Phosphatidate phosphatase Pah1 has a role in the hyphal growth and virulence of Candida albicans.

Graphical abstract Highlights • PAH1 deletion increases cell death in Candida albicans. • pah1 null mutant exhibits increased stress sensitivity and defects in hyphal growth. • PAH1 deletion decreases the expression levels of EFG1 , FLO8 and CPH1. • PAH1 deletion increases intracellular ROS and high levels of ROS inhibit the hyphal growth. • PAH1 deletion attenuates C. albicans virulence in mice. Abstract Phosphatidate phosphatases play essential roles in lipid metabolism by converting phosphatidic acid to diacylglycerol. Here, we have investigated the roles of a phosphatidate phosphatase, Pah1, in the fungal pathogen Candida albicans. Deleting PAH1 causes multiple phenotypes, especially severe hyphal defects, increased sensitivity to cell wall stress, and reduced virulence in mice. By qPCR, we detected a significant downregulation of hyphal-specific genes including two key hyphal-promoting genes UME6 and HGC1. Overexpression of UME6 in pah1 Δ/Δ cells largely restored the hyphal growth, indicating that the reduced expression of UME6 is primarily responsible for the hyphal defects. We also detected decreased expression of three hyphal-promoting transcription factors EFG1 , FLO8, and CPH1 in pah1 mutants, consistent with the reduced expression of UME6. Furthermore, the pah1 Δ/Δ mutant exhibited increased sensitivity to cell wall stress. During systemic infection of mice, the mutant showed significantly impaired ability to colonize the kidney and to kill the host. Together, C. albicans PAH1 plays an important role in hyphal growth, adaptability to environmental stresses, and virulence. Thus, Pah1 could be targeted for the development of new antifungal drugs. [ABSTRACT FROM AUTHOR]