Ohno H, Kohno S
Department of Internal Medicine, Hokusho Chuou Hospital.
Nihon Rinsho. 1998 Dec;56(12):3023-9.
According to the recent advances of molecular biological technics, some of the genetic mechanisms of drug-resistance of Mycobacteria has been uncovered. Generally, drug-resistance of Mycobacterium tuberculosis was caused by point mutations in chromosomal gene. In isoniazid (INH) resistant M. tuberculosis, mutations and genetic deletions in catalase-peroxidase gene (katG), inhA gene, or alkyl hydroperoxide reductase gene were reported. On the other hand, mutations and other genetic alterations in RNA polymerase beta subunit gene (rpoB) were the major mechanisms of resistance to rifampicin (RFP) with high frequencies of 90% or more. Moreover, these genetic alterations in rpoB gene were suspected as the resistant mechanism to other rifamycin antituberculosis drugs, such as rifabutin. In addition, it was reported that point mutations in 16S rRNA gene (rrs) and ribosomal protein S12 gene (rpsL) induced M. tuberculosis as streptomycin (SM) resistant phenotype. Furthermore, nicotinamidase (pncA) gene, DNA gyrase A subunit (gyrA) gene, and embB gene were reported as the responsible gene to pyrazinamide-, quinolone- and ethambutol-resistance, respectively. Although all mechanisms of drug-resistance were still unclear, these information are very useful and helpful for development of rapid diagnosis system of drug-resistant M. tuberculosis.
根据分子生物学技术的最新进展，分枝杆菌耐药性的一些遗传机制已被揭示。一般来说，结核分枝杆菌的耐药性是由染色体基因突变引起的。在耐异烟肼（INH）的结核分枝杆菌中，已报道过氧化氢酶-过氧化物酶基因（katG）、inhA基因或烷基过氧化氢还原酶基因发生突变和基因缺失。另一方面，RNA聚合酶β亚基基因（rpoB）的突变和其他基因改变是对利福平（RFP）耐药的主要机制，其频率高达90%或更高。此外，rpoB基因的这些基因改变被怀疑是对其他利福霉素抗结核药物（如利福布汀）的耐药机制。另外，据报道16S rRNA基因（rrs）和核糖体蛋白S12基因（rpsL）中的点突变诱导结核分枝杆菌产生对链霉素（SM）的耐药表型。此外，烟酰胺酶（pncA）基因、DNA回旋酶A亚基（gyrA）基因和embB基因分别被报道为对吡嗪酰胺、喹诺酮和乙胺丁醇耐药的相关基因。虽然所有耐药机制仍不清楚，但这些信息对于开发结核分枝杆菌耐药性快速诊断系统非常有用且有帮助。
