Selenate sensitivity of a laeA mutant is restored by overexpression of the bZIP protein MetR in Aspergillus fumigatus

LaeA is a conserved global regulator of secondary metabolism and development in filamentous fungi. Examination of Aspergillus fumigatus transcriptome data of laeA deletion mutants have been fruitful in identifying genes and molecules contributing to the laeA mutant phenotype. One of the genes significantly down regulated in A. fumigatus Delta laeA is metR, encoding a bZIP DNA binding protein required for sulfur and methionine metabolism in fungi. LaeA and MetR deletion mutants exhibit several similarities including down regulation of sulfur assimilation and methionine metabolism genes and ability to grow on the toxic sulfur analog, sodium selenate. However, unlike Delta metR, Delta laeA strains are able to grow on sulfur, sulfite, and cysteine. To examine if any parameter of the Delta laeA phenotype is due to decreased metR expression, an over-expression allele (OE::metR) was placed in a Delta laeA background. The OE::metR allele could not significantly restore expression of MetR regulated genes in Delta laeA but did restore sensitivity to sodium selenate. In A. nidulans a second bZIP protein, MetZ, also regulates sulfur and methionine metabolism genes. However, addition of an OE::metZ construct to the A. fumigatus Delta laeA OE::metR strain still was unable to rescue the Delta laeA phenotype to wildtype with regards gliotoxin synthesis and virulence in a zebrafish aspergillosis model.