合肥地区异烟肼耐药结核分枝杆菌KatG基因突变的分子特征  

Molecular characterization of katG mutations in the isoniazid-resistant Mycobacterium tuberculosis isolated in Hefei

作　　者：张文艳[1] 张洁莹[1] 柯文鸿[1] 金晶[1] 徐东芳[2] 王莉丽[1] 

机构地区：[1]合肥市疾病预防控制中心 [2]安徽省肺科医院检验科

出　　处：《现代预防医学》2013年第6期1102-1104,共3页Modern Preventive Medicine

摘　　要：目的了解合肥地区结核分枝杆菌异烟肼(Isoniazid,INH)耐药株katG基因突变特点。方法应用PCR-直接测序法对合肥地区肺结核病人痰液中分离的86株结核分枝杆菌的katG基因731bp序列进行测定分析。结果 86株结核分枝杆菌中67株对INH耐药,19株对INH敏感;67株耐INH临床分离株中PCR成功扩增61株,其中56株发生katG基因突变,突变率为91.8%(56/61);katG基因发生联合突变的有30株,突变率为49.2%(30/61),26株发生katG基因单位点突变,突变率为42.6%(26/61)。突变位点主要集中在463位精氨酸和315位丝氨酸,突变率分别为93.4%(57/61)和42.6%(26/61)。而在19株INH敏感株中发现有78.9%(15/19)株存在Arg4631eu突变,突变形式与INH耐药株相同。结论在合肥地区,KatG基因315位密码子突变是菌株INH表型耐药的重要分子基础,以Ser315Thr错义突变为主。KatG基因463位密码子突变与INH耐药表型没有相关性,不是结核杆菌INH耐药的分子标志。该位点突变可能是基因多态性,与结核茵治疗带来的选择性压力无关。OBJECTIVE To investigate the mutation characteristics of katG gene in isoniazid （INH） -resistant strains of My- cobacterium tuberculosis isolated in Hefei. METHODS Aanlyze sequences of 731bp DNA fragment of katG gene in 86 strains M. tuberculosis isolated from the sputum of tuberculosis patients in Hefei by DNA sequencing. RESULTS There were 67 strains of INH-resistant strains and 19 strains of INH-susceptible strains. In 67 INH-resistant strains, 61 strains were amplified suc- cessfully by PCR, 56 of 61 （91.8%） INH-resistant strains had katG gene mutation, Sequencing results showed that the muta- tions mainly located at 463-Arg （93.4%） and 315-Ser （42.6%）. 30 of 61 （49.2%） INH-resistant strains had combinative mutation; 26 of 61 （42.6%） INH-resistant strains had point mutation. Arg4631eu was also present in 15 of 19 INH- suscepti- ble strains. CONCLUSION KatG315 mutation is the main mechanism to INH-resistant strains in Hefei. 463 Arginine mutation in katG should be considered as polymorphism unrelated to the selective pressure of drug treatment in M.tuberculosis.

关 键 词：结核分枝杆菌 异烟肼耐药 KATG 基因突变 

分 类 号：R378.911[医药卫生—病原生物学]