REWIRED REGULATORY CASCADES INVOLVED IN THE GLCNAC INDUCING GENE EXPRESSION IN PATHOGENIC YEAST CANDIDA ALBICANS

Abstract

Candida albicans is an opportunistic fungal pathogen that survives in host environmental niche. Model yeast Saccharomyces cerevisiae that lives on plant available sugars like sucrose, generates energy by fermentation, while pathogenic yeast Candida albicans derives energy through respiration. C. albicans diverged from the S. cerevisiaeapproximately 300 million years ago. To survive under host contrasting micro environmental niches, pathogens have acquired metabolic flexibility for utilizing available nutrients through rewired regulatory cascades. N-acetylglucosamine, an important amino sugar present at the infection sites, acts as carbon and nitrogen source for the pathogen and can induce morphological transition. Very little is known about the regulatory cascades involved in GlcNAc catabolic gene expression. In this study we have shown that rewired regulatory cascades are involved in the GlcNAc regulated catabolic gene expression. Galactose responsive regulators/pathways, Cph1 (MAP kinase pathway) and Hgt4-Rgt1 have no role in the regulation of GlcNAc catabolic gene expression. Interestingly, Hxk1 seems to play a major role in regulating the wider array of metabolic genes in addition to GlcNAc catabolic genes. The conserved Tup1-Mig1 repressor loop also showed highly divergence and almost lost regulation over carbon responsive gene expression including GlcNAc inducible genes. Overall, our study indicates that the GlcNAc catabolic gene regulatory cascades are specialized and entirely rewired, probably because of the importance of this molecule in determining pathogens adaptability and survival inside the host environment.