SEP 13, 2017 7:30 AM PDT

Keynote Presentation: Using phage to select for evolution of reduced virulence in pathogenic bacteria

Speaker
  • Henry Ford II Professor and Departmental Chair of Ecology and Evolutionary Biology, Microbiology Faculty, Yale School of Medicine
    BIOGRAPHY

Abstract

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 a lytic bacteriophage, OMKO1, (family Myoviridae) 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 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. Although modern phage therapy is still in its infancy, we conclude that phages, such as OMKO1, represent a new approach to phage therapy where bacteriophages exert selection for MDR bacteria to become increasingly sensitive to traditional antibiotics. This approach, using phages as targeted antibacterials, could extend the lifetime of our current antibiotics and potentially reduce the incidence of antibiotic resistant infections.


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SEP 13, 2017 7:30 AM PDT

Keynote Presentation: Using phage to select for evolution of reduced virulence in pathogenic bacteria



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