{"title":"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","authors":"Hanieh Bagherifard, Mitra Salehi, Mona Ghazi","doi":"10.3103/s0891416823040092","DOIUrl":null,"url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>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 <i>Mycobacterium tuberculosis</i> 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.</p>","PeriodicalId":19005,"journal":{"name":"Molecular Genetics, Microbiology and Virology","volume":"28 1","pages":""},"PeriodicalIF":0.4000,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Association of Mutations in gyrA Gene with Resistance to Fluoroquinolones in Clinical Isolates of Multidrug-Resistant Mycobacterium tuberculosis\",\"authors\":\"Hanieh Bagherifard, Mitra Salehi, Mona Ghazi\",\"doi\":\"10.3103/s0891416823040092\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<h3 data-test=\\\"abstract-sub-heading\\\">Abstract</h3><p>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 <i>Mycobacterium tuberculosis</i> 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.</p>\",\"PeriodicalId\":19005,\"journal\":{\"name\":\"Molecular Genetics, Microbiology and Virology\",\"volume\":\"28 1\",\"pages\":\"\"},\"PeriodicalIF\":0.4000,\"publicationDate\":\"2024-03-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Molecular Genetics, Microbiology and Virology\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.3103/s0891416823040092\",\"RegionNum\":4,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Genetics, Microbiology and Virology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.3103/s0891416823040092","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Association of Mutations in gyrA Gene with Resistance to Fluoroquinolones in Clinical Isolates of Multidrug-Resistant Mycobacterium tuberculosis
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.
期刊介绍：
Molecular Genetics, Microbiology and Virology is a journal that covers most topical theoretical and applied problems of molecular genetics of pro- and eukaryotic organisms, molecular microbiology and molecular virology. An important part the journal assigns to investigations of the genetic apparatus of microorganisms, searching for forms of genetic exchange, genetic mapping of pathogenic causative agents, to ascertainment of the structure and functions of extrachromosomal factors of heredity and migratory genetic elements, to theoretical studies into the mechanisms of genetic regulation. The journal publishes results of research on molecular and genetic bases of an eukaryotic cell, functioning of chromosomes and chromatin, nature of genetic changes in malignization and a set of hereditary diseases. On the pages of the journal there is covered the formulation of molecular bases of virology including issues of integration of viral and cellular genomes, and issues of persistence. The journal plans to put materials on genetic engineering, envisaging synthesis and isolation of genes from natural reservoirs, creation of plasmid- and virus-based vector, production of recombinant DNA molecules, the creation of Gene Banks for Microbes, animals, and human; and also on biotechnological production of hormones, components of antiviral vaccines, diagnostic and therapeutic preparations.
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