【摘要】 目的了解浙江省耐多药结核分枝杆菌临床分离株rpo B、kat G、inh A启动子区基因突变特点,为建立本省快速耐多药检测方法提供参考。方法对浙江省第3次结核病耐药监测获得的MDR菌株扩增rpo B、kat G、inh A启动子区域基因测序后比对分析。结果 55株耐多药结核分枝杆菌rpo B、kat G、inh A启动子区域基因的突变率分别为94.6%、65.5%和10.9%,突变类型包括点突变和联合突变。在rpo B基因中,98.1%的突变发生在RRDR区域,最常见的点突变为S531L,占55.8%;在联合突变类型中,本文检测到新的突变类型为N568S+D516Y和较少报导的I561V+S531L。kat G基因突变中最常见的点突变为S315T,占80.6%;在295位点和327位点检测到同义突变。6株菌检测到inh A启动子区突变,主要为C15T突变,占83.3%。结论浙江省耐多药结核分枝杆菌耐药基因突变类型多态性明显,除常见突变类型外,存在一些特殊的突变类型,应进一步加强研究。更多还原

【Abstract】 Objective To investigate the gene mutation characteristics of rpo B,kat G and inh A promoter region in the multi-drug resistant tuberculosis( MDR-TB) isolates in Zhejiang,provide reference for building the suitable and fast method for detecting MDR-TB in Zhejiang. Methods MDR-TB strains were isolated from the third surveillance of drug resistance in tuberculosis in Zhejiang province,and the gene of rpo B,kat G and inh A promoter region was amplicated and comparatively analyzed after DNA-sequencing. Results The mutation rate of rpo B,kat G and inh A promoter region in all 55 MDR-TB strains were 94. 6%,65. 5% and 10. 9%,respectively. The models of mutation included point mutation and compound mutation.There was 98. 1 precent of the rpo B gene mutations occurring in the region of the RRDR,and the most frequency point mutaions model was S531 L,it accounted for 55. 8%. Two special mutation types were found in compound mutations,one was N568 S +D516Y,it’s a new mutation model,the other was a rarely report models,that was I561 V + S531 L. In kat G gene the most frequency point mutations model was S315 T,it accounted for 80. 6%. In codon 295 and 327,we detected the synonymous mutations. The C15 T mutation was the major types in inh A promoter region,it account for 83. 3% in whole 6 strains. Conclusion The gene mutation types has polymorphism of multidrug-resistant Mycobacterium tuberculosis in Zhejiang province. In addition to the common mutations type,there are some special types of mutations,and further research should be strengthened in this fields.更多还原