The acquisition of iron is known to be an essential step in any microbial infection process due to iron-limiting conditions in the human host. This iron limitation is caused by high-affinity iron-binding proteins like transferrin or lactoferrin in the host. Since iron plays an essential role in key metabolic processes like DNA synthesis, oxidative phosphorylation or electron transport A. fumigatus has to overcome the iron deficiency by the synthesis of siderophores, which chelate iron. It was shown that an A. fumigatus strain unable to synthesise siderophores was attenuated in virulence in a murine infection model (Schrettl et al. 2004). Moreover, regulation of iron homeostasis via two transcription factors was recently described in filamentous fungi (Hortschansky et al. 2007). To understand the cellular processes induced by iron starvation, we analysed the proteome of A. fumigatus strain ATCC 46645 grown under iron-deficiency conditions. In total 98 spots, representing 88 different proteins, were upregulated under -Fe conditions and 88 spots, representing 78 different proteins, were downregulated under iron deficiency conditions. The major parts of the downregulated proteins belonged to proteins involved in primary metabolism (31 %), ribosomal protein synthesis (13 %) and chaperone activity (9 %). Many iron-sulphur cluster and heme-containing enzymes such as aconitase and cytochrome c peroxidase were found to be downregulated. On the other hand, proteins involved in the amino acid metabolism (16 %) represented the major group of upregulated proteins under iron starvation. In addition, proteins, which were related to siderophore biosynthesis (3%) or protein degradation (5 %) or proteins involved in antioxidative response like Cu, Zn superoxide dismutases (4%) that lack iron, showed also an upregulation under iron deficiency. Further proteins analysed under different non-linear pH-scales will be presented and their putative roles during iron depletion will be discussed.
Full conference title:
9th EUROPEAN CONFERENCE ON FUNGAL GENETICS
- ECFG 9th (2008)