【摘要】 目的探讨江苏省结核分枝杆菌耐药相关基因的基因型特点及其与耐药表型的关系,为开展耐药结核病快速诊断提供依据。方法通过基因测序技术,分析结核分枝杆菌利福平(rifampin,RFP)耐药相关基因rpoB和异烟肼(isoniazid,INH)耐药相关基因katG不同位点的突变频率,探讨基因型与耐药表型的关系。结果共收集新登记涂阳病人菌株283株,其中255株结核分枝杆菌成功测序,包括38株RFP耐药株,50株INH耐药株,48株链霉素耐药菌株,21株乙胺丁醇耐药株,34株耐多药菌株。28株(11.0%)在rpoB 81bp的基因核心区发生了点突变,21株出现单个位点突变外,7株出现两位点突变,突变形式主要为rpoB531 TCG→TTG单个位点突变。30株(11.8%)发生了katG基因区的突变,所有突变形式为katG315AGC→ACC。rpoB基因突变全部发生于RFP耐药菌株中,katG基因突变全部发生于INH耐药菌株中。结论检测rpoB与katG基因位点的突变对判断江苏省地区耐药结核以及耐多药结核有重要的价值,可以为开展耐药结核病早期诊断提供科学依据。更多还原

【Abstract】 Objective To describe the genotype characteristics of mycobacterium tuberculosis and its association with the drug resistant phenotype.To explore the molecular mechanisms of drug-resistant,so as to provide evidences for the rapid diagnosis and screening of drug-resistant mycobacterium tuberculosis.Methods The mutations of rifampin resistance related rpoB gene and isoniazid resistance related katG gene were amplified and sequenced.The association between genotypes and phenotypes of drug resistance were analysed.Results 255 mycobacterium tuberculosis strains were sequenced and 28 isolates(11.0%) were found having point mutations at the 81bp core area of rpoB gene.The main mutation was rpoB531 TCG→TTG(46.4%).Besides,two simultaneous point mutations were found at rpoB gene in seven strains.For katG gene,11.8% strains had mutations.All mutations were located at katG 315 position,with the mutation form of katG 315AGC→ACC.rpoB gene mutations all occurred in the rifampicin resistant strains and katG gene mutations all occurred in the isoniazid resistant strains with high sensitivity and specificity of 100% for both.Conclusions rpoB and katG gene mutations are important molecular mechanisms of mycobacterium tuberculosis to rifampicin and isoniazid resistance.Molecular epidemiological studies of mycobacterium tuberculosis are useful for understanding the mechanisms of drug resistance,and can help develop tools for early diagnosis of drug-resistant tuberculosis.更多还原