The commensal fungal pathogen, Candida albicans (C. albicans) is a leading source of fungal infections in humans. C. albicans transports the renal metabolite glycerophosphocholine (GPC) into cells via Git3 and Git4 transporters. Previous studies have shown that the GIT transporters are required for full virulence of C. albicans in a mouse model of disseminated candidiasis. The mechanism by which GPC uptake impacts virulence is unknown, but likely involves either the catabolism of GPC to liberate free phosphate or the shunting of GPC into phosphatidylcholine (PC) biosynthesis. Indeed, previous studies have shown that C. albicans can use GPC as sole phosphate source. In addition, studies in Saccharomyces cerevisiae have shown that GPC can be acylated by the acyltransferase Gpc1, followed by a second acylation by Ale1 to form a PC molecule. A potential homolog for Gpc1 has been identified in C. albicans and in vivo studies have shown that Gpc1 impacts PC biosynthesis. Additional studies presented here probe the metabolic fates of GPC through growth, labeling, and expression analyses in various mutant backgrounds and with a focus on conditions associated with virulence. Our findings indicate that serum exposure upregulates Gpc1 and likely the conversion of GPC to PC. Conversely, phosphate limitation upregulates GPC transport and its conversion to free phosphate. These studies are ongoing.
National Institute of Health Grant NIH R15 GM104876 to JPV and Duquesne University for funding