{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T20:32:42Z","timestamp":1784752362223,"version":"3.55.0"},"reference-count":39,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[2019,5,30]],"date-time":"2019-05-30T00:00:00Z","timestamp":1559174400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Microbial Drug Resistance"],"published-print":{"date-parts":[[2019,6,1]]},"abstract":"<jats:p>\n                    <jats:italic toggle=\"yes\">Aspergillus clavatus<\/jats:italic>\n                    is a common environmental species known to cause occupational allergic disease in grain handlers. We have recently observed azole-resistant isolates of this fungus as a cause of onychomycosis. To further characterize the cause of resistance, the genes encoding 14 \u03b1-sterol demethylase enzyme (\n                    <jats:italic toggle=\"yes\">cyp51A<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">cyp51B<\/jats:italic>\n                    ) were characterized and analyzed in 9 ITC-susceptible isolates and 6 isolates with high minimum inhibitory concentrations (MICs) of clinical (nail and sputum) and environmental\n                    <jats:italic toggle=\"yes\">A. clavatus<\/jats:italic>\n                    strains. We found that six isolates with itraconazole MIC &gt;16\u2009mg\/L demonstrated nonsynonymous mutations, including V51I, L378P, E483K, and E506G, and synonymous mutations, including F53F, A186A, Q276Q, and H359H. Moreover, P486S was detected in five strains with ITR MIC &gt;16\u2009mg\/L. One mutation, F324S, was detected in an isolate with posaconazole MIC &gt;16\u2009mg\/L. The effect of E483K and P486S mutations of CYP51A on azole resistance was further investigated using homology modeling and molecular dynamics. We found that E483K and P486S mutations were located near the ligand access channel of CYP51A that could partly lead to narrowing the entry of the ligand access channels. Therefore, we concluded that E483K and P486S mutations may potentially contribute to the limited access of inhibitors to the binding pocket and therefore confer resistance to azole agents.\n                  <\/jats:p>","DOI":"10.1089\/mdr.2018.0300","type":"journal-article","created":{"date-parts":[[2019,1,18]],"date-time":"2019-01-18T11:18:36Z","timestamp":1547810316000},"page":"652-662","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":23,"title":["Novel Point Mutations in\n                    <i>cyp51A<\/i>\n                    and\n                    <i>cyp51B<\/i>\n                    Genes Associated with Itraconazole and Posaconazole Resistance in\n                    <i>Aspergillus clavatus<\/i>\n                    Isolates"],"prefix":"10.1177","volume":"25","author":[{"given":"Mahdi","family":"Abastabar","sequence":"first","affiliation":[{"name":"Invasive Fungi Research Center (IFRC), School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran."},{"name":"Department of Medical Mycology, Mazandaran University of Medical Sciences, Sari, Iran."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tahereh","family":"Hosseini","sequence":"additional","affiliation":[{"name":"Student Research Committee, Mazandaran University of Medical Sciences, Sari, Iran."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reza","family":"Valadan","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran."},{"name":"Molecular and Cell Biology Research Center, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milad","family":"Lagzian","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Science, University of Sistan and Baluchestan, Zahedan, Iran."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iman","family":"Haghani","sequence":"additional","affiliation":[{"name":"Invasive Fungi Research Center (IFRC), School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran."},{"name":"Department of Medical Mycology, Mazandaran University of Medical Sciences, Sari, Iran."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Narges","family":"Aslani","sequence":"additional","affiliation":[{"name":"Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamid","family":"Badali","sequence":"additional","affiliation":[{"name":"Invasive Fungi Research Center (IFRC), School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran."},{"name":"Department of Medical Mycology, Mazandaran University of Medical Sciences, Sari, Iran."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sadegh","family":"Nouripour-Sisakht","sequence":"additional","affiliation":[{"name":"Medicinal Plants Research Center, Yasuj University of Medical Sciences, Yasuj, Iran."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehdi","family":"Nazeri","sequence":"additional","affiliation":[{"name":"Medical Parasitology and Mycology Department, Kashan University of Medical Sciences, Kashan, Iran."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Gholami","sequence":"additional","affiliation":[{"name":"Department of Medical Mycology, Mazandaran University of Medical Sciences, Sari, Iran."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahshid","family":"Vakili","sequence":"additional","affiliation":[{"name":"Student Research Committee, Mazandaran University of Medical Sciences, Sari, Iran."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Bowyer","sequence":"additional","affiliation":[{"name":"Manchester Fungal Infection Group, Division of Infection Immunity and Respiratory Medicine, School of Biological Sciences, University of Manchester, Manchester, United Kingdom."},{"name":"Manchester Academic Health Science Centre, University NHS Foundation Trust (Wythenshawe), Manchester, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tahereh","family":"Shokohi","sequence":"additional","affiliation":[{"name":"Invasive Fungi Research Center (IFRC), School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran."},{"name":"Department of Medical Mycology, Mazandaran University of Medical Sciences, Sari, Iran."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad T.","family":"Hedayati","sequence":"additional","affiliation":[{"name":"Invasive Fungi Research Center (IFRC), School of 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