Control of citrate utilization by <i>Candida albicans</i> Adr1

<i>Candida albicans</i>, a fungal commensal and pathogen, occupies diverse niches in the human host. Its broad metabolic repertoire is critical for its survival. The model yeast <i>Saccharomyces cerevisiae</i> provides a starting point for analysis of <i>C. albicans</i> physiology and regulatory circuitry, but there are many examples of rewired transcription factors that govern different processes in the two organisms. We focus here on Adr1, which in <i>S. cerevisiae</i> promotes alternative carbon source utilization and in <i>C. albicans</i> promotes ergosterol synthesis. We find that <i>C. albicans</i> Adr1 is also required for growth on citrate and compounds that feed into the citric acid cycle, like glutamate and malate. RNA-sequencing (RNA-seq) shows that predicted citrate metabolic genes, representing both the citric acid cycle and gluconeogenesis, are downregulated in an <i>adr1</i>Δ/Δ mutant. In fact, the three Adr1-dependent genes <i>HGT17, MDH1,</i> and <i>PCK1</i> are required for growth on citrate, as indicated by deletion mutant phenotypes. The hyphal regulator <i>EED1</i> has a negative role in citrate utilization, and an <i>adr1</i>Δ/Δ <i>eed1</i>Δ/Δ double mutant is defective for growth on citrate. This result argues that Adr1 acts downstream or independently of Eed1 to govern citrate utilization. <i>C. albicans</i> Adr1 is rewired compared to its <i>S. cerevisiae</i> ortholog to govern the ability to use citrate, which <i>S. cerevisiae</i> lacks, and potentially to respond to Eed1, for which <i>S. cerevisiae</i> lacks an ortholog.IMPORTANCE<i>Candida albicans</i> is a major fungal pathogen of humans, and its ability to grow on a range of carbon sources is critical for pathogenicity. Here, we find that a known regulator of ergosterol synthesis, Adr1, is also required to use citrate as a carbon source. Adr1 acts downstream or independently of Eed1, a well-known regulator of hypha formation and citrate utilization.