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How to train your bacteriophage

Phage therapy—the use of bacterial viruses to treat bacterial infections—is one of the most promising solutions to the antibiotic resistance crisis. Phage therapy has been used to combat bacterial infections for over a century, and has successfully cleared life-threatening multidrug-resistant infections from patients after all chemical antibiotics have failed (1). However, one of the biggest hurdles to successful deployment of phage therapy in the clinic is bacterial phage resistance.

Adair L. Borges; PNAS; July 13, 2021 118 (28) e2109434118

 

Figure: Model of the impact of phage training on the ability of phage λ to suppress E. coli growth. (A) Bacteria rapidly develop strong resistance to the untrained phage (λunt). (B) The trained λ phage (λtrn) suppresses bacterial growth longer than the untrained phage, and the phage resistance that does arise is costly and incomplete.

 

Phage therapy—the use of bacterial viruses to treat bacterial infections—is one of the most promising solutions to the antibiotic resistance crisis. Phage therapy has been used to combat bacterial infections for over a century, and has successfully cleared life-threatening multidrug-resistant infections from patients after all chemical antibiotics have failed (1). However, one of the biggest hurdles to successful deployment of phage therapy in the clinic is bacterial phage resistance. Just like with chemical antibiotics, bacteria can readily evolve resistance to phages, and phage-resistant bacterial isolates are often recovered from patients treated with phage therapy (2). In a study in PNAS (3), Borin et al. rigorously explore the potential for “phage training” to suppress bacterial phage resistance using the well-established phage−host model system, Escherichia coli, and bacteriophage λ.

 

A massive benefit to using phages instead of chemical antibiotics as therapeutics is that, unlike chemicals, phages can evolve their own measures to counter bacterial resistance. This ability is fundamental to the evolutionary persistence of phage “in the wild,” and the back-and-forth arms race between phage and bacteria has been ongoing for millions of years. Phage training seeks to harness this evolutionary power of phages to make more-robust phage therapies. The idea is that, by preadapting the phage to a bacterial host, the phage will experience the ways in which the host evolves resistance, and will evolve reciprocally. These phages “from the future” should then preempt the rise of phage resistance when infecting the ancestral bacteria. Much is still unknown about how phage training will play out in practice, necessitating rigorous study of the ecology and coevolutionary dynamics of a trained phage and its host.

 

See more: https://www.pnas.org/content/118/28/e2109434118

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