摘要
近年来涌现出了耐多药结核病(Multidrug-resistant tuberculosis,MDR-TB)/广泛耐药结核病(Extensively drug-resistant tuberculosis,XDR-TB)。MDR-TB是指由耐异烟肼和利福平两种或以上抗结核药物的结核分枝杆菌引起的结核病。XDR-TB是指不仅对一线抗结核药物耐药,而且对主要的二线抗结核药物中的至少3种也耐药的结核分枝杆菌引起的结核病。抗结核的一线药物分别为异烟肼、利福平、吡嗪酰胺、链霉素和乙胺丁醇。与异烟肼的耐药相关的基因主要有katG,inhA等。它们的突变会引起结核分枝杆菌对异烟肼的耐药。rpoB、pncA及embB基因的突变分别是导致结核分枝杆菌对利福平、吡嗪酰胺、乙胺丁醇产生耐药性的主要原因。耐链霉素的结核菌主要突变基因rpsL基因,其次是rrs基因,它们的突变也会导致耐药性的产生。对药物耐药机制的深入研究极大地推动了抗结核药物的研发及化学治疗方案的发展。
In recent years, Emergence of multidrug-resistant tuberculosis (MDR-TB) and extensively drugresistant tuberculosis (XDR-TB) are reported world wide. MDR-TB is defined as TB caused by a Mycobacterium tuberculosis strain(MTB) that is resistant to at least the two best first-line medications, isoniazid and rifampicin. XDR- TB is TB showing resistance to at least rifampicin and isoniazid, which is the definition of MDR-TB, in addition to resistance to at least three of the six main classes of second-line drugs. There are five first-line antituberculosis drugs: isoniazid (INH), rifampicin (RIF), pyrazinamide (PZA), ethambutol (EMB) and streptomycin (SM). Resistance to first line anti-TB drugs has been linked to mutations in at least 7 main genes: katG, inhA for 1NH resistance, rpoB for RIF resistance, embB for EMB resistance, pncA for PZA resistance and rpsL and rrs for STR resistance. These genes encode either drug-targeting molecule or enzyme involving in activation of pro-drug, and their mutants result in drug-insensitive target and inactive drug. We here summarize the major progress in study of mechanism underlying resistance of Mycobacterium tuberculosis to first line anti-TB agents.
出处
《中国抗生素杂志》
CAS
CSCD
北大核心
2011年第7期487-491,共5页
Chinese Journal of Antibiotics
基金
十一五"新药创制"科技重大专项基金(编号:2009ZX09303-005)
国家自然科学基金(编号:30870026)
关键词
抗结核一线药
耐药
分子机制
First line anti-tuberculosis drugs
Drug-resistance
Molecular mechanism