深圳市耐多药结核分枝杆菌流行株耐药基因序列分析

摘要/Abstract

摘要： 目的了解深圳市耐多药结核分枝杆菌（multidrug-resistantMycobacterium tuberculosis ，MDR-TB）的分子流行病学特征。方法参照WHO/IUATLD标准，使用L-J药敏培养基，采用1％比例法药敏试验筛选出敏感株和异烟肼（isoniazid,INH）、利福平（rifampicin, RFP）双耐药临床分离株,通过DNA测序检测深圳地区153株敏感株与132株MDR-TB的INH耐药基因 kat G、inh A、oxy R- ahp C基因间区域及RFP耐药基因 rpo B碱基排列顺序，运用DNASTAR和blastn进行序列分析。结果 153株敏感株突变率为27.5%（42/153）。132株MDR-TB突变率为98.5%（130/132），其中kat G基因突变率为73.5%（97/132），68.9%（91/132）为 kat G315位突变； inh A基因突变率为18.2%（24/132），11.4%（15/132）为启动子区域突变，未发现 inh A94特异突变株； ahp C基因突变率为16.7%（22/132），10.6%（14/132）为启动子区域突变； rpo B基因81-bp核心区域突变率为93.2%（123/132）。结论 kat G315、inh A启动子区域、ahp C启动子区域以及 rpo B 81-bp核心区域突变为深圳地区耐多药结核分枝杆菌主要突变类型，与其他国家和地区差异无统计学意义；但深圳地区未见 inh A94突变株。

关键词: 分枝杆菌, 结核, 抗药性, 多种, 细菌, 序列分析, DNA, 突变, 深圳市

Abstract: Objective To investigate the epidemiologic characteristic of multidrug-resistant (MDR) Mycobacterium tuberculosis(MTB) in Shenzhen.Methods According to the standard of WHO, International Union Against Tuberculosis and Lung Disease (IUATLD), drug-susceptive and MDR MTB strains were collected by drug susceptibility test (DST) of 1% proportion method.kat G,inh A, intergenic region ofoxy R- ahp C and 81bp core region ofrpo B genes in 153 drug-susceptive strains and 132 MDR strains were analyzed by DNA sequencing. Results 27.5%（42/153）of drug-susceptive strains and 98.5%（130/132）of MDR strains showed gene mutations. Of 132 MDR strains, 73.5%（97/132）had kat G mutations, and 68.9%（91/132）of kat G mutations were at codon 315; 18.2%（24/132）had inh A mutations, and none specific mutations were found at codon 94 of inh A; 11.4%（15/132）had mutations at inh A-promoter region; 16.7%（22/132）had ahp C mutations, 10.6%（14/132）had mutations at intergenic region of oxy R- ahp C; 93.2%（123/132）had mutations at the 81bp core region of rpo B. Conclusion The codon 315 of kat G, promoter region of inh A,ahp C and the 81bp core region of rpo B play predominant roles in MDR-TB in Shenzhen.

Key words: Mycobacterium tuberculosis, Drug resistance,mutiple,bacterial, sequence analysis,DNA, mutation, Shenzhen city

崔运勇王峰刘小立杨慧桂静胡思玉. 深圳市耐多药结核分枝杆菌流行株耐药基因序列分析[J]. 中国防痨杂志, 2011, 33(5): 257-262.

Cui Yunyong, Wang Feng, Liu Xiaoli, Yang Hui, Gui Jing, Hu Siyu. Analyze the epidemical multidrug-resistant Mycobacterium tuberculosis from Shenzhen by DNA sequencing[J]. Chinese Journal of Antituberculosis, 2011, 33(5): 257-262.

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