Characterization of the SKN7 ortholog of Aspergillus fumigatus.
Reactive oxidant intermediates play a major role in the killing of Aspergillus fumigatus by phagocytes. In yeasts, SKN7 is a transcription factor contributing to the oxidative stress response. We investigated here the role of afSkn7p in the adaptation of A. fumigatus against oxidative stress. To analyze functionally the afSKN7 in A. fumigatus, we modified a quick PCR fusion methodology for targeted deletion in A. fumigatus. The afskn7Delta mutant was morphologically similar to the wild-type strain, but showed a growth inhibition phenotype associated with hydrogen peroxide and tert-butyl hydroperoxide. However, no significant virulence differences were observed between wild type, mutant and reconstituted strains in a murine model of pulmonary aspergillosis. This result indicated that an increased sensitivity of A. fumigatus to peroxides in vitro is not correlated with a modification of fungal virulence.
Lamarre
Claude
C
Unité des Aspergillus, Institut Pasteur, 25 rue du Docteur Roux, 75724 Cedex 15, France. clamarre@pasteur.fr
Ibrahim-Granet
Oumaïma
O
Du
Chen
C
Calderone
Richard
R
Latgé
Jean-Paul
JP
D000222:Adaptation, Physiological; D000595:Amino Acid Sequence; D000818:Animals; D001228:Aspergillosis / Q000382:microbiology; D001232:Aspergillus fumigatus / Q000187:drug effects / Q000472:pathogenicity / Q000502:physiology*; D005656:Fungal Proteins / Q000502:physiology*; D017353:Gene Deletion; D005800:Genes, Fungal; D006861:Hydrogen Peroxide / Q000494:pharmacology; D051379:Mice; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress; D010545:Peroxides / Q000494:pharmacology; D016415:Sequence Alignment; D014774:Virulence; D020122:tert-Butylhydroperoxide / Q000494:pharmacology
D005656:Fungal Proteins; D016877:Oxidants; D010545:Peroxides; D020122:tert-Butylhydroperoxide; D006861:Hydrogen Peroxide