Abstract
The first work reporting synthesis of glucosylceramide (cerebrin, GlcCer) by yeasts was published in 1930. During approximately 70 years members of this class of glycosphingolipids (GSL) were considered merely structural components of plasma membrane in fungi. However, in the last decade GlcCer was reported to be involved with fungal growth, differentiation, virulence, immunogenicity, and lipid raft architecture in at least two human pathogens. Fungal GlcCer are structurally distinct from their mammalian counterparts and enriched at the cell wall, which makes this molecule an effective target for antifungal activity of specific ligands (peptides and antibodies to GlcCer). Therefore, GSL are promising targets for new drugs to combat fungal diseases. This review discusses the most recent information on biosynthesis and role of GlcCer in fungal pathogens.
Highlights
The family of glycosphingolipids (GSL) combines a diversity of molecules consisting of at least one saccharide unit covalently linked to a ceramide (Schnaar et al, 2009)
A unit of inositol is covalently linked to the ceramide and the preformed molecule, which is not found in mammalian cells, is the substrate for mannosyltransferases for the synthesis of mannosylinositol phosphorylceramide (MIPC) and mannosyldiinositol phosphorylceramide [M(IP)2C]
FUNGAL GlcCer AS TARGETS TO NEW ANTIFUNGAL DRUGS Together with other groups we have demonstrated the use of antiGlcCer antibodies to prevent fungal differentiation and growth of fungal pathogens
Summary
The family of glycosphingolipids (GSL) combines a diversity of molecules consisting of at least one saccharide unit covalently linked to a ceramide (Schnaar et al, 2009). Inositol phosphorylceramides (IPC) are used to make complex fungal GSL and have been extensively studied in the yeast model Saccharomyces cerevisiae (Sugimoto et al, 2004; Dickson et al, 2006; Dickson, 2008) They consist of a ceramide usually containing phytosphingosine as long chain base, associated with a very long fatty acid (C24:1–C26:1). THE UNCOVERED PATHWAY FOR FUNGAL GlcCer SYNTHESIS Sphingoid bases of fungal GlcCer are structurally distinct from mannosylated IPCs and from their counterparts in animal cells They have a methyl group at C-9 and an extra unsaturation at C-8, forming the typical fungal base mentioned above (for review please see Barreto-Bergter et al, 2004). Initial steps of ceramide biosynthesis are the same independent of the cell type studied
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