THE CANDIDA ALBICANS GLYCOLYTIC REGULATORY NETWORK

The opportunistic human fungal pathogen Candida albicans assimilates diverse carbon sources to thrive in a wide range of host environments. Glycolysis is strictly regulated, and transcription of glycolytic enzyme genes is regulated in response to carbon source and availability, oxygen levels, and to cellular demands such as energy needs and metabolite concentrations. C. albicans Gal4 and Tye7 are known transcriptional activators of glycolytic genes. Tye7 also has roles in virulence traits, filamentation and biofilm formation. These functions have been defined through studies of only strain SC5314 and its marked derivatives. Recent work indicates that regulatory relationships vary considerably among C. albicans isolates. Here we analyzed Tye7- and Gal4-related phenotypes in five diverse clinical isolates of C. albicans. We conducted a basic phenotypic analysis and focused NanoString profiling of tye7dd, gal4dd, and gal4dd tye7dd mutants among the five strains. To achieve a global view of the Tye7/Gal4 regulatory network, we conducted RNA-seq analysis of the single and double deletion mutants generated from two strain background (SC5314 and P87) and cultured in two media (RPMI+FBS and YPD, only SC5314 strain). Our results indicate that the balance of activities of Tye7 and Gal4 varies among clinical isolates. Even a central metabolic regulatory network is subject to extensive strain variation.