鉴定与结核分枝杆菌高水平异烟肼耐药相关的 katG 突变。
Identification of katG mutations associated with high-level isoniazid resistance in Mycobacterium tuberculosis.
机构信息
Department of Infectious Diseases, Research Institute, International Medical Center of Japan, Tokyo, Japan.
出版信息
Antimicrob Agents Chemother. 2010 May;54(5):1793-9. doi: 10.1128/AAC.01691-09. Epub 2010 Mar 8.
Abstract
Isoniazid (INH) is an effective first-line antituberculosis drug. KatG, a catalase-peroxidase, converts INH to an active form in Mycobacterium tuberculosis, and katG mutations are major causes of INH resistance. In the present study, we sequenced katG of 108 INH-resistant M. tuberculosis clinical isolates. Consequently, 9 novel KatG mutants with a single-amino-acid substitution were found. All of these mutants had significantly lower INH oxidase activities than the wild type, and each mutant showed various levels of activity. Isolates having mutations with relatively low activities showed high-level INH resistance. On the basis of our results and known mutations associated with INH resistance, we developed a new hybridization-based line probe assay for rapid detection of INH-resistant M. tuberculosis isolates.
摘要
异烟肼（INH）是一种有效的一线抗结核药物。过氧化氢酶-过氧化物酶 KatG 将 INH 转化为结核分枝杆菌中的活性形式，而 katG 突变是 INH 耐药的主要原因。在本研究中，我们对 108 株 INH 耐药结核分枝杆菌临床分离株的 katG 进行了测序。结果发现了 9 种新型的 katG 突变体，它们都只有一个氨基酸的取代。所有这些突变体的 INH 氧化酶活性均明显低于野生型，并且每种突变体的活性水平均不同。具有相对较低活性的突变体的分离株表现出高水平的 INH 耐药性。基于我们的结果和已知与 INH 耐药性相关的突变，我们开发了一种新的基于杂交的线探针检测方法，用于快速检测 INH 耐药的结核分枝杆菌分离株。
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