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首页> 外文期刊>The Journal of Antibiotics: An International Journal >Prevalence of gyrA and B gene mutations in fluoroquinolone-resistant and -sensitive clinical isolates of Mycobacterium tuberculosis and their relationship with MIC of ofloxacin
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Prevalence of gyrA and B gene mutations in fluoroquinolone-resistant and -sensitive clinical isolates of Mycobacterium tuberculosis and their relationship with MIC of ofloxacin

机译：耐氟喹诺酮敏感性结核分枝杆菌临床分离株中gyrA和B基因突变的发生率及其与氧氟沙星MIC的关系

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摘要

The study was done to know the prevalent mutations of gyrA and gyrB genes, and their significance with drug resistance in clinical isolates of Mycobacterium tuberculosis. A total of 100 ofloxacin- (OFX) resistant and 100 OFX-sensitive isolates of M. tuberculosis were consecutively selected from routine Tuberculosis laboratory. Drug resistance pattern of these isolates was recorded. MIC of OFX was tested in all these isolates by absolute concentration method. Quinolone resistance determining region (QRDR) of gyrA and gyrB genes of 320 and 428 bp, respectively, were amplified and sequenced. Sequencing data were analyzed by BLAST on NCBI with reference strain H37Rv. Of 100 OFX-sensitive isolates, 30 were pansusceptible, 28 were monoresistant, 10 were polyresistant and 32 were multidrug resistant (MDR). Among 100 OFX-resistant isolates, 19 were OFX monoresistant, 16 were polyresistant and 65 were MDR. Mutations in gyrA and gyrB genes were observed in 79% and 5% of OFX-resistant isolates, respectively. Most prevalent mutation was found at codon 94 in QRDR of gyrA gene. Double mutations found in gyrA gene and in both gyrA and gyrB genes signifies higher levels of OFX resistance. In one isolate, a substitution at codon 592 (Pro592Ser) was found as a novel mutation outside the QRDR of gyrB gene. Our findings support previous studies that the OFX resistance to M. tuberculosis is associated with mutations in the QRDR of gyrA gene; however, the level of OFX resistance may not be predicted based on the mutation patterns in the gyrA gene.
机译：进行这项研究是为了了解gyrA和gyrB基因的普遍突变及其在结核分枝杆菌临床分离株中的耐药性意义。从常规结核病实验室连续选择了总共100株耐氧氟沙星（OFX）和100株OFX敏感的结核分枝杆菌。记录这些分离株的耐药模式。通过绝对浓缩法在所有这些分离物中测试了OFX的MIC。扩增并测序了分别为320和428 bp的gyrA和gyrB基因的喹诺酮抗性决定区（QRDR）。测序数据通过BLAST在NCBI上用参考菌株H37Rv进行分析。在100种对OFX敏感的分离株中，有30种是易感性的，28种是单药耐药的，10种是多药耐药的，32种是多药耐药的。在100株抗OFX的菌株中，单抗OFX的19株，多药耐药的16株，MDR的65株。分别在79％和5％的OFX耐药分离株中观察到gyrA和gyrB基因突变。在gyrA基因的QRDR的第94位密码子处发现了最普遍的突变。在gyrA基因以及gyrA和gyrB基因中发现的双突变表示较高水平的OFX耐药性。在一个分离物中，发现在gyrB基因QRDR之外的一个新突变是592位密码子（Pro592Ser）的取代。我们的发现支持以前的研究，即OFX对结核分枝杆菌的抗性与gyrA基因QRDR中的突变有关。但是，可能无法基于gyrA基因的突变模式预测OFX抗性水平。

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