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.
Highlights
Candida albicans is a commensal organism that lives as a benign resident of the microflora of the human oral, gastrointestinal, and vaginal tracts as well as the skin
When heterologously expressed in an S. cerevisiae Scopi1Δ mutant, the C. albicans OPI1 gene has been demonstrated to repress expression of a reporter gene that contains the inositol/ choline responsive element (ICRE) found in ScINO1 and other ScOpi1p-ScIno2p-ScIno4p target genes [24]
This data suggested that C. albicans Opi1p may regulate the cognate C. albicans INO1 gene, as its homolog does in S. cerevisiae
Summary
Candida albicans is a commensal organism that lives as a benign resident of the microflora of the human oral, gastrointestinal, and vaginal tracts as well as the skin. OPI1 Regulates SAP2 Not Inositol Biosynthesis albicans include growth at 37°C, dimorphism, and production of secreted hydrolases such as proteases, lipases, and phospholipases [1, 2]. The pathways that regulate the transcription of secreted aspartyl protease (SAP) virulence factors in C. albicans are beginning to be understood, but much remains to be learned. Unlike SAP1 to SAP8, which encode secreted proteases, SAP9 and SAP10 encode GPI-anchored proteases, located at the cell membrane or cell wall, and both are required for virulence [5]. Among this family of genes, Sap2p is the most well-studied protease since it is the major secreted protease during in vitro growth conditions. SAP2 is under the control of the STP1 transcription factor and STP1’s upstream GATA transcription factors GLN3 and GAT1 [6, 7]
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