Rifampicin resistance and mutation of the rpoB gene in Mycobacterium tuberculosis
Rifampicin resistance and mutation of the rpoB gene in Mycobacterium tuberculosis
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DOI：
10.1111/j.1574-6968.1996.tb08515.x
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发表时间：
1996-10-15
影响因子：
2.1
通讯作者：
Yoshida, S
中科院分区：
文献类型：
--
作者：
Taniguchi, H;Aramaki, H;Yoshida, S
以39株对利福平敏感的结核分枝杆菌临床分离株为研究对象，研究了利福平耐药程度与rpoB基因突变位点的关系。所有对利福平耐药的菌株都有错义突变。有20个菌株(95%)在簇I区有突变，在大肠杆菌中也有报道[金和格罗斯(1988)J.Mol]。比奥尔。202，45-58]，其余一株在N-末端密码子381[Ala--&Gt；Val]处发生突变，这在大肠杆菌中尚未报道。在18株利福平敏感株中，2株在第I簇区域发生突变，另外3株在第I簇发生突变。基因簇I区密码子513(5%)、526(33%)或531(43%)突变导致对利福平(50微克·毫升(-1)小于或等于最低抑菌浓度)产生高度耐药。在第III簇(密码子679或687)，甚至在第I簇(密码子514、521或533)的其他位点，对利福平表现出低水平(MIG=12.5微克毫升(-1))或无(MIC<；0.39微克毫升(-1))耐药。这些结果表明，rpoB基因突变主要但不一定与结核分枝杆菌对利福平的耐药性有关，rpoB基因突变的位置将影响对利福平的耐药性水平。
Using 39 clinical isolates of Mycobacterium tuberculosis strains with a broad range of susceptibility to rifampicin, we examined the relationship between the degree of resistance to rifampicin and mutational sites of the rpoB gene. All rifampicin-resistant strains had missense mutations. Twenty strains (95%) had a mutation in the cluster I region, which has also been reported in Escherichia coli [Jin and Gross (1988) J. Mol. Biol. 202, 45-58], and the remaining one strain had a mutation at codon 381 [Ala-->Val] in the N-terminal region, which has not been reported in E. coli. Among 18 rifampicin-susceptible strains, two had a mutation in the cluster I region and the other three strains had a mutation in the cluster In region. The mutations at codons 513 (5%), 526 (33%) or 531 (43%) in the cluster I region led to high level resistance to rifampicin (50 mu g ml(-1)less than or equal to MIC). The mutations at the other sites, in the cluster III region (codons 679 or 687) and even in the cluster I region (codon 514, 521, or 533), showed low level (MIG = 12.5 mu g ml(-1)) or no (MIC < 0.39 mu g ml(-1)) resistance to rifampicin. These results suggest that mutations in the rpoB gene are, mostly, but not necessarily, associated with rifampicin resistance of M. tuberculosis, and the sites of mutations on the rpoB gene will affect the level of resistance to rifampicin.