【摘要】 目的　研究结核分枝杆菌rpoB基因突变与多重耐药及利福平耐药程度强弱之间的关系。 方法　应用绝对浓度法测定 5 8株结核分枝杆菌对 4种一线抗结核药物的药敏特性 ,对耐利福平结核分枝杆菌的耐药谱进行分析。同时对含有核心突变区的结核分枝杆菌rpoB基因片段进行PCR扩增和DNA测序 ,分析rpoB基因突变与多重耐药的关系 ,以及突变位点和突变性质与利福平耐药强弱的相关性。结果　 5 8株结核分枝杆菌中 ,利福平耐药株 36株 ,敏感株 2 2株。 36株耐药株均存在rpoB基因突变 ,其中 88.9% (32 / 36 )至少对利福平和异烟肼同时耐药。 90 .0 %的利福平高度耐药株 (18/ 2 0 )与rpoB基因 5 31位和 5 2 6位密码子突变相关。密码子 5 31位和 5 2 6位各有 1株双碱基突变 ,且均为多重耐药株。结论　结核分枝杆菌rpoB基因突变所致的利福平耐药株大部分对异烟肼耐药 ,因此单独检测rpoB基因突变即可初步筛选多重耐药的结核分枝杆菌 ;而rpoB基因的突变位点与利福平耐药程度之间具有一定的相关性更多还原

【Abstract】 Purpose To study the relativity of rpoB gene mutations in Mycobacterium tuberculosis multi-drug resistance and degree of resistance to rifampin. Methods The susceptibilities of 58 isolates of M. tuberculosis to four first-line anti-tuberculosis drugs,including isonazid (INH),rifampin (RFP),streptomycin (SM) and ethambutol (EMB),were detected by absolute concentration method and the resistance patterns were analyzed.Then fragments covering 69-bp rifampin resistance determining region were analyzed by DNA sequencing in order to investigate the relationship between the degree of resistance to rifampin and mutational sites as well as genotypes of rpoB gene. Results There were 36 RFP-resistant isolates and 22 RFP-susceptible isolates among the 58 M. tuberculosis strains.All of the 36 rifampin-resistant isolates had mutation in the 69 bp region of rpoB gene,32 isolates (32/36,88.9%) were at least resistant to RFP and INH.Eighteen isolates (18/20,90%) with high level resistance to RFP were related with mutations of codes 531 and 526 in rpoB gene.Two isolates with mutations of two bases in codes 531 and 526 respectively were both mulit-drug rsistantstrains. Conclusions Detection of the mutations of rpoB in M. tuberculosis is helpful to identify the multi-drug resistant isolates since most of RFP-resistant M. tuberculosis strains caused by rpoB gene mutants were resistant to INH.And the degree of resistance to RFP is related with the mutations of rpoB gene.更多还原