Disruption of Protein Mannosylation Affects Candida guilliermondii Cell Wall, Immune Sensing, and Virulence
The fungal cell wall contains glycoproteins that interact with the host immune system. In the prominent pathogenic yeast Candida albicans, Pmr1 acts as a Golgi-resident ion pump that provides cofactors to mannosyltransferases, regulating the synthesis of mannans attached to glycoproteins. To gain in...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2016-12-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fmicb.2016.01951/full |
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| author | María J. Navarro-Arias Tatiana A. Defosse Tatiana A. Defosse Karine Dementhon Katalin Csonka Erika Mellado-Mojica Aline Dias Valério Roberto J. González-Hernández Vincent Courdavault Marc Clastre Nahúm V. Hernández Luis Antonio Pérez-García Dhirendra K. Singh Csaba Vizler Attila Gacser Ricardo S. Almeida Thierry Noël Mercedes G. López Nicolas Papon Hector M. Mora Montes |
| author_facet | María J. Navarro-Arias Tatiana A. Defosse Tatiana A. Defosse Karine Dementhon Katalin Csonka Erika Mellado-Mojica Aline Dias Valério Roberto J. González-Hernández Vincent Courdavault Marc Clastre Nahúm V. Hernández Luis Antonio Pérez-García Dhirendra K. Singh Csaba Vizler Attila Gacser Ricardo S. Almeida Thierry Noël Mercedes G. López Nicolas Papon Hector M. Mora Montes |
| author_sort | María J. Navarro-Arias |
| collection | DOAJ |
| description | The fungal cell wall contains glycoproteins that interact with the host immune system. In the prominent pathogenic yeast Candida albicans, Pmr1 acts as a Golgi-resident ion pump that provides cofactors to mannosyltransferases, regulating the synthesis of mannans attached to glycoproteins. To gain insight into a putative conservation of such a crucial process within opportunistic yeasts, we were particularly interested in studying the role of the PMR1 homolog in a low-virulent species that rarely causes candidiasis, Candida guilliermondii. We disrupted C. guilliermondii PMR1 and found that loss of Pmr1 affected cell growth and morphology, biofilm formation, susceptibility to cell wall perturbing agents, mannan levels, and the wall composition and organization. Despite there was a significant increment in the amount of β1,3-glucan exposed at the wall surface, this positively influenced only the ability of the mutant to stimulate IL-10 production by human monocytes, suggesting that recognition of both mannan and β1,3-glucan, is required to stimulate strong levels of pro-inflammatory cytokines. Accordingly, our results indicate C. guilliermondii sensing by monocytes was critically dependent on the recognition of N-linked mannans and β1,3-glucan, as reported in other Candida species. In addition, chemical remotion of cell wall O-linked mannans was found to positively influence the recognition of C. guilliermondii by human monocytes, suggesting that O-linked mannans mask other cell wall components from immune cells. This observation contrasts with that reported in C. albicans. Finally, mice infected with C. guilliermondii pmr1 null mutant cells had significantly lower fungal burdens compared to animals challenged with the parental strain. Accordingly, the null mutant showed inability to kill larvae in the Galleria mellonella infection model. This study thus demonstrates that mannans are relevant for the C. guilliermondii-host interaction, with an atypical role for O-linked mannans. |
| first_indexed | 2024-12-11T05:41:22Z |
| format | Article |
| id | doaj.art-4fdf3091cfd541e5a4b4fd0770927e22 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-11T05:41:22Z |
| publishDate | 2016-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-4fdf3091cfd541e5a4b4fd0770927e222022-12-22T01:19:07ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2016-12-01710.3389/fmicb.2016.01951230086Disruption of Protein Mannosylation Affects Candida guilliermondii Cell Wall, Immune Sensing, and VirulenceMaría J. Navarro-Arias0Tatiana A. Defosse1Tatiana A. Defosse2Karine Dementhon3Katalin Csonka4Erika Mellado-Mojica5Aline Dias Valério6Roberto J. González-Hernández7Vincent Courdavault8Marc Clastre9Nahúm V. Hernández10Luis Antonio Pérez-García11Dhirendra K. Singh12Csaba Vizler13Attila Gacser14Ricardo S. Almeida15Thierry Noël16Mercedes G. López17Nicolas Papon18Hector M. Mora Montes19Universidad de GuanajuatoUniversité François-Rabelais de ToursUniversité d'AngersUniversité Bordeaux 2University of SzegedCentro de Investigaciones y de Estudios Avanzados del IPNUniversidade Estadual de LondrinaUniversidad de GuanajuatoUniversité François-Rabelais de ToursUniversité François-Rabelais de ToursUniversidad de GuanajuatoUniversidad de GuanajuatoUniversity of SzegedBiological Research Center of the Hungarian Academy of SciencesUniversity of SzegedUniversidade Estadual de LondrinaUniversité Bordeaux 2Centro de Investigaciones y de Estudios Avanzados del IPNUniversité d'AngersUniversidad de GuanajuatoThe fungal cell wall contains glycoproteins that interact with the host immune system. In the prominent pathogenic yeast Candida albicans, Pmr1 acts as a Golgi-resident ion pump that provides cofactors to mannosyltransferases, regulating the synthesis of mannans attached to glycoproteins. To gain insight into a putative conservation of such a crucial process within opportunistic yeasts, we were particularly interested in studying the role of the PMR1 homolog in a low-virulent species that rarely causes candidiasis, Candida guilliermondii. We disrupted C. guilliermondii PMR1 and found that loss of Pmr1 affected cell growth and morphology, biofilm formation, susceptibility to cell wall perturbing agents, mannan levels, and the wall composition and organization. Despite there was a significant increment in the amount of β1,3-glucan exposed at the wall surface, this positively influenced only the ability of the mutant to stimulate IL-10 production by human monocytes, suggesting that recognition of both mannan and β1,3-glucan, is required to stimulate strong levels of pro-inflammatory cytokines. Accordingly, our results indicate C. guilliermondii sensing by monocytes was critically dependent on the recognition of N-linked mannans and β1,3-glucan, as reported in other Candida species. In addition, chemical remotion of cell wall O-linked mannans was found to positively influence the recognition of C. guilliermondii by human monocytes, suggesting that O-linked mannans mask other cell wall components from immune cells. This observation contrasts with that reported in C. albicans. Finally, mice infected with C. guilliermondii pmr1 null mutant cells had significantly lower fungal burdens compared to animals challenged with the parental strain. Accordingly, the null mutant showed inability to kill larvae in the Galleria mellonella infection model. This study thus demonstrates that mannans are relevant for the C. guilliermondii-host interaction, with an atypical role for O-linked mannans.http://journal.frontiersin.org/Journal/10.3389/fmicb.2016.01951/fullCell WallVirulenceprotein glycosylationCandida guilliermondiimannosylation pathwayhost-fungus interplay |
| spellingShingle | María J. Navarro-Arias Tatiana A. Defosse Tatiana A. Defosse Karine Dementhon Katalin Csonka Erika Mellado-Mojica Aline Dias Valério Roberto J. González-Hernández Vincent Courdavault Marc Clastre Nahúm V. Hernández Luis Antonio Pérez-García Dhirendra K. Singh Csaba Vizler Attila Gacser Ricardo S. Almeida Thierry Noël Mercedes G. López Nicolas Papon Hector M. Mora Montes Disruption of Protein Mannosylation Affects Candida guilliermondii Cell Wall, Immune Sensing, and Virulence Frontiers in Microbiology Cell Wall Virulence protein glycosylation Candida guilliermondii mannosylation pathway host-fungus interplay |
| title | Disruption of Protein Mannosylation Affects Candida guilliermondii Cell Wall, Immune Sensing, and Virulence |
| title_full | Disruption of Protein Mannosylation Affects Candida guilliermondii Cell Wall, Immune Sensing, and Virulence |
| title_fullStr | Disruption of Protein Mannosylation Affects Candida guilliermondii Cell Wall, Immune Sensing, and Virulence |
| title_full_unstemmed | Disruption of Protein Mannosylation Affects Candida guilliermondii Cell Wall, Immune Sensing, and Virulence |
| title_short | Disruption of Protein Mannosylation Affects Candida guilliermondii Cell Wall, Immune Sensing, and Virulence |
| title_sort | disruption of protein mannosylation affects candida guilliermondii cell wall immune sensing and virulence |
| topic | Cell Wall Virulence protein glycosylation Candida guilliermondii mannosylation pathway host-fungus interplay |
| url | http://journal.frontiersin.org/Journal/10.3389/fmicb.2016.01951/full |
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