Phage selection restores antibiotic sensitivity in MDR Pseudomonas aeruginosa

TLDR

The rising prevalence of multi‑drug‑resistant bacterial infections has spurred the search for novel antibacterial strategies that target pathogens while selecting for reduced virulence. The study proposes using phage OMKO1 to restore antibiotic sensitivity in MDR Pseudomonas aeruginosa, thereby extending the usefulness of existing antibiotics and lowering resistance rates. Researchers isolated the lytic Myoviridae phage OMKO1, which binds the OprM porin of the MexAB and MexXY efflux pumps in P. aeruginosa.

Abstract

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.