldi M, Fracchia L. Inhibition of Candida albicans biofilm by lipopeptide AC7 coated medical-grade silicone in combination with farnesol. AIMS Bioeng. 2018;5:192–208.

    Article  CAS  Google Scholar 

  105. Goncalves Mdos S, Delattre C, Balestrino D, Charbonnel N, Elboutachfaiti R, Wadouachi A, Badel S, Bernardi T, Michaud P, Forestier C. Anti-biofilm activity: a function of Klebsiella pneumoniae capsular polysaccharide. PLoS One. 2014;9:e99995.

    Article  PubMed  CAS  Google Scholar 

  106. Muszanska AK, Nejadnik MR, Chen Y, van den Heuvel ER, Busscher HJ, van der Mei HC, Norde W. Bacterial adhesion forces with substratum surfaces and the susceptibility of biofilms to antibiotics. Antimicrob Agents Chemother. 2012;56:4961–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Treter J, Bonatto F, Krug C, Soares GV, Baumvol IJR, Macedo AJ. Washing-resistant surfactant coated surface is able to inhibit pathogenic bacteria adhesion. Appl Surf Sci. 2014;303:147–54.

    Article  CAS  Google Scholar 

  108. Bazaka K, Jacob MV, Crawford RJ, Ivanova EP. Plasma-assisted surface modification of organic biopolymers to prevent bacterial attachment. Acta Biomater. 2011;7:2015–28.

    Article  CAS  PubMed  Google Scholar 

  109. Triandafillu K, Balazs DJ, Aronsson BO, Descouts P, Tu Quoc P, van Delden C, Mathieu HJ, Harms H. Adhesion of Pseudomonas aeruginosa strains to untreated and oxygen-plasma treated poly(vinyl chloride) (PVC) from endotracheal intubation devices. Biomaterials. 2003;24:1507–18.

    Article  CAS  PubMed  Google Scholar 

  110. Taheran L, Zarrini G, Khorram S, Zakerhamidi MS. Plasma surface modification as a new approach to protect urinary catheter against Escherichia coli biofilm formation. Iran J Microbiol. 2016;8:257–62.

    PubMed  PubMed Central  Google Scholar 

  111. Yang Y, Guo J, Zhou X, Liu Z, Wang C, Wang K, Zhang J, Wang Z. A novel cold atmospheric pressure air plasma jet for peri-implantitis treatment: an in vitro study. Dent Mater J. 2018;37:157–66.

    Article  CAS  PubMed  Google Scholar 

  112. Cusumano CK, Hultgren SJ. Bacterial adhesion—a source of alternate antibiotic targets. IDrugs. 2009;12:699–705.

    CAS  PubMed  Google Scholar 

  113. Kouki A, Pieters RJ, Nilsson UJ, Loimaranta V, Finne J, Haataja S. Bacterial adhesion of Streptococcus suis to host cells and its inhibition by carbohydrate ligands. Biology (Basel). 2013;2:918–35.

    CAS  Google Scholar 

  114. Haataja S, Verma P, Fu O, Papageorgiou AC, Pöysti S, Pieters RJ, Nilsson UJ, Finne J. Rationally designed chemically modified glycodendrimer inhibits streptococcus suis adhesin sadp at picomolar concentrations. Chemistry. 2018;24:1905–12.

    Article  CAS  PubMed  Google Scholar 

  115. Gustke H, Kleene R, Loers G, Nehmann N, Jaehne M, Bartels KM, Jaeger KE, Schachner M, Schumacher U. Inhibition of the bacterial lectins of Pseudomonas aeruginosa with monosaccharides and peptides. Eur J Clin Microbiol Infect Dis. 2012;31:207–15.

    Article  CAS  PubMed  Google Scholar 

  116. Rachmaninov O, Zinger-Yosovich KD, Gilboa-Garber N. Preventing Pseudomonas aeruginosa and Chromobacterium violaceum infections by anti-adhesion-active components of edible seeds. Nutr J. 2012;11:10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Kim HS, Cha E, Kim Y, Jeon YH, Olson BH, Byun Y, Park HD. Raffinose, a plant galactoside, inhibits Pseudomonas aeruginosa biofilm formation via binding to LecA and decreasing cellular cyclic diguanylate levels. Sci Rep. 2016;6:25318.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Han Z, Pinkner JS, Ford B, Chorell E, Crowley JM, Cusumano CK, Campbell S, Henderson JP, Hultgren SJ, Janetka JW. Lead optimization studies on FimH antagonists: discovery of potent and orally bioavailable ortho-substituted biphenyl mannosides. J Med Chem. 2012;55:3945–59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Khanal M, Larsonneur F, Raks V, Barras A, Baumann JS, Martin FA, Boukherroub R, Ghigo JM, Ortiz Mellet C, Zaitsev V, Garcia Fernandez JM, Beloin C, Siriwardena A, Szunerits S. Inhibition of type 1 fimbriae-mediated Escherichia coli adhesion and biofilm formation by trimeric cluster thiomannosides conjugated to diamond nanoparticles. Nanoscale. 2015;7:2325–35.

    Article  CAS  PubMed  Google Scholar 

  120. Gupta D, Sarkar S, Sharma M, Thapa BR, Chakraborti A. Inhibition of enteroaggregative Escherichia coli cell adhesion in-vitro by designed peptides. Microb Pathog. 2016;98:23–31.

    Article  CAS  PubMed  Google Scholar 

  121. Steadman D, Lo A, Waksman G, Remaut H. Bacterial surface appendages as targets for novel antibacterial therapeutics. Future Microbiol. 2014;9:887–900.

    Article  CAS  PubMed  Google Scholar 

  122. Chorell E, Pinkner JS, Bengtsson C, Edvinsson S, Cusumano CK, Rosenbaum E, Johansson LB, Hultgren SJ, Almqvist F. Design and synthesis of fluorescent pilicides and curlicides: bioactive tools to study bacterial virulence mechanisms. Chemistry. 2012;18:4522–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Piatek R, Zalewska-Piatek B, Dzierzbicka K, Makowiec S, Pilipczuk J, Szemiako K, Cyranka-Czaja A, Wojciechowski M. Pilicides inhibit the FGL chaperone/usher assisted biogenesis of the Dr fimbrial polyadhesin from uropathogenic Escherichia coli. BMC Microbiol. 2013;13:131.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Chorell E, Pinkner JS, Phan G, Edvinsson S, Buelens F, Remaut H, Waksman G, Hultgren SJ, Almqvist F. Design and synthesis of C-2 substituted thiazolo and dihydrothiazolo ring-fused 2-pyridones: pilicides with increased antivirulence activity. J Med Chem. 2010;53:5690–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Jaiswal SK, Sharma NK, Bharti SK, Krishnan S, Kumar A, Prakash O, Kumar P, Kumar A, Gupta AK. Phytochemicals as uropathognic Escherichia coli FimH antagonist: in vitro and in silico approach. Curr Mol Med. 2018;18:640–53.

    Article  CAS  PubMed  Google Scholar 

  126. Cegelski L, Pinkner JS, Hammer ND, Cusumano CK, Hung CS, Chorell E, Aberg V, Walker JN, Seed PC, Almqvist F, Chapman MR, Hultgren SJ. Small-molecule inhibitors target Escherichia coli amyloid biogenesis and biofilm formation. Nat Chem Biol. 2009;5:913–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Ning Y, Cheng L, Ling M, Feng X, Chen L, Wu M, Deng L. Efficient suppression of biofilm formation by a nucleic acid aptamer. Pathog Dis. 2015;73:ftv034.

    Article  PubMed  CAS  Google Scholar 

  128. Lijuan C, Xing Y, Minxi W, Wenkai L, Le D. Development of an aptamer-ampicillin conjugate for treating biofilms. Biochem Biophys Res Commun. 2017;483:847–54.

    Article  PubMed  CAS  Google Scholar 

  129. Waters CM, Bassler BL. Quorum sensing: cell-to-cell communication in bacteria. Annu Rev Cell Dev Biol. 2005;21:319–46.

    Article  CAS  PubMed  Google Scholar 

  130. Li YH, Tian X. Quorum sensing and bacterial social interactions in biofilms. Sensors (Basel). 2012;12:2519–38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Niu C, Clemmer KM, Bonomo RA, Rather PN. Isolation and characterization of an autoinducer synthase from acinetobacter baumannii. J Bacteriol. 2008;190:3386–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Balestrino D, Haagensen JA, Rich C, Forestier C. Characterization of type 2 quorum sensing in Klebsiella pneumoniae and relationship with biofilm formation. J Bacteriol. 2005;187:2870–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Yarwood JM, Bartels DJ, Volper EM, Greenberg EP. Quorum sensing in Staphylococcus aureus biofilms. J Bacteriol. 2004;186:1838–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Galante J, Ho AC, Tingey S, Charalambous BM. Quorum sensing and biofilms in the pathogen Streptococcus pneumoniae. Curr Pharm Des. 2015;21:25–30.

    Article  CAS  PubMed  Google Scholar 

  135. Brackman G, Coenye T. Quorum sensing inhibitors as anti-biofilm agents. Curr Pharm Des. 2015;21:5–11.

    Article  CAS  PubMed  Google Scholar 

  136. Bjarnsholt T, Tolker-Nielsen T, Høiby N, Givskov M. Interference of Pseudomonas aeruginosa signalling and biofilm formation for infection control. Expert Rev Mol Med. 2010;12:e11.

    Article  PubMed  CAS  Google Scholar 

  137. Tomlin KL, Malott RJ, Ramage G, Storey DG, Sokol PA, Ceri H. Quorum-sensing mutations affect attachment and stability of Burkholderia cenocepacia biofilms. Appl Environ Microbiol. 2005;71:5208–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Lynch MJ, Swift S, Kirke DF, Keevil CW, Dodd CE, Williams P. The regulation of biofilm development by quorum sensing in Aeromonas hydrophila. Environ Microbiol. 2002;4:18–28.

    Article  CAS  PubMed  Google Scholar 

  139. Zhao L, Xue T, Shang F, Sun H, Sun B. Staphylococcus aureus AI2 quorum sensing associates with the KdpDE two-component system to regulate capsular polysaccharide synthesis and virulence. Infect Immun. 2010;78:3506–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Novick RP, Geisinger E. Quorum sensing in staphylococci. Ann Rev Genetics. 2008;42:541–64.

    Article  CAS  Google Scholar 

  141. Kostakioti M, Hadjifrangiskou M, Pinkner JS, Hultgren SJ. QseC-mediated dephosphorylation of QseB is required for expression of genes associated with virulence in uropathogenic Escherichia coli. Mol Microbiol. 2009;73:1020–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Bearson BL, Bearson SM. The role of the QseC quorum-sensing sensor kinase in colonization and norepinephrine-enhanced motility of Salmonella enterica serovar Typhimurium. Microb Pathog. 2008;44:271–8.

    Article  CAS  PubMed  Google Scholar 

  143. Curtis MM, Russell R, Moreira CG, Adebesin AM, Wang C, Williams NS, Taussig R, Stewart D, Zimmern P, Lu B, Prasad RN, Zhu C, Rasko DA, Huntley JF, Falck JR, Sperandio V. QseC inhibitors as an antivirulence approach for Gram-negative pathogens. MBio. 2014;5:e02165.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Yadav MK, Park SW, Chae SW, Song JJ. Sinefungin, a natural nucleoside analogue of S-adenosylmethionine, inhibits Streptococcus pneumoniae Biofilm Growth. Biomed Res Int. 2014;2014:156987.

    PubMed  PubMed Central  Google Scholar 

  145. Almohaywi B, Yu TT, Iskander G, Chan DSH, Ho KKK, Rice S, Black DS, Griffith R, Kumar N. Dihydropyrrolones as bacterial quorum sensing inhibitors. Bioorg Med Chem Lett. 2019;29:1054–9.

    Article  CAS  PubMed  Google Scholar 

  146. Ciulla M, Di Stefano A, Marinelli L, Cacciatore I, Di Biase G. RNAIII inhibiting peptide (RIP) and derivatives as potential tools for the treatment of S. aureus biofilm infections. Curr Top Med Chem. 2018;18:2068–79.

    Article  CAS  PubMed  Google Scholar 

  147. Shen G, Rajan R, Zhu J, Bell CE, Pei D. Design and synthesis of substrate and intermediate analogue inhibitors of S-ribosylhomocysteinase. J Med Chem. 2006;49:3003–11.

    Article  CAS  PubMed  Google Scholar 

  148. Gutierrez JA, Crowder T, Rinaldo-Matthis A, Ho MC, Almo SC, Schramm VL. Transition state analogs of 5′-methylthioadenosine nucleosidase disrupt quorum sensing. Nat Chem Biol. 2009;5:251–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Rehman ZU, Leiknes T. Quorum-quenching bacteria isolated from red sea sediments reduce biofilm formation by Pseudomonas aeruginosa. Front Microbiol. 2018;9:1354.

    Article  PubMed  PubMed Central  Google Scholar 

  150. Kiymaci ME, Altanlar N, Gumustas M, Ozkan SA, Akin A. Quorum sensing signals and related virulence inhibition of Pseudomonas aeruginosa by a potential probiotic strain’s organic acid. Microb Pathog. 2018;121:190–7.

    Article  CAS  PubMed  Google Scholar 

  151. Muras A, Mayer C, Romero M, Camino T, Ferrer MD, Mira A, Otero A. Inhibition of Steptococcus mutans biofilm formation by extracts of Tenacibaculum sp. 20J, a bacterium with wide-spectrum quorum quenching activity. J Oral Microbiol. 2018;10:1429788.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  152. Vattem DA, Mihalik K, Crixell SH, McLean RJC. Dietary phytochemicals as quorum sensing inhibitors. Fitoterapia. 2007;78:302–10.

    Article  CAS  PubMed  Google Scholar 

  153. Rasmussen TB, Givskov M. Quorum-sensing inhibitors as anti-pathogenic drugs. Int J Med Microbiol. 2006;296:149–61.

    Article  CAS  PubMed  Google Scholar 

  154. Sarabhai S, Sharma P, Capalash N. Ellagic acid derivatives from Terminalia chebula Retz downregulate the expression of quorum sensing genes to attenuate Pseudomonas aeruginosa PAO1 virulence. PLoS One. 2013;8:e53441.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. Quave CL, Lyles JT, Kavanaugh JS, Nelson K, Parlet CP, Crosby HA, Heilmann KP, Horswill AR. Castanea sativa (European chestnut) leaf extracts rich in ursene and oleanene derivatives block Staphylococcus aureus virulence and pathogenesis without detectable resistance. PLoS One. 2015;10:e0136486.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  156. Bhargava N, Singh SP, Sharma A, Sharma P, Capalash N. Attenuation of quorum sensing-mediated virulence of Acinetobacter baumannii by Glycyrrhiza glabra flavonoids. Future Microbiol. 2015;10:1953–68.

    Article  CAS  PubMed  Google Scholar 

  157. Packiavathy IA, Priya S, Pandian SK, Ravi AV. Inhibition of biofilm development of uropathogens by curcumin—an anti-quorum sensing agent from Curcuma longa. Food Chem. 2014;148:453–60.

    Article  CAS  PubMed  Google Scholar 

  158. Gopu V, Kothandapani S, Shetty PH. Quorum quenching activity of Syzygium cumini (L.) Skeels and its anthocyanin malvidin against Klebsiella pneumoniae. Microb Pathog. 2015;79:61–9.

    Article  CAS  PubMed  Google Scholar 

  159. Kalia M, Yadav VK, Singh PK, Sharma D, Pandey H, Narvi SS, Agarwal V. Effect of cinnamon oil on quorum sensing-controlled virulence factors and biofilm formation in Pseudomonas aeruginosa. PLoS One. 2015;10:e0135495.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  160. Zhou L, Zheng H, Tang Y, Yu W, Gong Q. Eugenol inhibits quorum sensing at sub-inhibitory concentrations. Biotechnol Lett. 2013;35:631–7.

    Article  CAS  PubMed  Google Scholar 

  161. Burt SA, Ojo-Fakunle VTA, Woertman J, Veldhuizen EJA. The natural antimicrobial carvacrol inhibits quorum sensing in Chromobacterium violaceum and reduces bacterial biofilm formation at sub-lethal concentrations. PLoS One. 2014;9:e93414.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  162. Weiland-Bräuer N, Kisch MJ, Pinnow N, Liese A, Schmitz RA. Highly effective inhibition of biofilm formation by the first metagenome-derived AI-2 quenching enzyme. Front Microbiol. 2016;7:1098.

    Article  PubMed  PubMed Central  Google Scholar 

  163. Lauderdale KJ, Malone CL, Boles BR, Morcuende J, Horswill AR. Biofilm dispersal of community-associated methicillin-resistant Staphylococcus aureus on orthopedic implant material. J Orthop Res. 2010;28:55–61.

    CAS  PubMed  Google Scholar 

  164. Simonetti O, Cirioni O, Ghiselli R, Goteri G, Scalise A, Orlando F, Silvestri C, Riva A, Saba V, Madanahally KD, Offidani A, Balaban N, Scalise G. Giacometti. RNAIII-inhibiting peptide enhances healing of wounds infected with methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother. 2008;52:2205–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  165. Starkey M, Lepine F, Maura D, Bandyopadhaya A, Lesic B, He J, Kitao T, Righi V, Milot S, Tzika A, Rahme L. Identification of anti-virulence compounds that disrupt quorum-sensing regulated acute and persistent pathogenicity. PLoS Pathog. 2014;10:e1004321.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  166. Pan J, Ren D. Quorum sensing inhibitors: a patent overview. Expert Opin Ther Pat. 2009;19:1581–601.

    Article  CAS  PubMed  Google Scholar 

  167. Kaplan JB. Biofilm dispersal: mechanisms, clinical implications, and potential therapeutic uses. J Dent Res. 2010;89:205–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  168. Flemming HC, Neu TR, Wozniak DJ. The EPS matrix: the “house of biofilm cells”. J Bacteriol. 2007;189:7945–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  169. Flemming HC. EPS-then and now. Microorganisms. 2016;4:E41.

    Article  PubMed  CAS  Google Scholar 

  170. Ramirez T, Shrestha A, Kishen A. Inflammatory potential of monospecies biofilm matrix components. Int Endod J. 2019;52:1020–7.

    Article  CAS  PubMed  Google Scholar 

  171. Fleming D, Rumbaugh KP. Approaches to dispersing medical biofilms. Microorganisms. 2017;5:15.

    Article  PubMed Central  CAS  Google Scholar 

  172. Ramasubbu N, Thomas LM, Ragunath C, Kaplan JB. Structural analysis of dispersin B, a biofilm-releasing glycoside hydrolase from the periodontopathogen Actinobacillus actinomycetemcomitans. J Mol Biol. 2005;349:475–86.

    Article  CAS  PubMed  Google Scholar 

  173. Donelli G, Francolini I, Romoli D, Guaglianone E, Piozzi A, Ragunath C, Kaplan JB. Synergistic activity of dispersin B and cefamandole nafate in inhibition of staphylococcal biofilm growth on polyurethanes. Antimicrob Agents Chemother. 2007;51:2733–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  174. Papi M, Maiorana A, Bugli F, Torelli R, Posteraro B, Maulucci G, De Spirito M, Sanguinetti M. Detection of biofilm-grown Aspergillus fumigatus by means of atomic force spectroscopy: ultrastructural effects of alginate lyase. Microsc Microanal. 2012;18:1088–94.

    Article  CAS  PubMed  Google Scholar 

  175. Cho H, Huang X, Lan Piao Y, Eun Kim D, Yeon Lee S, Jeong Yoon E, Hee Park S, Lee K, Ho Jang C, Zhan CG. Molecular modeling and redesign of alginate lyase from Pseudomonas aeruginosa for accelerating CRPA biofilm degradation. Proteins. 2016;84:1875–87.

    Article  CAS  PubMed  Google Scholar 

  176. Kalpana BJ, Aarthy S, Pandian SK. Antibiofilm activity of α-amylase from Bacillus subtilis s8-18 against biofilm forming human bacterial pathogens. Appl Biochem Biotechnol. 2012;167:1778–94.

    Article  CAS  PubMed  Google Scholar 

  177. Craigen B, Dashiff A, Kadouri DE. The use of commercially available alpha-amylase compounds to inhibit and remove Staphylococcus aureus biofilms. Open Microbiol J. 2011;5:21–31.

    Article  PubMed  PubMed Central  Google Scholar 

  178. Chen KJ, Lee CK. Twofold enhanced dispersin B activity by N-terminal fusion to silver-binding peptide for biofilm eradication. Int J Biol Macromol. 2018;118:419–26.

    Article  CAS  PubMed  Google Scholar 

  179. Gawande PV, Leung KP, Madhyastha S. Antibiofilm and antimicrobial efficacy of DispersinB®-KSL-W peptide-based wound gel against chronic wound infection associated bacteria. Curr Microbiol. 2014;68:635–41.

    Article  CAS  PubMed  Google Scholar 

  180. Torelli R, Cacaci M, Papi M, Paroni Sterbini F, Martini C, Posteraro B, Palmieri V, De Spirito M, Sanguinetti M, Bugli F. Different effects of matrix degrading enzymes towards biofilms formed by E. faecalis and E. faecium clinical isolates. Colloids Surf B Biointerfaces. 2017;158:349–55.

    Article  CAS  PubMed  Google Scholar 

  181. Waryah CB, Wells K, Ulluwishewa D, Chen-Tan N, Gogoi-Tiwari J, Ravensdale J, Costantino P, Gökçen A, Vilcinskas A, Wiesner J, Mukkur T. In vitro antimicrobial efficacy of tobramycin against Staphylococcus aureus biofilms in combination with or without DNase I and/or dispersin B: a preliminary investigation. Microb Drug Resist. 2017;23:384–90.

    Article  CAS  PubMed  Google Scholar 

  182. Germoni LA, Bremer PJ, Lamont IL. The effect of alginate lyase on the gentamicin resistance of Pseudomonas aeruginosa in mucoid biofilms. J Appl Microbiol. 2016;121:126–35.

    Article  CAS  PubMed  Google Scholar 

  183. Ivanova K, Fernandes MM, Francesko A, Mendoza E, Guezguez J, Burnet M, Tzanov T. Quorum-quenching and matrix-degrading enzymes in multilayer coatings synergistically prevent bacterial biofilm formation on urinary catheters. ACS Appl Mater Interfaces. 2015;7:27066–77.

    Article  CAS  PubMed  Google Scholar 

  184. Kaplan JB, Mlynek KD, Hettiarachchi H, Alamneh YA, Biggemann L, Zurawski DV, Black CC, Bane CE, Kim RK, Granick MS. Extracellular polymeric substance (EPS)-degrading enzymes reduce staphylococcal surface attachment and biocide resistance on pig skin in vivo. PLoS One. 2018;13:e0205526.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  185. Zhu L, Poosarla VG, Song S, Wood TL, Miller DS, Yin B, Wood TK. Glycoside hydrolase DisH from Desulfovibrio vulgaris degrades the N-acetylgalactosamine component of diverse biofilms. Environ Microbiol. 2018;20:2026–37.

    Article  CAS  PubMed  Google Scholar 

  186. Snarr BD, Baker P, Bamford NC, Sato Y, Liu H, Lehoux M, Gravelat FN, Ostapska H, Baistrocchi SR, Cerone RP, Filler EE, Parsek MR, Filler SG, Howell PL, Sheppard DC. Microbial glycoside hydrolases as antibiofilm agents with cross-kingdom activity. Proc Natl Acad Sci USA. 2017;114:7124–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  187. Banar M, Emaneini M, Satarzadeh M, Abdellahi N, Beigverdi R, Leeuwen WB, Jabalameli F. Evaluation of mannosidase and trypsin enzymes effects on biofilm production of Pseudomonas aeruginosa isolated from burn wound infections. PLoS One. 2016;11:e0164622.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  188. Das T, Sehar S, Manefield M. The roles of extracellular DNA in the structural integrity of extracellular polymeric substance and bacterial biofilm development. Environ Microbiol Rep. 2013;5:778–86.

    Article  CAS  PubMed  Google Scholar 

  189. Sugimoto S, Sato F, Miyakawa R, Chiba A, Onodera S, Hori S, Mizunoe Y. Broad impact of extracellular DNA on biofilm formation by clinically isolated Methicillin-resistant and -sensitive strains of Staphylococcus aureus. Sci Rep. 2018;8:2254.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  190. Ye J, Shao C, Zhang X, Guo X, Gao P, Cen Y, Ma S, Liu Y. Effects of DNase I coating of titanium on bacteria adhesion and biofilm formation. Mater Sci Eng C Mater Biol Appl. 2017;78:738–47.

    Article  CAS  PubMed  Google Scholar 

  191. Tetz VV, Tetz GV. Effect of extracellular DNA destruction by DNase I on characteristics of forming biofilms. DNA Cell Biol. 2010;29:399–405.

    Article  CAS  PubMed  Google Scholar 

  192. Tan Y, Ma S, Leonhard M, Moser D, Haselmann GM, Wang J, Eder D, Schneider-Stickler B. Enhancing antibiofilm activity with functional chitosan nanoparticles targeting biofilm cells and biofilm matrix. Carbohydr Polym. 2018;200:35–42.

    Article  CAS  PubMed  Google Scholar 

  193. Belfield K, Bayston R, Hajduk N, Levell G, Birchall JP, Daniel M. Evaluation of combinations of putative anti-biofilm agents and antibiotics to eradicate biofilms of Staphylococcus aureus and Pseudomonas aeruginosa. J Antimicrob Chemother. 2017;72:2531–8.

    Article  CAS  PubMed  Google Scholar 

  194. Cavaliere R, Ball JL, Turnbull L, Whitchurch CB. The biofilm matrix destabilizers, EDTA and DNaseI: enhance the susceptibility of nontypeable Hemophilus influenzae biofilms to treatment with ampicillin and ciprofloxacin. Microbiol Open. 2014;3:557–67.

    Article  CAS  Google Scholar 

  195. Southern KW, Clancy JP, Ranganathan S. Aerosolized agents for airway clearance in cystic fibrosis. Pediatr Pulmonol. 2019;54:858–64.

    Article  PubMed  Google Scholar 

  196. Chen Z, Ji H, Liu C, Bing W, Wang Z, Qu X. A multinuclear metal complex based DNase-mimetic artificial enzyme: matrix cleavage for combating bacterial biofilms. Angew Chem Int Ed Engl. 2016;55:10732–6.

    Article  CAS  PubMed  Google Scholar 

  197. Nijland R, Hall MJ, Burgess JG. Dispersal of biofilms by secreted, matrix degrading, bacterial DNase. PLoS One. 2010;5:e15668.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  198. Shields RC, Mokhtar N, Ford M, Hall MJ, Burgess JG, ElBadawey MR, Jakubovics NS. Efficacy of a marine bacterial nuclease against biofilm forming microorganisms isolated from chronic rhinosinusitis. PLoS One. 2013;8:e55339.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  199. Shakir A, Elbadawey MR, Shields RC, Jakubovics NS, Burgess JG. Removal of biofilms from tracheoesophageal speech valves using a novel marine microbial deoxyribonuclease. Otolaryngol Head Neck Surg. 2012;147:509–14.

    Article  PubMed  Google Scholar 

  200. Liu J, Sun L, Liu W, Guo L, Liu Z, Wei X, Ling J. A nuclease from Streptococcus mutans facilitates biofilm dispersal and escape from killing by neutrophil extracellular traps. Front Cell Infect Microbiol. 2017;7:97.

    CAS  PubMed  PubMed Central  Google Scholar 

  201. Tan A, Li WS, Verderosa AD, Blakeway LV, D Mubaiwa T, Totsika M, Seib KL. Moraxella catarrhalis NucM is an entry nuclease involved in extracellular DNA and RNA degradation, cell competence and biofilm scaffolding. Sci Rep. 2019;9:2579.

  202. Lasa I, Penades JR. Bap: a family of surface proteins involved in biofilm formation. Res Microbiol. 2006;157:99–107.

    Article  CAS  PubMed  Google Scholar 

  203. Niazi SA, Clark D, Do T, Gilbert SC, Foschi F, Mannocci F, Beighton D. The effectiveness of enzymic irrigation in removing a nutrient-410 stressed endodontic multispecies biofilm. Int Endod J. 2014;47:756–68.

    Article  CAS  PubMed  Google Scholar 

  204. Shukla SK, Rao TS. Staphylococcus aureus biofilm removal by targeting biofilm-associated extracellular proteins. Indian J Med Res. 2017;146:S1–8.

    PubMed  PubMed Central  Google Scholar 

  205. Nguyen UT, Burrows LL. DNase I and proteinase K impair Listeria monocytogenes biofilm formation and induce dispersal of pre-existing biofilms. Int J Food Microbiol. 2014;187:26–32.

    Article  CAS  PubMed  Google Scholar 

  206. Ali Mohammed MM, Nerland AH, Al-Haroni M, Bakken V. Characterization of extracellular polymeric matrix, and treatment of Fusobacterium nucleatum and Porphyromonas gingivalis biofilms with DNase I and proteinase K. J Oral Microbiol. 2013;5.

    Article  CAS  Google Scholar 

  207. Boles BR, Horswill AR. Agr-mediated dispersal of Staphylococcus aureus biofilms. PLoS Pathog. 2008;4:e1000052.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  208. Mugita N, Nambu T, Takahashi K, Wang PL, Komasa Y. Proteases, actinidin, papain and trypsin reduce oral biofilm on the tongue in elderly subjects and in vitro. Arch Oral Biol. 2017;82:233–40.

    Article  CAS  PubMed  Google Scholar 

  209. Nohno K, Yamaga T, Kaneko N, Miyazaki H. Tablets containing a cysteine protease, actinidine, reduce oral malodor: a crossover study. J Breath Res. 2012;6:017107.

    Article  CAS  PubMed  Google Scholar 

  210. Mootz JM, Malone CL, Shaw LN, Horswill AR. Staphopains modulate Staphylococcus aureus biofilm integrity. Infect Immun. 2013;81:3227–38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  211. Loughran AJ, Atwood DN, Anthony AC, Harik NS, Spencer HJ, Beenken KE, Smeltzer MS. Impact of individual extracellular proteases on Staphylococcus aureus biofilm formation in diverse clinical isolates and their isogenic sarA mutants. Microbiologyopen. 2014;3:897–909.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  212. Sonesson A, Przybyszewska K, Eriksson S, Mörgelin M, Kjellström S, Davies J, Potempa J, Schmidtchen A. Identification of bacterial biofilm and the Staphylococcus aureus derived protease, staphopain, on the skin surface of patients with atopic dermatitis. Sci Rep. 2017;7:8689.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  213. Kumar L, Cox CR, Sarkar SK. Matrix metalloprotease-1 inhibits and disrupts Enterococcus faecalis biofilms. PLoS ONE. 2019;14:e0210218.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  214. Petrova OE, Schurr JR, Schurr MJ, Sauer K. Microcolony formation by the opportunistic pathogen Pseudomonas aeruginosa requires pyruvate and pyruvate fermentation. Mol Microbiol. 2012;86(4):819–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  215. Sutherland IW. EPS: a complex mixture. In: Hans-Curt Flemming, Dr Thomas R. Neu, Dr Jost Wingender, editors. The Perfect Slime: Microbial Extracellular Polymeric Substances (EPS). IWA Publishing, 2016. Pp. 15-24.

  216. Goodwine J, Gil J, Doiron A, Valdes J, Solis M, Higa A, Davis S, Sauer K. Pyruvate-depleting conditions induce biofilm dispersion and enhance the efficacy of antibiotics in killing biofilms in vitro and in vivo. Sci Rep. 2019;9:3763.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  217. Percival SL, Mayer D, Kirsner RS, Schultz G, Weir D, Roy S, Alavi A, Romanelli M. Surfactants: role in biofilm management and cellular behaviour. Int Wound J. 2019;16:753–60.

    Article  PubMed  PubMed Central  Google Scholar 

  218. Simões M, Pereira MO, Vieira MJ. Action of a cationic surfactant on the activity and removal of bacterial biofilms formed under different flow regimes. Water Res. 2005;39:478–86.

    Article  PubMed  CAS  Google Scholar 

  219. Chen X, Stewart PS. Biofilm removal caused by chemical treatments. Water Res. 2000;34:4229–33.

    Article  CAS  Google Scholar 

  220. Brandl MT, Huynh S. Effect of the surfactant tween 80 on the detachment and dispersal of Salmonella enterica serovar Thompson single cells and aggregates from cilantro leaves as revealed by image analysis. Appl Environ Microbiol. 2014;80:5037–42.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  221. Azeredo L, Pacheco AP, Lopes I, Oliveira R, Vieira MJ. Monitoring cell detachment by surfactants in a parallel plate flow chamber. Water Sci Technol. 2003;47:77–82.

    Article  CAS  PubMed  Google Scholar 

  222. Yang Q, Larose C, Della Porta AC, Schultz GS, Gibson DJ. A surfactant-based wound dressing can reduce bacterial biofilms in a porcine skin explant model. Int Wound J. 2017;14:408–13.

    Article  PubMed  Google Scholar 

  223. Zölß C, Cech JD. Efficacy of a new multifunctional surfactant-based biomaterial dressing with 1% silver sulphadiazine in chronic wounds. Int Wound J. 2016;13:738–43.

    Article  PubMed  Google Scholar 

  224. Varjani SJ, Upasani VN. Critical review on biosurfactant analysis, purification and characterization using rhamnolipid as a model biosurfactant. Bioresour Technol. 2017;232:389–97.

    Article  CAS  PubMed  Google Scholar 

  225. Rendell NB, Taylor GW, Somerville M, Todd H, Wilson R, Cole PJ. Characterisation of Pseudomonas rhamnolipids. Biochim Biophys Acta. 1990;1045:189–93.

    Article  CAS  PubMed  Google Scholar 

  226. Davey ME, Caiazza NC, O’Toole GA. Rhamnolipid surfactant production affects biofilm architecture in Pseudomonas aeruginosa PAO1. J Bacteriol. 2003;18:1027–36.

    Article  CAS  Google Scholar 

  227. Díaz De Rienzo MA, Stevenson PS, Marchant R, Banat IM. Pseudomonas aeruginosa biofilm disruption using microbial surfactants. J Appl Microbiol. 2016;120:868–76.

    Article  PubMed  CAS  Google Scholar 

  228. Wood TL, Gong T, Zhu L, Miller J, Miller DS, Yin B, Wood TK. Rhamnolipids from Pseudomonas aeruginosa disperse the biofilms of sulfate-reducing bacteria. NPJ Biofilms Microbiomes. 2018;4:22.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  229. Bhattacharjee A, Nusca TD, Hochbaum AI. Rhamnolipids mediate an interspecies biofilm dispersal signaling pathway. ACS Chem Biol. 2016;11:3068–76.

    Article  CAS  PubMed  Google Scholar 

  230. De Rienzo MA, Martin PJ. Effect of mono and di-rhamnolipids on biofilms pre-formed by Bacillus subtilis BBK006. Curr Microbiol. 2016;73:183–9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  231. Aleksic I, Petkovic M, Jovanovic M, Milivojevic D, Vasiljevic B, Nikodinovic-Runic J, Senerovic L. Anti-biofilm properties of bacterial di-rhamnolipids and their semi-synthetic amide derivatives. Front Microbiol. 2017;8:2454.

    Article  PubMed  PubMed Central  Google Scholar 

  232. Diaz De Rienzo MA, Stevenson PS, Marchant R, Banat IM. Effect of biosurfactants on Pseudomonas aeruginosa and Staphylococcus aureus biofilms in a BioFlux channel. Appl Microbiol Biotechnol. 2016;100:5773–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  233. Díaz De Rienzo MA, Stevenson P, Marchant R, Banat IM. Antibacterial properties of biosurfactants against selected Gram-positive and -negative bacteria. FEMS Microbiol Lett. 2016;363:fnv224.

  234. Díaz De Rienzo MA, Banat IM, Dolman B, Winterburn J, Martin PJ. Sophorolipid biosurfactants: possible uses as antibacterial and antibiofilm agent. N Biotechnol. 2015;32:720–6.

  235. Mireles JR 2nd, Toguchi A, Harshey RM. Salmonella enterica serovar typhimurium swarming mutants with altered biofilm-forming abilities: surfactin inhibits biofilm formation. J Bacteriol. 2001;183:5848–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  236. Kolodkin-Gal I, Romero D, Cao S, Clardy J, Kolter R, Losick R. D-Amino acids trigger biofilm disassembly. Science. 2010;328:627–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  237. Lam H, Oh DC, Cava F, Takacs CN, Clardy J, de Pedro MA, Waldor MK. D-amino acids govern stationary phase cell wall remodeling in bacteria. Science. 2009;325:1552–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  238. Rosen E, Tsesis I, Elbahary S, Storzi N, Kolodkin-Gal I. Eradication of Enterococcus faecalis biofilms on human dentin. Front Microbiol. 2016;7:2055.

    Article  PubMed  PubMed Central  Google Scholar 

  239. Ampornaramveth RS, Akeatichod N, Lertnukkhid J, Songsang N. Application of d-amino acids as biofilm dispersing agent in dental unit waterlines. Int J Dent. 2018;2018:9413925.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  240. Brandenburg KS, Rodriguez KJ, McAnulty JF, Murphy CJ, Abbott NL, Schurr MJ, Czuprynski CJ. Tryptophan inhibits biofilm formation by Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2013;57:1921–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  241. Kolderman E, Bettampadi D, Samarian D, Dowd SE, Foxman B, Jakubovics NS, Rickard AH. L-arginine destabilizes oral multi-species biofilm communities developed in human saliva. PLoS One. 2015;10:e0121835.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  242. Hengge R. Principles of c-di-GMP signalling in bacteria. Nat Rev Microbiol. 2009;7:263–73.

    Article  CAS  PubMed  Google Scholar 

  243. Barraud N, Kelso MJ, Rice SA, Kjelleberg S. Nitric oxide: a key mediator of biofilm dispersal with applications in infectious diseases. Curr Pharm Des. 2015;21:31–42.

    Article  CAS  PubMed  Google Scholar 

  244. Barraud N, Schleheck D, Klebensberger J, Webb JS, Hassett DJ, Rice SA, Kjelleberg S. Nitric oxide signaling in Pseudomonas aeruginosa biofilms mediates phosphodiesterase activity, decreased cyclic di-GMP levels, and enhanced dispersal. J Bacteriol. 2009;191:7333–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  245. Barraud N, Hassett DJ, Hwang SH, Rice SA, Kjelleberg S, Webb JS. Involvement of nitric oxide in biofilm dispersal of Pseudomonas aeruginosa. J Bacteriol. 2006;188:7344–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  246. Howlin RP, Cathie K, Hall-Stoodley L, Cornelius V, Duignan C, Allan RN, Fernandez BO, Barraud N, Bruce KD, Jefferies J, Kelso M, Kjelleberg S, Rice SA, Rogers GB, Pink S, Smith C, Sukhtankar PS, Salib R, Legg J, Carroll M, Daniels T, Feelisch M, Stoodley P, Clarke SC, Connett G, Faust SN, Webb JS. Low-dose nitric oxide as targeted anti-biofilm adjunctive therapy to treat chronic Pseudomonas aeruginosa infection in cystic fibrosis. Mol Ther. 2017;25:2104–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  247. Antoniani D, Bocci P, Maciag A, Raffaelli N, Landini P. Monitoring of diguanylate cyclase activity and of cyclic-di- GMP biosynthesis by whole-cell assays suitable for high-throughput screening of biofilm inhibitors. Appl Microbiol Biotechnol. 2010;85:1095–104.

    Article  CAS  PubMed  Google Scholar 

  248. Davies DG, Marques CN. A fatty acid messenger is responsible for inducing dispersion in microbial biofilms. J Bacteriol. 2009;191:1393–403.

    Article  CAS  PubMed  Google Scholar 

  249. Marques CN, Davies DG, Sauer K. Control of biofilms with the fatty acid signaling molecule cis-2-decenoic acid. Pharmaceuticals (Basel). 2015;8:816–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  250. Jennings JA, Courtney HS, Haggard WO. Cis-2-decenoic acid inhibits S. aureus growth and biofilm in vitro: a pilot study. Clin Orthop Relat Res. 2012;470:2663–70.

    Article  PubMed  PubMed Central  Google Scholar 

  251. Rahmani-Badi A, Sepehr S, Mohammadi P, Soudi MR, Babaie-Naiej H, Fallahi H. A combination of cis-2-decenoic acid and antibiotics eradicates pre-established catheter-associated biofilms. J Med Microbiol. 2014;63:1509–16.

    Article  PubMed  CAS  Google Scholar 

  252. Rahmani-Badi A, Sepehr S, Babaie-Naiej H. A combination of cis-2-decenoic acid and chlorhexidine removes dental plaque. Arch Oral Biol. 2015;60:1655–61.

    Article  CAS  PubMed  Google Scholar 

  253. Marques CN, Morozov A, Planzos P, Zelaya HM. The fatty acid signaling molecule cis-2-decenoic acid increases metabolic activity and reverts persister cells to an antimicrobial-susceptible state. Appl Environ Microbiol. 2014;80:6976–91.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  254. Dow JM, Crossman L, Findlay K, He YQ, Feng JX, Tang JL. Biofilm dispersal in Xanthomonas campestris is controlled by cell–cell signaling and is required for full virulence to plants. Proc Natl Acad Sci USA. 2003;100:10995–1000.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  255. Overhage J, Campisano A, Bains M, Torfs EC, Rehm BH, Hancock RE. Human host defense peptide LL-37 prevents bacterial biofilm formation. Infect Immun. 2008;76:4176–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  256. Aka ST. Killing efficacy and anti-biofilm activity of synthetic human cationic antimicrobial peptide cathelicidin hCAP-18/LL37 against urinary tract pathogens. J Microbiol Infect Dis. 2015;5:15–20.

    Article  Google Scholar 

  257. de la Fuente-Nunez C, Reffuveille F, Haney EF, Straus SK, Hancock REW. Broad-spectrum anti-biofilm peptide that targets a cellular stress response. PLoS Pathog. 2014;10:e1004152.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  258. Reffuveille F, de la Fuente-Núñez C, Mansour S, Hancock RE. A broad-spectrum antibiofilm peptide enhances antibiotic action against bacterial biofilms. Antimicrob Agents Chemother. 2014;58:5363–71.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  259. de la Fuente-Nunez C, Reffuveille F, Mansour SC, Reckseidler-Zenteno SL, Hernandez D, Brackman G, Coenye T, Hancock REW. D-enantiomeric peptides that eradicate wild-type and multidrug-resistant biofilms and protect against lethal Pseudomonas aeruginosa infections. Chem Biol. 2015;22:196–205.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  260. Ribeiro SM, de la Fuente-Núñez C, Baquir B, Faria-Junior C, Franco OL, Hancock RE. Antibiofilm peptides increase the susceptibility of carbapenemase-producing Klebsiella pneumoniae clinical isolates to β-lactam antibiotics. Antimicrob Agents Chemother. 2015;59:3906–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  261. Batoni G, Casu M, Giuliani A, Luca V, Maisetta G, Mangoni ML, Manzo G, Pintus M, Pirri G, Rinaldi AC, et al. Rational modification of a dendrimeric peptide with antimicrobial activity: consequences on membrane-binding and biological properties. Amino Acids. 2016;48:887–900.

    Article  CAS  PubMed  Google Scholar 

  262. Mishra B, Golla RM, Lau K, Lushnikova T, Wang G. Anti-Staphylococcal biofilm effects of human cathelicidin peptides. ACS Med Chem Lett. 2016;7:117–21.

    Article  CAS  PubMed  Google Scholar 

  263. Anunthawan T, de la Fuente-Nunez C, Hancock REW, Klaynongsruang S. Cationic amphipathic peptides KT2 and RT2 are taken up into bacterial cells and kill planktonic and biofilm bacteria. Biochim Biophys Acta. 2015;1848:1352–8.

    Article  CAS  PubMed  Google Scholar 

  264. Bionda N, Fleeman RM, de la Fuente-Nunez C, Rodriguez MC, Reffuveille F, Shaw LN, Pastar I, Davis SC, Hancock REW, Cudic P. Identification of novel cyclic lipopeptides from a positional scanning combinatorial library with enhanced antibacterial and antibiofilm activities. Eur J Med Chem. 2016;108:354–63.

    Article  CAS  PubMed  Google Scholar 

  265. De Brucker K, Delattin N, Robijns S, Steenackers H, Verstraeten N, Landuyt B, Luyten W, Schoofs L, Dovgan B, Frohlich M, et al. Derivatives of the mouse cathelicidin-related antimicrobial peptide (CRAMP) inhibit fungal and bacterial biofilm formation. Antimicrob Agents Chemother. 2014;58:5395–404.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  266. de la Fuente-Nunez C, Reffuveille F, Haney EF, Straus SK, Hancock REW. Broad-spectrum anti-biofilm peptide that targets a cellular stress response. PLoS Pathog. 2014;10:e1004152.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  267. de la Fuente-Nunez C, Reffuveille F, Mansour SC, Reckseidler-Zenteno SL, Hernandez D, Brackman G, Coenye T, Hancock REW. D-enantiomeric peptides that eradicate wild-type and multidrug-resistant biofilms and protect against lethal Pseudomonas aeruginosa infections. Chem Biol. 2015;22:196–205.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  268. Moryl M, Spętana M, Dziubek K, Paraszkiewicz K, Różalska S, Płaza GA, Różalski A. Antimicrobial, antiadhesive and antibiofilm potential of lipopeptides synthesised by Bacillus subtilis, on uropathogenic bacteria. Acta Biochim Pol. 2015;62:725–32.

    Article  CAS  PubMed  Google Scholar 

  269. Harper DR, Parracho HMRT, Walker J, Sharp R, Hughes G, Werthén M, Lehman S, Morales S. Bacteriophages and biofilms. Antibiotics (Basel). 2014;3:270–84.

    Article  CAS  PubMed Central  Google Scholar 

  270. Fong SA, Drilling A, Morales S, Cornet ME, Woodworth BA, Fokkens WJ, Psaltis AJ, Vreugde S, Wormald PJ. Activity of bacteriophages in removing biofilms of pseudomonas aeruginosa isolates from chronic rhinosinusitis patients. Front Cell Infect Microbiol. 2017;7:418.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  271. Lehman SM, Donlan RM. Bacteriophage-mediated control of a two-species biofilm formed by microorganisms causing catheter-associated urinary tract infections in an in vitro urinary catheter model. Antimicrob Agents Chemother. 2015;59:1127–37.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  272. Holguín AV, Rangel G, Clavijo V, Prada C, Mantilla M, Gomez MC, Kutter E, Taylor C, Fineran PC, Barrios AF, Vives MJ. Phage ΦPan70, a putative temperate phage, controls Pseudomonas aeruginosa in planktonic, biofilm and burn mouse model assays. Viruses. 2015;7:4602–23.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  273. Forti F, Roach DR, Cafora M, Pasini ME, Horner DS, Fiscarelli EV, Rossitto M, Cariani L, Briani F, Debarbieux L, Ghisotti D. Design of a broad-range bacteriophage cocktail that reduces Pseudomonas aeruginosa biofilms and treats acute infections in two animal models. Antimicrob Agents Chemother. 2018;62:e02573-17.

    Article  PubMed  PubMed Central  Google Scholar 

  274. Regeimbal JM, Jacobs AC, Corey BW, Henry MS, Thompson MG, Pavlicek RL, Quinones J, Hannah RM, Ghebremedhin M, Crane NJ, Zurawski DV, Teneza-Mora NC, Biswas B, Hall ER. Personalized therapeutic cocktail of wild environmental phages rescues mice from acinetobacter baumannii wound infections. Antimicrob Agents Chemother. 2016;60:5806–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  275. Patey O, McCallin S, Mazure H, Liddle M, Smithyman A, Dublanchet A. Clinical indications and compassionate use of phage therapy: personal experience and literature review with a focus on osteoarticular infections. Viruses. 2018;11:18.

    Article  PubMed Central  Google Scholar 

  276. Marks LR, Davidson BA, Knight PR, Hakansson AP. Interkingdom signaling induces Streptococcus pneumoniae biofilm dispersion and transition from asymptomatic colonization to disease. MBio. 2013;4:e00438-13.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  277. Sambanthamoorthy K, Luo C, Pattabiraman N, Feng X, Koestler B, Waters CM, Palys TJ. Identification of small molecules inhibiting diguanylate cyclases to control bacterial biofilm development. Biofouling. 2014;30:17–28.

    Article  CAS  PubMed  Google Scholar 

  278. Rumbo C, Vallejo JA, Cabral MP, Martínez-Guitián M, Pérez A, Beceiro A, Bou G. Assessment of antivirulence activity of several d-amino acids against acinetobacter baumannii and Pseudomonas aeruginosa. J Antimicrob Chemother. 2016;71:3473–81.

    Article  CAS  PubMed  Google Scholar 

  279. Han D, Matsumaru K, Rettori D, Kaplowitz N. Usnic acid-induced necrosis of cultured mouse hepatocytes: inhibition of mitochondrial function and oxidative stress. Biochem Pharmacol. 2004;67:439–51.

    Article  CAS  PubMed  Google Scholar 

  280. Lu L, Hu W, Tian Z, Yuan D, Yi G, Zhou Y, Cheng Q, Zhu J, Li M. Developing natural products as potential anti-biofilm agents. Chin Med. 2019;14:11.

    Article  PubMed  PubMed Central  Google Scholar 

  281. Tyldesley HC, Salisbury AM, Chen R, Mullin M and Percival SL. Surfactants and their role in biofilm management in chronic wounds. Wounds Int 2019;10(1).

  282. Totsika M. Disarming pathogens: benefits and challenges of antimicrobials that target bacterial virulence instead of growth and viability. Future Med Chem. 2017;9:267–9.

    Article  CAS  PubMed  Google Scholar 

  283. García-Contreras R, Martínez-Vázquez M, Velázquez Guadarrama N, Villegas Pañeda AG, Hashimoto T, Maeda T, Quezada H, Wood TK. Resistance to the quorum-quenching compounds brominated furanone C-30 and 5-fluorouracil in Pseudomonas aeruginosa clinical isolates. Pathog Dis. 2013;68:8–11.

    Article  PubMed  CAS  Google Scholar 

  284. García-Contreras R, Peréz-Eretza B, Jasso-Chávez R, Lira-Silva E, Roldán-Sánchez JA, González-Valdez A, Soberón-Chávez G, Coria-Jiménez R, Martínez-Vázquez M, Alcaraz LD, Maeda T, Wood TK. High variability in quorum quenching and growth inhibition by furanone C-30 in Pseudomonas aeruginosa clinical isolates from cystic fibrosis patients. Pathog Dis. 2015;73:ftv040.

    Article  PubMed  CAS  Google Scholar 

  285. Travier L, Rendueles O, Ferrieres L, Herry JM, Ghigo JM. Escherichia coli resistance to nonbiocidal antibiofilm polysaccharides is rare and mediated by multiple mutations leading to surface physicochemical modifications. Antimicrob Agents Chemother. 2013;57:3960–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Vuotto, C., Donelli, G. Novel Treatment Strategies for Biofilm-Based Infections. Drugs 79, 1635–1655 (2019). https://doi.org/10.1007/s40265-019-01184-z

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