HdaA, a class 2 histone deacetylase of Aspergillus fumigatus, affects germination and secondary metabolite production

Histone deacetylases (HDACs) play an important role in regulation of gene expression through histone modifications. Here we show that the Aspergillus fumigatus HDAC HdaA is involved in regulation of secondary metabolite production and is required for normal germination and vegetative growth. Deletion of the hdaA gene increased the production of several secondary metabolites but decreased production of gliotoxin whereas over-expression hdaA increased production of gliotoxin. RT-PCR analysis of 14 nonribosomal peptide synthases indicated HdaA regulation of up to nine of them. A mammalian cell toxicity assay indicated increased activity in the over-expression strain. Neither mutant affected virulence of the fungus as measured by macrophage engulfment of conidia or virulence in a neutropenic mouse model.