Genome-Wide Identification of Antimicrobial Intrinsic Resistance Determinants in Staphylococcus aureus.

摘要: The emergence of antimicrobial resistance severely threatens our ability to treat bacterial infections. While acquired has received considerable attention, relatively little is known intrinsic that allows bacteria naturally withstand antimicrobials. Gene products confer agents may be explored for alternative therapies, by potentiating the efficacy existing In this study, we identified resistome a broad spectrum antimicrobials in human pathogen, Staphylococcus aureus. We screened Nebraska Transposon Mutant Library 1920 single-gene inactivations S. aureus strain JE2, increased susceptibility anti-staphylococcal (ciprofloxacin, oxacillin, linezolid, fosfomycin, daptomycin, mupirocin, vancomycin and gentamicin). 68 mutants were confirmed E-test display at least two-fold one or more agents. majority genes have not previously been associated with For example, inactivation encoding subunits ATP synthase, atpA, atpB, atpG atpH, reduced minimum inhibitory concentration (MIC) gentamicin 16-fold. To elucidate potential screen, examined treatment Galleria mellonella infection model. Gentamicin was significantly improved, when treating larvae infected atpA mutant compared wild type cells clinically relevant concentration. Our results demonstrate many gene contribute Knowledge these determinants provides targets compounds potentiate against important pathogen.