Virus evolvability and the consequences for antibacterial phage therapy

15 February 2019

Paul Turner
Department of Ecology & Evolutionary Biology
Yale University


Increasing prevalence and severity of multi-drug-resistant (MDR) bacterial infections has necessitated novel antibacterial strategies. Ideally, new approaches would target bacterial pathogens while exerting selection for reduced pathogenesis when these bacteria inevitably evolve resistance to therapeutic intervention. As an example of such a management strategy, we isolated lytic bacteriophage OMKO1 of Pseudomonas aeruginosa that utilizes the outer membrane porin M (OprM) of the multidrug efflux systems MexAB and MexXY as a receptor-binding site. Results of in vitro studies show that phage selection produces an evolutionary trade-off in MDR P. aeruginosa, whereby the evolution of bacterial resistance to phage attack changes the efflux pump mechanism, causing increased sensitivity to drugs from several antibiotic classes. Similarly, data from safety/efficacy experiments in a mouse model show synergy between phage and antibiotics that improves treatment of acute pneumonia. Last, results of two clinical cases show that phage OMKO1 therapy can resolve chronic MDR P. aeruginosa infection. Phages such as OMKO1 represent a new approach to phage therapy where viruses exert selection for MDR bacteria to become increasingly sensitive to traditional antibiotics, thereby extending the lifetime of our current antibiotics and potentially reducing incidence of antibiotic resistant infections.

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