Purpose: Reactive oxygen species (ROS) produced by phagocytic cells have been reported as being involved in the killing of A. fumigatus. Fungal SODs that detoxify superoxide anions, the initial precursor of ROS, could be putative virulence factors for this opportunistic pathogen. Methods: Four genes encoding putative superoxide dismutases have been identified in the A. fumigatus genome: a cytoplasmic Cu/ZnSOD (AfSod1p), a mitochondrial MnSOD (AfSod2p), a cytoplasmic MnSOD (AfSod3p) and a protein (AfSod4) displaying a MnSOD C-terminal domain. Results: During growth, AfSOD1 and AfSOD2 expression were highly expressed in conidia whereas AfSOD3 was only strongly expressed in mycelium. AfSOD4 was weakly expressed compared to AfSOD1, AfSOD2 and AfSOD3. Single and multiple mutants were constructed. The deletion of AfSOD4 was lethal. The sod1 and sod2 mutant strains showed a growth inhibition at high temperature and an hypersensitivity to menadione whereas the sod3 mutant had only a slight growth delay at high temperature. Multiple mutations have only an additive effect on the mutant phenoptype. The triple mutant was characterized by a delay in the conidial germination and the highest sensitivity to menadione. In spite of these phenotypes, no significant virulence difference was observed between the sod1Dsod2sod3 triple mutant and wild type parental strain in experimental murine aspergillosis models. Conclusions: This conserved virulence of the triple mutant probably results from the fact that the Sodps of A. fumigatus are only involved in detoxification of the intracellular superoxide anions.
Full conference title:
4th Advances Against Aspergillosis
- AAA 4th (2010)