{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T05:58:51Z","timestamp":1788501531688,"version":"build-2803163510"},"update-to":[{"DOI":"10.1371\/journal.ppat.1012225","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,5,23]],"date-time":"2024-05-23T00:00:00Z","timestamp":1716422400000}}],"reference-count":64,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T00:00:00Z","timestamp":1715558400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH\/NIAID","award":["R01 AI146103"],"award-info":[{"award-number":["R01 AI146103"]}]},{"name":"NIH\/NIAID","award":["R01 AI073289"],"award-info":[{"award-number":["R01 AI073289"]}]},{"name":"NIH\/NIAID","award":["R01 AI125770"],"award-info":[{"award-number":["R01 AI125770"]}]},{"DOI":"10.13039\/100007699","name":"University of Georgia","doi-asserted-by":"crossref","award":["Startup funds"],"award-info":[{"award-number":["Startup funds"]}],"id":[{"id":"10.13039\/100007699","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Biofilm formation by the fungal pathogen <jats:italic>Candida albicans<\/jats:italic> is the basis for its ability to infect medical devices. The metabolic gene <jats:italic>ERG251<\/jats:italic> has been identified as a target of biofilm transcriptional regulator Efg1, and here we report that <jats:italic>ERG251<\/jats:italic> is required for biofilm formation but not conventional free-living planktonic growth. An <jats:italic>erg251<\/jats:italic>\u0394\/\u0394 mutation impairs biofilm formation <jats:italic>in vitro<\/jats:italic> and in an <jats:italic>in vivo<\/jats:italic> catheter infection model. In both <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> biofilm contexts, cell number is reduced and hyphal length is limited. To determine whether the mutant defect is in growth or some other aspect of biofilm development, we examined planktonic cell features in a biofilm-like environment, which was approximated with sealed unshaken cultures. Under those conditions, the <jats:italic>erg251<\/jats:italic>\u0394\/\u0394 mutation causes defects in growth and hyphal extension. Overexpression in the <jats:italic>erg251<\/jats:italic>\u0394\/\u0394 mutant of the paralog <jats:italic>ERG25<\/jats:italic>, which is normally expressed more weakly than <jats:italic>ERG251<\/jats:italic>, partially improves biofilm formation and biofilm hyphal content, as well as growth and hyphal extension in a biofilm-like environment. GC-MS analysis shows that the <jats:italic>erg251<\/jats:italic>\u0394\/\u0394 mutation causes a defect in ergosterol accumulation when cells are cultivated under biofilm-like conditions, but not under conventional planktonic conditions. Overexpression of <jats:italic>ERG25<\/jats:italic> in the <jats:italic>erg251<\/jats:italic>\u0394\/\u0394 mutant causes some increase in ergosterol levels. Finally, the hypersensitivity of <jats:italic>efg1<\/jats:italic>\u0394\/\u0394 mutants to the ergosterol inhibitor fluconazole is reversed by <jats:italic>ERG251<\/jats:italic> overexpression, arguing that reduced <jats:italic>ERG251<\/jats:italic> expression contributes to this <jats:italic>efg1<\/jats:italic>\u0394\/\u0394 phenotype. Our results indicate that <jats:italic>ERG251<\/jats:italic> is required for biofilm formation because its high expression levels are necessary for ergosterol synthesis in a biofilm-like environment.<\/jats:p>","DOI":"10.1371\/journal.ppat.1012225","type":"journal-article","created":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T17:40:38Z","timestamp":1715622038000},"page":"e1012225","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":20,"title":["Biofilm-associated metabolism via ERG251 in Candida albicans"],"prefix":"10.1371","volume":"20","author":[{"given":"Liping","family":"Xiong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nivea","family":"Pereira De 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