Control of citrate utilization by Candida albicans Adr1

Opportunistic fungal pathogen Candida albicans often encounters host niches where it must survive on alternative carbon sources alone. In Saccharomyces cerevisiae, transcription factor Adr1 activates genes required for acetate and glycerol utilization. However, previous researchers found that CaADR1 deletion mutants have robust growth on acetate and glycerol. We have found that Adr1 is required for growth on citrate. This phenotype is manifested among multiple strains isolated from all known host niches. RNA sequencing analyses of adr1?/? and wild-type strains show that Adr1 is required for expression of genes within the TCA cycle and gluconeogenesis. Major targets include enzymes Mdh1 and Pck1. Unexpectedly, one of the most downregulated genes is not within the central metabolic pathway. HGT17 is a putative glucose transporter. Phenotypic analyses support the hypothesis that Hgt17 is able to transport citrate. Overall design: RNA-seq profiling of WT C. albicans cells and their knockdown derivatives (adr1?? and hgt17??). Cells were grown for 4h at 37 degrees in either YNB+1% citrate or YNB + 1% acetate