Functional and Genetic Characterization of the Tap Efflux Pump in Mycobacterium bovis BCG

摘要: Efflux pumps extrude a wide variety of chemically unrelated compounds conferring multidrug resistance and participating in numerous physiological processes. Mycobacterium tuberculosis possesses many efflux pumps, their roles drug physiology are actively investigated. In this work we found that tap mutant cells showed changes morphology progressive loss viability upon subcultivation liquid medium. Transcriptome analysis bovis BCG revealed disruption the Rv1258c gene, encoding Tap pump, led to an extensive change gene expression patterns during stationary phase, with no exponential growth. inactivation triggered general stress response repression genes involved cell wall biosynthesis, particular formation peptidoglycan; suggested accumulation unknown substrate reaches toxic concentrations phase. We also both overexpression altered susceptibility clinically approved antibiotics M. BCG. Acriflavine tetracycline assays carbonyl cyanide m-chlorophenylhydrazone (CCCP) potentiation experiments demonstrated phenotype was due active mechanism. These findings emphasize important role pump bacterial intrinsic resistance.