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

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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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Funding

This work was supported by ongoing institutional funding. No additional grants to carry out or direct this particular research were obtained.

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Authors and Affiliations

  1. Department of Microbiology, Faculty of Biological Sciences, North Tehran Branch, Islamic Azad University, Tehran, Iran

    Hanieh Bagherifard & Mitra Salehi

  2. Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Mona Ghazi

Authors
  1. Hanieh Bagherifard
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  2. Mitra Salehi
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  3. Mona Ghazi
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Correspondence to Mitra Salehi.

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Bagherifard, H., Salehi, M. & Ghazi, M. Association of Mutations in gyrA Gene with Resistance to Fluoroquinolones in Clinical Isolates of Multidrug-Resistant Mycobacterium tuberculosis. Mol. Genet. Microbiol. Virol. 38, 264–268 (2023). https://doi.org/10.3103/S0891416823040092

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  • DOI: https://doi.org/10.3103/S0891416823040092

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