O'Brien K L, Dietz H C, Romagnoli M, Eiden J
Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Mol Cell Probes. 1996 Feb;10(1):1-6. doi: 10.1006/mcpr.1996.0001.
The katG gene and the inhA gene of 30 INH-resistant (INH-R) and 28 INH-sensitive (INH-S) isolates of M. tuberculosis from Haiti and Maryland were analysed by PCR to establish the presence and frequency of two postulated mechanisms of INH-resistance, total katG gene deletion and inhA Ser94 to Ala94 amino acid substitution. Only two of 30 INH-R isolates (3%) appear to have total katG gene deletions. All 28 INH-S isolates (100%) produced a PCR product at both the 5' and the 3' ends of the katG gene. Gene deletion of katG is a rare mechanism of INH resistance. Allele specific oligonucleotide hybridisation analysis of the inhA PCR products from the same 58 isolates revealed no mutation at amino acid 94 or directly surrounding it. Other inhA gene mutations may be responsible for INH resistance in M. tuberculosis. Diagnostic strategies using katG gene deletion or inhA Ser94 mutations would fail to detect almost all INH-R isolates.
采用聚合酶链反应（PCR）对来自海地和马里兰州的30株耐异烟肼（INH-R）结核分枝杆菌和28株对异烟肼敏感（INH-S）结核分枝杆菌的katG基因和inhA基因进行分析，以确定两种假定的异烟肼耐药机制（katG基因完全缺失和inhA基因第94位丝氨酸至丙氨酸的氨基酸替换）的存在情况和频率。30株INH-R分离株中只有2株（3%）似乎存在katG基因完全缺失。所有28株INH-S分离株（100%）在katG基因的5'端和3'端均产生了PCR产物。katG基因缺失是异烟肼耐药的一种罕见机制。对来自相同58株分离株的inhA PCR产物进行等位基因特异性寡核苷酸杂交分析，结果显示第94位氨基酸或其紧邻区域未发生突变。其他inhA基因突变可能是结核分枝杆菌对异烟肼耐药的原因。利用katG基因缺失或inhA第94位丝氨酸突变的诊断策略几乎无法检测到所有INH-R分离株。
