结核分枝杆菌耐氧氟沙星临床分离株gyrA基因突变的研究  

Study on gyrA mutation in ofloxacin-resistant clinical isolates of Mycobacterium tuberculosis

作　　者：闫丽萍[1] 肖和平[1] 郑瑞娟[1] 胡忠义[1] 乐军[1] 景玲杰[1] 

机构地区：[1]同济大学附属上海市肺科医院结核科,上海市结核(肺)重点实验室,200433

出　　处：《中国感染与化疗杂志》2010年第1期31-34,共4页Chinese Journal of Infection and Chemotherapy

基　　金：国家十一五重大专项(2008ZX10003-015);上海市公共卫生重点学科建设项目(08GWZX0104);上海市结核病(肺)重点实验室开放基金项目(200801)

摘　　要：目的了解结核分枝杆菌(MTB)临床分离株对氧氟沙星的耐药性与gyrA基因突变的关系。方法对20株随机筛选的耐氧氟沙星MTB临床分离株行gyrA基因喹诺酮类药物耐药决定区(QRDR)序列测定。结果18株发现了有义突变,其中2株第91位密码子由TCG(丝氨酸)→CCG(脯氨酸),3株第90位密码子由CCG(甘氨酸)→GTG(缬氨酸),10株第94位密码子由GAC(天冬氨酸)→GGC(赖氨酸),2株第94位密码子由GAC(天冬氨酸)→GCC(甘氨酸),1株第94位密码子由GAC(天冬氨酸)→GTC(缬氨酸)。6例既往未应用过氟喹诺酮类药物抗结核治疗,2例曾在结核诊断前应用氟喹诺酮类药物经验性抗感染治疗1周,12例曾应用氟喹诺酮类药物抗结核治疗。结论gyrA基因突变是MTB对氟喹诺酮类药物产生耐药的机制之一;gyrA基因的有义突变主要发生在第90位、91位、94位密码子上。Objective To investigate the relation between ofloxacin resistance and gyrA mutations in clinical isolates of M.tuberculosis.Methods The gyrA genes were identified and the corresponding quinolone resistance-determining region（QRDR） was sequenced in 20 clinical isolates of ofloxacin-resistant M.tuberculosis.Results Eighteen isolates showed gyrA mutations.Two isolates had TCG（Ser）→CCG（Pro） mutation at codon 91.Three isolates had CCG（Ala）→GTG（Va1） mutation at codon 90.Ten isolates had GAC（Asp）→GGC（Lys） mutation.Two isolates had GAC（Asp）→GCC（Ala） at codon 94.One isolate showed GAC（Asp）→GTC（Val） at codon 94.Six patients had not received fluoroquinolones.Two patients had received fluoroquinolones as empirical treatment for one week before pulmonary tuberculosis was diagnosed.Twelve patients had antituberculous history with fluoroquinolones.Conclusions GyrA mutation is the main cause of M.tuberculosis resistance to fluoroquinolones.Mutation is mainly at codon 90,91,94.Fluoroquinolone used as the only antituberculous agent for one week can induce gyrA mutation.

关 键 词：肺结核 耐多药 氧氟沙星 

分 类 号：R450[医药卫生—治疗学] R521[医药卫生—临床医学]