{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T10:25:51Z","timestamp":1790504751016,"version":"4.1.0"},"posted":{"date-parts":[[2023,12,15]]},"group-title":"Microbiology","reference-count":23,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,12,15]]},"abstract":"<jats:title>Abstract<\/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 disease in humans. Its ability to cause disease has been closely linked to its ability to undergo a morphological transition from budding yeast to filamentous forms (hyphae and pseudohyphae). The ability of\n                  <jats:italic>C. albicans<\/jats:italic>\n                  strains isolated from patients to 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, in vitro and in vivo filamentation, and in vitro and in vivo hypha-associated gene expression profiles of 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 in vivo filamentation while remaining predominately yeast phase exposed to RPMI+10% bovine calf serum at 37\u00b0C; the two low virulence strains (94015 and 78042) do not filament well under either condition. 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 in vivo. Deletion of\n                  <jats:italic>NRG1<\/jats:italic>\n                  modestly increased the virulence of 78042 which was accompanied by increased expression of hyphae-associated genes without an increase in filamentation. Strikingly, deletion of\n                  <jats:italic>NRG1<\/jats:italic>\n                  in 78048 reduced filamentation, expression of candidalysin (\n                  <jats:italic>ECE1<\/jats:italic>\n                  ) and virulence in vivo without dramatically altering establishment of infection. Thus, the function of\n                  <jats:italic>NRG1<\/jats:italic>\n                  varies significantly within this set of\n                  <jats:italic>C. albicans<\/jats:italic>\n                  isolates and can actually suppress filamentation in vivo.\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 in vitro 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 background.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2023.12.15.571891","type":"posted-content","created":{"date-parts":[[2023,12,16]],"date-time":"2023-12-16T01:50:15Z","timestamp":1702691415000},"source":"Crossref","is-referenced-by-count":2,"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":"10.64898","author":[{"given":"Rohan S.","family":"Wakade","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Wellington","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6330-3365","authenticated-orcid":false,"given":"Damian J.","family":"Krysan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2023121910001392000_2023.12.15.571891v1.1","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/j.chom.2023.02.010","article-title":"One population, multiple lifestyles: commensalism and pathogenesis in the human mycobiome","volume":"31","year":"2023","journal-title":"Cell Host 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commensalism","volume":"14","year":"2023","journal-title":"mBio"},{"key":"2023121910001392000_2023.12.15.571891v1.15","doi-asserted-by":"crossref","first-page":"e85114","DOI":"10.7554\/eLife.85114","article-title":"Intravital imaging-based genetic screen reveals the transcriptional network governing Candida albicans filamentation during mammalian 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