Biological Foundations of Successful Bacteriophage Therapy

Overview

Journal EMBO Mol Med

Specialty Molecular Biology

Date 2022 May 27

PMID 35620963

Authors

Carola Venturini

Aleksandra Petrovic Fabijan

Alicia Fajardo Lubian

Stefanie Barbirz

Jonathan Iredell

Affiliations

Soon will be listed here.

Abstract

Bacteriophages (phages) are selective viral predators of bacteria. Abundant and ubiquitous in nature, phages can be used to treat bacterial infections (phage therapy), including refractory infections and those resistant to antibiotics. However, despite an abundance of anecdotal evidence of efficacy, significant hurdles remain before routine implementation of phage therapy into medical practice, including a dearth of robust clinical trial data. Phage-bacterium interactions are complex and diverse, characterized by co-evolution trajectories that are significantly influenced by the environments in which they occur (mammalian body sites, water, soil, etc.). An understanding of the molecular mechanisms underpinning these dynamics is essential for successful clinical translation. This review aims to cover key aspects of bacterium-phage interactions that affect bacterial killing by describing the most relevant published literature and detailing the current knowledge gaps most likely to influence therapeutic success.

Citing Articles

Differences in Phage Recognition and Immunogenicity Contribute to Divergent Human Immune Responses to Escherichia coli and Klebsiella pneumoniae Phages.

Le H, Venturini C, Lubian A, Bowring B, Iredell J, George J Eur J Immunol. 2025; 55(3):e202451543.

PMID: 40071703 PMC: 11898580. DOI: 10.1002/eji.202451543.

Isolation and characterization of new lytic bacteriophage PSA-KC1 against Pseudomonas aeruginosa isolates from cystic fibrosis patients.

Can Kurt K, Kurt H, Tokuc E, Ozbey D, Arabaci D, Aydin S Sci Rep. 2025; 15(1):6551.

PMID: 39994360 PMC: 11850609. DOI: 10.1038/s41598-025-91073-1.

Phage therapeutic delivery methods and clinical trials for combating clinically relevant pathogens.

Selim H, Gomaa F, Alshahrani M, Morgan R, Aboshanab K Ther Deliv. 2024; 16(3):247-269.

PMID: 39545771 PMC: 11875505. DOI: 10.1080/20415990.2024.2426824.

The Evolution of Phage Therapy: A Comprehensive Review of Current Applications and Future Innovations.

Sahoo K, Meshram S Cureus. 2024; 16(9):e70414.

PMID: 39473661 PMC: 11519598. DOI: 10.7759/cureus.70414.

Evaluation of the Feasibility of Using Commercial Wound Coatings as a Carrier Matrix for Bacteriophages.

Beschastnov V, Shirokova I, Belyanina N, Pogodin I, Tulupov A, Tochilina A Sovrem Tekhnologii Med. 2024; 16(1):45-52.

PMID: 39421627 PMC: 11482097. DOI: 10.17691/stm2024.16.1.05.

References

Nale J, Clokie M . Preclinical data and safety assessment of phage therapy in humans. Curr Opin Biotechnol. 2021; 68:310-317. PMC: 8150739. DOI: 10.1016/j.copbio.2021.03.002. View

Morrisette T, Kebriaei R, Lev K, Morales S, Rybak M . Bacteriophage Therapeutics: A Primer for Clinicians on Phage-Antibiotic Combinations. Pharmacotherapy. 2019; 40(2):153-168. DOI: 10.1002/phar.2358. View

Levin B, Bull J . Population and evolutionary dynamics of phage therapy. Nat Rev Microbiol. 2004; 2(2):166-73. DOI: 10.1038/nrmicro822. View

Secor P, Sweere J, Michaels L, Malkovskiy A, Lazzareschi D, Katznelson E . Filamentous Bacteriophage Promote Biofilm Assembly and Function. Cell Host Microbe. 2015; 18(5):549-59. PMC: 4653043. DOI: 10.1016/j.chom.2015.10.013. View

Petrovic Fabijan A, Ben Zakour N, Ho J, Lin R, Iredell J . Polyclonal Staphylococcus aureus Bacteremia. Ann Intern Med. 2019; 171(12):940-941. DOI: 10.7326/L19-0369. View

Pohlschroder M, Esquivel R . Archaeal type IV pili and their involvement in biofilm formation. Front Microbiol. 2015; 6:190. PMC: 4371748. DOI: 10.3389/fmicb.2015.00190. View

Bjarnsholt T . The role of bacterial biofilms in chronic infections. APMIS Suppl. 2013; (136):1-51. DOI: 10.1111/apm.12099. View

de Sousa J, Buffet A, Haudiquet M, Rocha E, Rendueles O . Modular prophage interactions driven by capsule serotype select for capsule loss under phage predation. ISME J. 2020; 14(12):2980-2996. PMC: 7784688. DOI: 10.1038/s41396-020-0726-z. View

Balasubramanian S, Osburne M, BrinJones H, Tai A, Leong J . Prophage induction, but not production of phage particles, is required for lethal disease in a microbiome-replete murine model of enterohemorrhagic E. coli infection. PLoS Pathog. 2019; 15(1):e1007494. PMC: 6328086. DOI: 10.1371/journal.ppat.1007494. View

10.

Salje J . Plasmid segregation: how to survive as an extra piece of DNA. Crit Rev Biochem Mol Biol. 2010; 45(4):296-317. DOI: 10.3109/10409238.2010.494657. View

11.

Khatami A, Lin R, Petrovic-Fabijan A, Alkalay-Oren S, Almuzam S, Britton P . Bacterial lysis, autophagy and innate immune responses during adjunctive phage therapy in a child. EMBO Mol Med. 2021; 13(9):e13936. PMC: 8422068. DOI: 10.15252/emmm.202113936. View

12.

Pires D, Oliveira H, Melo L, Sillankorva S, Azeredo J . Bacteriophage-encoded depolymerases: their diversity and biotechnological applications. Appl Microbiol Biotechnol. 2016; 100(5):2141-51. DOI: 10.1007/s00253-015-7247-0. View

13.

Mondal S, Draper L, Ross R, Hill C . Bacteriophage endolysins as a potential weapon to combat infection. Gut Microbes. 2020; 12(1):1813533. PMC: 7524323. DOI: 10.1080/19490976.2020.1813533. View

14.

Cossart P, Sansonetti P . Bacterial invasion: the paradigms of enteroinvasive pathogens. Science. 2004; 304(5668):242-8. DOI: 10.1126/science.1090124. View

15.

Nobrega F, Vlot M, de Jonge P, Dreesens L, Beaumont H, Lavigne R . Targeting mechanisms of tailed bacteriophages. Nat Rev Microbiol. 2018; 16(12):760-773. DOI: 10.1038/s41579-018-0070-8. View

16.

Hu B, Margolin W, Molineux I, Liu J . Structural remodeling of bacteriophage T4 and host membranes during infection initiation. Proc Natl Acad Sci U S A. 2015; 112(35):E4919-28. PMC: 4568249. DOI: 10.1073/pnas.1501064112. View

17.

Benler S, Koonin E . Phage lysis-lysogeny switches and programmed cell death: Danse macabre. Bioessays. 2020; 42(12):e2000114. DOI: 10.1002/bies.202000114. View

18.

Testa S, Berger S, Piccardi P, Oechslin F, Resch G, Mitri S . Spatial structure affects phage efficacy in infecting dual-strain biofilms of . Commun Biol. 2019; 2:405. PMC: 6828766. DOI: 10.1038/s42003-019-0633-x. View

19.

Sarker S, McCallin S, Barretto C, Berger B, Pittet A, Sultana S . Oral T4-like phage cocktail application to healthy adult volunteers from Bangladesh. Virology. 2012; 434(2):222-32. DOI: 10.1016/j.virol.2012.09.002. View

20.

Abedon S, Danis-Wlodarczyk K, Wozniak D . Phage Cocktail Development for Bacteriophage Therapy: Toward Improving Spectrum of Activity Breadth and Depth. Pharmaceuticals (Basel). 2021; 14(10). PMC: 8541335. DOI: 10.3390/ph14101019. View