Banerjee A, Dubnau E, Quemard A, Balasubramanian V, Um K S, Wilson T, Collins D, de Lisle G, Jacobs W R
Howard Hughes Medical Institute, Albert Einstein College of Medicine, Bronx, NY 10461.
Science. 1994 Jan 14;263(5144):227-30. doi: 10.1126/science.8284673.
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.
异烟肼（异烟酸肼，INH）是使用最广泛的抗结核药物之一，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基因内的一个错义突变在耻垢分枝杆菌和牛分枝杆菌中显示出对异烟肼和乙硫异烟胺（ETH）均具有抗性。当野生型inhA基因通过多拷贝质粒载体转移至耻垢分枝杆菌和卡介苗时，也赋予了对异烟肼和乙硫异烟胺的抗性。InhA蛋白与大肠杆菌的EnvM酶具有显著的序列保守性，无细胞试验表明它可能参与了分枝菌酸的生物合成。这些结果表明，InhA可能是异烟肼和乙硫异烟胺的主要作用靶点。
