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• cdc55 null mutant grows slowly as pseudohyphae with some cells lacking the nucleus. • rts1 null mutant cells are round and enlarged and seem to undergo incomplete cell separation producing multinucleated cells. • Strong chitin deposition occurs at the septum of cdc55 null mutant cells and on the surface of rts1 null mutant cells. • Deletion of cdc55 exhibits severe defects in hyphal and biofilm formation, while deletion of rts1 is partially defective. • cdc55 and rts1 null mutants show reduced virulence in mice. Protein phosphatase-2A (PP2A) is a heterotrimeric enzyme composed of a catalytic subunit, a regulatory subunit, and a structural subunit. In Candida albicans , Cdc55 and Rts1 have been identified as possible regulatory subunits of PP2A containing the catalytic subunit Pph21 and structural subunit Tpd3. The Tpd3-Pph21 phosphatase regulates cell morphogenesis and division. However, the functions of Cdc55 and Rts1 remain unclear. Here, we constructed cdc55 Δ/Δ and rts1 Δ/Δ mutants and found that they exhibit different defects in multiple phenotypes although both show similar hyperphosphorylation of the septin Sep7 and aberrant septin organization. Under yeast growth conditions, the cdc55 Δ/Δ mutant grows slowly as pseudohyphae with some cells lacking the nucleus, while rts1 Δ/Δ cells are round and enlarged and seem to undergo incomplete cell separation producing multinucleated cells. Strong chitin deposition occurs at the septum of cdc55 Δ/Δ cells and on the surface of rts1 Δ/Δ cells, which likely contributes to increased susceptibility to caspofungin. Also, cdc55 Δ/Δ exhibits severe defects in hyphal and biofilm formation, while rts1 Δ/Δ is partially defective. Both mutants show reduced virulence in mice, suggesting that PP2A-B subunits could serve as potential antifungal targets. [ABSTRACT FROM AUTHOR]

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]