{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T05:56:58Z","timestamp":1790661418708,"version":"4.1.0"},"posted":{"date-parts":[[2023,6,17]]},"group-title":"Microbiology","reference-count":35,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,6,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  <jats:italic>Candida albicans<\/jats:italic>\n                  is a diploid human fungal pathogen that displays significant genomic and phenotypic heterogeneity over a range of virulence traits and in the context of a variety of environmental niches. Here, we show that the effects of Rob1 on biofilm and filamentation virulence traits is dependent on both the specific environmental condition and the clinical strain of\n                  <jats:italic>C. albicans<\/jats:italic>\n                  . The\n                  <jats:italic>C. albicans<\/jats:italic>\n                  reference strain SC5314 is a\n                  <jats:italic>ROB1<\/jats:italic>\n                  heterozygote with two alleles that differ by a single nucleotide polymorphism at position 946 resulting in a serine or proline containing isoform. An analysis of 224 sequenced\n                  <jats:italic>C. albicans<\/jats:italic>\n                  genomes indicates that SC5314 is the only\n                  <jats:italic>ROB1<\/jats:italic>\n                  heterozygote documented to date and that the dominant allele contains a proline at position 946. Remarkably, the\n                  <jats:italic>ROB1<\/jats:italic>\n                  alleles are functionally distinct and the rare\n                  <jats:italic>\n                    ROB1\n                    <jats:sup>946S<\/jats:sup>\n                  <\/jats:italic>\n                  allele supports increased filamentation in vitro and increased biofilm formation in vitro and in vivo, suggesting it is a phenotypic gain-of-function allele. SC5314 is amongst the most highly filamentous and invasive strains characterized to date. Introduction of the\n                  <jats:italic>\n                    ROB1\n                    <jats:sup>946S<\/jats:sup>\n                  <\/jats:italic>\n                  allele into a poorly filamenting clinical isolate increases filamentation and conversion of an SC5314 laboratory strain to a\n                  <jats:italic>\n                    ROB1\n                    <jats:sup>946S<\/jats:sup>\n                  <\/jats:italic>\n                  homozygote increases in vitro filamentation and biofilm formation. In a mouse model of oropharyngeal infection, the predominant\n                  <jats:italic>\n                    ROB1\n                    <jats:sup>946P<\/jats:sup>\n                  <\/jats:italic>\n                  allele establishes a commensal state while the\n                  <jats:italic>\n                    ROB1\n                    <jats:sup>946S<\/jats:sup>\n                  <\/jats:italic>\n                  phenocopies the parent strain and invades into the mucosae. These observations provide an explanation for the distinct phenotypes of SC5314 and highlight the role of heterozygosity as a driver of\n                  <jats:italic>C. albicans<\/jats:italic>\n                  phenotypic heterogeneity.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Importance<\/jats:title>\n                  <jats:p>\n                    <jats:italic>Candida albicans<\/jats:italic>\n                    is a commensal fungus that colonizes human oral cavity and gastrointestinal tracts but also causes mucosal as well as invasive disease. The expression of virulence traits in\n                    <jats:italic>C. albicans<\/jats:italic>\n                    clinical isolates is heterogenous and the genetic basis of this heterogeneity is of high interest. The\n                    <jats:italic>C. albicans<\/jats:italic>\n                    reference strain SC5314 is highly invasive and expresses robust filamentation and biofilm formation relative to many other clinical isolates. Here, we show that SC5314 derivatives are heterozygous for the transcription factor Rob1 and contain an allele with a rare gain-of-function SNP that drives filamentation, biofilm formation, and virulence in a model of oropharyngeal candidiasis. These finding explain, in part, the outlier phenotype of the reference strain and highlight the role of heterozygosity plays in the strain-to-strain variation of diploid fungal pathogens.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2023.06.17.545405","type":"posted-content","created":{"date-parts":[[2023,6,18]],"date-time":"2023-06-18T02:45:11Z","timestamp":1687056311000},"source":"Crossref","is-referenced-by-count":5,"title":["The\n                  <i>Candida albicans<\/i>\n                  reference strain SC5314 contains a rare, dominant allele of the transcription factor Rob1 that modulates biofilm formation and oral commensalism"],"prefix":"10.64898","author":[{"given":"Virginia E.","family":"Glazier","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juraj","family":"Kramara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomye","family":"Ollinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norma V.","family":"Solis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Zarnowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rohan S.","family":"Wakade","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min-Ju","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel J.","family":"Weigel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shen-Huan","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7563-484X","authenticated-orcid":false,"given":"Richard J.","family":"Bennett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Wellington","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7927-9950","authenticated-orcid":false,"given":"David R.","family":"Andes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark A.","family":"Stamnes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7278-3700","authenticated-orcid":false,"given":"Scott G.","family":"Filler","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":"2023062014450470000_2023.06.17.545405v1.1","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1080\/21505594.2021.2019950","article-title":"Pathogenesis and virulence of Candida albicans","volume":"13","year":"2022","journal-title":"Virulence"},{"key":"2023062014450470000_2023.06.17.545405v1.2","first-page":"15","article-title":"Oral candidiasis: a disease of opportunity","volume":"16","year":"2020","journal-title":"J Fungi"},{"key":"2023062014450470000_2023.06.17.545405v1.3","doi-asserted-by":"crossref","first-page":"18026","DOI":"10.1038\/nrdp.2018.26","article-title":"Invasive candidiasis","volume":"4","year":"2018","journal-title":"Nat Rev Dis Primers"},{"key":"2023062014450470000_2023.06.17.545405v1.4","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2636"},{"key":"2023062014450470000_2023.06.17.545405v1.5","first-page":"e1010012","volume":"18","year":"2022","journal-title":"Candida albicans commensalism in the oral mucosa is favoured by limited virulence and metabolic adaptation. 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