{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T07:06:16Z","timestamp":1792307176796,"version":"4.4.0"},"reference-count":35,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T00:00:00Z","timestamp":1698710400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T00:00:00Z","timestamp":1698710400000},"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":["F32AI26634"],"award-info":[{"award-number":["F32AI26634"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["R01AI073289"],"award-info":[{"award-number":["R01AI073289"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["R01AI141893"],"award-info":[{"award-number":["R01AI141893"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["R01AI081704"],"award-info":[{"award-number":["R01AI081704"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["R01DE026600"],"award-info":[{"award-number":["R01DE026600"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"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":["mBio"],"published-print":{"date-parts":[[2023,10,31]]},"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 effect 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\n                    <jats:italic>in vitro<\/jats:italic>\n                    and increased biofilm formation\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    , suggesting it is a phenotypic gain-of-function allele. SC5314 is among 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\n                    <jats:italic>in vitro<\/jats:italic>\n                    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 the human oral cavity and gastrointestinal tract 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 heterogeneous 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 findings explain, in part, the outlier phenotype of the reference strain and highlight the role heterozygosity plays in the strain-to-strain variation of diploid fungal pathogens.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/mbio.01521-23","type":"journal-article","created":{"date-parts":[[2023,9,22]],"date-time":"2023-09-22T09:04:30Z","timestamp":1695373470000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":41,"title":["The\n                    <i>Candida albicans<\/i>\n                    reference strain SC5314 contains a rare, dominant allele of the transcription factor Rob1 that modulates filamentation, biofilm formation, and oral commensalism"],"prefix":"10.1128","volume":"14","author":[{"given":"Virginia E.","family":"Glazier","sequence":"first","affiliation":[{"name":"Department of Biology, Niagara University , Niagara Falls, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juraj","family":"Kramara","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Carver College of Medicine, University of Iowa , Iowa City, Iowa, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomye","family":"Ollinger","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Carver College of Medicine, University of Iowa , Iowa City, Iowa, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norma V.","family":"Solis","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Los Angeles Biomedical Research Institute and Harbor-UCLA Medical Center , Torrance, California, USA"},{"name":"Department of Medicine, David Geffen School of Medicine at UCLA , Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Zarnowski","sequence":"additional","affiliation":[{"name":"Department of Medicine, Section of Infectious Disease, University of Wisconsin , Madison, Wisconsin, USA"},{"name":"Department of Medical Microbiology and Immunology, University of Wisconsin , Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rohan S.","family":"Wakade","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Carver College of Medicine, University of Iowa , Iowa City, Iowa, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min-Ju","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Georgia , Athens, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel J.","family":"Weigel","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Carver College of Medicine, University of Iowa , Iowa City, Iowa, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shen-Huan","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Brown University , Providence, Rhode Island, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard J.","family":"Bennett","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Brown University , Providence, Rhode Island, 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"}]},{"given":"David R.","family":"Andes","sequence":"additional","affiliation":[{"name":"Department of Medicine, Section of Infectious Disease, University of Wisconsin , Madison, Wisconsin, USA"},{"name":"Department of Medical Microbiology and Immunology, University of Wisconsin , Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark A.","family":"Stamnes","sequence":"additional","affiliation":[{"name":"Department of Molecular Physiology and Biophysics, Carver College of Medicine, University of Iowa , Iowa City, Iowa, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott G.","family":"Filler","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Los Angeles Biomedical Research Institute and Harbor-UCLA Medical Center , Torrance, California, USA"},{"name":"Department of Medicine, David Geffen School of Medicine at UCLA , Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6330-3365","authenticated-orcid":false,"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"},{"name":"Department of Microbiology and Immunology, Carver College of Medicine, University of Iowa , Iowa City, Iowa, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1080\/21505594.2021.2019950"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.3390\/jof6010015"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2018.26"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2636"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1010012"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.2.5.1053-1060.2003"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2006.10.003"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/apm.13310"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.10.048"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.01937-22"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.03447-21"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.85114"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1534\/g3.117.300515"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000783"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.605"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1007787"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1006948"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1002076"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1011109"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.3791\/64258"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.00662"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.174623.114"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2019.01.005"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-04787-4"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1097\/INF.0b013e31815bb69d"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3001822"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.00015-06"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2012.08210.x"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2019.02.008"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00328721"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2019.05.001"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.3390\/jof6010010"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.03498-22"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.107524.110"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-61779-539-8_40"}],"container-title":["mBio"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mbio.01521-23","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mbio.01521-23","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,11]],"date-time":"2024-08-11T14:26:13Z","timestamp":1723386373000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/mbio.01521-23"}},"subtitle":[],"editor":[{"given":"James W.","family":"Kronstad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2023,10,31]]},"references-count":35,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2023,10,31]]}},"alternative-id":["10.1128\/mbio.01521-23"],"URL":"https:\/\/doi.org\/10.1128\/mbio.01521-23","relation":{},"ISSN":["2150-7511"],"issn-type":[{"value":"2150-7511","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,31]]},"assertion":[{"value":"2023-06-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-07-27","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-09-22","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01521-23"}}