{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:12:27Z","timestamp":1791295947409,"version":"4.1.0"},"reference-count":45,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2015,1,1]],"date-time":"2015-01-01T00:00:00Z","timestamp":1420070400000},"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":[[2015,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    In\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Candida albicans<\/jats:named-content>\n                    , the\n                    <jats:italic>ERG11<\/jats:italic>\n                    gene encodes lanosterol demethylase, the target of the azole antifungals. Mutations in\n                    <jats:italic>ERG11<\/jats:italic>\n                    that result in an amino acid substitution alter the abilities of the azoles to bind to and inhibit Erg11, resulting in resistance. Although\n                    <jats:italic>ERG11<\/jats:italic>\n                    mutations have been observed in clinical isolates, the specific contributions of individual\n                    <jats:italic>ERG11<\/jats:italic>\n                    mutations to azole resistance in\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                    have not been widely explored. We sequenced\n                    <jats:italic>ERG11<\/jats:italic>\n                    in 63 fluconazole (FLC)-resistant clinical isolates. Fifty-five isolates carried at least one mutation in\n                    <jats:italic>ERG11<\/jats:italic>\n                    , and we observed 26 distinct positions in which amino acid substitutions occurred. We mapped the 26 distinct variant positions in these alleles to four regions in the predicted structure for Erg11, including its predicted catalytic site, extended fungus-specific external loop, proximal surface, and proximal surface-to-heme region. In total, 31 distinct\n                    <jats:italic>ERG11<\/jats:italic>\n                    alleles were recovered, with 10\n                    <jats:italic>ERG11<\/jats:italic>\n                    alleles containing a single amino acid substitution. We then characterized 19 distinct\n                    <jats:italic>ERG11<\/jats:italic>\n                    alleles by introducing them into the wild-type azole-susceptible\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                    SC5314 strain and testing them for susceptibilities to FLC, itraconazole (ITC), and voriconazole (VRC). The strains that were homozygous for the single amino acid substitutions Y132F, K143R, F145L, S405F, D446E, G448E, F449V, G450E, and G464S had a \u22654-fold increase in FLC MIC. The strains that were homozygous for several double amino acid substitutions had decreased azole susceptibilities beyond those conferred by any single amino acid substitution. These findings indicate that mutations in\n                    <jats:italic>ERG11<\/jats:italic>\n                    are prevalent among azole-resistant clinical isolates and that most mutations result in appreciable changes in FLC and VRC susceptibilities.\n                  <\/jats:p>","DOI":"10.1128\/aac.03470-14","type":"journal-article","created":{"date-parts":[[2014,11,11]],"date-time":"2014-11-11T00:42:42Z","timestamp":1415666562000},"page":"450-460","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":297,"title":["Contribution of Clinically Derived Mutations in\n                    <i>ERG11<\/i>\n                    to Azole Resistance in Candida albicans"],"prefix":"10.1128","volume":"59","author":[{"given":"Stephanie A.","family":"Flowers","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brendan","family":"Col\u00f3n","sequence":"additional","affiliation":[{"name":"Department of Cell and Developmental Biology, University of Illinois, Urbana, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah G.","family":"Whaley","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary A.","family":"Schuler","sequence":"additional","affiliation":[{"name":"Department of Cell and Developmental Biology, University of Illinois, Urbana, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. 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