embAC与embB共突变对结核分枝杆菌乙胺丁醇药物敏感性的调节机制研究

项目名称： embAC与embB共突变对结核分枝杆菌乙胺丁醇药物敏感性的调节机制研究

项目编号： No.81201323

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学四处

项目作者： 崔振玲

作者单位： 同济大学

项目金额： 23万元

中文摘要： 结核分枝杆菌(MTB)抗药性发展非常迅速，为结核病的防治带来巨大困难。乙胺丁醇 (EMB)是重要的一线抗结核药物之一。已知embB突变可导致MTB对EMB耐药，但尚无法解释同样embB突变菌株EMB的药物敏感性存在巨大差异。本研究前期在embB突变的EMB敏感和耐药株中检测到embA或embC突变。embA、embC与embB共同编码阿拉伯糖基转移酶，embAC与embB共突变现象提示embA和embC基因可能参与调节embB突变的MTB菌株对EMB的药物敏感性。本研究将分析MTB中embA或者embC与embB共突变对EMB药物敏感性、EmbABC表达、EmABC酶活性及细胞壁渗透性的作用。该项目的实施将不仅阐明embA或者embC与embB共突变对EMB药物敏感性的调节机制，而且为基因药敏检测MTB的EMB药物敏感性提供更明确的检测位点和检测依据.

中文关键词： 结核分枝杆菌；乙胺丁醇；药物敏感性；基因突变；阿拉伯糖基转移酶

英文摘要： The drug resistance of Mycobacterium tuberculosis (MTB) developed very quickly and bring a huge difficulties for the prevention and treatment of tuberculosis. Ethambutol (EMB) is an important first-line anti-TB drugs. It's well known that embB mutation leads to MTB resistant to EMB, but embB mutation still can't explain why the drug resistant level of the isolates with same embB mutant were quite different and why the embB mutation occurred in isolates susceptible to EMB. Our early study showed the mutation of embA or embC was detected in the isolates resistant to EMB and susceptible to EMB with embB mutations. Due to embA,embB and embC encoding arabinosyltransferase，this phenomena suggested embA and embC may be involved in regulating drug susceptibility to EMB in the MTB isolates with embB mutation. In this study, we aim to further analyze the effect of embA or embC mutation on the drug susceptibility to EMB, the expression of EmbABC, the enzyme activity of EmbABC and the structure of cell wall in the MTB strains with embB mutation. Implementation of this study will not only clarify the regulation mechanism of drug susceptibility to ethambutol of Mycobacterium tuberculosis by embA or embC in MTB strains with embB simultaneous mutation but also supply the clear target gene sites and evidences of genetic drug su

英文关键词： Mycobacterium tuberculosis；ethambutol；drug susceptibility；gene mutant；arabinosyltransferase