Initiation of phospholipomannan β-1,2 mannosylation involves Bmts with redundant activity, influences its cell wall location and regulates β-glucans homeostasis but is dispensable for Candida albicans systemic infection

F. Courjol, C. Mille, R. A. Hall, A. Masset, R. Aijjou, N. A R Gow, D. Poulain, T. Jouault, C. Fradin*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

Pathogenic and non-pathogenic fungi synthesize glycosphingolipids, which have a crucial role in growth and viability. Glycosphingolipids also contribute to fungal-associated pathogenesis. The opportunistic yeast pathogen Candida albicans synthesizes phospholipomannan (PLM), which is a glycosphingolipid of the mannosylinositol phosphorylceramide family. Through its lipid and glycan moieties, PLM contributes to the initial recognition of the yeast, causing immune system disorder and persistent fungal disease through activation of host signaling pathways. The lipid moiety of PLM activates the deregulation signaling pathway involved in yeast phagocytosis whereas its glycan moiety, composed of β-1,2 mannosides (β-Mans), participates to inflammatory processes through a mechanism involving Galectin-3. Biosynthesis of PLM β-Mans involves two β-1,2 mannosyltransferases (Bmts) that initiate (Bmt5) and elongate (Bmt6) the glycan chains. After generation of double bmtsΔ mutants, we show that Bmt5 has redundant activity with Bmt2, which can replace Bmt5 in bmt5Δ mutant. We also report that PLM is located in the inner layer of the yeast cell wall. PLM seems to be not essential for systemic infection of the yeast. However, defect of PLM β-mannosylation increases resistance of C. albicans to inhibitors of β-glucans and chitin synthesis, highlighting a role of PLM in cell wall homeostasis.

Original languageEnglish
Pages (from-to)96-104
Number of pages9
JournalBiochimie
Volume120
Early online date30 Sept 2015
DOIs
Publication statusPublished - Jan 2016

Bibliographical note

This work was supported by the “Agence Nationale de la Recherche” (grant ANR-09-MIE-031-01); the European project “AllFun” from the 7thFramework 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).

We gratefully acknowledge Prof. A. P. Mitchell (Carnegie Mellon University, Pittsburgh, USA), Prof. A. J. P. Brown (Department of Molecular and Cell Biology, Aberdeen, UK) and Prof. R. Robert (GEIHP, Univesrité d'Angers, France) for providing pDDB57 and CIp10 plasmids and mAb 5B2, respectively.

We thank the animal facility “Département Hospitalo-Universitaire de Recherche Expérimentale” from IMPRT-IFR114 for the maintenance of mice.

In memorandum to Pierre-André Trinel who discovered and characterized phospholipomannan from Candida albicans.

Keywords

  • Cell wall
  • Glycosphingolipid
  • Virulence
  • Yeast
  • β-1,2 Mannosyltransferases

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