Lytic bacteriophages facilitate antibiotic sensitization of Enterococcus faecium .

摘要: Enterococcus faecium, a commensal of the human intestine, has emerged as hospital-adapted, multi-drug resistant (MDR) pathogen. Bacteriophages (phages), natural predators bacteria, have regained attention therapeutics to stem rise MDR bacteria. Despite their potential curtail E. faecium infections, molecular events governing faecium-phage interactions remain largely unknown. Such are important delineate because phage selective pressure imposed on will undoubtedly result in resistance phenotypes that could threaten efficacy therapy. In an effort understand emergence three newly isolated lytic phages were used demonstrate is conferred through array cell wall-associated molecules, including secreted antigen A (SagA), enterococcal polysaccharide (Epa), wall teichoic acids, capsule, and arginine-aspartate-aspartate (RDD) protein unknown function. We find capsule Epa for robust adsorption mutations sagA, epaR, epaX enhance susceptibility ceftriaxone, antibiotic normally ineffective due its low affinity penicillin binding proteins. Consistent with these findings, we provide evidence potently synergize (ceftriaxone ampicillin) membrane-acting (daptomycin) antimicrobials slow or completely inhibit growth Our work demonstrates evolution comes fitness defects resulting drug sensitization serve effective treatment infections.