β-1,2-Mannosyltransferases 1 and 3 Participate in Yeast and Hyphae O- and N-Linked Mannosylation and Alter Candida albicans Fitness During Infection

Flavie Courjol; Thierry Jouault; Céline Mille; Rebecca Hall; Emmanuel Maes; Boualem Sendid; Jean Maurice Mallet; Yann Guerardel; Neil A R Gow; Daniel Poulain; Chantal Fradin

doi:10.1093/ofid/ofv116

β-1,2-Mannosyltransferases 1 and 3 Participate in Yeast and Hyphae O- and N-Linked Mannosylation and Alter Candida albicans Fitness During Infection

Flavie Courjol, Thierry Jouault, Céline Mille, Rebecca Hall, Emmanuel Maes, Boualem Sendid, Jean Maurice Mallet, Yann Guerardel, Neil A R Gow, Daniel Poulain, Chantal Fradin

Medical Sciences

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Abstract

β-1,2-mannosylation of Candida albicans glycoconjugates has been investigated through the identification of enzymes involved in the addition of β-1,2-oligomannosides (β-Mans) to phosphopeptidomannan and phospholipomannan. β-1,2-oligomannosides are supposed to have virulence properties that they confer to these glycoconjugates. In a previous study, we showed that cell wall mannoproteins (CWMPs) harbor β-Mans in their O-mannosides; therefore, we analyzed their biosynthesis and impact on virulence. In this study, we demonstrate that O-mannans are heterogeneous and that α-mannosylated O-mannosides, which are biosynthesized by Mnt1 and Mnt2 α-1,2-mannosyltransferases, can be modified with β-Mans but only at the nonreducing end of α-1,2-mannotriose. β-1,2-mannosylation of this O-mannotriose depends on growth conditions, and it involves 2 β-1,2-mannosyltransferases, Bmt1 and Bmt3. These Bmts are essential for β-1,2-mannosylation of CWMPs and expression of β-Mans on germ tubes. A bmt1Δ mutant and a mutant expressing no β-Mans unexpectedly disseminated more in BALB/c mice, whereas they had neither attenuated nor enhanced virulence in C57BL/6 mice. In galectin (Gal)3 knockout mice, the reference strain was more virulent than in C57BL/6 mice, suggesting that the β-Mans innate receptor Gal3 is involved in C. albicans fitness during infection.

Original language	English
Article number	ofv116
Number of pages	11
Journal	Open forum infectious diseases
Volume	2
Issue number	3
Early online date	10 Sept 2015
DOIs	https://doi.org/10.1093/ofid/ofv116
Publication status	Published - 10 Sept 2015

Bibliographical note

Acknowledgments
We gratefully acknowledge Professor A. P. Mitchell (Carnegie Mellon University, Pittsburgh, PA), Professor A. J. P. Brown (Department of Molecular and Cell Biology, Aberdeen, UK), and Professor R. Robert (GEIHP, Univesrité d'Angers, France), for providing pDDB57 and CIp10 plasmids and mAb 16B1. We are indebted to Annick Masset for excellent technical assistance. This work has benefited from the facilities and expertise of the SICaPS platform of IMAGIF (Centre de Recherche de Gif-www.imagif.cnrs.fr). We thank the animal facility Département Hospitalo-Universitaire de Recherche Expérimentale from IMPRT-IFR114 for the maintenance of mice.

Financial support. This work was supported by the Agence Nationale de la Recherche (grant ANR-09-MIE-031-01); the European project AllFun from the 7th Framework Programme-Health (grant 260338), and the College Doctoral Lille Nord de France (Ouverture Internationale des Etudes et de la Formation Doctorale en Région Nord-Pas de Calais). N. A. R. G. was also supported by the Wellcome Trust (grants 080088, 086827, 075470, and 099215).

Keywords

Candida albicans
O-mannosylation
fungal virulence
mannosyltransferase
β-1,2-oligomannosides

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10.1093/ofid/ofv116Licence: CC BY-NC-ND

β-1,2-Mannosyltransferases 1 and 3 Participate in Yeast and Hyphae O- and N-Linked Mannosylation and Alter Candida albicans Fitness During Infection
© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com. DOI: 10.1093/ofid/ofv116
Final published version, 477 KBLicence: CC BY-NC-ND

Cite this

Courjol, F., Jouault, T., Mille, C., Hall, R., Maes, E., Sendid, B., Mallet, J. M., Guerardel, Y., Gow, N. A. R., Poulain, D., & Fradin, C. (2015). β-1,2-Mannosyltransferases 1 and 3 Participate in Yeast and Hyphae O- and N-Linked Mannosylation and Alter Candida albicans Fitness During Infection. Open forum infectious diseases, 2(3), Article ofv116. https://doi.org/10.1093/ofid/ofv116

Courjol, F, Jouault, T, Mille, C, Hall, R, Maes, E, Sendid, B, Mallet, JM, Guerardel, Y, Gow, NAR, Poulain, D & Fradin, C 2015, 'β-1,2-Mannosyltransferases 1 and 3 Participate in Yeast and Hyphae O- and N-Linked Mannosylation and Alter Candida albicans Fitness During Infection', Open forum infectious diseases, vol. 2, no. 3, ofv116. https://doi.org/10.1093/ofid/ofv116

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abstract = "β-1,2-mannosylation of Candida albicans glycoconjugates has been investigated through the identification of enzymes involved in the addition of β-1,2-oligomannosides (β-Mans) to phosphopeptidomannan and phospholipomannan. β-1,2-oligomannosides are supposed to have virulence properties that they confer to these glycoconjugates. In a previous study, we showed that cell wall mannoproteins (CWMPs) harbor β-Mans in their O-mannosides; therefore, we analyzed their biosynthesis and impact on virulence. In this study, we demonstrate that O-mannans are heterogeneous and that α-mannosylated O-mannosides, which are biosynthesized by Mnt1 and Mnt2 α-1,2-mannosyltransferases, can be modified with β-Mans but only at the nonreducing end of α-1,2-mannotriose. β-1,2-mannosylation of this O-mannotriose depends on growth conditions, and it involves 2 β-1,2-mannosyltransferases, Bmt1 and Bmt3. These Bmts are essential for β-1,2-mannosylation of CWMPs and expression of β-Mans on germ tubes. A bmt1Δ mutant and a mutant expressing no β-Mans unexpectedly disseminated more in BALB/c mice, whereas they had neither attenuated nor enhanced virulence in C57BL/6 mice. In galectin (Gal)3 knockout mice, the reference strain was more virulent than in C57BL/6 mice, suggesting that the β-Mans innate receptor Gal3 is involved in C. albicans fitness during infection.",

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author = "Flavie Courjol and Thierry Jouault and C{\'e}line Mille and Rebecca Hall and Emmanuel Maes and Boualem Sendid and Mallet, {Jean Maurice} and Yann Guerardel and Gow, {Neil A R} and Daniel Poulain and Chantal Fradin",

note = "Acknowledgments We gratefully acknowledge Professor A. P. Mitchell (Carnegie Mellon University, Pittsburgh, PA), Professor A. J. P. Brown (Department of Molecular and Cell Biology, Aberdeen, UK), and Professor R. Robert (GEIHP, Univesrit{\'e} d'Angers, France), for providing pDDB57 and CIp10 plasmids and mAb 16B1. We are indebted to Annick Masset for excellent technical assistance. This work has benefited from the facilities and expertise of the SICaPS platform of IMAGIF (Centre de Recherche de Gif-www.imagif.cnrs.fr). We thank the animal facility D{\'e}partement Hospitalo-Universitaire de Recherche Exp{\'e}rimentale from IMPRT-IFR114 for the maintenance of mice. Financial support. This work was supported by the Agence Nationale de la Recherche (grant ANR-09-MIE-031-01); the European project AllFun from the 7th Framework Programme-Health (grant 260338), and the College Doctoral Lille Nord de France (Ouverture Internationale des Etudes et de la Formation Doctorale en R{\'e}gion Nord-Pas de Calais). N. A. R. G. was also supported by the Wellcome Trust (grants 080088, 086827, 075470, and 099215).",

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T1 - β-1,2-Mannosyltransferases 1 and 3 Participate in Yeast and Hyphae O- and N-Linked Mannosylation and Alter Candida albicans Fitness During Infection

AU - Courjol, Flavie

AU - Jouault, Thierry

AU - Mille, Céline

AU - Hall, Rebecca

AU - Maes, Emmanuel

AU - Sendid, Boualem

AU - Mallet, Jean Maurice

AU - Guerardel, Yann

AU - Gow, Neil A R

AU - Poulain, Daniel

AU - Fradin, Chantal

N1 - Acknowledgments We gratefully acknowledge Professor A. P. Mitchell (Carnegie Mellon University, Pittsburgh, PA), Professor A. J. P. Brown (Department of Molecular and Cell Biology, Aberdeen, UK), and Professor R. Robert (GEIHP, Univesrité d'Angers, France), for providing pDDB57 and CIp10 plasmids and mAb 16B1. We are indebted to Annick Masset for excellent technical assistance. This work has benefited from the facilities and expertise of the SICaPS platform of IMAGIF (Centre de Recherche de Gif-www.imagif.cnrs.fr). We thank the animal facility Département Hospitalo-Universitaire de Recherche Expérimentale from IMPRT-IFR114 for the maintenance of mice. Financial support. This work was supported by the Agence Nationale de la Recherche (grant ANR-09-MIE-031-01); the European project AllFun from the 7th Framework Programme-Health (grant 260338), and the College Doctoral Lille Nord de France (Ouverture Internationale des Etudes et de la Formation Doctorale en Région Nord-Pas de Calais). N. A. R. G. was also supported by the Wellcome Trust (grants 080088, 086827, 075470, and 099215).

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N2 - β-1,2-mannosylation of Candida albicans glycoconjugates has been investigated through the identification of enzymes involved in the addition of β-1,2-oligomannosides (β-Mans) to phosphopeptidomannan and phospholipomannan. β-1,2-oligomannosides are supposed to have virulence properties that they confer to these glycoconjugates. In a previous study, we showed that cell wall mannoproteins (CWMPs) harbor β-Mans in their O-mannosides; therefore, we analyzed their biosynthesis and impact on virulence. In this study, we demonstrate that O-mannans are heterogeneous and that α-mannosylated O-mannosides, which are biosynthesized by Mnt1 and Mnt2 α-1,2-mannosyltransferases, can be modified with β-Mans but only at the nonreducing end of α-1,2-mannotriose. β-1,2-mannosylation of this O-mannotriose depends on growth conditions, and it involves 2 β-1,2-mannosyltransferases, Bmt1 and Bmt3. These Bmts are essential for β-1,2-mannosylation of CWMPs and expression of β-Mans on germ tubes. A bmt1Δ mutant and a mutant expressing no β-Mans unexpectedly disseminated more in BALB/c mice, whereas they had neither attenuated nor enhanced virulence in C57BL/6 mice. In galectin (Gal)3 knockout mice, the reference strain was more virulent than in C57BL/6 mice, suggesting that the β-Mans innate receptor Gal3 is involved in C. albicans fitness during infection.

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KW - Candida albicans

KW - O-mannosylation

KW - fungal virulence

KW - mannosyltransferase

KW - β-1,2-oligomannosides

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DO - 10.1093/ofid/ofv116

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JO - Open forum infectious diseases

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ER -

β-1,2-Mannosyltransferases 1 and 3 Participate in Yeast and Hyphae O- and N-Linked Mannosylation and Alter Candida albicans Fitness During Infection

Abstract

Bibliographical note

Keywords

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