Cross-Pathway Control, Nitrogen Metabolism and their Role in Pathogenicity of Aspergillus fumigatus

• Applicant: Professor Dr. Sven Krappmann
• Subject Area: Parasitology and Biology of Tropical Infectious Disease Pathogens
• Term: from 2004 to 2011
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5426824

Aspergillus fumigatus is the primary mold pathogen causing Aspergillosis, especially in immunocompromised individuals. We have shown that the metabolic transcriptional regulator protein CPCA is required for its full virulence. In other fungi, this transcription factor represents a master regulator affecting gene expression of a network of hundreds of genes, termed the Cross-Pathway Control response. Mutant A. fumigatus strains deleted in the corresponding cpcA genetic locus display significantly reduced mortality rates in a murine model of pulmonary aspergillosis. The goals of this proposal are: (1) We will analyse whether varying amounts of CPCA have an influence on virulence capacities. Therefore we will introduce various mutant alleles of the cpcC-encoded sensor kinase, which controls the degree of CPCA expression. (2) We will identify direct target genes of the transcriptional activator CPCA in A. fumigatus by chromatin immunoprecipitation (ChIP) and analyse which of them are required for full virulence of this opportunistic pathogenic fungus. This analysis of CPCA downstream components will be accompanied by proteome analyses.

• DFG Programme: Priority Programmes
• Subproject of: SPP 1160: Colonisation and Infection by Human-pathogenic Fungi