中国耐利福平结核分支杆菌rpoB基因突变特点  

Characterization of rpoB mutation in rifampin resistant clinical Mycobacterium tuberculosis isolates from China

作　　者：黄海荣[1] 金奇[2] 马玙[1] 陈曦[1] 李惠文[1] 庄玉辉[3] 

机构地区：[1]北京市结核病胸部肿瘤研究所,101149 [2]病毒基因工程国家重点实验室 [3]解放军第三○九医院

出　　处：《中华结核和呼吸杂志》2001年第4期231-235,共5页Chinese Journal of Tuberculosis and Respiratory Diseases

基　　金：国家重大基础研究发展规划! (973)"严重传染病防治基础研究"课题资助项目 (G19990 5 410 4)

摘　　要：目的　为了阐明中国结核分支杆菌耐利福平株rpoB基因突变特点。方法　对 2 42株结核分支杆菌临床分离株包括rpoB基因核心区域 81个碱基在内的 5 88个碱基进行序列测定 ,其中耐利福平株 193株 ,利福平敏感株 46株 ,人工诱导的耐利福平株 3株。结果　 89 1% (172 / 193)的临床分离耐药株存在rpoB基因突变 ,而 46株敏感株无突变。 5 31位氨基酸突变率为 46 1% ;5 2 6位氨基酸突变率为 17 1% ;联合突变发生率为 12 4% ;还有 4株细菌发生同义突变 ;未检测到发生缺失或插入突变的菌株。高耐药组 (耐 2 5 0 μg/ml利福平 ) 5 31位氨基酸的突变率显著高于低耐药组 (耐 5 0 μg/ml利福平 ) ,P <0 0 5。结论　中国结核分支杆菌耐利福平株的rpoB基因突变的发生率约为 90 % ,其中最常见的突变位点是 5 31位丝氨酸和 5 2 6位组氨酸 ,两者突变率之和约为 6 3 % ;利福平高耐药组 5 31位氨基酸发生突变的几率高于低耐药组 ;受试菌株未发现插入或缺失突变 ;Objective To elucidate the characterization of rpoB mutation in rifampin resistant clinical isolates of Mycobacterium tuberculosis from China. Methods 588 bp DNA fragment of rpoB gene including 81 bp code region (rifampin resistance determination region,RRDR) was sequenced 242 strains of Mycobacterium tuberculosis , including 193 rifampin resistant strains and 46 rifampin susceptible strains and 3 artificially induced rifampin resistant strains were sequenced. Results 89 1%(172/193) rifampin resistant strains had rpoB gene mutations in RRDR, no mutation was found in rifampin susceptible strains. 46 1% rifampin resistant strains had mutations located at 531 Ser; 17 1% strains had mutations located at 526 His; Combinative mutation rate was 12 4%;4 strains had synonymous mutations; No deletion or insertion mutation was found among all strains High level rifampin resistant strains (250 μg/ml rifampin resistant) had higher mutation frequency at 531 Ser than low level rifampin resistant strains (50 μg/ml rifampin resistant) ( P <0 05). Conclusions About 90% rifampin resistant clinical strains of Mycobacterium tuberculosis from China had rpoB mutations; 531 Ser and 526 His were the most common positions to be substituted, the added mutation rate was about 46%;High level rifampin resistant strains had a higher frequency of 531 Ser mutation than low level rifampin resistant strains; No insertion or deletion mutation was found in these specimens; DNA sequencing is significant in drug choosing for tuberculosis treatment

关 键 词：结核分支杆菌 利福利 药物耐受性 ropB基因 DNA序列分析 

分 类 号：R378.911[医药卫生—病原生物学]