title: Candida albicans OPI1 regulates filamentous growth and virulence in vaginal infections, but not inositol biosynthesis.
abstract: ScOpi1p is a well-characterized transcriptional repressor and master regulator of inositol and phospholipid biosynthetic genes in the baker's yeast Saccharomyces cerevisiae. An ortholog has been shown to perform a similar function in the pathogenic fungus Candida glabrata, but with the distinction that CgOpi1p is essential for growth in this organism. However, in the more distantly related yeast Yarrowia lipolytica, the OPI1 homolog was not found to regulate inositol biosynthesis, but alkane oxidation. In Candida albicans, the most common cause of human candidiasis, its Opi1p homolog, CaOpi1p, has been shown to complement a S. cerevisiae opi1∆ mutant for inositol biosynthesis regulation when heterologously expressed, suggesting it might serve a similar role in this pathogen. This was tested in the pathogen directly in this report by disrupting the OPI1 homolog and examining its phenotypes. It was discovered that the OPI1 homolog does not regulate INO1 expression in C. albicans, but it does control SAP2 expression in response to bovine serum albumin containing media. Meanwhile, we found that CaOpi1 represses filamentous growth at lower temperatures (30 °C) on agar, but not in liquid media. Although, the mutant does not affect virulence in a mouse model of systemic infection, it does affect virulence in a rat model of vaginitis. This may be because Opi1p regulates expression of the SAP2 protease, which is required for rat vaginal infections.
authors.affiliation: Department of Plant Pathology & Microbiology, National Taiwan University, Taipei, Taiwan.
authors.forename: Ying-Lien
authors.initials: YL
authors.lastname: Chen
authors.affiliation: Department of Infectious, Parasitic and Immunomediated Diseases, Rome, Italy.
authors.forename: Flavia
authors.initials: F
authors.lastname: de Bernardis
authors.affiliation: Department of Plant Pathology & Microbiology, National Taiwan University, Taipei, Taiwan.
authors.forename: Shang-Jie
authors.initials: SJ
authors.lastname: Yu
authors.affiliation: Department of Infectious, Parasitic and Immunomediated Diseases, Rome, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Sandini
authors.affiliation: Department of Microbiology, University of Tennessee, Knoxville, TN, United States of America.
authors.forename: Sarah
authors.initials: S
authors.lastname: Kauffman
authors.affiliation: Department of Microbiology, University of Tennessee, Knoxville, TN, United States of America.
authors.forename: Robert N
authors.initials: RN
authors.lastname: Tams
authors.affiliation: Department of Microbiology, University of Tennessee, Knoxville, TN, United States of America.
authors.forename: Emily
authors.initials: E
authors.lastname: Bethea
authors.affiliation: Department of Microbiology, University of Tennessee, Knoxville, TN, United States of America.
authors.forename: Todd B
authors.initials: TB
authors.lastname: Reynolds
mesh_terms: D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000235:genetics / Q000378:metabolism; D002176:Candida albicans / Q000254:growth & development / Q000378:metabolism* / Q000472:pathogenicity*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D007294:Inositol / Q000378:metabolism; D051379:Mice; D014774:Virulence; D025062:Yarrowia / Q000254:growth & development / Q000378:metabolism / Q000472:pathogenicity
chemical_list: D005656:Fungal Proteins; D007294:Inositol; D016282:Aspartic Acid Endopeptidases; C090753:SAP2 protein, Candida