{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T14:49:47Z","timestamp":1790434187353,"version":"4.1.0"},"reference-count":36,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2017,9,1]],"date-time":"2017-09-01T00:00:00Z","timestamp":1504224000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01 AI058145"],"award-info":[{"award-number":["R01 AI058145"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2017,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Among emerging non-\n            <jats:named-content content-type=\"genus-species\">albicans Candida<\/jats:named-content>\n            species,\n            <jats:named-content content-type=\"genus-species\">Candida parapsilosis<\/jats:named-content>\n            is of particular concern as a cause of nosocomial bloodstream infections in neonatal and intensive care unit patients. While fluconazole and echinocandins are considered effective treatments for such infections, recent reports of fluconazole and echinocandin resistance in\n            <jats:named-content content-type=\"genus-species\">C. parapsilosis<\/jats:named-content>\n            indicate a growing problem. The present study describes a novel mechanism of antifungal resistance in this organism affecting susceptibility to azole and echinocandin antifungals in a clinical isolate obtained from a patient with prosthetic valve endocarditis. Transcriptome analysis indicated differential expression of several genes in the resistant isolate, including upregulation of ergosterol biosynthesis pathway genes\n            <jats:italic>ERG2<\/jats:italic>\n            ,\n            <jats:italic>ERG5<\/jats:italic>\n            ,\n            <jats:italic>ERG6<\/jats:italic>\n            ,\n            <jats:italic>ERG11<\/jats:italic>\n            ,\n            <jats:italic>ERG24<\/jats:italic>\n            ,\n            <jats:italic>ERG25<\/jats:italic>\n            , and\n            <jats:italic>UPC2<\/jats:italic>\n            . Whole-genome sequencing revealed that the resistant isolate possessed an\n            <jats:italic>ERG3<\/jats:italic>\n            mutation resulting in a G111R amino acid substitution. Sterol profiles indicated a reduction in sterol desaturase activity as a result of this mutation. Replacement of both mutant alleles in the resistant isolate with the susceptible isolate's allele restored wild-type susceptibility to all azoles and echinocandins tested. Disruption of\n            <jats:italic>ERG3<\/jats:italic>\n            in the susceptible and resistant isolates resulted in a loss of sterol desaturase activity, high-level azole resistance, and an echinocandin-intermediate to -resistant phenotype. While disruption of\n            <jats:italic>ERG3<\/jats:italic>\n            in\n            <jats:named-content content-type=\"genus-species\">C. albicans<\/jats:named-content>\n            resulted in azole resistance, echinocandin MICs, while elevated, remained within the susceptible range. This work demonstrates that the G111R substitution in Erg3 is wholly responsible for the altered azole and echinocandin susceptibilities observed in this\n            <jats:named-content content-type=\"genus-species\">C. parapsilosis<\/jats:named-content>\n            isolate and is the first report of an\n            <jats:italic>ERG3<\/jats:italic>\n            mutation influencing susceptibility to the echinocandins.\n          <\/jats:p>","DOI":"10.1128\/aac.00651-17","type":"journal-article","created":{"date-parts":[[2017,6,20]],"date-time":"2017-06-20T00:30:28Z","timestamp":1497918628000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":55,"title":["Loss of C-5 Sterol Desaturase Activity Results in Increased Resistance to Azole and Echinocandin Antifungals in a Clinical Isolate of Candida parapsilosis"],"prefix":"10.1128","volume":"61","author":[{"given":"Jeffrey M.","family":"Rybak","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy, College of Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. Michael","family":"Dickens","sequence":"additional","affiliation":[{"name":"W. Harry Feinstone Center for Genomic Research, University of Memphis, Memphis, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josie E.","family":"Parker","sequence":"additional","affiliation":[{"name":"Institute of Life Science, Swansea University Medical School, Swansea, Wales, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly E.","family":"Caudle","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, College of Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kayihura","family":"Manigaba","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, College of Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah G.","family":"Whaley","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, College of Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew T.","family":"Nishimoto","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, College of Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arturo","family":"Luna-Tapia","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, College of Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sujoy","family":"Roy","sequence":"additional","affiliation":[{"name":"Fungus Testing Laboratory, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, College of Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine S.","family":"Barker","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, College of Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glen E.","family":"Palmer","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, College of Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas R.","family":"Sutter","sequence":"additional","affiliation":[{"name":"W. 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