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

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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 languageEnglish
Article numberofv116
Number of pages11
JournalOpen forum infectious diseases
Volume2
Issue number3
Early online date10 Sep 2015
DOIs
Publication statusPublished - 10 Sep 2015

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Mannosyltransferases
Hyphae
Candida albicans
Yeasts
Mannosides
Virulence
Infection
Glycoconjugates
Inbred C57BL Mouse
Cell Wall
Galectin 3
Mannans
Knockout Mice
Enzymes
Growth

Keywords

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

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β-1,2-Mannosyltransferases 1 and 3 Participate in Yeast and Hyphae O- and N-Linked Mannosylation and Alter Candida albicans Fitness During Infection. / Courjol, Flavie; Jouault, Thierry; Mille, Céline; Hall, Rebecca; Maes, Emmanuel; Sendid, Boualem; Mallet, Jean Maurice; Guerardel, Yann; Gow, Neil A R; Poulain, Daniel; Fradin, Chantal.

In: Open forum infectious diseases, Vol. 2, No. 3, ofv116, 10.09.2015.

Research output: Contribution to journalArticle

Courjol, Flavie ; Jouault, Thierry ; Mille, Céline ; Hall, Rebecca ; Maes, Emmanuel ; Sendid, Boualem ; Mallet, Jean Maurice ; Guerardel, Yann ; Gow, Neil A R ; Poulain, Daniel ; Fradin, Chantal. / β-1,2-Mannosyltransferases 1 and 3 Participate in Yeast and Hyphae O- and N-Linked Mannosylation and Alter Candida albicans Fitness During Infection. In: Open forum infectious diseases. 2015 ; Vol. 2, No. 3.
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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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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).

PY - 2015/9/10

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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.

AB - 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.

KW - Candida albicans

KW - O-mannosylation

KW - fungal virulence

KW - mannosyltransferase

KW - β-1,2-oligomannosides

U2 - 10.1093/ofid/ofv116

DO - 10.1093/ofid/ofv116

M3 - Article

VL - 2

JO - Open forum infectious diseases

JF - Open forum infectious diseases

SN - 2328-8957

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