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While phages hold promise as an antibiotic alternative, they encounter significant challenges in combating bacterial infections, primarily due to the emergence of phage-resistant bacteria. Bacterial defence mechanisms like superinfection exclusion, CRISPR, and restriction-modification systems can hinder phage effectiveness. Innovative strategies, such as combining different phages into cocktails, have been explored to address these challenges. This review delves into these defence mechanisms and their impact at each stage of the infection cycle, their challenges, and the strategies phages have developed to counteract them. Additionally, we examine the role of phage cocktails in the evolving landscape of antibacterial treatments and discuss recent studies that highlight the effectiveness of diverse phage cocktails in targeting essential bacterial receptors and combating resistant strains.
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http://dx.doi.org/10.1016/j.virol.2024.110209 | DOI Listing |
Philos Trans R Soc Lond B Biol Sci
September 2025
Division of Evolution, Infection and Genomics, University of Manchester, Manchester M13 9PT, UK.
chronic lung infections pose serious challenges for phage therapy due to high between-patient strain diversity and rapid within-patient phenotypic and genetic diversification, necessitating simple predictors of efficacy to streamline phage cocktail design. We quantified bacteria-phage infection networks (BPINs) for six phages against 900 clones previously isolated from 10 bronchiectasis infections ( = 90 isolates per patient). BPIN structure varied extensively between patients.
View Article and Find Full Text PDFBrief Bioinform
August 2025
Department of Environmental Systems Science, Institute of Integrative Biology, ETH Zürich, Universitätstrasse 16, 8092 Zürich, Switzerland.
The increasing interest in finding new viruses within (meta)genomic datasets has fueled the development of computational tools for virus detection and characterization from environmental samples. One key driver is phage therapy, the treatment of drug-resistant bacteria with tailored bacteriophage cocktails. Yet, keeping up with the growing number of automated virus detection and analysis tools has become increasingly difficult.
View Article and Find Full Text PDFViruses
August 2025
Department of Microbiology, The Ohio State University, Mansfield, OH 44906, USA.
Treatments for bacterial infections can be less effective due to toxicities, bacterial tolerance, or genetic resistance to antibacterial agents. The emphasis here is on combating genetic bacterial resistance to bacteriophages. Commonly described simply as phages, bacteriophages are the viruses of bacteria.
View Article and Find Full Text PDFViruses
August 2025
Department of Veterinary Medicine, Rakuno Gakuen University, Ebetsu 069-8501, Japan.
Phage therapy, long overshadowed by antibiotics in Western medicine, has a well-established history in some Eastern European countries and is now being revitalized as a promising strategy against antimicrobial resistance (AMR). This resurgence of phage therapy is driven by the urgent need for innovative countermeasures to AMR, which will cause an estimated 10 million deaths annually by 2050. However, the emergence of phage-resistant variants presents challenges similar to AMR, thus necessitating a deeper understanding of phage resistance mechanisms and control strategies.
View Article and Find Full Text PDFViruses
July 2025
Laboratory of Bacteriophages and Phage Therapy, Center for Research and Innovation in Clinical Pharmaceutical Sciences (CRISP), Lausanne University Hospital (CHUV), CH-1011 Lausanne, Switzerland.
Phage therapy shows promise as an adjunct to antibiotics for treating Staphylococcus aureus infections. We previously reported a combined flucloxacillin/two-phage cocktail treatment selected for resistance to podovirus phage 66 in a rodent model of methicillin-susceptible (MSSA) endocarditis. Here we show that resistant clones harbor mutations in , which encodes a glycosyltransferase essential for β-GlcNAcylation of wall teichoic acid (WTA).
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