Phage Selection Restores Antibiotic Sensitivity in MDR Pseudomonas Aeruginosa

Sci Rep. 2016 May 26;6:26717. doi: 10.1038/srep26717.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Bacterial Outer Membrane Proteins* / genetics
  • Bacterial Outer Membrane Proteins* / metabolism
  • Bacterial Proteins* / genetics
  • Bacterial Proteins* / metabolism
  • Membrane Transport Proteins* / genetics
  • Membrane Transport Proteins* / metabolism
  • Myoviridae* / genetics
  • Myoviridae* / metabolism
  • Pseudomonas aeruginosa* / genetics
  • Pseudomonas aeruginosa* / metabolism
  • Pseudomonas aeruginosa* / virology

Substances

  • Bacterial Outer Membrane Proteins
  • Bacterial Proteins
  • Membrane Transport Proteins
  • MexA protein, Pseudomonas aeruginosa
  • MexB protein, Pseudomonas aeruginosa
  • MexXY protein, Pseudomonas aeruginosa
  • OprM protein, Pseudomonas aeruginosa