Designing Effective Phage Therapies

Bacteriophages are emerging as promising alternatives to conventional antimicrobials, but their successful application depends on overcoming challenges such as bacterial resistance, effective cocktail design, and real-world implementation. This curated collection brings together recent Open Access research on phage therapy, phage resistance, antiphage defence, cocktail design, and applications in clinical and food microbiology.


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In vitro and in vivo selection and cost of bacteriophage resistance on natural Escherichia coli

Luís Leónidas Cardoso and others

microLife, Volume 6, 2025, uqaf017, https://doi.org/10.1093/femsml/uqaf017

Bacteriophages offer a promising alternative to antibiotics. However, bacteria can develop resistance to phages, potentially limiting treatment success. This study examines how such resistance emerges and what it costs bacteria, using a clinically important E. coli strain and a tailored phage cocktail. Under nutrient-rich lab conditions, phage resistance had a relatively low cost. But in the gut of mice, resistant bacteria paid a high price due to changes in their cell surface. These findings highlight the importance of testing phage therapies in realistic conditions, as results can vary significantly depending on the environment.

Heterodimerization of staphylococcal phage φ2638A endolysin isoforms and their functional role in bacterial lysis

Léa V Zinsli and others

microLife, Volume 6, 2025, uqaf011,
https://doi.org/10.1093/femsml/uqaf011

Phage φ2638A co-expresses a short variant endolysin from an internal translational start site (iTSS), which heterodimerizes with the full-length isoform. This interaction enhances bacterial cell lysis and phage progeny release, providing a functional explanation for the conservation of iTSSs across diverse phage genomes.

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