The mold Aspergillus fumigatus is the most important airborne fungal pathogen. Adaptation to
hypoxia represents an important virulence attribute for A. fumigatus. Therefore, we aimed at obtaining a comprehensive overview about this process on the
proteome level. To ensure highly reproducible growth conditions, an
oxygen-controlled,
glucose-limited chemostat cultivation was established. Two-dimensional gel electrophoresis analysis of mycelial and
mitochondrial proteins as well as two-dimensional Blue Native/SDS-gel separation of mitochondrial membrane
proteins led to the identification of 117
proteins with an altered abundance under hypoxic in comparison to normoxic conditions.
Hypoxia induced an increased activity of glycolysis, the TCA-cycle, respiration, and
amino acid metabolism. Consistently, the cellular contents in
heme,
iron,
copper, and
zinc increased. Furthermore,
hypoxia induced biosynthesis of the secondary metabolite
pseurotin A as demonstrated at proteomic, transcriptional, and metabolite levels. The observed and so far not reported stimulation of the biosynthesis of a secondary metabolite by
oxygen depletion may also affect the survival of A. fumigatus in hypoxic niches of the human host. Among the
proteins so far not implicated in
hypoxia adaptation, an NO-detoxifying flavohemoprotein was one of the most highly up-regulated
proteins which indicates a link between
hypoxia and the generation of nitrosative stress in A. fumigatus.