耐异烟肼结核分枝杆菌及其katG与inhA基因突变的研究  

Study of the relationship between resistant to isoniazid and mutation of KatG and inhA in Mycobacterium tuberculosis isolates

作　　者：陈杨[1] 陈玲[1] 张泓 王建华[1] 李娜娜[1] 李开伦[1] 甘辛[1] 张建勇[1] 

机构地区：[1]贵州省遵义医学院附属医院呼吸内科及呼吸医学研究室,遵义563003 [2]美国Z-BioMed公司,罗克维尔20847

出　　处：《中国抗生素杂志》2010年第10期788-792,共5页Chinese Journal of Antibiotics

基　　金：贵州省遵义市"15851人才工程"培养人才资助项目(黔科合J字[2007]2223号);美国CDC中小企业创业项目(200-2007-M-22792)

摘　　要：目的探讨耐异烟肼临床分离结核分枝杆菌与其katG及inhA基因突变的相关性。方法对87例临床肺结核患者痰标本进行培养、鉴定及药物敏感性试验,提取菌落DNA、PCR扩增katG和inhA基因片段,并对所有扩增片段进行序列分析。结果 87例菌株经鉴定均为结核分枝杆菌,30(34.5%)例为耐异烟肼菌株,57(65.5%)例异烟肼敏感菌株。30例耐异烟肼株中,18(60%)株出现katG和(或)inhA基因突变。在突变株中,9(50%)株为katG单基因突变,5(27.8%)株为inhA单基因突变,4(22.2%)株为katG和inhA双基因联合突变。两个新突变位点(Val230Met和Pro232Gln)为首次发现,已被美国,欧洲和日本的基因库收录。结论该研究证实结核分枝杆菌katG和inhA基因突变与耐异烟肼相关,为进一步研究异烟肼的抗菌机制奠定了基础。Objective To characterize relationship between gene mutations in katG and inhA and resistant clinical Mycobacterium tuberculosis（M, th） isolates to isoniazid. Methods A total of 87 clinical Mtb isolates from Guizhou Province were used for drug susceptibility testing, and mutation analysis of katG and inhA genes. Results 87 clinical isolates were proved to be Mtb. 30（34. 5%） isolates was resistant to isoniazid, 57（65.5%） isolates were sensitive to isoniazid. Of 30 isolates, 18（60%） isolates had mutations in the katG and （or） inhA genes. In these mutation isolates, 9（50%） mutations appeared in katG gene, 5（27.8%） in inhA, and 4（22.2%） in both katG and inhA genes. Two of the mutations in the katG gene （Va1230Met and Pro232Gln） were not reported previously and therefore were submitted to the GenBank as new sequences （GQ250582 and GQ250583）. Conclusions Results from this study with clinical isolates from Guizhou Province further confirmed that mutations in katG and inhA genes are related to the isoniazid resistance in Mtb and two new point mutations in the katG gene have been identified from the study, which provide a basis for further understanding the anti-bacterium mechanism of isoniazid.

关 键 词：耐异烟肼 结核分枝杆菌 聚合酶链式反应 序列分析 基因突变 

分 类 号：R378.911[医药卫生—病原生物学]