# Endocytosis Mediated by Candida albicans END3 Is Required for Its In Vivo Virulence as an Opportunistic Fungal Pathogen

## TL;DR

The study shows that a gene called END3 in Candida albicans is essential for its ability to cause disease in a mouse model.

## Contribution

The novel finding is that END3-mediated endocytosis is required for the in vivo virulence of Candida albicans.

## Key findings

- The end3 null mutant of Candida albicans is hypovirulent in a murine model of disseminated candidiasis.
- END3 is crucial for processes like filamentation, biofilm formation, and extracellular protease secretion in C. albicans.
- Loss of END3 leads to impaired actin patch formation and reduced host-cell damage in vitro.

## Abstract

Endocytic trafficking in Candida albicans is a fundamental cellular process that is crucial for its secretion, filamentation, and virulence-related processes. We have previously demonstrated that loss of the key endocytosis-related C. albicans gene END3 disrupts clathrin-mediated endocytosis, leading to impairments in actin patch formation, filamentation, biofilm formation, cell wall integrity, and extracellular protease secretion. The end3 null mutant also exhibits altered antifungal susceptibility and reduced host-cell damage in an in vitro keratinocyte infection model. To ascertain whether endocytosis is required for virulence in vivo, we assessed virulence of the C. albicans end3 null mutant in a murine model of disseminated candidiasis. After infection via the tail vein, and analysis of host survival over 28 days, the end3 null mutant was markedly hypovirulent compared to corresponding control strains. These results indicate that endocytosis mediated by END3 in C. albicans contributes to pathogenesis in vivo.