P4-ATPase subunit Cdc50 plays a role in yeast budding and cell wall integrity in Candida glabrata

BackgroundAs highly-conserved types of lipid flippases among fungi, P4-ATPases play a significant role in various cellular processes. Cdc50 acts as the regulatory subunit of flippases, forming heterodimers with Drs2 to translocate aminophospholipids. Cdc50 homologs have been reported to be implicated in protein trafficking, drug susceptibility, and virulence in Saccharomyces cerevisiae, Candida albicans and Cryptococcus neoformans. It is likely that Cdc50 has an extensive influence on fungal cellular processes. The present study aimed to determine the function of Cdc50 in Candida glabrata by constructing a Delta cdc50 null mutant and its complemented strain.ResultsIn Candida glabrata, the loss of Cdc50 led to difficulty in yeast budding, probably caused by actin depolarization. The Delta cdc50 mutant also showed hypersensitivity to azoles, caspofungin, and cell wall stressors. Further experiments indicated hyperactivation of the cell wall integrity pathway in the Delta cdc50 mutant, which elevated the major cell wall contents. An increase in exposure of beta-(1,3)-glucan and chitin on the cell surface was also observed through flow cytometry. Interestingly, we observed a decrease in the phagocytosis rate when the Delta cdc50 mutant was co-incubated with THP-1 macrophages. The Delta cdc50 mutant also exhibited weakened virulence in nematode survival tests.ConclusionThe results suggested that the lipid flippase subunit Cdc50 is implicated in yeast budding and cell wall integrity in C. glabrata, and thus have a broad influence on drug susceptibility and virulence. This work highlights the importance of lipid flippase, and offers potential targets for new drug research.

Automated summary

This study aimed to determine the function of Cdc50 in Candida glabrata by constructing a Delta cdc50 null mutant and its complemented strain. The results showed that loss of Cdc50 led to difficulties in yeast budding, increased cell wall integrity, enhanced drug susceptibility and weakened virulence. These findings highlight the importance of Cdc50 in C. glabrata and provide potential targets for new drug research.