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异烟肼耐药耻垢分枝杆菌的建立及药物敏感性的测定
引用本文:Jia PP,Zhao LL,Li XY,Zhang Q,Liu ZL,Wang X,Yu LY,Zhao LX,Cen S. 异烟肼耐药耻垢分枝杆菌的建立及药物敏感性的测定[J]. 药学学报, 2011, 46(4): 377-382
作者姓名:Jia PP  Zhao LL  Li XY  Zhang Q  Liu ZL  Wang X  Yu LY  Zhao LX  Cen S
作者单位:中国医学科学院医药生物技术研究所免疫生物学室;中国医学科学院医药生物技术研究所菌种保藏中心;中国医学科学院医药生物技术研究所发酵工程室;
基金项目:国家“重大新药创制”科技重大专项(2009ZX09303-005)
摘    要:
耐药结核病的涌现,使发展新型抗耐药结核药物变得尤为迫切。本研究选择生长快且无致病性的耻垢分枝杆菌为研究对象,探索快速评价药物抗异烟肼耐药结核分枝杆菌的能力。inhA是异烟肼的作用靶点,由于inhA的突变或者过表达可以引起结核分枝杆菌对异烟肼耐药性的产生。通过将inhA克隆入pMV261中,构建过表达inhA的耻垢分枝杆菌。结果显示,过量表达inhA的耻垢分枝杆菌对异烟肼的敏感性下降了100倍以上。建立了利用刃天青为指示剂的抗异烟肼耐药株的快速药效评价方法,可快速对药物的活性进行定性或定量评价,为进行新型抗结核药物的高通量筛选和药效评价奠定基础。

关 键 词:耻垢分枝杆菌  inhA过表达  异烟肼耐药  评价方法  

Establishment and drug susceptibility test of isoniazid resistant Mycobacterium smegmatis
Jia Ping-ping,Zhao Li-li,Li Xiao-yu,Zhang Quan,Liu Zhen-long,Wang Xin,Yu Li-yan,Zhao Li-xun,Cen Shan. Establishment and drug susceptibility test of isoniazid resistant Mycobacterium smegmatis[J]. Acta pharmaceutica Sinica, 2011, 46(4): 377-382
Authors:Jia Ping-ping  Zhao Li-li  Li Xiao-yu  Zhang Quan  Liu Zhen-long  Wang Xin  Yu Li-yan  Zhao Li-xun  Cen Shan
Affiliation:JIA Ping-ping1,ZHAO Li-li2,LI Xiao-yu1,ZHANG Quan1,LIU Zhen-long1,WANG Xin1,YU Li-yan2,ZHAO Li-xun3,CEN Shan1(1.Laboratory of Immunobiology,2.Center for Culture Collection,3.Fermentation Engineering Laboratory,Institute of Medicinal Biotechnology,Chinese Academy of Medical Sciences,Beijing 100050,China)
Abstract:
With the emergence of drug resistant tuberculosis,it is very urgent to find novel anti-tuberculosis drugs,especially novel anti-drug-resistant tuberculosis drugs.Because of the slow growth and the need to work in a biosafty environment of Mycobacterium tuberculosis,the development of evaluation of drug effect is severely impeded.In order to solve these issues,non-pathogenic fast-growing Mycobacterium smegmatis is introduced as test organism.The inhA is one of a target of isoniazid(INH) overexpression or mut...
Keywords:Mycobacterium smegmatis  overexpression of inhA  isoniazid-resistance  evaluation method  
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