|HEAD||Prof. Latgé Jean-Paul / firstname.lastname@example.org|
|MEMBERS||Dr AIMANIANDA BOPAIAH Kumar Vishu Post Doct/ BEAU Rémi, Technician/ Dr BEAUVAIS Anne/ Dr CLAVAUDCécilePost Doct/ COMTE Catherine, Lab support/ Dr DESANGLE Aurélie Post Doct/ Dr FONTAINE Thierry
GASTEBOIS Amandine, PhD Student/ Dr HARTL Lukas Post Doct/ HENRY Christine, Technician/ Dr LAMARRE Claude Post Doct/ Dr LAMBOU Karine Post Doct/ Dr MOUYNA Isabelle
PACORY Fabienne, Secretary/ SARFATI-BERT Jacqueline, INSERM / Dr WONG Joanne Post Doct
Aspergillus fumigatus is a ubiquitous thermophilic, saprophytic filamentous fungus that disseminates by producing spores that are present in all environments and are continuously inhaled by the humans. For that reason, this mould is responsible for invasive pulmonary diseases, most often fatal among immunocompromised patients. A.fumigatus has become today the major fungal air-borne pathogen in terms of morbidity and mortality in developed countries. The expertise of our unit in biochemistry and molecular biology of A.fumigatus is unique in the world and has allowed to progress significantly in the understanding of the pathology of these threatening infections.
In A.fumigatus , like in other pathogenic fungi, the cell wall is essential for fungal growth as well as for resisting environmental stresses. The cell wall of A.fumigatus is exclusively composed of polysaccharides. The fibrillar core of the A.fumigatus cell wall is basically composed of branched β1-3 glucan – chitin complex, embedded in an amorphous cement composed of linear chains of α(1-3) (1-4) glucan associated to galactomannan. These two polysaccharides are also major components of the extracellular matrix that hold hyphae together as a biofilm. This biofilm favours growth and increases resistance to antifungals. New polysaccharides with a potential in aspergillosis diagnosis have been identified. Organizing the three-dimensional network of polysaccharides responsible for the rigidity of the cell wall is a very complex and sequential enzymatic process. The enzymes involved in the biosynthesis of α and β1-3 glucans, chitin, galactan and N-and O- mannans are analyzed using genomic and biochemical approaches. New enzymatic activities that are responsible for the branching and cross-linking of the cell wall polysaccharides have been recently identified.
In collaboration with several other research laboratories, PAMPs and PRRs involved in the immune response of the immunocompetent and immunocompromised mammalian host against A.fumigatus are currently analysed. This approach will open the way to new cellular immunotherapies that are a promising alternative to the poorly efficient antifungal therapies currently available.
Keywords: Aspergillus, aspergillosis, cell wall, glycobiology, genetics
Costachel C, Coddeville B, Latgé JP, Fontaine T (2005) Glycosylphosphatidylinositol-anchored fungal polysaccharide in Aspergillus fumigatus. J. Biol. Chem. 280:39835-39842.
Mouyna I, Morelle W, Vai M, Mono, M, Léchenne B, Fontaine T, Beauvais A, Sarfati J, Prévost MC, Henry C, Latgé JP (2005) Deletion of GEL2 encoding for a ß(1-3) glucanosyltransferase affects morphogenesis and virulence in Aspergillus fumigatus. Mol. Microbiol. 56:1675-1688.
Beauvais A, Schmidt C, Guadagnisi S, Roux P, Perret E, Henry C, Paris S, Mallet A, Prevost MC, Latgé JP (2007). An extracellular matrix glues together the aerial grown hyphae of Aspergillus fumigatus. Cell Microbiol. 9:1588-600.
Lamarre C, Sokol S, Debeaupuis JP, Henry C, Lacroix C, Glaser P, Coppée JY, François JM, Latgé JP (2008) Transcriptomic analysis of the exit from dormancy of Aspergillus fumigatus conidia. BMC Genomics. 9:417.
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Activity Reports 2009 - Institut Pasteur
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