The role of the Aspergillus fumigatus areA gene in invasive pulmonary aspergillosis

The areA gene of Aspergillus nidulans is a positive-acting transcriptional factor required for the expression of genes involved in the utilization of a broad range of nitrogen sources other than ammonium and glutamine. We have investigated the role in pathogenesis of the corresponding gene (AfareA) of Aspergillus fumigatus, a causative agent of invasive pulmonary aspergillosis. Stable and unstable AfaveA(-) strains were constructed and tested for altered virulence in mice on the basis of host survival, mixed infection experiments and genetic reversion studies. These showed that the AfareA gene contributes to, but is not essential for, virulence. Strains carrying extragenic mutations that partially suppress the AfareA(-) phenotype for growth on different nitrogen sources were tested for altered virulence in mixed infection studies. One of these was found to be more virulent than the parental AfareA- strain.