摘要
目的:探索新疆南疆部分地区维吾尔族结核病人群中分离到的结核分枝杆菌基因组中的katG、inhA、kasA、ahpC基因突变与耐异烟肼的关联,揭示新疆肺结核病高患病率、高死亡率的可能原因。方法:收集新疆南疆部分地区维吾尔族结核病患者痰液标本,对MTB进行分离培养后,应用比例法检测其对异烟肼耐药性,运用PCR技术对所分离菌株的上述基因相关片段扩增并进行测序及序列分析。结果:筛选出实验菌株99株,其中敏感株63株,耐异烟肼菌株36株,耐药率为36.4%。耐药株中katG基因突变率为63.9%,315位点突变,突变类型AGC→ACC(Ser→Thr)、AGC→AAC(Ser→Asn);inhA基因突变率为47.2%,有缺失、同义突变和错义突变;kasA基因突变率为41.7%,突变类型为缺失和错义突变;ahpC基因突变率为8.3%,属于错义突变。结论:新疆南疆结核病高患病率、高死亡率的可能原因之一是结核分枝杆菌对INH产生了耐药,结核分枝杆菌对INH耐药机制可能与耐药菌株基因组内katG、inhA、kasA和ahpC基因发生了突变有关。
Objective：To ascertain the relationship between the drugresistance of isoniazid and katG,inhA,kasA,and ahpC gene mutations in clinical isolates Mycobacterium tuberculosis（MTB） from Uyger ethgic tuberculosis（TB） patients who live in the south region of Xinjiang,and reveal likely reasons why the rate of TB infection and TB patients’death is higher in Xinjiang.Methods：Sputum samples from TB patients were collected from several areas of southern Xinjiang.Then the separa-tion and culture of MTB were finished.Next drug sensitivity test（DST） to isoniazid was used to detect drug-resistance MTB by the proportion method.Genetic mutations in the related resistance genes（katG,inhA,kasA,and ahpC） in these MTB clinical isolates were identified by PCR,which was followed by DNA sequencing of the purified PCR products.Results：A total of 99 isolates were collected,including 63 INH sensitive isolates and 36 INH resistant isolates.The rate of drug resistance is 36.4%.Among the INH-resistance strains,the proportion of isolates which have mutations in the respective genes（katG,inhA,kasA,and ahpC） was 63.9%,47.2%,41.7% and 8.3%.For katG gene,the mutation found was Ser315Thr or Ser315Asn.For inhA,mutations detected were small deletion,same sense mutation and missense mutation.For kasA,found changes were small deletion and missense mutation.There only was missense mutation in ahpC gene.Conclusion：A possible reason for higher rate of TB infection and TB patients’death in the south region of Xinjiang is that MTB has become resistant to INH,and INH resis-tance is associated with katG,inhA,kasA,and ahpC gene mutations in MTB.
出处
《现代生物医学进展》
CAS
2010年第21期4025-4029,共5页
Progress in Modern Biomedicine
基金
国家大学生创新性实验计划(NO081075917)
国家自然科学基金资助项目(30960356)
关键词
结核分枝杆菌
异烟肼
耐药
基因突变
Mycobacterium tuberculosis
Isoniazid
Drug resistance
Genetic mutation
