结核分枝杆菌thyA基因突变与对氨基水杨酸钠耐药关系的研究

A Study of Relationship between Mycobacterium tuberculosis thyA Mutation and Resistantance to Para-aminosalicylic Acid

目的了解Mtb临床分离菌株中对氨基水杨酸钠（PAS）的耐药率及PAS耐药性与thyA基因突变的关系。方法从肺结核患者的痰液或咽拭子标本中分离并鉴定Mtb96株，采用比例法、PCR的方法检测上述Mtb临床菌株对PAS的耐药性情况及其thyA基因突变情况。结果分离得到的96株Mtb中，65株为PAS敏感菌株和31株为PAS耐药菌株。以Mtb标准菌株H37Rv为对照，筛选敏感和耐药菌株中的thyA突变率分别是46．1％（30／65）、71％（22／31），突变多为单个碱基的缺失和插入突变，其中又以第19位密码子缺失C、第168位密码子缺失C为主，在耐药中所占比率分别是54．8％（17／31）、25．8％（8／31），其在敏感菌株中的比率也分别是35．5％（23／65）、12．3％（8／65）。结论thyA基因可能是PAS耐药潜在靶点，但本研究未发现其特异性突变位点。

Objective To study the resistance rates of clinical isolated Mycobactedum tuberculosis strains to para- aminosalicylic acid （PAS） and the relationship between PAS resistance with thyA gene mutation. Methods 96 strains isolated and identified in sputum or throat swab specimens from tuberculosis patients were analyzed for PAS resistance situation and thyA gene mutation using proportiona method and PCR method. Results Among 96 identified strains of Mycobactenum tuberculosis, 65 were PAS sensitive strains and 31 PAS resistance strains. The standard strains H37Rv M. tuberculosis was as a control, thyA gene mutation rates of the sensitive and resistant strains were 46.1%（30/65） and 71%（22/31）, mostly with single base deletion and insertion mutations, which mainly presented missing at codon 19 C and deletion at codon 168 C. The percentage of mutation in the drug resistant strains were 54.8%（17/31）, 25.8%（8/31） and 35.5%（23/65）, 12.3%（8/65） in the sensitive strains. Conclusion ThyA gene could be a potential target for development of PAS resistance, but a specific mutation site has not been found in this study.