Oxidative inactivation of primary metabolism pathways in the human pathogenic fungus Aspergillus fumigatus
Aspergillus fumigatus is an ubiquitous filamentous ascomycete with a generally saprophytic lifestyle, but also one of the most important fungal pathogens. Especially immunocompromised patients like those with chronic granulomatous disease (CDD) or transplant recipients are at a high risk to develop an Invasive Aspergillosis (IA) with a mortality rate of 30 – 98 %. The number of infections is expected to grow in the next few years and there are not many antifungals for clinical use, which highlights the need of new therapeutic approaches.
Since patients with CGD are at a high risk, and their disease is based on a mutation in a subunit of the NADPH oxidase (NOX) complex, which catalyzes the oxidative burst and releases reactive oxygen species (ROS), it seems possible that ROS are of great importance during the defense against A. fumigatus infection. Yet the exact role of ROS needs to be determined in future, since the deletion of genes like yap1, which render the fungus highly sensitive to ROS like H2O2, do not seem to affect virulence. This thesis will target the question of whether specific molecular targets of host derived ROS exist in A. fumigatus. It will also try to elucidate not only the ROS-protective mechanism of the peroxiredoxin AspF3, but also the possible role of the other peroxiredoxin-like proteins encoded in the A. fumigatus genome.
(2018) Yeast two-hybrid screening reveals a dual function for the histone acetyltransferase GcnE by controlling glutamine synthesis and development in Aspergillus fumigatus. Curr Genet ,
Start of PhD
June 1, 2016