Overexpression of the chromosomally encoded aminoglycoside acetyltransferase eis confers kanamycin resistance in Mycobacterium tuberculosis
Overexpression of the chromosomally encoded aminoglycoside acetyltransferase eis confers kanamycin resistance in Mycobacterium tuberculosis
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DOI：
10.1073/pnas.0907925106
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发表时间：
2009-11-24
影响因子：
11.1
通讯作者：
Posey, James E.
中科院分区：
文献类型：
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作者：
Zaunbrecher, M. Analise;Sikes, R. David, Jr.;Posey, James E.
耐多药结核病（MDR）的出现突出表明迫切需要了解对用于治疗这种疾病的药物的耐药性机制。氨基糖苷卡那霉素和阿米卡星是用于治疗耐多药结核病的重要杀菌药物，对其中一种或两种药物的耐药性是广泛耐药结核病的一个决定性特征。我们在eis基因的-10和-35启动子区域发现了突变，该区域编码一种以前未被表征的氨基糖苷乙酰转移酶。这些突变导致eis无前导mRNA转录量增加20-180倍，蛋白表达相应增加。重要的是，这些启动子突变赋予了对卡那霉素的抗性[5 μ g/mL <最低抑制浓度（MIC）]
The emergence of multidrug-resistant (MDR) tuberculosis (TB) highlights the urgent need to understand the mechanisms of resistance to the drugs used to treat this disease. The aminoglycosides kanamycin and amikacin are important bactericidal drugs used to treat MDR TB, and resistance to one or both of these drugs is a defining characteristic of extensively drug-resistant TB. We identified mutations in the -10 and -35 promoter region of the eis gene, which encodes a previously uncharacterized aminoglycoside acetyltransferase. These mutations led to a 20-180-fold increase in the amount of eis leaderless mRNA transcript, with a corresponding increase in protein expression. Importantly, these promoter mutations conferred resistance to kanamycin [5 mu g/mL < minimum inhibitory concentration (MIC)