河南省结核分枝杆菌吡嗪酰胺耐药基因pncA 分析.docVIP

河南省结核分枝杆菌吡嗪酰胺耐药基因pncA分析 石洁，李辉，马晓光，闫国蕊，赵玉玲，邢进 （(河南省疾病预防控制中心, 郑州 450016)） 石洁，手机单位名称详细通讯地址电子邮箱；、单位名称详细通讯地址 电子邮箱； [摘要] 本研究为了了解河南地区结核分支杆菌耐吡嗪酰胺( PZA) 分离株pncA 基因突变的情况,探讨其与耐PZA 之间的关系。对41例结核分支杆菌临床分离株进行结核分支杆菌常规培养和药敏检测,聚合酶链反应-测序技术检测pncA 基因的突变。结果：有68% （28/41）的耐药菌株pncA发生突变，从而改变了吡嗪酰胺酶氨基酸序列的一级结构。这28株临床分离突变株涵盖了突变的各种类型，包括了碱基替代，插入突变和缺失突变。突变分布在pncA 基因整个序列，位于开读框架的3 ~ 535位的核苷酸。结论：河南地区结核分支杆菌临床分离株耐PZA主要分子机制之一为pncA 基因的突变。 [关键词] 结核分枝杆菌；pncA基因；PZA耐药；吡嗪酰胺酶 Detection of pyrazinamid-resistant gene pncA of Mycobacterium tuberculosis in Henan Province SHI Jie, LI Hui ,MA Xiao-guang, YAN Guo-rui, XING Jin ( Henan Province Center for Disease Control and Prevention, Zheng zhou 450016 China) [Abstract] The aim of this study is to observe themutations of pncA gene in pyrazinamide（PZA）-resistant mycobacterium tuberculosis strains from Henan province. From 41 clinical isolates of Mycobacterium tuberculosis , the routine culture and drug susceptibility detection were done , and the mutations of pncA gene were detected by PCR-sequencing. Results：The results showed that 68% ( 28 /41) PZA-resistant isolates had pncA mutations which altered the primary amino acid sequence of py razinamidase. The 28 PZA-resistant clinical isolated mutant contained various mutations，including nucleotide substitutions, insertions, or deletions in the pncA gene. The identified mutations were dispersed along the pncA gene, and the mutations within the open reading frame were distributed in the region from nucleotide 3 to nucleotide 535. Conclution：Mutation of pncA gene might be one of the major molecular mechanisms in pyrazinamide-resistance of clinical isolates of Mycobacterium tuberculosis. [Keywords]Mycobacterium tuberculosis; pncA gene; pyrazinamide-resistance; pyrazinamidase 近年来，结核分枝杆菌（Mycobacterium Tuberculosis ）耐药菌株，尤其是耐多药菌株（multidrug-resistant，MDR）菌株的出现，严重威胁了结核病的治疗，使其成为影响公众健康的重要疾病之一[1]。结核杆菌的耐药性是由于基因组上相关位点的突变，其耐药性的产生主要归结于不合理用药引起的结核菌内抗结核药物作用靶基因突变。 吡嗪酰胺（PZA）作为尼克酰胺的类似物，是一种重要的抗结核药物。由于PZA能杀死半休眠期的结核分枝杆菌，因此与异烟肼和利福