Identification of virulence determinants of the human-pathogenic fungus Aspergillus fumigatus by proteome analysis

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Aspergillus fumigatus has become the most important airborne fungal pathogen of humans causing pneumonia and invasive disseminated disease with high mortality in the immunocompromised host. Pathogenic fungi need to deal with a variety of environmental challenges during the course of an infection. The ability to meet these challenges requires the expression of many genes. To obtain a comprehensive overview about the proteins present during different infectious processes and potentially important for virulence, we have started to establish proteome analysis for A. fumigatus. Within this priority programme we aim at generating proteome data of A. fumigatus growing under different conditions including the cocultivation of the fungus with macrophages, neutrophils and the reisolation of the fungus from infected mice. Based on these data together with data from other groups, a proteome data base will be established. Interesting genes identified by proteome analysis will be analysed both genetically and biochemically. Deletion mutants of the respective genes will be tested in both macrophage assays and in a low dose, inhalative mouse infection model to determine the contribution of these genes to virulence. An immunogenic transgenic A. fumigatus strain will be generated to analyse the development of a specific immune reaction in living mice. These investigations will lead to the identification of regulatory circuits important for virulence, a better understanding of the communication between pathogen and host and eventually to the identification of targets for antifungal drugs.