{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T21:17:06Z","timestamp":1784668626060,"version":"3.55.0"},"reference-count":25,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2024,3,26]],"date-time":"2024-03-26T00:00:00Z","timestamp":1711411200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,3,26]],"date-time":"2024-03-26T00:00:00Z","timestamp":1711411200000},"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":"crossref","award":["R01AI133409"],"award-info":[{"award-number":["R01AI133409"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mSphere"],"published-print":{"date-parts":[[2024,3,26]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              <jats:italic>Candida albicans<\/jats:italic>\n              is one of the most common causes of superficial and invasive fungal diseases in humans. Its ability to cause disease is closely linked to its ability to undergo a morphological transition from budding yeast to filamentous forms (hyphae and pseudohyphae). The extent to which\n              <jats:italic>C. albicans<\/jats:italic>\n              strains isolated from patients undergo filamentation varies significantly. In addition, the filamentation phenotypes of mutants involving transcription factors that positively regulate hyphal morphogenesis can also vary from strain to strain. Here, we characterized the virulence,\n              <jats:italic>in vitro<\/jats:italic>\n              and\n              <jats:italic>in vivo<\/jats:italic>\n              filamentation, and\n              <jats:italic>in vitro<\/jats:italic>\n              and\n              <jats:italic>in vivo<\/jats:italic>\n              hypha-associated gene expression profiles for four poorly filamenting\n              <jats:italic>C. albicans<\/jats:italic>\n              isolates and their corresponding deletion mutants of the repressor of filamentation\n              <jats:italic>NRG1<\/jats:italic>\n              . The two most virulent strains, 57055 and 78048, show robust\n              <jats:italic>in vivo<\/jats:italic>\n              filamentation but are predominately yeast phase under\n              <jats:italic>in vitro<\/jats:italic>\n              hypha induction; the two low-virulence strains (94015 and 78042) do not undergo filamentation well under either condition.\n              <jats:italic>In vitro<\/jats:italic>\n              , deletion of\n              <jats:italic>NRG1<\/jats:italic>\n              increases hyphae formation in the SC5314 derivative SN250, but only pseudohyphae are formed in the clinical isolates. Deletion of\n              <jats:italic>NRG1<\/jats:italic>\n              modestly increased the virulence of 78042, which was accompanied by increased expression of hypha-associated genes without an increase in filamentation. Strikingly, deletion of\n              <jats:italic>NRG1<\/jats:italic>\n              in 78048 reduced filamentation\n              <jats:italic>in vivo<\/jats:italic>\n              , expression of candidalysin (\n              <jats:italic>ECE1<\/jats:italic>\n              ), and virulence without dramatically altering establishment of infection. Thus, the function of the conserved repressor\n              <jats:italic>NRG1<\/jats:italic>\n              in\n              <jats:italic>C. albicans<\/jats:italic>\n              shows strain-based heterogeneity during infection.\n            <\/jats:p>\n            <jats:sec>\n              <jats:title>IMPORTANCE<\/jats:title>\n              <jats:p>\n                Clinical isolates of the human fungal pathogen\n                <jats:italic>Candida albicans<\/jats:italic>\n                show significant variation in their ability to undergo\n                <jats:italic>in vitro<\/jats:italic>\n                filamentation and in the function of well-characterized transcriptional regulators of filamentation. Here, we show that Nrg1, a key repressor of filamentation and filament specific gene expression in standard reference strains, has strain-dependent functions, particularly during infection. Most strikingly, loss of\n                <jats:italic>NRG1<\/jats:italic>\n                function can reduce filamentation, hypha-specific gene expression such as the toxin candidalysin, and virulence in some strains. Our data emphasize that the functions of seemingly fundamental and well-conserved transcriptional regulators such as Nrg1 are contextual with respect to both environment and genetic backgrounds.\n              <\/jats:p>\n            <\/jats:sec>\n          <\/jats:sec>","DOI":"10.1128\/msphere.00785-23","type":"journal-article","created":{"date-parts":[[2024,2,20]],"date-time":"2024-02-20T14:04:53Z","timestamp":1708437893000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":11,"title":["The role of the\n            <i>C. albicans<\/i>\n            transcriptional repressor\n            <i>NRG1<\/i>\n            during filamentation and disseminated candidiasis is strain dependent"],"prefix":"10.1128","volume":"9","author":[{"given":"Rohan S.","family":"Wakade","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Wellington","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6330-3365","authenticated-orcid":true,"given":"Damian J.","family":"Krysan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA"},{"name":"Department of Molecular Physiology and Biophysics, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2023.02.010"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2636"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/femsyr\/foaa005"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.174623.114"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1007787"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.01937-22"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2007.05759.x"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3001822"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/mSphere.00436-21"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.17.4753"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.17.4742"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002663"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.2.5.1053-1060.2003"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.01521-23"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.85114"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.27663-0"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e07-11-1110"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature17625"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiz322"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2019.02.008"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1010012"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000783"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/mSphere.00130-16"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0100390"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.3791\/64258"}],"container-title":["mSphere"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/msphere.00785-23","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/msphere.00785-23","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,5]],"date-time":"2024-04-05T01:35:38Z","timestamp":1712280938000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/msphere.00785-23"}},"subtitle":[],"editor":[{"given":"J. Andrew","family":"Alspaugh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,3,26]]},"references-count":25,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2024,3,26]]}},"alternative-id":["10.1128\/msphere.00785-23"],"URL":"https:\/\/doi.org\/10.1128\/msphere.00785-23","relation":{},"ISSN":["2379-5042"],"issn-type":[{"value":"2379-5042","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,26]]},"assertion":[{"value":"2023-12-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-01-26","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-20","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00785-23"}}