Abstract
To formulate the optimal strategy of combatting bacterial biofilms, in this review we update current knowledge on the growing problem of biofilm formation and its resistance to antibiotics which has spurred the search for new strategies to deal with this complication. Based on recent findings, the role of bacteriophages in the prevention and elimination of biofilm-related infections has been emphasized. In vitro, ex vivo and in vivo biofilm treatment models with single bacteriophages or phage cocktails have been compared. A combined use of bacteriophages with antibiotics in vitro or in vivo confirms earlier reports of the synergistic effect of these agents in improving biofilm removal. Furthermore, studies on the application of phage-derived lysins in vitro, ex vivo or in vivo against biofilm-related infections are encouraging. The strategy of combined use of phage and antibiotics seems to be different from using lysins and antibiotics. These findings suggest that phages and lysins alone or in combination with antibiotics may be an efficient weapon against biofilm formation in vivo and ex vivo, which could be useful in formulating novel strategies to combat bacterial infections. Those findings proved to be relevant in the prevention and destruction of biofilms occurring during urinary tract infections, orthopedic implant-related infections, periodontal and peri-implant infections. In conclusion, it appears that most efficient strategy of eliminating biofilms involves phages or lysins in combination with antibiotics, but the optimal scheme of their administration requires further studies.
Access this article
We’re sorry, something doesn't seem to be working properly.
Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.
Similar content being viewed by others
References
Abedon ST (2018) Bacteriophage-mediated biocontrol of wound infections, and ecological exploitation of biofilms by phages. In: Shiffman MA, Low M (eds) Recent clinical techniques, results, and research in wounds. Springer, Berlin, pp 1–38
Abedon ST, Garcia P, Mullany P, Aminov R (2017) Editorial: phage therapy: past, present and future. Front Microbiol 8:981
Akanda ZZ, Taha M, Abdelbary H (2018) Current review-The rise of bacteriophage as a unique therapeutic platform in treating peri-prosthetic joint infections. J Orthop Res 36:1051–1060
Bai J, Jeon B, Ryu S (2019) Effective inhibition of Salmonella typhimurium in fresh produce by a phage cocktail targeting multiple host receptors. Food Microbiol 77:52–60
Borysowski J, Weber-Dąbrowska B, Górski A (2006) Bacteriophage endolysins as a novel class of antibacterial agents. Exp Biol Med (Maywood) 231:366–377
Borysowski J, Lobocka M, Międzybrodzki R, Weber-Dąbrowska B, Górski A (2011) Potential of bacteriophages and their lysins in the treatment of MRSA: current status and future perspectives. BioDrugs 25(6):347–355
Chan BK, Abedon ST (2015) Bacteriophages and their enzymes in biofilm control. Curr Pharm Des 21:85–99
Chaudhry WN, Concepción-Acevedo J, Park T, Andleeb S, Bull JJ, Levin BR (2017) Synergy and order effects of antibiotics and phages in killing Pseudomonas aeruginosa biofilms. PLoS ONE 12:e0168615
Chopra S, Harjai K, Chhibber S (2015) Potential of sequential treatment with minocycline and S. aureus specific phage lysin in eradication of MRSA biofilms: an in vitro study. Appl Microbiol Biotechnol 99:3201–3210
Fischetti VA (2017) Lysin therapy for Staphylococcus aureus and other bacterial pathogens. Curr Top Microbiol Immunol 409:529–540
Fischetti VA (2018) Development of phage lysins as novel therapeutics: a historical perspective. Viruses 10:E310
Fu W, Forster T, Mayer O, Curtin JJ, Lehman SM, Donlan RM (2010) Bacteriophage cocktail for the prevention of biofilm formation by Pseudomonas aeruginosa on catheters in an in vitro model system. Antimicrob Agents Chemother 54:397–404
Górski A, Międzybrodzki R, Węgrzyn G, Jończyk-Matysiak E, Borysowski J, Weber-Dąbrowska B (2019) Phage therapy: current status and perspectives. Med Res Rev. https://doi.org/10.1002/med.21593
Gray JA, Chandry PS, Kaur M, Kocharunchitt C, Bowman JP, Fox EM (2018) Novel biocontrol methods for Listeria monocytogenes biofilms in food production facilities. Front Microbiol 9:605
Guo M, Feng C, Ren J, Zhuang X, Zhang Y, Zhu Y, Dong K, He P, Guo X, Qin J et al (2017) A novel antimicrobial endolysin, LysPA26, against Pseudomonas aeruginosa. Front Microbiol 8:293
Henriksen K, RØrbo N, Rybtke ML, Martinet MG, Tolker-Nielsen T, Høiby N, Middelboe M, Ciofu O (2019) P. aeruginosa flow-cell biofilms are enhanced by repeating phage treatments but can be eradicated by phage-ciprofloxacin combination. Pathog Dis 77:ftz011
Hesse S, Adhya S (2019) Phage therapy in the twenty-first century: facing the decline of the antibiotic era; is it finally time for the age of the phage. Annu Rev Microbiol 73:155–174
Issa R, Chanishvili N, Caplin J, Kakabadze E, Bakuradze N, Makalatia K, Cooper I (2019) Anti-biofilm potential of purified environmental bacteriophage preparations against early stage Pseudomonas aeruginosa biofilms. J Appl Microbiol 126:1657–1667
Kaur S, Harjai K, Chhibber S (2016) In vivo assessment of phage and linezolid based implant coating for treatment of Methicillin Resistant S. aureus (MRSA) mediated orthopaedic device related infections. PLoS ONE 11:e0157626
Khalifa L, Brosh Y, Gelman D, Coppenhagen-Glazer S, Beyth S, Poradosu-Cohen R, Que YA, Beyth N, Hazan R (2015) Targeting Enterococcus faecalis biofilms with phage therapy. Appl Environ Microbiol 81:2696–2705
Khalifa L, Shlezinger M, Beyth S, Houri-Haddad Y, Coppenhagen-Glazer S, Beyth N, Hazan R (2016) Phage therapy against Enterococcus faecalis in dental root canals. J Oral Microbiol 8:32157
Kropinski AM (2006) Phage therapy—everything old is new again. Can J Infect Dis Med Microbiol 17(5):297–306
Kumaran D, Taha M, Yi Q, Ramirez-Arcos S, Diallo JS, Carli A, Abdelbary H (2018) Does treatment order matter? Investigating the ability of bacteriophage to augment antibiotic activity against Staphylococcus aureus biofilms. Front Microbiol 9:127
Lood R, Winer BY, Pelzek AJ, Diez-Martinez R, Thandar M, Euler CW, Schuch R, Fischetti VA (2015) Novel phage lysin capable of killing the multidrug-resistant gram-negative bacterium Acinetobacter baumannii in a mouse bacteremia model. Antimicrob Agents Chemother 59(4):1983–1991
Mah TF, O’Toole GA (2001) Mechanisms of biofilm resistance to antimicrobial agents. Trends Microbiol 9:34–39
Malik S, Sidhu PK, Rana JS, Nehra K (2019) Managing urinary tract infections through phage therapy: a novel approach. Folia Microbiol (Praha) Sep 7. https://doi.org/10.1007/s12223-019-00750-y
Maszewska A, Zygmunt M, Grzejdziak I, Różalski A (2018) Use of polyvalent bacteriophages to combat biofilm of Proteus mirabilis causing catheter-associated urinary tract infections. J Appl Microbiol 125:1253–1265
McCallin S, Sacher JC, Zheng J, Chan BK (2019) Current state of compassionate phage therapy. Viruses 11:E343
Melo LD, Veiga P, Cerca N, Kropinski AM, Almeida C, Azeredo J, Sillankorva S (2016) Development of a phage cocktail to control Proteus mirabilis catheter-associated urinary tract infections. Front Microbiol 7:1024
Melo LDR, Brandao A, Akturk E, Santos SB, Azeredo J (2018) Characterization of a new Staphylococcus aureus Kayvirus harboring a lysin active against biofilms. Viruses 10:E182
Melo LDR, Pires DP, Monteiro R, Azeredo J (2019) Phage therapy of infectious biofilms: challenges and strategies. In: Górski A, Międzybrodzki R, Borysowski J (eds) Phage therapy: a Practical approach. Springer, Switzerland, pp 295–313
Morris J, Kelly N, Elliot L, Grant A, Wilkinson M, Hazratwala K, McEwen P (2019) Evaluation of bacteriophage anti-biofilm activity for potential control of orthopedic implant-related infections caused by Staphylococcus aureus. Surg Infect (Larchmt) 20:16–24
Nale JY, Chutia M, Carr P, Hickenbotham PT, Clokie M (2016) ‘Get in early’; Biofilm and wax moth (Galleria mellonella) models reveal new insights into the therapeutic potential of Clostridium difficile bacteriophages. Front Microbiol 7:1383
Oechslin F (2018) Resistance development to bacteriophages occurring during bacteriophage therapy. Viruses 10:351
Pinto G, Silva MD, Peddey M, Sillankorva S, Azeredo J (2016) The role of bacteriophages in periodontal health and disease. Future Microbiol 11:1359–1369
Pires DP, Dötsch A, Anderson EM, Hao Y, Khursigara CM, Lam JS, Sillankorva S, Azeredo J (2017a) A genotyping analysis of five P. aeruginosa strains after biofilm infection by phages targeting different cell surface receptors. Front Microbiol 8:1229
Pires DP, Melo LDR, Vilas Boas D, Sillankorva S, Azeredo J (2017b) Phage therapy as an alternative or complementary strategy to prevent and control biofilm-related infections. Curr Opin Microbiol 39:48–56
Poonacha N, Nair S, Desai S, Tuppad D, Hiremath D, Mohan T, Vipra A, Sharma U (2017) Efficient killing of planktonic and biofilm-embedded coagulase-negative staphylococci by bactericidal protein P128. Antimicrob Agents Chemother 61:e00457-17
Ryan EM, Alkawareek MY, Donnelly RF, Gilmore BF (2012) Synergistic phage-antibiotic combinations for the control of Escherichia coli biofilms in vitro. FEMS Immunol Med Microbiol 65:395–398
Sass P, Bierbaum G (2007) Lytic activity of recombinant bacteriophage phi11 and phi12 endolysins on whole cells and biofilms of Staphylococcus aureus. Appl Environ Microbiol 73:347–352
Schuch R, Khan BK, Raz A, Rotolo JA, Wittekind M (2017) Bacteriophage lysin CF-301, a potent antistaphyloccocal biofilm agent. Antimicrob Agents Chemother 61:e02666-16
Sharma U, Vipra A, Channabasappa S (2018) Phage-derived lysins as potential agents for eradication biofilms and persisters. Drug Discov Today 23:848–856
Sillankorva S, Azeredo J (2014) The use of bacteriophages and bacteriophage-derived enzymes for clinically relevant biofilm control. In: Borysowski J, Międzybrodzki R, Górski A (eds) Phage therapy: current research and application. Caister Academic Press, Wymondham (chapter 13)
Simmons M, Morales CA, Oakley BB, Seal BS (2012) Recombinant expression of a putative amidase cloned from the genome of Listeria monocytogenes that lyses the bacterium and its monolayer in conjunction with a protease. Probiotics Antimicrob Proteins 4:1–10
Singh PK, Donovan DM, Kumar A (2014) Intravitreal injection of the chimeric phage endolysin Ply187 protects mice from Staphylococcus aureus endophthalmitis. Antimicrob Agents Chemother 58:4621–4629
Szafrański SP, Winkel A, Stiesch M (2017) The use of bacteriophages to biocontrol oral biofilms. J Biotechnol 250:29–44
Taha M, Abdelbary H, Ross FP, Carli AV (2018) New innovations in the treatment of PJI and biofilms-clinical and preclinical topics. Curr Rev Musculoskelet Med 11:380–388
Thandar M, Lood R, Winer BY, Deutsch DR, Euler CW, Fischetti VA (2016) Novel engineered peptides of a phage lysin as effective antimicrobials against multidrug-resistant Acinetobacter baumanii. Antimicrob Agents Chemother 60:2671–2679
Tkhilaishvili T, Lombardi L, Klatt AB, Trampuz A, Di Luca M (2018) Bacteriophage Sb-1 enhances antibiotic activity against biofilm, degrades exopolysaccharide matrix and targets persisters of Staphylococcus aureus. Int J Antimicrob Agents 52:842–853
Yang H, Yu J, Wei H (2014) Engineered bacteriophage lysins as novel anti-infectives. Front Microbiol 5:542
Yilmaz C, Colak M, Yilmaz BC, Ersoz G, Kutatelidze M, Gozlugol M (2013) Bacteriophage therapy in implant-related infections: an experimental study. J Bone Joint Surg Am 95:117–125
Acknowledgements
This work was supported by the statutory funds from the Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences.
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Conflict of interest
A Górski and B Weber-Dąbrowska are co-inventors of patents owned by the Hirszfeld Institute of Immunology and Experimental Therapy and covering phage preparations. M Łusiak-Szelachowska declares that she has no conflict of interest.
Animal and Human Rights Statement
This article does not contain any studies with human participants or animals performed by any of the authors.
Rights and permissions
About this article
Cite this article
Łusiak-Szelachowska, M., Weber-Dąbrowska, B. & Górski, A. Bacteriophages and Lysins in Biofilm Control. Virol. Sin. 35, 125–133 (2020). https://doi.org/10.1007/s12250-019-00192-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12250-019-00192-3

