Expression and Activity of Catalases Is Differentially Affected by GpaA (Ga) and FlbA (Regulator of G Protein Signaling) in Aspergillus fumigatus

Vegetative growth signaling of the opportunistic human pathogenic fungus Aspergillus fumigatus is mediated by GpaA ($G{\alpha}$). FlbA is a regulator of G protein signaling, which attenuates GpaA-mediated growth signaling in this fungus. The flbA deletion (${\Delta}flbA$) and the constitutively active GpaA ($GpaA^{Q204L}$) mutants exhibit enhanced proliferation, precocious autolysis, and reduced asexual sporulation. In this study, we demonstrate that both mutants also show enhanced tolerance against $H_2O_2$ and their radial growth was approximately 1.6 fold higher than that of wild type (WT) in medium with 10 mM $H_2O_2$. We performed quantitative PCR (qRT-PCR) for examination of mRNA levels of three catalase encoding genes (catA, cat1, and cat2) in WT and the two mutants. According to the results, while levels of spore-specific catA mRNA were comparable among the three strains, cat1 and cat2 mRNA levels were significantly higher in the two mutants than in WT. In particular, the ${\Delta}flbA$ mutant showed significantly enhanced and prolonged expression of cat1 and precocious expression of cat2. In accordance with this result, activity of the Cat1 protein in the ${\Delta}flbA$ mutant was higher than that of $gpaA^{Q204L}$ and WT strains. For activity of the Cat2 protein, both mutants began to show enhanced activity at 48 and 72 hr of growth compared to WT. These results lead to the conclusion that GpaA activates expression and activity of cat1 and cat2, whereas FlbA plays an antagonistic role in control of catalases, leading to balanced responses to neutralizing the toxicity of reactive oxygen species.