Function of glucanases in the morphogenesis of Aspergillus fumigatus

Together with the increasing number of immunocompromised patients, the number of hosts for invasive fungal infections has continuously risen in the recent past. Due to the limited efficiency of antifungal treatments, filamentous fungi like Aspergillus fumigatus have become to date the most threatening and problematic aerial pathogens in developed countries. The cell wall of fungi plays an essential biological role in terms of cell protection and invasion of its environment (hosts, insoluble substrates). If it is removed or weakened, the fungus usually dies. Because of its unique biochemistry and structural organization and the absence of most of its constitutive components in mammalian cells, the cell wall is an attractive target for the development of new antifungal agents. Changes in shape of fungal cells during their life cycle, for example spore germination, require a rebuilding of the cell wall. This is accompanied with a softening of the cell wall, which is accomplished by various chitinases and glucanases, cleaving the major cell wall components. Because alpha- and beta-1,3-glucans are the most abundant constitutive polysaccharides of the cell wall next to chitin, endo alpha- and beta-1,3-glucanases should play a major role in its biochemical modifications during morphogenesis. The aim of this study is to investigate the role of different glucanases in cell wall morphogenesis using both a biochemical and genetic approach. Based on a genome wide analysis of Aspergillus fumigatus various glucanases have been identified. Now a transcriptional analysis shall demonstrate, under which conditions they are active. Relying on the transcriptional characterization of the glucanases, their role in spore germination of A. fumigatus will be investigated. Together with a biochemical characterization of the relevant glucanases, this project shall help finding new approaches for the development of effective antifungal treatments.