The inositol regulon controls viability in Candida glabrata

Abstract

Inositol is essential in eukaryotes, and must be imported or synthesized. Inositol biosynthesis inSaccharomyces cerevisiaeis controlled by three non-essential genes that make up the inositol regulon:ScINO2andScINO4, which together encode a heterodimeric transcriptional activator, andScOPI1, 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 isScINO1, which encodes inositol-3-phosphate synthase, a key enzyme in inositol biosynthesis. In the pathogenic yeastCandida albicans, homologues of theS. cerevisiaeinositol regulon genes are ‘transcriptionally rewired’. Instead of regulating theCaINO1gene,CaINO2andCaINO4regulate ribosomal genes. AnotherCandidaspecies that is a prevalent cause of infections isCandida glabrata; however,C. glabratais phylogenetically more closely related toS. cerevisiaethanC. albicans. Experiments were designed to determine ifC. glabratahomologues of the inositol regulon genes function similarly toS. cerevisiaeor are transcriptionally rewired.CgINO2,CgINO4andCgOPI1regulateCgINO1in a manner similar to that observed inS. cerevisiae. However, unlike inS. cerevisiae,CgOPI1is essential. Genetic data indicate thatCgOPI1is a repressor that affects viability by regulating activation of a target of the inositol regulon.