中华结核和呼吸杂志
中華結覈和呼吸雜誌
중화결핵화호흡잡지
Chinese Journal of Tuberculosis and Respiratory Diseases
2001年
1期
48-51
,共4页
朱中元%邵寒霜%陈允凤%王海波
硃中元%邵寒霜%陳允鳳%王海波
주중원%소한상%진윤봉%왕해파
分支杆菌,结核%异烟肼%基因,耐药%序列分析
分支桿菌,結覈%異煙肼%基因,耐藥%序列分析
분지간균,결핵%이연정%기인,내약%서렬분석
目的 对耐药结核分支杆菌的inhA基因进行测序分析以研究其变异的分子机制。方法 以inhA片段为引物,聚合酶链反应扩增H37Rv、耐药株和敏感株的inhA基因,产物克隆后制备质粒,ABI 377全自动核酸测序系统测定DNA序列。结果 在17个耐异烟肼菌株中,11株出现inhA基因变异,突变率为65%,其中10株至少每株有1个错义突变。变异主要为点突变,包括碱基置换和缺失。各菌株变异不同。katG和inhA同时变异的达62%。首次发现了18个与结核分支杆菌耐INH和EMB特性有关的inhA基因位点。结论 结核分支杆菌耐INH和EMB特性与inhA突变导致药物结合位点减少有关。
目的 對耐藥結覈分支桿菌的inhA基因進行測序分析以研究其變異的分子機製。方法 以inhA片段為引物,聚閤酶鏈反應擴增H37Rv、耐藥株和敏感株的inhA基因,產物剋隆後製備質粒,ABI 377全自動覈痠測序繫統測定DNA序列。結果 在17箇耐異煙肼菌株中,11株齣現inhA基因變異,突變率為65%,其中10株至少每株有1箇錯義突變。變異主要為點突變,包括堿基置換和缺失。各菌株變異不同。katG和inhA同時變異的達62%。首次髮現瞭18箇與結覈分支桿菌耐INH和EMB特性有關的inhA基因位點。結論 結覈分支桿菌耐INH和EMB特性與inhA突變導緻藥物結閤位點減少有關。
목적 대내약결핵분지간균적inhA기인진행측서분석이연구기변이적분자궤제。방법 이inhA편단위인물,취합매련반응확증H37Rv、내약주화민감주적inhA기인,산물극륭후제비질립,ABI 377전자동핵산측서계통측정DNA서렬。결과 재17개내이연정균주중,11주출현inhA기인변이,돌변솔위65%,기중10주지소매주유1개착의돌변。변이주요위점돌변,포괄감기치환화결실。각균주변이불동。katG화inhA동시변이적체62%。수차발현료18개여결핵분지간균내INH화EMB특성유관적inhA기인위점。결론 결핵분지간균내INH화EMB특성여inhA돌변도치약물결합위점감소유관。
Objective To determine and characterize inhA mutations of drug-resistant isolates of Mycobacterium tuberculosis.Methods PCR products of inhA of drug-resistant and susceptible isolates and H37Rv were purified,cloned and analyzed by ABI 377 auto-DNA sequencing system.Results 11 out of 17 drug-resistant M. Tuberculosis isolates were detected having inhA variations. 10 out of the 11 strains with variations had at least one missense mutation. The variations consisted of point mutation (transition,transversion and deletion). Molecular mechanisms were different from strain to strain. 8 of 13 (62%) strains had both katG and inhA mutations. 18 variation positions and mechanisms different from previous report have been described.Conclusion These results suggested that binding sites decrease caused by inhA point mutations be associated with M. tuberculosis′ resistance to INH and EMB.