Vacuole and mitochondria patch (vCLAMP) protein Mcp1 reduces the pathogenesis of Candida albicans by impeding the function of Cap1-mediated oxidative stress response.

Abstract

BACKGROUND: Vacuole and mitochondria patch (vCLAMP) is a novel organelle membrane contact site. The vCLAMP protein Mcp1 plays a crucial role in cellular signaling and homeostasis. However, its role in the virulence of Candida albicans remains to be elucidated. RESULTS: This study explored the function of Mcp1 in the oxidative stress response of C. albicans. Fluorescence co-localization and immune transmission electron microscopy results suggested that Mcp1 was located on vacuolar and mitochondrial membranes. RNA sequencing and Gene Ontology enrichment analyses showed that the deletion of MCP1 inhibited the expression of genes related to the oxidative stress response, such as GLR1, TRR1, and SOD2, in C. albicans. In addition, the deletion of MCP1 diminished the activity of antioxidant enzymes. Further studies found that MCP1 deletion impeded the phosphorylation and nuclear localization of the transcription factor Cap1, leading to an increase in intracellular reactive oxygen species (ROS) levels. The elevated ROS levels impaired mitochondrial function and morphology and reduced hyphal development and biofilm formation. Notably, the continuous expression of phosphorylated Cap1 in MCP1 deletion strains could restore the expression level of GLR1. Furthermore, a mouse model revealed that the deletion of MCP1 reduced the ability of C. albicans to infect the host. CONCLUSION: This study reveals that the vCLAMP protein Mcp1 plays an essential role in the hyphal development and virulence of C. albicans via the Cap1-mediated oxidative stress response, which provides a promising drug target for the treatment of Candida infections.