Vacuolar Proteases of <i>Candida auris</i> 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 enabl...

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Main Authors: Daniel Clark-Flores, Alvaro Vidal-Montiel, Ricardo Mondragón-Flores, Eulogio Valentín-Gómez, César Hernández-Rodríguez, Margarita Juárez-Montiel, Lourdes Villa-Tanaca
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Language:English
Published: MDPI AG 2025-05-01
Series:Journal of Fungi
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Online Access:https://www.mdpi.com/2309-608X/11/5/388
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author Daniel Clark-Flores
Alvaro Vidal-Montiel
Ricardo Mondragón-Flores
Eulogio Valentín-Gómez
César Hernández-Rodríguez
Margarita Juárez-Montiel
Lourdes Villa-Tanaca
author_facet Daniel Clark-Flores
Alvaro Vidal-Montiel
Ricardo Mondragón-Flores
Eulogio Valentín-Gómez
César Hernández-Rodríguez
Margarita Juárez-Montiel
Lourdes Villa-Tanaca
author_sort Daniel Clark-Flores
collection DOAJ
description <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.
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spelling doaj-art-c763219baf834969a094ca4f4e87c96a2025-08-20T01:56:16ZengMDPI AGJournal of Fungi2309-608X2025-05-0111538810.3390/jof11050388Vacuolar Proteases of <i>Candida auris</i> from Clades III and IV and Their Relationship with AutophagyDaniel Clark-Flores0Alvaro Vidal-Montiel1Ricardo Mondragón-Flores2Eulogio Valentín-Gómez3César Hernández-Rodríguez4Margarita Juárez-Montiel5Lourdes Villa-Tanaca6Laboratorio de Biología Molecular de Bacterias y Levaduras, Departamento de Microbiología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Prol. de Carpio y Plan de Ayala. Col. Sto. Tomás, Ciudad de México 11340, MexicoLaboratorio de Biología Molecular de Bacterias y Levaduras, Departamento de Microbiología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Prol. de Carpio y Plan de Ayala. Col. Sto. Tomás, Ciudad de México 11340, MexicoDepartamento de Bioquímica, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), Av. IPN No. 2508, Ciudad de México 07360, MexicoDepartmento de Microbiología y Ecología, Universidad de Valencia, 46100 Valencia, SpainLaboratorio de Biología Molecular de Bacterias y Levaduras, Departamento de Microbiología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Prol. de Carpio y Plan de Ayala. Col. Sto. Tomás, Ciudad de México 11340, MexicoLaboratorio de Biología Molecular de Bacterias y Levaduras, Departamento de Microbiología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Prol. de Carpio y Plan de Ayala. Col. Sto. Tomás, Ciudad de México 11340, MexicoLaboratorio de Biología Molecular de Bacterias y Levaduras, Departamento de Microbiología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Prol. de Carpio y Plan de Ayala. Col. Sto. Tomás, Ciudad de México 11340, Mexico<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.https://www.mdpi.com/2309-608X/11/5/388<i>Candida auris</i><i>Candidozyma auris</i>autophagyvacuolar proteasespeptidasesnutritional stress
spellingShingle Daniel Clark-Flores
Alvaro Vidal-Montiel
Ricardo Mondragón-Flores
Eulogio Valentín-Gómez
César Hernández-Rodríguez
Margarita Juárez-Montiel
Lourdes Villa-Tanaca
Vacuolar Proteases of <i>Candida auris</i> from Clades III and IV and Their Relationship with Autophagy
Journal of Fungi
<i>Candida auris</i>
<i>Candidozyma auris</i>
autophagy
vacuolar proteases
peptidases
nutritional stress
title Vacuolar Proteases of <i>Candida auris</i> from Clades III and IV and Their Relationship with Autophagy
title_full Vacuolar Proteases of <i>Candida auris</i> from Clades III and IV and Their Relationship with Autophagy
title_fullStr Vacuolar Proteases of <i>Candida auris</i> from Clades III and IV and Their Relationship with Autophagy
title_full_unstemmed Vacuolar Proteases of <i>Candida auris</i> from Clades III and IV and Their Relationship with Autophagy
title_short Vacuolar Proteases of <i>Candida auris</i> from Clades III and IV and Their Relationship with Autophagy
title_sort vacuolar proteases of i candida auris i from clades iii and iv and their relationship with autophagy
topic <i>Candida auris</i>
<i>Candidozyma auris</i>
autophagy
vacuolar proteases
peptidases
nutritional stress
url https://www.mdpi.com/2309-608X/11/5/388
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