{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T16:01:21Z","timestamp":1790179281542,"version":"4.1.0"},"reference-count":36,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2022,7,12]],"date-time":"2022-07-12T00:00:00Z","timestamp":1657584000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"\n This study was designed to understand the molecular mechanisms of azole resistance in\n Candida tropicalis<\/jats:italic>\n using genetic and bioinformatics approaches. Thirty-two azole-resistant and 10 azole-susceptible (S) clinical isolates of\n C<\/jats:italic>\n .\n tropicalis<\/jats:italic>\n were subjected to mutation analysis of the azole target genes including\n ERG11<\/jats:italic>\n . Inducible expression analysis of 17 other genes potentially associated with azole resistance was also evaluated. Homology modeling and molecular docking analysis were performed to study the effect of amino acid alterations in mediating azole resistance. Of the 32 resistant isolates, 12 (37.5%) showed A395T and C461T mutations in the\n ERG11<\/jats:italic>\n gene. The mean overexpression of\n CDR1<\/jats:italic>\n ,\n CDR3<\/jats:italic>\n ,\n TAC1<\/jats:italic>\n ,\n ERG1<\/jats:italic>\n ,\n ERG2<\/jats:italic>\n ,\n ERG3<\/jats:italic>\n ,\n ERG11<\/jats:italic>\n ,\n UPC2<\/jats:italic>\n , and\n MKC1<\/jats:italic>\n in resistant isolates without mutation (R-WTM) was significantly higher (p<0.05) than those with mutation (R-WM) and the sensitive isolates (3.2\u201311 vs. 0.2\u20132.5 and 0.3\u20132.2 folds, respectively). Although the R-WTM and R-WM had higher (p<0.05)\n CDR2<\/jats:italic>\n and\n MRR1<\/jats:italic>\n expression compared to S isolates, noticeable variation was not seen among the other genes. Protein homology modelling and molecular docking revealed that the mutations in the\n ERG11<\/jats:italic>\n gene were responsible for structural alteration and low binding efficiency between ERG11p and ligands. Isolates with\n ERG11<\/jats:italic>\n mutations also presented A220C in\n ERG1<\/jats:italic>\n and together T503C, G751A mutations in\n UPC2<\/jats:italic>\n . Nonsynonymous mutations in the\n ERG11<\/jats:italic>\n gene and coordinated overexpression of various genes including different transporters, ergosterol biosynthesis pathway, transcription factors, and stress-responsive genes are associated with azole resistance in clinical isolates of\n C<\/jats:italic>\n .\n tropicalis<\/jats:italic>\n .\n <\/jats:p>","DOI":"10.1371\/journal.pone.0269721","type":"journal-article","created":{"date-parts":[[2022,7,12]],"date-time":"2022-07-12T13:31:58Z","timestamp":1657632718000},"page":"e0269721","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":50,"title":["Mechanisms of azole antifungal resistance in clinical isolates of Candida tropicalis"],"prefix":"10.1371","volume":"17","author":[{"given":"Saikat","family":"Paul","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dipika","family":"Shaw","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Himanshu","family":"Joshi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shreya","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arunaloke","family":"Chakrabarti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9097-9253","authenticated-orcid":true,"given":"Shivaprakash M.","family":"Rudramurthy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0341-6680","authenticated-orcid":true,"given":"Anup K.","family":"Ghosh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,7,12]]},"reference":[{"key":"pone.0269721.ref001","doi-asserted-by":"crossref","first-page":"2173","DOI":"10.3389\/fmicb.2016.02173","article-title":"Azole Antifungal Resistance in Candida albicans and Emerging Non-albicans Candida Species","volume":"7","author":"SG Whaley","year":"2017","journal-title":"Front Microbiol"},{"key":"pone.0269721.ref002","doi-asserted-by":"crossref","first-page":"e383","DOI":"10.1016\/S1473-3099(17)30316-X","article-title":"The global problem of antifungal resistance: prevalence, mechanisms, and management","volume":"17","author":"DS Perlin","year":"2017","journal-title":"The 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