Aspergillus fumigatus is a ubiquitous, filamentous fungus which may cause a broad spectrum of disease in the human host, ranging from allergic or locally restricted infections to invasive mycoses. The most fatal A. fumigatus disease, invasive aspergillosis occurs in patients who are severely immunocompromised and is characterized by a high mortality. During the course of the infection A. fumigatus has to cope with several kinds of stress conditions including low oxygen levels (hypoxia). Just recently it was shown that hypoxia adaptation is an important virulence attribute of A. fumigatus. To identify novel hypoxia-sensing and adapting pathways we have characterized the changes of the A. fumigatus proteome in response to short (3-24 hours) and long periods (7-10 days) of hypoxia (1% O2). To maintain reproducible culture conditions, an oxygen-controlled fermenter was used. During long-term cultivation under hypoxia, proteins involved in glycolysis, the pentose phosphate shunt, amino acid biosynthesis, NO-detoxification and respiration showed an increased level. In contrast, proteins involved in sulfate assimilation and acetate activation were down-regulated. Strikingly, hypoxia also induced biosynthesis of the secondary metabolite pseurotin A. The proteomic response of A. fumigatus to short periods of hypoxia showed some similarities, but also marked differences: The level of glycolytic, NO-detoxifying and amino acid biosynthesis enzymes increased under both hypoxic growth conditions. However, the abundance of enzymes of the pentose-phosphate pathway decreased, whereas enzymes involved in ethanol fermentation significantly increased. To get a deeper knowledge about the specific role of metabolic pathways in adaptation to hypoxia, we have started to characterize candidate genes for their role in hypoxia by generating deletion mutants. First data will be presented and discussed.
Full conference title:
27th Fungal Genetics Conference
- FGC 27th (2013)