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

中国防痨杂志 ›› 2012, Vol. 34 ›› Issue (6): 350-353.

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

孙勇洪峰许绍发邢青刘毅任卫聪孙照刚高铁杰张治国易俊莉王甦民李传友

101149 首都医科大学附属北京胸科医院细菌免疫学研究室（孙勇、刘毅、任卫聪、李传友、孙照刚），胸外科(许绍发)；北京结核病控制研究所(洪峰、邢青、易俊莉、王甦民)；北京市昌平区结核病防治所(高铁杰、张治国)

收稿日期:2012-02-19 出版日期:2012-06-10 发布日期:2012-06-13
通信作者: 李传友；王甦民 E-mail:lichuanyou6688＠hotmail.com；suminwang085@126.com
基金资助:
首都医学发展科研基金(2009-1055)

Relationship between gene thyA mutation with para-aminosalicylic acid resistance in Mycobacterium tuberculosis

SUN Yong, HONG Feng, XU Shao-fa, XING Qing, LIU Yi, REN Wei-cong, SUN Zhao-gang, GAO Tie-jie, ZHANG Zhi-guo, YI Jun-li, WANG Su-min, LI Chuan-you

Department of Bacteriology and Immunology,Beijing Chest hospital,Capital Medical university,Beijing 101149,China

Received:2012-02-19 Online:2012-06-10 Published:2012-06-13
Contact: LI Chuan-you,WANG Su-min E-mail:lichuanyou6688＠hotmail.com；suminwang085@126.com

摘要/Abstract

摘要： 目的了解Mtb临床分离菌株中对于对氨基水杨酸钠（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标本中分离并鉴定Mtb 96株，采用比例法、全基因测序的方法检测上述Mtb临床菌株对PAS的耐药性情况及其thyA基因突变情况。结果 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基因突变率分别是46.15%（30/65）、70.97%（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54.84%（17/31）、25.81%（8/31），其在敏感菌株中的比率也分别是35.38%（23/65）、12.31%（8/65）。结论耐药菌株中thyA基因的突变频率明显高于敏感菌株，thyA基因可能是PAS耐药潜在靶点，但未发现其特异性突变位点。

关键词: 分枝杆菌, 结核, 对氨基水杨酸钠, 抗药性, 细菌, 胸苷酸合酶

Abstract: Objective To study para-aminosalicylic acid (PAS) resistance rates in M. tuberculosis isolates and the relationship with thyA gene mutation. Methods Ninety-six M. tuberculosis strains were isolated and identified from the sputa or throat swab specimens of tuberculosis patients. M. tuberculosis strains resistance to PAS was determined by the proportional method, and their thyA gene mutation was detected by PCR-DNA sequencing. Results Of 96 M. tuberculosis isolates, 65 were PAS-sensitive, and 31 were PAS-resistant. Using M. tuberculosis H37Rv as a control, the thyA gene mutation rate in PAS-sensitive and PAS-resistant strains of M. tuberculosis were 46.15% (30/65) and 70.97% (22/31), respectively. Most of stains showed single base deletion and insertion mutations, in which C deletion at codon 19 and codon 168 were 54.84% (17/31), 25.81% (8/31) in PAS-resistant stains respectively, and 35.38% (23/65) and 12.31%(8/65) in PAS-sensitive strains respectively. Conclusion The frequency of the thyA gene mutation in PAS-resistant strains was significantly higher than that in PAS-sensitive strains. The thyA gene could be a potential target for the development of PAS resistance. But there were not any site with specific mutation found in this study.

Key words: Mycobacterium tuberculosis, p-Aminosalicyclic acid, Drug resistance, bacterial, Thymidylate synthase

孙勇洪峰许绍发邢青刘毅任卫聪孙照刚高铁杰张治国易俊莉王甦民李传友. 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[J]. 中国防痨杂志, 2012, 34(6): 350-353.

SUN Yong, HONG Feng, XU Shao-fa, XING Qing, LIU Yi, REN Wei-cong, SUN Zhao-gang, GAO Tie-jie, ZHANG Zhi-guo, YI Jun-li, WANG Su-min, LI Chuan-you. Relationship between gene thyA mutation with para-aminosalicylic acid resistance in Mycobacterium tuberculosis[J]. Chinese Journal of Antituberculosis, 2012, 34(6): 350-353.

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