Candida Albicans PPG1, a Serine/threonine Phosphatase, Plays a Vital Role in Central Carbon Metabolisms under Filament-Inducing Conditions: A Multi-Omics Approach

Candida albicans is the leading cause of life-threatening bloodstream candidiasis, especially among immunocompromised patients. The reversible morphological transition from yeast to hyphal filaments in response to host environmental cues facilitates C. albicans tissue invasion, immune evasion, and dissemination. Hence, it is widely considered that filamentation represents one of the major virulence properties in C. albicans. We have previously characterized Ppg1, a PP2A-type protein phosphatase that controls filament extension and virulence in C. albicans. This study conducted RNA sequencing analysis of samples obtained from C. albicans wild type and ppg1Δ/Δ strains grown under filament-inducing conditions. Overall, ppg1Δ/Δ strain showed 1448 upregulated and 710 downregulated genes, representing approximately one-third of the entire annotated C. albicans genome. Transcriptomic analysis identified significant downregulation of well-characterized genes linked to filamentation and virulence, such as ALS3, HWP1, ECE1, and RBT1. Expression analysis showed that essential genes involved in C. albicans central carbon metabolisms, including GDH3, GPD1, GPD2, RHR2, INO1, AAH1, and MET14 were among the top upregulated genes. Subsequent metabolomics analysis of C. albicans ppg1Δ/Δ strain revealed a negative enrichment of metabolites with carboxylic acid substituents and a positive enrichment of metabolites with pyranose substituents. Altogether, Ppg1 in vitro analysis revealed a link between metabolites substituents and filament formation controlled by a phosphatase to regulate morphogenesis and virulence.