{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T13:44:13Z","timestamp":1790948653216,"version":"4.1.0"},"reference-count":46,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2012,4,1]],"date-time":"2012-04-01T00:00:00Z","timestamp":1333238400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2012,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The inactivation of\n            <jats:italic>ERG3<\/jats:italic>\n            , a gene encoding sterol \u0394\n            <jats:sup>5,6<\/jats:sup>\n            -desaturase (essential for ergosterol biosynthesis), is a known mechanism of\n            <jats:italic>in vitro<\/jats:italic>\n            resistance to azole antifungal drugs in the human pathogen\n            <jats:italic>Candida albicans. ERG3<\/jats:italic>\n            inactivation typically results in loss of filamentation and attenuated virulence in animal models of disseminated candidiasis. In this work, we identified a\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. albicans<\/jats:named-content>\n            clinical isolate (VSY2) with high-level resistance to azole drugs\n            <jats:italic>in vitro<\/jats:italic>\n            and an absence of ergosterol but normal filamentation. Sequencing of\n            <jats:italic>ERG3<\/jats:italic>\n            in VSY2 revealed a double base deletion leading to a premature stop codon and thus a nonfunctional enzyme. The reversion of the double base deletion in the mutant allele (\n            <jats:italic>erg3-1<\/jats:italic>\n            ) restored ergosterol biosynthesis and full fluconazole susceptibility in VSY2, confirming that\n            <jats:italic>ERG3<\/jats:italic>\n            inactivation was the mechanism of azole resistance. Additionally, the replacement of both\n            <jats:italic>ERG3<\/jats:italic>\n            alleles by\n            <jats:italic>erg3-1<\/jats:italic>\n            in the wild-type strain SC5314 led to the absence of ergosterol and to fluconazole resistance without affecting filamentation. In a mouse model of disseminated candidiasis, the clinical\n            <jats:italic>ERG3<\/jats:italic>\n            mutant VSY2 produced kidney fungal burdens and mouse survival comparable to those obtained with the wild-type control. Interestingly, while VSY2 was resistant to fluconazole both\n            <jats:italic>in vitro<\/jats:italic>\n            and\n            <jats:italic>in vivo<\/jats:italic>\n            , the\n            <jats:italic>ERG3<\/jats:italic>\n            -derived mutant of SC5314 was resistant only\n            <jats:italic>in vitro<\/jats:italic>\n            and was less virulent than the wild type. This suggests that VSY2 compensated for the\n            <jats:italic>in vivo<\/jats:italic>\n            fitness defect of\n            <jats:italic>ERG3<\/jats:italic>\n            inactivation by a still unknown mechanism(s). Taken together, our results provide evidence that contrary to previous reports inactivation of\n            <jats:italic>ERG3<\/jats:italic>\n            does not necessarily affect filamentation and virulence.\n          <\/jats:p>","DOI":"10.1128\/aac.05720-11","type":"journal-article","created":{"date-parts":[[2012,1,18]],"date-time":"2012-01-18T05:13:08Z","timestamp":1326863588000},"page":"1960-1968","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":94,"title":["Azole Resistance by Loss of Function of the Sterol \u0394\n            <sup>5,6<\/sup>\n            -Desaturase Gene (\n            <i>ERG3<\/i>\n            ) in Candida albicans Does Not Necessarily Decrease Virulence"],"prefix":"10.1128","volume":"56","author":[{"given":"L. 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L.","family":"Kelly","sequence":"additional","affiliation":[{"name":"Institute of Life Science and College of Medicine, Swansea University, Swansea, Wales, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Pinto","sequence":"additional","affiliation":[{"name":"CEQUIMED-UP, Laboratory of Microbiology, Biological Sciences Department, Faculty of Pharmacy, University of Porto, Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Sanglard","sequence":"additional","affiliation":[{"name":"Institute of Microbiology, University of Lausanne and University Hospital Center, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi900578y"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.00008-07"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.diagmicrobio.2005.03.001"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.3.4.900-909.2004"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.9.3646-3651.2005"},{"key":"e_1_3_3_7_2","unstructured":"Clinical and Laboratory Standards Institute. 2008. 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