The incidence of human fungal infections has strongly increased over the last years and Aspergillus fumigatus causes approximately 80 % of all cases in often fatal invasive aspergillosis. A. fumigatus is a ubiquitous ascomycete with a generally saprophytic lifestyle but is also known as an opportunistic human pathogen for immunocompromised individuals. Options for diagnosis and treatment are limited and decline further due to antimycotic resistances. Thus, development of better diagnostic methods as well as the discovery and development of new antifungal treatment options are urgently required. To successfully establish an infection, the fungus must adapt its metabolism to the environment of its human host. This includes adaptation to general conditions like low oxygen or iron deficiency and protection against active innate immune defence mechanisms. The aim of this thesis was to elucidate the functional role of peroxiredoxin Asp f3 in virulence and how it is involved in sensing and detoxification of ROS-associated stress in A. fumigatus. Asp f3 is a two-cysteine type peroxiredoxin that was first identified as a major allergen of A. fumigatus and later as a virulence determinant in a murine model of pulmonary aspergillosis. Here I show that the loss of Asp f3 leads to a shift in the transcriptome upon challenge with reactive oxygen species. Amongst the affected genes are several of putative Afyap1 target genes and subsequently is was shown that Afyap1 fails to sufficiently accumulate in the nucleus to activate ROS-detoxification mechanisms in the Asp f3 deficient background. However, loss of virulence is not caused by insufficient Afyap1 activation, but more likely linked to the fungus ability to grow under low iron conditions or loss thereof in the asp f3 deficient strain and iron supplementation even leads to a full restoration of virulence in a murine infection model
