Developing Phage Therapy That Overcomes the Evolution of Bacterial Resistance

Abstract

The global rise of antibiotic resistance in bacterial pathogens and the waning efficacy of antibiotics urge consideration of alternative antimicrobial strategies. Phage therapy is a classic approach where bacteriophages (bacteria-specific viruses) are used against bacterial infections, with many recent successes in personalized medicine treatment of intractable infections. However, a perpetual challenge for developing generalized phage therapy is the expectation that viruses will exert selection for target bacteria to deploy defenses against virus attack, causing evolution of phage resistance during patient treatment. Here we review the two main complementary strategies for mitigating bacterial resistance in phage therapy: minimizing the ability for bacterial populations to evolve phage resistance and driving (steering) evolution of phage-resistant bacteria toward clinically favorable outcomes. We discuss future research directions that might further address the phage-resistance problem, to foster widespread development and deployment of therapeutic phage strategies that outsmart evolved bacterial resistance in clinical settings. Expected final online publication date for the Annual Review of Virology, Volume 10 is September 2023. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Phage P2-71 against multi-drug resistant Proteus mirabilis: isolation, characterization, and non-antibiotic antimicrobial potential

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“…3 B) at the cost of phage resistance. [120] , [121] , [122] Bacteria harbour saccharides and membrane proteins on their surface, which define bacterial virulence and many other characteristics. In Escherichia, Shigella and Pseudomonas that developed resistance against LPS-targeting phages, decreased virulence and increased clearance due to changes in LPS structure were observed.…”

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