Loss of Kex2 Affects the <i>Candida albicans</i> Cell Wall and Interaction with Innate Immune Cells

The secretory pathway in <i>Candida albicans</i> involves the protein translocation into the lumen of the endoplasmic reticulum and transport to the Golgi complex, where proteins undergo posttranslational modifications, including glycosylation and proteolysis. The Golgi-resident Kex2 pro...

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Main Authors: Manuela Gómez-Gaviria, Nancy E. Lozoya-Pérez, Monika Staniszewska, Bernardo Franco, Gustavo A. Niño-Vega, Hector M. Mora-Montes
Format: Article
Language:English
Published: MDPI AG 2020-04-01
Series:Journal of Fungi
Subjects:
Online Access:https://www.mdpi.com/2309-608X/6/2/57
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author Manuela Gómez-Gaviria
Nancy E. Lozoya-Pérez
Monika Staniszewska
Bernardo Franco
Gustavo A. Niño-Vega
Hector M. Mora-Montes
author_facet Manuela Gómez-Gaviria
Nancy E. Lozoya-Pérez
Monika Staniszewska
Bernardo Franco
Gustavo A. Niño-Vega
Hector M. Mora-Montes
author_sort Manuela Gómez-Gaviria
collection DOAJ
description The secretory pathway in <i>Candida albicans</i> involves the protein translocation into the lumen of the endoplasmic reticulum and transport to the Golgi complex, where proteins undergo posttranslational modifications, including glycosylation and proteolysis. The Golgi-resident Kex2 protease is involved in such processing and disruption of its encoding gene affected virulence and dimorphism. These previous studies were performed using cells without <i>URA3</i> or with <i>URA3</i> ectopically placed into the <i>KEX2</i> locus. Since these conditions are known to affect the cellular fitness and the host–fungus interaction, here we generated a <i>kex2</i>Δ null mutant strain with <i>URA3</i> placed into the neutral locus <i>RPS1</i>. The characterization of this strain showed defects in the cell wall composition, with a reduction in the <i>N</i>-linked mannan content, and the increment in the levels of <i>O</i>-linked mannans, chitin, and β-glucans. The defects in the mannan content are likely linked to changes in Golgi-resident enzymes, as the α-1,2-mannosyltransferase and α-1,6-mannosyltransferase activities were incremented and reduced, respectively. The mutant cells also showed reduced ability to stimulate cytokine production and phagocytosis by human mononuclear cells and macrophages, respectively. Collectively, these data showed that loss of Kex2 affected the cell wall composition, the protein glycosylation pathways, and interaction with innate immune cells.
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spelling doaj.art-d5fa32f9a33c4147ab4dc8bdbd3440362023-11-19T23:00:19ZengMDPI AGJournal of Fungi2309-608X2020-04-01625710.3390/jof6020057Loss of Kex2 Affects the <i>Candida albicans</i> Cell Wall and Interaction with Innate Immune CellsManuela Gómez-Gaviria0Nancy E. Lozoya-Pérez1Monika Staniszewska2Bernardo Franco3Gustavo A. Niño-Vega4Hector M. Mora-Montes5Departamento de Biología, División de Ciencias Naturales y Exactas, Campus Guanajuato, Universidad de Guanajuato, Guanajuato Gto 36050, MexicoDepartamento de Biología, División de Ciencias Naturales y Exactas, Campus Guanajuato, Universidad de Guanajuato, Guanajuato Gto 36050, MexicoFaculty of Chemistry, Warsaw University of Technology, Noakowskiego 3, 00-664 Warsaw, PolandDepartamento de Biología, División de Ciencias Naturales y Exactas, Campus Guanajuato, Universidad de Guanajuato, Guanajuato Gto 36050, MexicoDepartamento de Biología, División de Ciencias Naturales y Exactas, Campus Guanajuato, Universidad de Guanajuato, Guanajuato Gto 36050, MexicoDepartamento de Biología, División de Ciencias Naturales y Exactas, Campus Guanajuato, Universidad de Guanajuato, Guanajuato Gto 36050, MexicoThe secretory pathway in <i>Candida albicans</i> involves the protein translocation into the lumen of the endoplasmic reticulum and transport to the Golgi complex, where proteins undergo posttranslational modifications, including glycosylation and proteolysis. The Golgi-resident Kex2 protease is involved in such processing and disruption of its encoding gene affected virulence and dimorphism. These previous studies were performed using cells without <i>URA3</i> or with <i>URA3</i> ectopically placed into the <i>KEX2</i> locus. Since these conditions are known to affect the cellular fitness and the host–fungus interaction, here we generated a <i>kex2</i>Δ null mutant strain with <i>URA3</i> placed into the neutral locus <i>RPS1</i>. The characterization of this strain showed defects in the cell wall composition, with a reduction in the <i>N</i>-linked mannan content, and the increment in the levels of <i>O</i>-linked mannans, chitin, and β-glucans. The defects in the mannan content are likely linked to changes in Golgi-resident enzymes, as the α-1,2-mannosyltransferase and α-1,6-mannosyltransferase activities were incremented and reduced, respectively. The mutant cells also showed reduced ability to stimulate cytokine production and phagocytosis by human mononuclear cells and macrophages, respectively. Collectively, these data showed that loss of Kex2 affected the cell wall composition, the protein glycosylation pathways, and interaction with innate immune cells.https://www.mdpi.com/2309-608X/6/2/57secretory pathwayproteasemannanimmune sensingmannanglycoproteins
spellingShingle Manuela Gómez-Gaviria
Nancy E. Lozoya-Pérez
Monika Staniszewska
Bernardo Franco
Gustavo A. Niño-Vega
Hector M. Mora-Montes
Loss of Kex2 Affects the <i>Candida albicans</i> Cell Wall and Interaction with Innate Immune Cells
Journal of Fungi
secretory pathway
protease
mannan
immune sensing
mannan
glycoproteins
title Loss of Kex2 Affects the <i>Candida albicans</i> Cell Wall and Interaction with Innate Immune Cells
title_full Loss of Kex2 Affects the <i>Candida albicans</i> Cell Wall and Interaction with Innate Immune Cells
title_fullStr Loss of Kex2 Affects the <i>Candida albicans</i> Cell Wall and Interaction with Innate Immune Cells
title_full_unstemmed Loss of Kex2 Affects the <i>Candida albicans</i> Cell Wall and Interaction with Innate Immune Cells
title_short Loss of Kex2 Affects the <i>Candida albicans</i> Cell Wall and Interaction with Innate Immune Cells
title_sort loss of kex2 affects the i candida albicans i cell wall and interaction with innate immune cells
topic secretory pathway
protease
mannan
immune sensing
mannan
glycoproteins
url https://www.mdpi.com/2309-608X/6/2/57
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