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Identification of Mycobacterial Genes Involved in Antibiotic Sensitivity: Implications for the Treatment of Tuberculosis with ?-Lactam-Containing Regimens.


ABSTRACT: In a Mycobacterium smegmatis mutant library screen, transposon mutants with insertions in fhaA, dprE2, rpsT, and parA displayed hypersusceptibility to antibiotics, including the ?-lactams meropenem, ampicillin, amoxicillin, and cefotaxime. Sub-MIC levels of octoclothepin, a psychotic drug inhibiting ParA, phenocopied the parA insertion and enhanced the bactericidal activity of meropenem against Mycobacterium tuberculosis in combination with clavulanate. Our study identifies novel factors associated with antibiotic resistance, with implications in repurposing ?-lactams for tuberculosis treatment.

SUBMITTER: Viswanathan G 

PROVIDER: S-EPMC5487644 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Identification of Mycobacterial Genes Involved in Antibiotic Sensitivity: Implications for the Treatment of Tuberculosis with β-Lactam-Containing Regimens.

Viswanathan Gopinath G   Yadav Sangya S   Raghunand Tirumalai R TR  

Antimicrobial agents and chemotherapy 20170627 7


In a <i>Mycobacterium smegmatis</i> mutant library screen, transposon mutants with insertions in <i>fhaA</i>, <i>dprE2</i>, <i>rpsT</i>, and <i>parA</i> displayed hypersusceptibility to antibiotics, including the β-lactams meropenem, ampicillin, amoxicillin, and cefotaxime. Sub-MIC levels of octoclothepin, a psychotic drug inhibiting ParA, phenocopied the <i>parA</i> insertion and enhanced the bactericidal activity of meropenem against <i>Mycobacterium tuberculosis</i> in combination with clavul  ...[more]

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