Abstract
The human fungal pathogen Candida albicans can cause lethal systemic infections due to its ability to resist stress from the host and to undergo invasive hyphal growth. Previous studies showed that plasma membrane MCC/eisosome domains were important for virulence by promoting the ability of Sur7 to mediate normal cell wall morphogenesis and stress resistance. The sur7Δ mutant displayed abnormal clusters of PI(4,5)P(2), suggesting that misregulation of this lipid underlies the sur7Δ phenotype. To test this, we increased PI(4,5)P(2) levels by deleting combinations of the three PI(4,5)P(2) 5' phosphatase genes (INP51, INP52, and INP54) and found that some combinations, such as inp51Δ inp52Δ, gave phenotypes similar the sur7Δ mutant. In contrast, deleting one copy of MSS4, the gene that encodes the 5' kinase needed to create PI(4,5)P(2), reduced the abnormal PI(4,5)P(2) clusters and also decreased the abnormal cell wall and stress sensitive phenotypes of the sur7Δ mutant. Additional studies support a model that the abnormal PI(4,5)P(2) patches recruit septin proteins, which in turn promote aberrant cell wall growth. These results identify Sur7 as a novel regulator of PI(4,5)P(2) and highlight the critical role of PI(4,5)P(2) in the regulation of C. albicans virulence properties.