Hgt17-Adr1 Relationship in Candida albicans Citrate Utilization

The fungal pathogen <i>Candida albicans</i> can infect diverse tissues, a reflection of its broad metabolic repertoire. The transcription factor Adr1 is required for utilization of several citric acid cycle intermediates that are found in tissue. Many Adr1-activated genes encode enzymes with well-defined roles in citrate metabolism or gluconeogenesis. Here, we focus on <i>HGT17</i> (C4_01070W, orf19.4682), an Adr1-activated gene that encodes a possible citrate transporter. We provide two lines of evidence that <i>HGT17</i> is a key functional target of Adr1. First, forced expression of <i>HGT17</i> in an <i>adr1</i>Δ/Δ mutant improves growth on citrate as a carbon source. Second, <i>hgt17</i>Δ/Δ and <i>adr1</i>Δ/Δ mutants incubated in citrate medium present similar gene expression defects compared to the wild type. Noteworthy is down-regulation in both mutants of citric acid cycle genes, glycolysis/gluconeogenesis genes, and ergosterol synthesis genes. These common features may reflect a specific effect of citrate as an inducer of citric acid cycle enzymes or a global effect of carbon and energy limitation. In either case, the results argue that reduced <i>HGT17</i> expression contributes substantially to the impact of an <i>adr1</i>Δ/Δ mutation on growth and gene expression.