The Aspergillus fumigatus transcription factor Ace2 governs pigment production, conidiation and virulence

Aspergillus fumigatus causes serious and frequently fatal infections in immunocompromised patients. To investigate the regulation of virulence of this fungus, we constructed and analysed an A. fumigatus mutant that lacked the transcription factor Ace2, which influences virulence in other fungi. The Deltaace2 mutant had dysmorphic conidiophores, reduced conidia production and abnormal conidial cell wall architecture. This mutant produced an orange pigment when grown on solid media, although its conidia had normal pigmentation. Conidia of the Deltaace2 mutant were larger and had accelerated germination. The resulting germlings were resistant to hydrogen peroxide, but not other stressors. Non-neutropenic mice that were immunosuppressed with cortisone acetate and infected with the Deltaace2 mutant had accelerated mortality, greater pulmonary fungal burden, and increased pulmonary inflammatory responses compared with mice infected with the wild-type or Deltaace2::ace2-complemented strains. The Deltaace2 mutant had reduced ppoC, ecm33 and ags3 mRNA expression. It is known that A. fumigatus mutants with absent or reduced expression of these genes have increased virulence in mice, as well as other phenotypic similarities to the Deltaace2 mutant. Therefore, reduced expression of these genes likely contributes to the increased virulence of the Deltaace2 mutant.