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.
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).
- Candida albicans
- fungal virulence