Aspergillus  


  HEADProf. Latgé Jean-Paul / jplatge@pasteur.fr
  MEMBERSDr AIMANIANDA BOPAIAH Kumar Vishu Post-Doct/ BEAU Rémi, Technician/ Dr BEAUVAIS Anne, Scientist/ Dr CLAVAUD Cécile Post-Doct/ COMTE Catherine, Lab support/ Dr FONTAINE Thierry Scientist/ Dr HARTL Lukas Post-Doct/ HENRY Christine, Technician/ Dr JANBON Guilhem, Head of laboratory/ Dr LAMBOU Karine Post-Doct/ MOYRAND Frédérique, Technician/ MELLOUL Elise, PhD student/ Dr MOUYNA Isabelle Scientist/ PACORY Fabienne, Secretary/ Dr TADA Rui, Post-doc/ Dr WONG SAK HOI Joanne, Post-Doct


  Annual Report

Among infectious diseases, mycoses are often forgotten actors. Although they do not convey the miracle attribute "epidemics", systemic fungal infections are an increasingly significant medical problem in industrialised countries. Fungal infections are associated with a high mortality mainly because of the lack of accurate and speedy diagnostic tests for these infections, but also because current systemic antifungal therapies are not always effective. In spite of this poor efficiency, the cost of antifungals has become now the second or first drug expenses in the hospital.

The purpose of our research is to better understand the biology of fungal pathogens through genetic, biochemical and immunological approaches. More precisely, studies are concentrated on the biosynthesis of the cell wall and associated extracellular matrix and the role of the components of these fungal structures during the fungal developmentin vivoandin vitro.t. The research in our unit is centered onthe two major fungal respiratory fungal pathogens Aspergillus fumigatusand Cryptococcus neoformans.The expertise of our unit in the biochemistry and molecular biology of these two pathogens is unique in the world and has allowed to progress significantly in the understanding of the pathology of these threatening infections.

The cell wallis essential for fungal life. The fibrillar core of the A.fumigatuscell wall is basically composed of branched β1-3 glucan – chitin complex, embedded in an amorphous cement composed of linear chains of α(1-3) glucan associated to galactomannan. These two polysaccharides are also major components of the extracellular matrix that hold hyphae together as a biofilm that resists to antifungals. 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 the atmosphere, there is thousands of conidia/m3originating from more than hundred fungal genera, which enter the host through the respiratory system. These spores are full of antigens and allergens. It was not understood until recently how these spores did not initiate a huge inflammatory reaction in the lung upon conidial inhalation. Airborne conidia are covered by a layer of hydrophobic proteins (hydrophobins) arranged as a rodlet layer. Using our model fungus A. fumigatus, we demonstrated recently the role of the spore-surface rodlet layer in preventing their recognition by the immune system. Upon removal of this rodlet layer by chemical, genetic or biological means, the resulting morphotypes were immunostimulatory in effect, confirming the essentiality of the role of the rodlet layer for the fungal survival in vivo. In collaboration with other laboratories, carbohydrate PAMPs and PRRs triggering the immune response against A.fumigatusare currently analysed. This approach has opened the way to new cellular immunotherapies that are a promising alternative to the poorly efficient antifungal therapies currently available.

The capsule is the main virulence factor of C. neoformans. It is composed of large polysaccharides. Analysis of its structure using different anti capsule monoclonal antibodies revealed a great cell to cell variability in a clonal population. Our working hypothesis is that the differential splicing of some capsule genes could be responsible for such an antigenic heterogeneity.

Keywords: Aspergillus, aspergillosis, cell wall, glycobiology, genetics



  Publications

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.

Moyrand F., Fontaine, T. & Janbon G. (2007) Systematic capsule gene disruption reveals the central role of galactose metabolism on Cryptococcus neoformans virulence. Mol. Microbiol. 64, 771-781

Aimanianda V, Bayry J, Biozza S, Kniemeyer O, Perruccio K, Elluru R, Clavaud C, Paris S, Brakhage AA, Kaveri SV, Romani L, Latgé JP (2009) Surface hydrophobin prevents immune recognition of airborne fungal conidia. Nature. 460:1117-21.

Gastebois A, Mouyna I, Simenel C, Clavaud C, Coddeville B, Delepierre M, Latgé JP, Fontaine T. (2010) Characterization of a new {beta}(1-3)glucan branching activity of Aspergillus fumigatus. J Biol Chem. 285:2386-96



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Activity Reports 2009 - Institut Pasteur
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