The ESCRT System Plays an Important Role in the Germination in Candida albicans by Regulating the Expression of Hyphal-Specific Genes and the Localization of Polarity-Related Proteins.

Abstract

Candida albicans is an important opportunistic fungal pathogen, and its pathogenicity is closely related to its ability to form hyphae. ESCRT system was initially discovered as a membrane-budding machinery involved in the formation of multivesicular bodies. More recently, the role of ESCRT is vastly expanded. Early reports showed that the ESCRT system is involved in inducing hyphae under neutral-alkaline environment via the Rim101 pathway. We previously found that in the environment that contains serum, one ESCRT protein, Vps4, is essential for polarity maintenance during hyphal formation, as its deletion causes the formation of multiple hyphae. In this study, we found that Vps4 is also essential for the proper localization of Cdc42 and Cdc3, which may be related to its role in polarity maintenance. We also discovered that deletions of the ESCRT proteins significantly delay germination and cause downregulation of hyphal-specific genes, most prominent of which is HGC1. Since Hgc1 is essential for many aspects of hyphal growth, its downregulation could explain our observed phenotypes. Our further studies show that ESCRT proteins are involved in the dynamics of Ras1. Deletions of VPS4 or SNF7 significantly decrease the recovery rate of GFP-Ras1 in the fluorescence recovery after photobleaching experiment. The decreased Ras1 dynamics may disrupt the signaling pathway and lead to downregulation of hyphal-specific genes. Therefore, in this study we discovered a novel and Rim101 independent mechanism used by the ESCRT system to regulate hyphal induction and polarity maintenance, which could provide insights on the pathogenicity mechanism of Candia albicans.