THE CATALASE PEROXIDASE GENE AND ISONIAZID RESISTANCE OF MYCOBACTERIUM-TUBERCULOSIS
THE CATALASE PEROXIDASE GENE AND ISONIAZID RESISTANCE OF MYCOBACTERIUM-TUBERCULOSIS
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DOI：
10.1038/358591a0
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发表时间：
1992-08-13
期刊：
影响因子：
64.8
通讯作者：
COLE, S
中科院分区：
文献类型：
--
作者：
ZHANG, Y;HEYM, B;COLE, S
在发展中国家所有可避免的成人死亡中，有四分之一是由结核病造成的。在感染人类免疫缺陷病毒的个人中，这种疾病的频率增加和死亡速度加快，这引起了全世界的关注，即控制方案可能不足2，结核分枝杆菌耐多药菌株的出现已导致美国最近几次致命的疫情3。异烟酸肼(异烟肼，INH)构成了抗结核方案的核心；然而，对异烟肼耐药的临床分离株在豚鼠4-7中表现出过氧化氢酶活性降低和相对缺乏毒力。在这里，我们使用分枝杆菌基因8，9来研究异烟肼耐药性的分子基础。同时编码过氧化氢酶和过氧化物酶的单一结核分枝杆菌基因katG恢复了耻垢分枝杆菌耐药突变株对异烟肼的敏感性，并使某些菌株对异烟肼的敏感性增加。在两个结核分枝杆菌患者分离株中，katG基因的缺失与异烟肼耐药有关。
TUBERCULOSIS is responsible for one in four of all avoidable adult deaths in developing countries1. Increased frequency and accelerated fatality of the disease among individuals infected with human immunodeficiency virus has raised worldwide concern that control programmes may be inadequate2, and the emergence of multidrug-resistant strains of Mycobacterium tuberculosis has resulted in several recent fatal outbreaks in the United States3. Isonicotinic acid hydrazide (isoniazid, INH) forms the core of antituberculosis regimens; however, clinical isolates that are resistant to INH show reduced catalase activity and a relative lack of virulence in guinea-pigs4-7. Here we use mycobacterial genetics8,9 to study the molecular basis of INH resistance. A single M. tuberculosis gene, katG, encoding both catalase and peroxidase, restored sensitivity to INH in a resistant mutant of Mycobacterium smegmatis, and conferred INH susceptibility in some strains of Escherichia coli. Deletion of katG from the chromosome was associated with INH resistance in two patient isolates of M. tuberculosis.