HEADProf. LATGÉ Jean-Paul /
Dr IBRAHIM-GRANET Oumaima / Dr LAMARRE Claude / Dr MOUYNA Isabelle / SARFATI Jacqueline

  Annual Report

Aspergillus fumigatus is a ubiquitous thermophilic, saprophytic filamentous fungus that disseminates by producing air-borne spores (fig.) 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 immunocompromized patients. A. fumigatus has become today the major fungal air-borne pathogen in terms of morbidity and mortality in developed countries.

A prominent fungal feature: The cell wall

In A. fumigatus, like in other pathogenic fungi, the cell wall is essential for fungal growth as well as for resisting environmental stresses. Moreover, cell wall biosynthetic enzymes represent unique drug targets. The cell wall of A. fumigatus is almost exclusively composed of polysaccharides. The fibrillar core of the cell wall of A. fumigatus is basically composed of a ß1,3 branched glucan – chitin complex, embedded in an amorphous cement composed of linear chains of α(1-3) (1-4) glucan linked to galactomannan. These two polysaccharides are also major components of the extracellular matrix that hold hyphae together as a biofilm.

This biofilm favours fungal growth and increases resistance to antifungals. Enzymes involved in the biosynthesis of α and β1-3 glucans, chitin, galactan and N- and O- mannans have been analyzed using genomic and biochemical approaches. The enzymes that are responsible for the branching and cross-linking of the three-dimensional network of cell wall polysaccharides are also investigated, especially among proteins anchored to plasma membrane by a glycosylphosphatidylinositol moiety.

Host-pathogen interactions

Targeted or random gene disruption strategies were not able to identify true virulence determinants of this fungus. The analysis of two metabolic pathways (the methyl citrate and glyoxylate pathways that are “satellites” of the Krebs cycle) and the uptake of divalent cations (Mg, Zn and Fe) have shown that auxotrophy results in a decrease in virulence of this organism. The phagocytosis of A. fumigatus by the alveolar macrophage, the main phagocyte against the fungus, has been investigated. Receptors, signal transduction cascades and effectors activated by the phagocytosis of the fungus have been identified. We also studied the fungal effector molecules able to counteract the reactive oxidant damages responsible for the intraphagocytic killing of Aspergillus. The immunomodulatory activity and diagnosis potential of antigens of A. fumigatus have been investigated and have lead to the development of new kits for the diagnosis of invasive aspergillosis.



Publications 2006 of the unit on Pasteur's references database

Activity Reports 2006 - Institut Pasteur
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