INHA, A GENE ENCODING A TARGET FOR ISONIAZID AND ETHIONAMIDE IN MYCOBACTERIUM-TUBERCULOSIS
INHA, A GENE ENCODING A TARGET FOR ISONIAZID AND ETHIONAMIDE IN MYCOBACTERIUM-TUBERCULOSIS
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DOI：
10.1126/science.8284673
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发表时间：
1994-01-14
期刊：
影响因子：
56.9
通讯作者：
JACOBS, WR
中科院分区：
文献类型：
--
作者：
BANERJEE, A;DUBNAU, E;JACOBS, WR
异烟肼（异烟酸酰肼，INH）是最广泛使用的抗结核药物之一，但其对结核分枝杆菌的确切作用靶点尚不清楚。分枝杆菌inhA基因内的错义突变被证明赋予分枝杆菌对INH和乙硫异烟胺（ETH）的耐药性。megaeae和M.牛当将野生型inhA基因转移到多拷贝质粒载体上时，也赋予INH和ETH抗性。耻垢分枝杆菌和M.牛卡介苗InhA蛋白与大肠杆菌酶EnvM显示出显著的序列保守性，并且无细胞测定表明其可能参与分枝菌酸生物合成。这些结果表明，InhA可能是INH和ETH的主要作用靶点。
Isoniazid (isonicotinic acid hydrazide, INH) is one of the most widely used antituberculosis drugs, yet its precise target of action on Mycobacterium tuberculosis is unknown. A missense mutation within the mycobacterial inhA gene was shown to confer resistance to both INH and ethionamide (ETH) in M. smegmatis and in M. bovis. The wild-type inhA gene also conferred INH and ETH resistance when transferred on a multicopy plasmid vector to M. smegmatis and M. bovis BCG. The InhA protein shows significant sequence conservation with the Escherichia coli enzyme EnvM, and cell-free assays indicate that it may be involved in mycolic acid biosynthesis. These results suggest that InhA is likely a primary target of action for INH and ETH.