On the relevance of Aspergillus fumigatus sexuality for virulence and secondary metabolism of this human pathogenic mould.

• Applicant: Professor Dr. Sven Krappmann
• Subject Area: Medical Microbiology and Mycology, Hygiene, Molecular Infection Biology
• Term: from 2012 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 228000846

Invasive aspergillosis caused by the environmental mould Aspergillosis is an often life-threatening complication for immunsosuppressed patients. Being a typical saprobe, Aspergillus fumigatus has evolved a variety of characteristics that support growth and disease in a susceptible host. The recent discovery that A. fumigatus is able to form fruiting bodies that contain recombinant ascospores under highly specific environmental conditions has raised the question whether such a restricted sexuality might influence virulence of this opportunistic pathogen. During the former funding period, the mating-type loci-dependent transcriptomes had been analysed to reveal a significant impact of the sexual identity of A. fumigatus on its secondary metabolism and the profile of natural products. Moreover and using a congenic pair of MAT strains, preliminary data were generated that imply an influence of the mating-type on virulence of A. fumigatus. In this proposed further funding period, the MAT-specific regulation of the fumagillin/pseurotin supercluster will be scrutinized on a mechanistic level, and direct target genes of the MAT-encoded factors shall be identified. Furthermore, the impact of A. fumigatus sexuality on its virulence as well as the development of resistance of this fungal pathogen shall be explored. These scheduled tasks are based on the underlying hypothesis that the sexual phase during the lifecycle of A. fumigatus affects its genetic plasticity and therefore virulence determinants as well as the pathogenesis of invasive aspergillosis.

• DFG Programme: Research Grants