Programmpunkt

Titel: The fungal peroxiredoxin Asp f3 of Aspergillus fumigatus is essential for redox homeostasis during exposure to external reactive oxygen species
ID: 145/EKP
Art: Abstractautor
Session: P1
Eukaryotic Pathogens (FG EK)

Referent: Jana Boysen (Jena\Jena, Jena)


Abstract - Text

The ubiquitous filamentous ascomycete Aspergillus fumigatus is generally known for its saprophytic lifestyle but very often also occurs as an opportunistic pathogen. Immunocompromised patients are at the highest risk to develop A. fumigatus derived infections, ranging from allergic reactions to often fatal invasive aspergillosis (IA). Especially patients suffering chronic granulomatous disease (CGD) are highly susceptible, due to a defect in their NADPH-oxidase, leading to a reduced capability to produce reactive oxygen species (ROS).

We have recently characterized the two-cysteine type peroxiredoxin Asp f3 which is also known as a major allergen and was shown to be of crucial relevance for the fungus when challenged with ROS. The deletion of asp f3 resulted not only in a high susceptibility to ROS but moreover led to avirulence in a mouse model of pulmonary aspergillosis. The ROS sensitive phenotype was further found to depend on both conserved cysteine residues whose exchange yielded a phenotype comparable to the deletion mutant. To elucidate the biochemical targets of Asp f3 we took a redox proteomic approach comparing the oxidation status of the total protein content of the wild type and the Δaspf3 strain following hydrogen peroxide treatment to gain insight into the main targets of ROS-associated damage. We could identify central metabolic enzymes as well as proteins with proposed extracellular function in protein folding. Additionally, we established an in vivo assay, which allows specific exposure to external pulses of superoxide (O2-), the primary product of the NADPH oxidase in cells of the innate immunity, to monitor the effect of ROS and the transcriptional changes in A. fumigatus confronted with ROS. Here, we will present first results on how the absence of a functional asp f3 affects gene expression in this fungal pathogen.