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.

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.

• Authors: F Courjol, C Mille, R A Hall, A Masset, R Aijjou, N A R Gow, D Poulain, T Jouault, C Fradin
• Journal: Biochimie (Biochimie) Vol. 120 Pg. 96-104 (Jan 2016) ISSN: 1638-6183 [Electronic] France
• PMID: 26427558 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

Chemical References

• Glycolipids
• phospholipomannan
• Methyltransferases

Topics

• Animals
• Candida albicans (genetics, metabolism, pathogenicity)
• Candidiasis, Invasive (genetics, metabolism, pathology)
• Cell Wall (genetics, metabolism)
• Female
• Gene Deletion
• Glycolipids (genetics, metabolism)
• Methyltransferases (genetics, metabolism)
• Mice
• Mice, Inbred BALB C