Resist or die: Identification and functional characterization of cell wall integrity determinants important for the survival of Aspergillus fumigatus challenged by neutrophil granulocytes.

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The airborne opportunistic fungal pathogen Aspergillus fumigatus causes severe systemic infections in the immunocompromised host. Neutrophil granulocytes play a key role in the defense against invasive infections caused by this mold. The mechanisms how granulocytes detect and kill Aspergillus hyphae and especially how Aspergillus copes with granulocyte-triggered stress remain largely uncharacterized. Using a newly established killing assay, we unveiled the importance of fungal stress response pathway to counter the attack of human granulocytes. This research proposal aims on identifying and characterizing novel factors that determine survival of A. fumigatus hyphae challenged by human granulocytes. We will explore the molecular mechanisms responsible for protecting the mold’s hyphae in detail, study the influence on the fungal cell wall and identify and investigate further signaling routs and stress responses by studying the cellular response of hyphae challenged by human granulocytes. Our results will shed more light on the important interaction of neutrophil granulocytes and Aspergillus hyphae and disclose novel therapeutic approaches to treat invasive fungal infections.