With the increasing number of immunocompromised individuals Aspergillus fumigatus has become one of the most important opportunistic fungal pathogens. During infection A. fumigatus is confronted with a number of defence mechanisms in the host, in particular neutrophiles and macrophages, which kill conidia by producing reactive oxygen intermediates (ROI). We identified a homolog of the AP1 like transcription factor Yap1 from yeast in A. fumigatus, which we designated Afyap1. In yeast, Yap1p was found to be a global regulator for oxidative stress response and required for the protection of the cell against H2O2 and other ROI. Similarly, deletion of Afyap1 led to an A. fumigatus mutant strain which showed drastically increased sensitivity against ROI. Nuclear localisation of an Afyap1-eGFP fusion in A. fumigatus was dependent on the presence of H2O2 and diamide. To identify new targets of Afyap1, we compared the proteome pattern of H2O2 treated and non-treated wild-type mycelia and of an Afyap1 deletion strain by 2D-gel analysis. Moreover, despite the importance of Afyap1 for defence against ROS, the Afyap1 deletion mutant was not reduced in pathogenicity in a low dose murine infection model for invasive aspergillosis. These data indicate that at least in the mouse infection model, ROI do not play a significant role in killing of A. fumigatus by immune effector cells.
Full conference title:
9th EUROPEAN CONFERENCE ON FUNGAL GENETICS
- ECFG 9th (2008)