Dataset Information

Role of Protein Mannosylation in the Candida tropicalis-Host Interaction.

ABSTRACT: Mannans are components of the fungal wall attached to proteins via N- or O-linkages. In Candida albicans, Och1 is an ?1,6-mannosyltransferase that adds the first mannose unit to the N-linked mannan outer chain; whereas Pmr1 is an ion pump that imports Mn2+ into the Golgi lumen. This cation is the cofactor of Golgi-resident mannosyltransferases, and thus Pmr1 is involved in the synthesis of both N- and O-linked mannans. Since we currently have limited information about the genetic network behind the Candida tropicalis protein mannosylation machinery, we disrupted OCH1 and PMR1 in this organism. The C. tropicalis pmr1? and och1? mutants showed increased doubling times, aberrant colony and cellular morphology, reduction in the wall mannan content, and increased susceptibility to wall perturbing agents. These changes were accompanied by increased exposure of both ?1,3-glucan and chitin at the wall surface of both mutant strains. Our results showed that O-linked mannans are dispensable for cytokine production by human mononuclear cells, but N-linked mannans and ?1,3-glucan are key ligands to trigger cytokine production in a co-stimulatory pathway involving dectin-1 and mannose receptor. Moreover, we found that the N-linked mannan core found on the surface of C. tropicalis och1? null mutant was capable of inducing cytokine production; and that a mannan-independent pathway for IL-10 production is present in the C. tropicalis-mononuclear cell interaction. Both mutant strains showed virulence attenuation in the Galleria mellonella and the mouse model of systemic candidiasis. Therefore, mannans are relevant for cell wall composition and organization, and for the C. tropicalis-host interaction.

SUBMITTER: Hernandez-Chavez MJ

PROVIDER: S-EPMC6892782 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Role of Protein Mannosylation in the Candida tropicalis-Host Interaction.

Hernández-Chávez Marco J MJ Clavijo-Giraldo Diana M DM Novák Ádám Á Lozoya-Pérez Nancy E NE Martínez-Álvarez José A JA Salinas-Marín Roberta R Hernández Nahúm V NV Martínez-Duncker Iván I Gácser Attila A Mora-Montes Héctor M HM

Frontiers in microbiology 20191128

Mannans are components of the fungal wall attached to proteins via N- or O-linkages. In Candida albicans, Och1 is an α1,6-mannosyltransferase that adds the first mannose unit to the N-linked mannan outer chain; whereas Pmr1 is an ion pump that imports Mn2+ into the Golgi lumen. This cation is the cofactor of Golgi-resident mannosyltransferases, and thus Pmr1 is involved in the synthesis of both N- and O-linked mannans. Since we currently have ...[more]

PMID: 31849889

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Project 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 the 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 pmr1Δ 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.

Dataset Information

Role of Protein Mannosylation in the Candida tropicalis-Host Interaction.

Publications

Role of Protein Mannosylation in the <i>Candida tropicalis</i>-Host Interaction.

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