LIPID RAFTS AND EPIGENETICS IN FUNGAL INFECTION BIOLOGY

Axel A. Brakhage

Abstract: 

The filamentous fungus Aspergillus fumigatus is the most important air-borne fungal pathogen causing 90% 
of all systemic Aspergillus infections in humans. The most severe disease caused by A. fumigatus is invasive 
aspergillosis which almost exclusively occurs in immunocompromised patients. A lack of reliable diagnostic 
tools and effective treatment options results in high mortality rates despite therapy. In my laboratory, we aim 
at identifying pathogenicity determinants and mechanisms how A. fumigatus can overcome the response 
of immune effector cells. For addressing these questions we apply transcriptome and (immune)proteome 
analyses including systems biological analyses with subsequent generation of deletion mutants and their 
analysis in processing by the immune system like neutrophilic granulocytes, alveolar macrophages and 
complement. Furthermore, we test mutants in a mouse infection model.

A. fumigatus has developed immune evasion mechanisms which interfere at the different levels of the 
infection process with the response of the human host. These include recognition of conidia, modulation of 
phagocytosis, intracellular processing, neutrophil extracellular trap formation, and complement activation. We 
have identified several molecules including surface components such as proteins and dihydroxynaphthalene 
melanin as well as secondary metabolites, which manipulate the immune response. Furthermore, fungus- 
specific T cells were identified which allow novel approaches for diagnosis and therapy. A recent interesting 
finding is that lipid rafts appear to be important for the interaction of A. fumigatus with immune effector 
cells. Also, in a study with A. nidulans and A. fumigatus we found the concept that bacteria are able to 
reprogram the fungal metabolism by targeting the chromatin modification system.

2016

Full conference title: 

7th Advances Against Aspergillosis