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Recent Patents on Biotechnology

Editor-in-Chief

ISSN (Print): 1872-2083
ISSN (Online): 2212-4012

Mini-Review Article

Bacteriophages as Therapeutic Agents: Alternatives to Antibiotics

Author(s): Safia Samir *

Volume 15, Issue 1, 2021

Published on: 21 January, 2021

Page: [25 - 33] Pages: 9

DOI: 10.2174/1872208315666210121094311

Price: $65

Abstract

Bacteriophages are bacterio-specific viruses that constitute the main portion of the environment. Bacteriophages inject their genome into the targeted bacterial cells and some of them can disrupt the metabolism of bacteria and cause bacterial cell disintegration. The application of bacteriophages to kill bacteria is known as bacteriophage therapy. Since bacteriophages target bacteria and are strain-specific, every bacteriophage/bacterial host pair is unique. They are believed to cause no harm to humans. An additional advantage of the strain-specific nature of bacteriophages is that they do not disrupt the beneficial natural flora in the body. Bacteriophage therapy in the West is not a recognized medicine at this time, and no products are registered. Some clinicians are turning to bacteriophage therapy for the treatment of antibiotic-resistant infections. Lack of adverse effects makes bacteriophage therapy ideal for use. Funding research, media attention, and the increased publication of articles helped in a widespread understanding of its therapeutic potential. The first prerequisite for the use of bacteriophage therapy is simply the availability of bacteriophages for treatment, which is often complicated at this stage of bacteriophage production. This includes providing access to all biologically active bacteriophages against the bacterial isolate of the patient and meeting regulatory criteria of purity, traceability, and characterization. A monophage preparation, which is a single bacteriophage, or a phage cocktail, which consists of a number of combined bacteriophages against one or more bacterial species may be used. Accordingly, the antibiotic resistance crisis brought back bacteriophage therapy as a potential complementary or alternative treatment. Bacteriophages are promising cheap antibacterials.

Keywords: Bacterial infection, antibiotic therapy, antibiotic resistance, bacteriophage therapy, staphylococcus, phage.

Graphical Abstract
[1]
WHO. The World is running out of antibiotics, WHO report confirms 2017. Available at: https://www.who.int/news/item/20-09-2017-the-world-is-running-out-of-antibiotics-who-report-confirms
[2]
Liu J, Gefen O, Ronin I, Bar-Meir M, Balaban NQ. Effect of tolerance on the evolution of antibiotic resistance under drug combinations. Science 2020; 367(6474): 200-4.
[3]
Romero-Calle D, Guimarães Benevides R, Góes-Neto A, Billington C. Bacteriophages as Alternatives to Antibiotics in Clinical Care. Antibiotics (Basel) 2019; 8(3): 138.
[http://dx.doi.org/10.3390/antibiotics8030138] [PMID: 31487893]
[4]
Abedon ST. Phage-Antibiotic Combination Treatments: Antagonistic Impacts of Antibiotics on the Pharmacodynamics of Phage Therapy? Antibiotics (Basel) 2019; 8(4): 182.
[http://dx.doi.org/10.3390/antibiotics8040182] [PMID: 31614449]
[5]
Sime-Ngando T. Environmental bacteriophages: viruses of microbes in aquatic ecosystems. Front Microbiol 2014; 5: 355.
[http://dx.doi.org/10.3389/fmicb.2014.00355] [PMID: 25104950]
[6]
Ninawe AS, Sivasankari S, Ramasamy P, Kiran GS, Selvin J. Bacteriophages for aquaculture disease control. Aquacult Int 2020; 28(5): 1925-38.
[http://dx.doi.org/10.1007/s10499-020-00567-4]
[7]
Ghosh C, Sarkar P, Issa R, Haldar J. Alternatives to Conventional Antibiotics in the Era of Antimicrobial Resistance. Trends Microbiol 2019; 27(4): 323-38.
[http://dx.doi.org/10.1016/j.tim.2018.12.010] [PMID: 30683453]
[8]
Mathur MD, Vidhani S, Mehndiratta PL. Bacteriophage therapy: an alternative to conventional antibiotics. J Assoc Physicians India 2003; 51: 593-6.
[PMID: 15266928]
[9]
Alisky J, Iczkowski K, Rapoport A, Troitsky N. Bacteriophages show promise as antimicrobial agents. J Infect 1998; 36(1): 5-15.
[http://dx.doi.org/10.1016/S0163-4453(98)92874-2] [PMID: 9515662]
[10]
Trifonova A, Todorova I, Savov E. Bacteriophage therapy. Probl Infect Parasit Dis 2016; 44(2): 46-50.
[11]
Soothill JS. Bacteriophage prevents destruction of skin grafts by Pseudomonas aeruginosa. Burns 1994; 20(3): 209-11.
[http://dx.doi.org/10.1016/0305-4179(94)90184-8] [PMID: 8054131]
[12]
Pouillot F, Blois H. Phage therapy. WO2016071503, 2016.
[13]
Jurczak-Kurek A, Gąsior T, Nejman-Faleńczyk B, Bloch S, Dydecka A, Topka G, et al. Biodiversity of bacteriophages: morphological and biological properties of a large group of phages isolated from urban sewage. Sci Rep 2016; 6: 34338.
[http://dx.doi.org/10.1038/srep34338] [PMID: 27698408]
[14]
Clokie MRJ, Kropinski AM, Therapy G, et al. Biodiversity of Bacteriophages: Morphological and Biological Properties of a Large Group of Phages Isolated from Urban Sewage. Sci Rep 2020; 6(1): 1-7.
[http://dx.doi.org/10.1006/rwgn.2001.1297]
[15]
White HE, Orlova EV. Bacteriophages: their structural organisation and function. In: Savva R, Ed. Bacteriophages - perspectives and future United Kingdom IntechOpen. 2020.
[16]
Casey E, Sinderen D-V, Mahony J. In Vitro characteristics of phages to guide ‘real life’ phage therapy suitability. Viruses 2018; 10(4): 163.
[17]
Fernández L, Gutiérrez D, García P, Rodríguez A. The Perfect Bacteriophage for Therapeutic Applications-A Quick Guide. Antibiotics (Basel) 2019; 8(3): 126.
[http://dx.doi.org/10.3390/antibiotics8030126] [PMID: 31443585]
[18]
Gibson SB, Green SI, Liu CG, Salazar KC, Clark JR, Terwilliger AL, et al. Constructing and Characterizing Bacteriophage Libraries for Phage Therapy of Human Infections. Front Microbiol 2019; 10: 2537.
[http://dx.doi.org/10.3389/fmicb.2019.02537] [PMID: 31781060]
[19]
Chan BK, Abedon ST, Loc-Carrillo C. Phage cocktails and the future of phage therapy. Future Microbiol 2013; 8(6): 769-83.
[http://dx.doi.org/10.2217/fmb.13.47] [PMID: 23701332]
[20]
EudraLex; European Commission. Good Manufacturing Practice (GMP) Guidelines - European Commission. European Commission: Public Health 2017; 4 Available at: https://ec.europa.eu/health/documents/eudralex/vol-4_en
[21]
Hyman P. Phages for Phage Therapy: Isolation, Characterization, and Host Range Breadth. Pharmaceuticals (Basel) 2019; 12(1): 35.
[http://dx.doi.org/10.3390/ph12010035] [PMID: 30862020]
[22]
Principi N, Silvestri E, Esposito S. Advantages and Limitations of Bacteriophages for the Treatment of Bacterial Infections. Front Pharmacol 2019; 10: 513.
[http://dx.doi.org/10.3389/fphar.2019.00513] [PMID: 31139086]
[23]
Loc-Carrillo C, Abedon ST. Pros and cons of phage therapy. Bacteriophage 2011; 1(2): 111-4.
[http://dx.doi.org/10.4161/bact.1.2.14590] [PMID: 22334867]
[24]
Goodridge LD. Designing phage therapeutics. Curr Pharm Biotechnol 2010; 11(1): 15-27.
[http://dx.doi.org/10.2174/138920110790725348] [PMID: 20214605]
[25]
Łusiak-Szelachowska M, Weber-Dąbrowska B, Górski A. Bacteriophages and Lysins in Biofilm Control. Virol Sin 2020; 35(2): 125-33.
[http://dx.doi.org/10.1007/s12250-019-00192-3] [PMID: 32125643]
[26]
Álvarez A, Fernández L, Iglesias B, Rodríguez J, Rodríguez A, García P. Phage Therapy: Unexpected Drawbacks to Reach Hospitals. Future Virol 2020; 14(2): 779-82.
[http://dx.doi.org/10.2217/fvl-2019-0154]
[27]
Melo LDR, Oliveira H, Pires DP, Dabrowska K, Azeredo J. Phage therapy efficacy: a review of the last 10 years of preclinical studies. Crit Rev Microbiol 2020; 46(1): 78-99.
[http://dx.doi.org/10.1080/1040841X.2020.1729695] [PMID: 32091280]
[28]
Buchon N, Silverman N, Cherry S. Immunity in Drosophila melanogaster- from microbial recognition to whole-organism physiology. Nat Rev Immunol 2014; 14(12): 796-810.
[http://dx.doi.org/10.1038/nri3763] [PMID: 25421701]
[29]
Hill L, Veli N, Coote PJ. Evaluation of Galleria mellonella larvae for measuring the efficacy and pharmacokinetics of antibiotic therapies against Pseudomonas aeruginosa infection. Int J Antimicrob Agents 2014; 43(3): 254-61.https://doi.org/110.1016/j.ijantimicag.2013.11.001
[http://dx.doi.org/10.1016/j.ijantimicag.2013.11.001] [PMID: 24361354]
[30]
Seed KD, Dennis JJ. Experimental bacteriophage therapy increases survival of Galleria mellonella larvae infected with clinically relevant strains of the Burkholderia cepacia complex. Antimicrob Agents Chemother 2009; 53(5): 2205-8.
[http://dx.doi.org/10.1128/AAC.01166-08] [PMID: 19223640]
[31]
Al-Zubidi M, Widziolek M, Court EK, et al. Identification of Novel Bacteriophages with Therapeutic Potential That Target Enterococcus faecalis. Infect Immun 2019; 87(11): e00512-9.
[http://dx.doi.org/10.1128/IAI.00512-19] [PMID: 31451618]
[32]
Cafora M, Deflorian G, Forti F, Ferrari L, Binelli G, Briani F, et al. Phage therapy against Pseudomonas aeruginosa infections in a cystic fibrosis zebrafish model. Sci Rep 2019; 9(1): 1527.
[http://dx.doi.org/10.1038/s41598-018-37636-x] [PMID: 30728389]
[33]
Ahmadi M, Karimi Torshizi MA, Rahimi S, Dennehy JJ. Prophylactic bacteriophage administration more effective than post-infection administration in reducing salmonella enterica serovar enteritidis shedding in quail. Front Microbiol 2016; 7(e52781): 1253.
[http://dx.doi.org/10.3389/fmicb.2016.01253] [PMID: 27555842]
[34]
Wernicki A, Nowaczek A, Urban-Chmiel R. Bacteriophage therapy to combat bacterial infections in poultry. Virol J 2017; 14(1): 179.
[http://dx.doi.org/10.1186/s12985-017-0849-7] [PMID: 28915819]
[35]
Colom J, Cano-Sarabia M, Otero J, et al. Microencapsulation with alginate/CaCO3: A strategy for improved phage therapy. Sci Rep 2017; 7: 41441.
[http://dx.doi.org/10.1038/srep41441] [PMID: 28120922]
[36]
Wills QF, Kerrigan C, Soothill JS. Experimental bacteriophage protection against Staphylococcus aureus abscesses in a rabbit model. Antimicrob Agents Chemother 2005; 49(3): 1220-1.
[http://dx.doi.org/10.1128/AAC.49.3.1220-1221.2005] [PMID: 15728933]
[37]
Leshkasheli L, Kutateladze M, Balarjishvili N, Bolkvadze D, Save J, Oechslin F, et al. Efficacy of newly isolated and highly potent bacteriophages in a mouse model of extensively drug-resistant Acinetobacter baumannii bacteraemia. J Glob Antimicrob Resist 2019; 19: 255-61.https://doi.org/https://doi.org/10.1016/j.jgar.2019.05.005
[http://dx.doi.org/10.1016/j.jgar.2019.05.005] [PMID: 31100499]
[38]
Furfaro LL, Payne MS, Chang BJ. Bacteriophage therapy: clinical trials and regulatory hurdles. Front Cell Infect Microbiol 2018; 8: 376.
[http://dx.doi.org/10.3389/fcimb.2018.00376] [PMID: 30406049]
[39]
McCallin S, Sacher JC, Zheng J, Chan BK. Current state of compassionate phage therapy. Viruses 2019; 11(4): 343.
[http://dx.doi.org/10.3390/v11040343] [PMID: 31013833]
[40]
Monteiro R, Pires DP, Costa AR, Azeredo J. Phage therapy: going temperate? Trends Microbiol 2019; 27(4): 368-78.
[http://dx.doi.org/10.1016/j.tim.2018.10.008] [PMID: 30466900]
[41]
Duplessis CA. A case series of emergency investigational new drug applications for bacteriophages treating recalcitrant multi-drug resistant bacterial infections: confirmed safety and a signal of efficacy. J Intensive Crit Care 2019; 5(2): 11.
[42]
Taati Moghadam M, Amirmozafari N, Shariati A, Hallajzadeh M, Mirkalantari S, Khoshbayan A, et al. How phages overcome the challenges of drug resistant bacteria in clinical infections. Infect Drug Resist 2020; 13: 45-61.
[http://dx.doi.org/10.2147/IDR.S234353] [PMID: 32021319]
[43]
Merabishvili M, Pirnay JP, De Vos D. Guidelines to compose an ideal bacteriophage cocktail. In: Walker JM, Ed. Methods in molecular biology Heidelberg Springer. 2018.
[http://dx.doi.org/10.1007/978-1-4939-7395-8_9]
[44]
Barr JJ, Auro R, Furlan M, Whiteson KL, Erb ML, Pogliano J, et al. Bacteriophage adhering to mucus provide a non-host-derived immunity. Proc Natl Acad Sci USA 2013; 110(26): 10771-6.
[http://dx.doi.org/10.1073/pnas.1305923110] [PMID: 23690590]
[45]
Sulakvelidze A. The challenges of bacteriophage therapy. Ind Pharm 2011; 14(5): 524-31.

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