Structural diversity and biological significance of glycosphingolipids in pathogenic and opportunistic fungi
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 th...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2014-09-01
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| Series: | Frontiers in Cellular and Infection Microbiology |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fcimb.2014.00138/full |
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| author | Luciana Lopes Guimaraes Luciana Lopes Guimaraes Marcos Sergio Toledo Felipe Araujo Souza Ferreira Anita Hilda Straus Helio K Takahashi |
| author_facet | Luciana Lopes Guimaraes Luciana Lopes Guimaraes Marcos Sergio Toledo Felipe Araujo Souza Ferreira Anita Hilda Straus Helio K Takahashi |
| author_sort | Luciana Lopes Guimaraes |
| collection | DOAJ |
| description | 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 (Galfβ6[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. |
| first_indexed | 2024-12-14T02:38:40Z |
| format | Article |
| id | doaj.art-c75434e3abf2493aa115e9fd54c617eb |
| institution | Directory Open Access Journal |
| issn | 2235-2988 |
| language | English |
| last_indexed | 2024-12-14T02:38:40Z |
| publishDate | 2014-09-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj.art-c75434e3abf2493aa115e9fd54c617eb2022-12-21T23:20:04ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882014-09-01410.3389/fcimb.2014.00138110808Structural diversity and biological significance of glycosphingolipids in pathogenic and opportunistic fungiLuciana Lopes Guimaraes0Luciana Lopes Guimaraes1Marcos Sergio Toledo2Felipe Araujo Souza Ferreira3Anita Hilda Straus4Helio K Takahashi5Escola Paulista de Medicina/Universidade Federal de São PauloUniversidade Santa CeciliaEscola Paulista de Medicina/Universidade Federal de São PauloEscola Paulista de Medicina/Universidade Federal de São PauloEscola Paulista de Medicina/Universidade Federal de São PauloEscola Paulista de Medicina/Universidade Federal de São PauloGlycosphingolipids (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 (Galfβ6[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.http://journal.frontiersin.org/Journal/10.3389/fcimb.2014.00138/fullglucosylceramidefungal glycosphingolipidsglycosphingolipid synthesis inhibitorsfungal membrane microdomainsglycosylinositol phosphorylceramides |
| spellingShingle | Luciana Lopes Guimaraes Luciana Lopes Guimaraes Marcos Sergio Toledo Felipe Araujo Souza Ferreira Anita Hilda Straus Helio K Takahashi Structural diversity and biological significance of glycosphingolipids in pathogenic and opportunistic fungi Frontiers in Cellular and Infection Microbiology glucosylceramide fungal glycosphingolipids glycosphingolipid synthesis inhibitors fungal membrane microdomains glycosylinositol phosphorylceramides |
| title | Structural diversity and biological significance of glycosphingolipids in pathogenic and opportunistic fungi |
| title_full | Structural diversity and biological significance of glycosphingolipids in pathogenic and opportunistic fungi |
| title_fullStr | Structural diversity and biological significance of glycosphingolipids in pathogenic and opportunistic fungi |
| title_full_unstemmed | Structural diversity and biological significance of glycosphingolipids in pathogenic and opportunistic fungi |
| title_short | Structural diversity and biological significance of glycosphingolipids in pathogenic and opportunistic fungi |
| title_sort | structural diversity and biological significance of glycosphingolipids in pathogenic and opportunistic fungi |
| topic | glucosylceramide fungal glycosphingolipids glycosphingolipid synthesis inhibitors fungal membrane microdomains glycosylinositol phosphorylceramides |
| url | http://journal.frontiersin.org/Journal/10.3389/fcimb.2014.00138/full |
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