Association of Mutations in gyrA Gene with Resistance to Fluoroquinolones in Clinical Isolates of Multidrug-Resistant Mycobacterium tuberculosis

Pub Date : 2024-03-20 DOI:10.3103/s0891416823040092

Hanieh Bagherifard, Mitra Salehi, Mona Ghazi

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Abstract

The purpose of the present study was to evaluate the association of mutations inside and outside quinolone-resistance determining region (QRDR) of gyrA gene with resistance to fluoroquinolones, particularly levofloxacin (LFX), moxifloxacin (MFX), ofloxacin (OFX), and ciprofloxacin (CIP). Therefore, a total of 255 clinical isolates of Mycobacterium tuberculosis were tested for drug susceptibility. Accordingly, 68 multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis strains were subjected to molecular analysis. Mutations were found in 25 (43.1%) of fluoroquinolone-resistant isolates including two rare mutations at codons 93 and 124. We then proceeded to predict the functional and structural impacts of the identified mutations on the protein via PredictSNP, PROVEAN, PoPMuSiC, and HoTMuSiC tools which revealed that they could be deleterious and/or destabilizing to GyrA. Our findings suggest that coupling genetic analysis with computational approaches could be of great value for unraveling molecular mechanisms involved in drug resistance.

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gyrA基因突变与耐多药结核分枝杆菌临床分离株对氟喹诺酮类药物耐药性的关系

摘要本研究的目的是评估gyrA基因耐喹诺酮决定区（QRDR）内外的突变与氟喹诺酮类药物耐药性的相关性，特别是对左氧氟沙星（LFX）、莫西沙星（MFX）、氧氟沙星（OFX）和环丙沙星（CIP）的耐药性。因此，共对 255 株临床分离的结核分枝杆菌进行了药敏试验。因此，对 68 株耐多药（MDR）和广泛耐药（XDR）结核菌株进行了分子分析。在 25 株（43.1%）耐氟喹诺酮的分离株中发现了突变，包括两个位于密码子 93 和 124 的罕见突变。随后，我们通过 PredictSNP、PROVEAN、PoPMuSiC 和 HoTMuSiC 工具预测了所发现的突变对蛋白质功能和结构的影响，结果显示这些突变可能会对 GyrA 造成有害影响和/或破坏其稳定性。我们的研究结果表明，将遗传分析与计算方法相结合，对于揭示耐药性的分子机制具有重要价值。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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