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Abstract
Aspergillus fumigatus is the most important air-borne fungal pathogen, causing severe
infections in immunocompromised patients. Mitogen-activated protein kinase (MAPK)
signaling pathways are involved in the regulation of various cellular responses to
environmental changes in eukaryotes. Genome Blast analysis revealed that the central
core of the cell wall integrity signaling pathway in A. fumigatus is composed of three
protein kinases designated Bck1, Mkk2 and MpkA. This pathway is of particular interest
because it represents a possible target for new antifungal drugs. Deletion of these
genes resulted in severe sensitivity of the mutants against cell wall-disturbing compounds
and drastic alterations of the fungal morphology. Western blot analysis demonstrated
that Bck1 and Mkk2 directly activate MpkA during vegetative growth and under cell
wall stress conditions further confirming that Bck1, Mkk2 and MpkA form a MAP kinase
module. Interestingly, this MAP kinase module affects the formation of pyomelanin
derived from tyrosine degradation.