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James's will be giving a practice job talk, entitled: Evolution-informed strategies to improve efficacy and evolutionary robustness of phage therapy: phage steering and phage re-use
Phage therapy has the potential to treat currently intractable infections, yet multiple challenges remain over initial efficacy and also over the rapidity of failure due to the evolution of resistance.
Focusing on phages of the major opportunistic pathogen Pseudomonas aeruginosa, I will demonstrate a series of novel phage therapy strategies that can extend the effective use of phages by harnessing their evolutionary potential, including the predictable co-evolutionary dynamics that play out between bacteria and phage. Specifically, I will introduce ‘phage steering’, featuring the use of targeted phages to both kill and also select against pathogenic phenotypes among surviving bacteria (reducing virulence and drug resistance). I will also discuss ‘phage re-use’, featuring the targeted implementation of specific co-evolutionary mechanisms to allow for repeated use of a single, standardized (i.e. FDA approvable) phage therapy. I conclude with a survey of the clinical relevance of my results, with a focus on chronic infections.