Identification of mycobacterial genes involved in antibiotic sensitivity - Implications in the treatment of tuberculosis with {beta}-lactam containing regimens [PublishAheadOfPrint]

In a Mycobacterium smegmatis mutant library screen, transposon mutants with insertions in fhaA, dprE2, rpsT and parA, 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 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 β-lactams for tuberculosis treatment.

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