{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T17:05:26Z","timestamp":1784307926200,"version":"3.55.0"},"reference-count":72,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2019,7,7]],"date-time":"2019-07-07T00:00:00Z","timestamp":1562457600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Helicobacter"],"published-print":{"date-parts":[[2019,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Fluoroquinolones hinder bacterial DNA replication by inhibiting DNA gyrase. However, mutations, in the QRDR segment of its A subunit (GyrA), cause antibiotic resistance. Here, the interactions of levofloxacin (LVX), gemifloxacin (GXN), and moxifloxacin (MXN) with <jats:italic>Helicobacter pylori<\/jats:italic> GyrA, in LVX\u2010resistant vs \u2010sensitive strains, were studied.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Levoflixacin\u2010sensitive (n\u00a0=\u00a04) and \u2010resistant (n\u00a0=\u00a09) <jats:italic>H\u00a0pylori<\/jats:italic> strains, randomly selected from another antibiotic susceptibility study, underwent PCR amplification of <jats:italic>gyrA<\/jats:italic> gene, spanning the QRDR segment. The amplified gene fragments were sequenced and aligned. The homology model of <jats:italic>H\u00a0pylori<\/jats:italic> GyrA was built based on that of <jats:italic>Escherichia coli,<\/jats:italic> and energy minimization was done. The interaction patterns of LVX, GXN, and MXN with GyrA were analyzed <jats:italic>via<\/jats:italic> molecular docking studies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Sequence alignment of the 13 studied strains, created 5 categories of strains: (A) wild type\u2010like (<jats:italic>H pylori<\/jats:italic> ATCC26695), (B) N87K\u2010only, (C) D91N\u2010only, (D) N87K\u00a0+\u00a0V94L, and (E) D91N\u00a0+\u00a0A97V mutations. The minimum inhibitory concentrations (MIC) for LVX\u2010sensitive (category A) and \u2010resistant (categories B\u2010E) strains were &lt;1\u00a0mg\/L and \u226532\u00a0mg\/L, respectively. The binding mode of GyrA in category A with LVX identified G35\/N87\/Y90\/D91\/V94\/G114\/S115\/I116\/D117\/G118\/D119, as key residues, some residing outside the QRDR segment. Category B strains lost only one interaction (G35), which led to elevated binding free energy (\u2206G) and full LVX resistance. Categories C\u2010E lost more contacts, with higher \u2206G and again full LVX resistance. GXN bound to GyrA of categories A and B <jats:italic>via<\/jats:italic> a different set of key residues, while MXN retained the lost contact (G35) in LVX\u2010resistant, category B strains.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Using molecular docking tools, we identified the key residues responsible for interaction of GyrA with LVX, GXN, and MXN. In the presence of N87K\u2010only mutation, the loss of one of these contacts (ie, G35) led to full LVX resistance. Yet, GXN and MXN overcame this mutation, by retaining all key contacts with GyrA.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hel.12628","type":"journal-article","created":{"date-parts":[[2019,7,8]],"date-time":"2019-07-08T06:54:59Z","timestamp":1562568899000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["New insights into resistance of <i>Helicobacter pylori<\/i> against third\u2010 and fourth\u2010generation fluoroquinolones: A molecular docking study of prevalent GyrA mutations"],"prefix":"10.1111","volume":"24","author":[{"given":"Najmeh","family":"Salehi","sequence":"first","affiliation":[{"name":"Department of Bioinformatics, Institute of Biochemistry and Biophysics University of Tehran Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bahareh","family":"Attaran","sequence":"additional","affiliation":[{"name":"HPGC Research Group, Department of Medical Biotechnology Pasteur Institute of Iran Tehran Iran"},{"name":"Department of Microbiology, Faculty of Biology Alzahra University Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Negin","family":"Eskini","sequence":"additional","affiliation":[{"name":"HPGC Research Group, Department of Medical Biotechnology Pasteur Institute of Iran Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryam","family":"Esmaeili","sequence":"additional","affiliation":[{"name":"HPGC Research Group, Department of Medical Biotechnology Pasteur Institute of Iran Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atefeh","family":"Sharifirad","sequence":"additional","affiliation":[{"name":"HPGC Research Group, Department of Medical Biotechnology Pasteur Institute of Iran Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehdi","family":"Sadeghi","sequence":"additional","affiliation":[{"name":"National Institute for Genetic Engineering and Biotechnology Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4970-3455","authenticated-orcid":false,"given":"Marjan","family":"Mohammadi","sequence":"additional","affiliation":[{"name":"HPGC Research Group, Department of Medical Biotechnology Pasteur Institute of Iran Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,7,7]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2017.04.022"},{"key":"e_1_2_7_3_1","volume-title":"Helicobacter Pylori","author":"Parikh 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