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
      Paul Turner is the Elihu Professor of Ecology and Evolutionary Biology at Yale University, where he has served as Interim Dean of Science and Departmental Chair. He is also a faculty member in Microbiology at Yale University School of Medicine. Dr. Turner's research interests include: evolutionary biology, evolutionary medicine, infectious disease, microbiology, phage therapy, RNA viruses, vector-borne disease, and virology. He uses an interdisciplinary approach in his research laboratory, employing techniques from microbiology, population genetics, genomics, molecular biology and mathematical modeling to study hypotheses in ecology and evolutionary biology.

      Paul Turner received his Ph.D. from the Center for Microbial Ecology at Michigan State University. He then conducted postdoctoral work at University of Maryland College Park, University of Valencia in Spain, and the National Institutes of Health. He regularly serves on committees for the National Science Foundation, National Institutes of Health and the American Society for Microbiology. He was elected chair of international meetings, such as the 2013 Gordon Research Conference on Microbial Population Biology, and the 2018 Jacques Monod Conference on Viral Emergence. He has authored nearly 100 scholarly journal articles, reviews and book chapters.

    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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