Aspergillus terreus as a cause of invasive aspergillosis: Impact of secondary metabolites on pathogenesis

• Applicant: Professor Dr. Matthias Brock
• Subject Area: Parasitology and Biology of Tropical Infectious Disease Pathogens
• Term: from 2009 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 150413556

Oral application of culture extracts from the emerging pathogenic fungus Aspergillus terreus causes morphological changes of liver cells, indicating the production of mycotoxins. Consistently, our preliminary investigations on murine infection models for invasive aspergillosis revealed major hepatic lesions in mice suffering from A. terreus infections. Although A. terreus is less frequently isolated from patients with invasive aspergillosis than A. fumigatus, the resistance against the potent antifungal drug amphotericin B hampers treatment of A. terreus infections and leads to up to 100% mortality. Despite the severe outcome of A. terreus infections, pathogenesis has hardly been studied. To elucidate the impact of the production of secondary metabolites on A. terreus virulence, infection models will be established, which allow monitoring the temporal and spatial development of the infection under in vivo conditions by using bioluminescent A. terreus strains. Microarrays covering representatives from all secondary metabolite biosynthesis clusters will be used to correlate the progression of infection with secondary metabolite production. The use of reporter strains will allow following the metabolite production under in vitro conditions to enable the identification, purification and characterisation of the respective compounds. By studying the virulence of mutants defective in secondary metabolite production we expect to gain new insights into the pathophysiology of A. terreus.

• DFG Programme: Research Grants
• Participating Person: Professorin Dr. Ilse Denise Jacobsen