Vacuolar Proteases of Candida auris from Clades III and IV and Their Relationship with Autophagy

<i>Candida auris</i> is a multidrug-resistant pathogen with a high mortality rate and widespread distribution. Additionally, it can persist on inert surfaces for extended periods, facilitating its transmissibility in hospital settings. Autophagy is a crucial cellular mechanism that enables fungal survival under adverse conditions. A fundamental part of this process is mediated by vacuolar proteases, which play an essential role in the degradation and recycling of cellular components. The present work explores the relationship between <i>C. auris</i> vacuolar peptidases and autophagy, aiming to establish a precedent for understanding the survival mechanisms of this emerging fungus. Thus, eight genes encoding putative vacuolar peptidases in the <i>C. auris</i> genomes were identified: <i>PEP4</i>, <i>PRB1</i>, <i>PRC1</i>, <i>ATG42</i>, <i>CPS</i>, <i>LAP4</i>, <i>APE3</i>, and <i>DAP2</i>. Analysis of the protein domains and their phylogenetic relationships suggests that these enzymes are orthologs of <i>Saccharomyces cerevisiae</i> vacuolar peptidases. Notably, both vacuolar protease gene expression and the proteolytic activity of cell-free extracts increased under nutritional stress and rapamycin. An increase in the expression of the <i>ATG8</i> gene and the presence of autophagic bodies were also observed. These results suggest that proteases could play a role in yeast autophagy and survival during starvation conditions.