The oxidative stress response highly depends on glucose and iron availability in Aspergillus fumigatus
Pathogens have to cope with oxidative, iron- and carbon-limitation stresses in the human body. To understand how combined iron-carbon limitation alters oxidative stress response, Aspergillus fumigatus was cultured in glucose-peptone or peptone containing media supplemented or not with deferiprone as iron chelator. Changes in the transcriptome in these cultures were recorded after H2O2 treatment. Responses to oxidative stress were highly dependent on the availability of glucose and iron. Out of the 16 stress responsive antioxidative enzyme genes only the cat2 catalase-peroxidase gene was upregulated in more than two culturing conditions. The transcriptional responses observed in iron metabolism also varied substantially in these cultures. Only extracellular siderophore production appeared important regardless to culturing conditions in oxidative stress protection, while enhanced synthesis of Fe-S cluster proteins seemed to be crucial for oxidative stress treated iron-limited and fast growing (glucose rich) cultures. Although pathogens and host cells live together in the same place, their culturing conditions (e.g. iron availability, or occurrence of oxidative stress) can be different. Therefore, inhibition of a universally important biochemical process, like Fe-S cluster assembly, may selectively inhibit the pathogen growth in vivo and represent a potential target for antifungal therapy. Overall design: Comparative gene expression profiling analysis of RNA-seq data for mycelia of A. fumigatus (Af293 reference strain) on glucose+peptone or on peptone, in the presence of 1 mM deferiprone (DFP) and/or 75 mM H2O2 with three biological replicates.