[结核分枝杆菌临床分离株多药耐药分子机制的研究]
[Study on the molecular mechanism of multi-drug resistance in clinical isolates of Mycobacterium tuberculosis].
作者信息
Wu X, Zhuang Y, Zhang J
机构信息
Tuberculosis Research Laboratory, 309th Hospital, P.L.A., Beijing.
出版信息
Zhonghua Jie He He Hu Xi Za Zhi. 1997 Dec;20(6):332-5.
OBJECTIVE
To study the molecular mechanism of multi-drug resistance in M. Tuberculosis, and to develop a new method for detecting genes related with multi-drug resistance.
METHOD
The ropB, rpsL, katG genes and inhA regulatory sequence in clinical isolates of M. tuberculosis were analyzed with PCR and PCR-SSCP techniques.
RESULT
The sensitivity of amplifing the drug-resistant genes with PCR was 1-10 pg DNA. Of the 20 multiple resistant strains with reduced sensitivity to streptomycin, rifampin and isoniazid, 90% showed mutations in more than two genetic markers associated with resistance to each of these three drugs, 10% revealed only mutations in rpoB gene.
CONCLUSION
Multi-drug resistance in M. tuberculosis could be caused by an accumulation of mutations in chromosomal genes encoding drug targets or an alteration at a single multiple resistance locus. PCR and PCR-SSCP techniques might become simple, rapid and reliable diagnostic tests for multi-drug resistance.
目的
研究结核分枝杆菌多药耐药的分子机制，并开发一种检测与多药耐药相关基因的新方法。
方法
采用PCR和PCR-SSCP技术分析结核分枝杆菌临床分离株中的ropB、rpsL、katG基因及inhA调控序列。
结果
用PCR扩增耐药基因的灵敏度为1-10 pg DNA。在对链霉素、利福平及异烟肼敏感性降低的20株多重耐药菌株中，90%在与这三种药物耐药相关的两个以上遗传标记中出现突变，10%仅在rpoB基因中出现突变。
结论
结核分枝杆菌的多药耐药可能是由编码药物靶点的染色体基因突变积累或单个多重耐药位点改变引起的。PCR和PCR-SSCP技术可能成为简单、快速且可靠的多药耐药诊断检测方法。
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