title: Structural diversity and biological significance of glycosphingolipids in pathogenic and opportunistic fungi.
abstract: Glycosphingolipids (GSLs) are ubiquitous membrane components and have key roles in biological systems, acting as second messengers or modulators of signal transduction by affecting several events, ranging from cell adhesion, cell growth, cell motility, regulation of apoptosis and cell cycle. Over the last 20 years our laboratory and other research groups determined the glycan and ceramide structures of more than 20 GSLs from several pathogenic/opportunistic fungi, using a combination of gas chromatography, mass spectrometry, nuclear magnetic resonance as well as other immunochemical and biochemical techniques. Fungal GSLs can be divided in two major classes: neutral GSLs, galactosyl- and glucosylceramide (GlcCer), and acidic GSLs, the glycosylinositol-phosphorylceramides (GIPCs). Glycosyl structures in fungal GIPCs exhibited significant structural diversity and distinct composition when compared to mammalian GSLs, e.g., the expression of inositol-mannose and inositol-glucosamine cores and the terminal residue of β-D-galactofuranose which are absent in mammalian cells. Studies performed by our group demonstrated that GIPC (Galfβ 6[Manα3]Manα2InsPCer) elicited in patients with paracoccidioidomycosis an immune response with production of antibodies directed to the terminal residue of β-D-galactofuranose. Further studies also showed that inhibition of GlcCer biosynthetic pathways affects fungal colony formation, spore germination and hyphal growth, indicating that enzymes involved in GlcCer biosynthesis may represent promising targets for the therapy of fungal infections. Recently, it was shown that GlcCer and GIPCs are preferentially localized in membrane microdomains and monoclonal antibodies directed to these GSLs interfere in several fungal biological processes such as growth and morphological transition. This review focuses on glycan structures carried on sphingolipids of pathogenic/opportunistic fungi, and aspects of their biological significance are discussed.
authors.affiliation: Laboratory of Glycoconjugate Immunochemistry, Department of Biochemistry, Escola Paulista de Medicina, Universidade Federal de São Paulo São Paulo, Brazil ; Laboratory of Natural Products, Department of Pharmaceutical Sciences, Universidade Santa Cecilia Santos, Brazil.
authors.forename: Luciana L
authors.initials: LL
authors.lastname: Guimarães
authors.affiliation: Laboratory of Glycoconjugate Immunochemistry, Department of Biochemistry, Escola Paulista de Medicina, Universidade Federal de São Paulo São Paulo, Brazil.
authors.forename: Marcos S
authors.initials: MS
authors.lastname: Toledo
authors.affiliation: Laboratory of Glycoconjugate Immunochemistry, Department of Biochemistry, Escola Paulista de Medicina, Universidade Federal de São Paulo São Paulo, Brazil.
authors.forename: Felipe A S
authors.initials: FA
authors.lastname: Ferreira
authors.affiliation: Laboratory of Glycoconjugate Immunochemistry, Department of Biochemistry, Escola Paulista de Medicina, Universidade Federal de São Paulo São Paulo, Brazil.
authors.forename: Anita H
authors.initials: AH
authors.lastname: Straus
authors.affiliation: Laboratory of Glycoconjugate Immunochemistry, Department of Biochemistry, Escola Paulista de Medicina, Universidade Federal de São Paulo São Paulo, Brazil.
authors.forename: Helio K
authors.initials: HK
authors.lastname: Takahashi
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology; D053898:Biosynthetic Pathways / Q000187:drug effects; D005658:Fungi / Q000145:classification / Q000187:drug effects / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006028:Glycosphingolipids / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism*; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D007155:Immunologic Factors / Q000737:chemistry / Q000378:metabolism; D021962:Membrane Microdomains / Q000737:chemistry / Q000378:metabolism; D015394:Molecular Structure; D009181:Mycoses / Q000188:drug therapy / Q000276:immunology / Q000382:microbiology
chemical_list: D000935:Antifungal Agents; D006028:Glycosphingolipids; D007155:Immunologic Factors
keywords: fungal glycosphingolipids; fungal membrane microdomains; glucosylceramide; glycosphingolipid synthesis inhibitors; glycosylinositol phosphorylceramides