Overexpression of the chromosomally encoded aminoglycoside acetyltransferase eis confers kanamycin resistance in Mycobacterium tuberculosis

摘要: Abstract The emergence of multidrug-resistant (MDR) tuberculosis (TB) highlights the urgent need to understand mechanisms resistance drugs used treat this disease. aminoglycosides kanamycin and amikacin are important bactericidal MDR TB, one or both these is a defining characteristic extensively drug-resistant TB. We identified mutations in −10 −35 promoter region eis gene, which encodes previously uncharacterized aminoglycoside acetyltransferase. These led 20–180-fold increase amount leaderless mRNA transcript, with corresponding protein expression. Importantly, conferred [5 μg/mL < minimum inhibitory concentration (MIC) ≤40 μg/mL] but not (MIC <4 μg/mL). Additionally, 80% clinical isolates examined study that exhibited low-level harbored mutations. results have implications determined be resistant may cross-resistant amikacin, as often assumed. Molecular detection should distinguish strains those amikacin. This help avoid excluding potentially effective drug from treatment regimen for