The inositol regulon controls viability in Candida glabrata

Abstract

Inositol is essential in eukaryotes, and must be imported or synthesized. Inositol biosynthesis in Saccharomyces cerevisiae is controlled by three non-essential genes that make up the inositol regulon: ScINO2 and ScINO4, which together encode a heterodimeric transcriptional activator, and ScOPI1, which encodes a transcriptional repressor. ScOpi1p inhibits the ScIno2-ScIno4p activator in response to extracellular inositol levels. An important gene controlled by the inositol regulon is ScINO1, which encodes inositol-3-phosphate synthase, a key enzyme in inositol biosynthesis. In the pathogenic yeast Candida albicans, homologues of the S. cerevisiae inositol regulon genes are ‘transcriptionally rewired’. Instead of regulating the CaINO1 gene, CaINO2 and CaINO4 regulate ribosomal genes. Another Candida species that is a prevalent cause of infections is Candida glabrata; however, C. glabrata is phylogenetically more closely related to S. cerevisiae than C. albicans. Experiments were designed to determine if C. glabrata homologues of the inositol regulon genes function similarly to S. cerevisiae or are transcriptionally rewired. CgINO2, CgINO4 and CgOPI1 regulate CgINO1 in a manner similar to that observed in S. cerevisiae. However, unlike in S. cerevisiae, CgOPI1 is essential. Genetic data indicate that CgOPI1 is a repressor that affects viability by regulating activation of a target of the inositol regulon.

Two Major Inositol Transporters and Their Role in Cryptococcal Virulence

“…Our results showed that INO1 expression was not regulated by the availability of extracellular inositol; instead, it was upregulated by the nutrient limitation condition. Such an outcome is consistent with earlier studies in C. neoformans, which suggest that expression of Cryptococcus Ino1 and cellular phosphatidylinositol (PI) levels are not regulated by inositol (38,62), but these results differ from what has been observed in S. cerevisiae (10) and Candida glabrata (8). In S. cerevisiae, Ino1 expression is highly regulated by inositol concentrations.…”

Candida glabrata: a review of its features and resistance

“…This species lacks a number of the virulence factors allied to other Candida pathogenicity, such as hyphal growth or the ability to secrete proteases [12]. Despite that, C. glabrata is a growing concern in clinical settings, where it causes mucosal infections and is related to around 15 % of all Candida-related systemic bloodstream infections [13][14][15][16][17][18][19].…”

FLO11expression and lipid biosynthesis are required for air-liquid biofilm formation in aSaccharomyces cerevisiaeflor strain

“…As FLO11 transcription is also subject to Opi1p regulation (Reynolds, ), a role for inositol in air–liquid biofilm formation was hypothesized. In particular, we postulated that in biofilm cells overexpressing FLO11 , inositol is used as a precursor of phosphatidylinositol, which is required for the assembly of the GPI‐anchor of Flo11p (Chen et al ., ; Bethea et al ., ). To assess this hypothesis, the transcription levels of three key genes in inositol biosynthesis and uptake, namely INO1 , ITR1 and PIS1 , were evaluated in biofilm and bottom cells.…”