title: 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: 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.
authors.affiliation: Université de Lille ; Institut National de la Santé et de la Recherche Médicale, Lille Inflammation Research International Center-Unité Mixte de Recherche 995 , France.
authors.forename: Flavie
authors.initials: F
authors.lastname: Courjol
authors.affiliation: Université de Lille ; Institut National de la Santé et de la Recherche Médicale, Lille Inflammation Research International Center-Unité Mixte de Recherche 995 , France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Jouault
authors.affiliation: Université de Lille ; Institut National de la Santé et de la Recherche Médicale, Lille Inflammation Research International Center-Unité Mixte de Recherche 995 , France.
authors.forename: Céline
authors.initials: C
authors.lastname: Mille
authors.affiliation: Aberdeen Fungal Group, School of Medical Sciences , Institute of Medical Sciences , University of Aberdeen , Foresterhill , United Kingdom.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Hall
authors.affiliation: Université de Lille , Unité de Glycobiologie Structurale et Fonctionnelle ; Centre National de la Recherche Scientifique , Unité Mixte de Recherche 8576 , Villeneuve d'Ascq.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Maes
authors.affiliation: Université de Lille ; Institut National de la Santé et de la Recherche Médicale, Lille Inflammation Research International Center-Unité Mixte de Recherche 995 , France ; Centre Hospitalier Régional Universitaire de Lille, Centre Biologie et Pathologie.
authors.forename: Boualem
authors.initials: B
authors.lastname: Sendid
authors.affiliation: Laboratoire des Biomolécules Unité Mixte de Recherche 7203 , Université Pierre et Marie Curie, Ecole Normale Supérieure , Paris , France.
authors.forename: Jean Maurice
authors.initials: JM
authors.lastname: Mallet
authors.affiliation: Université de Lille , Unité de Glycobiologie Structurale et Fonctionnelle ; Centre National de la Recherche Scientifique , Unité Mixte de Recherche 8576 , Villeneuve d'Ascq.
authors.forename: Yann
authors.initials: Y
authors.lastname: Guerardel
authors.affiliation: Aberdeen Fungal Group, School of Medical Sciences , Institute of Medical Sciences , University of Aberdeen , Foresterhill , United Kingdom.
authors.forename: Neil A R
authors.initials: NA
authors.lastname: Gow
authors.affiliation: Université de Lille ; Institut National de la Santé et de la Recherche Médicale, Lille Inflammation Research International Center-Unité Mixte de Recherche 995 , France ; Centre Hospitalier Régional Universitaire de Lille, Centre Biologie et Pathologie.
authors.forename: Daniel
authors.initials: D
authors.lastname: Poulain
authors.affiliation: Université de Lille ; Institut National de la Santé et de la Recherche Médicale, Lille Inflammation Research International Center-Unité Mixte de Recherche 995 , France.
authors.forename: Chantal
authors.initials: C
authors.lastname: Fradin
keywords: Candida albicans; O-mannosylation; fungal virulence; mannosyltransferase; β-1,2-oligomannosides