HosA-mediated epigenetic regulation of growth, virulence and secondary metabolism in Aspergillus fumigatus

Aspergillus fumigatus is a major opportunistic fungal pathogen whose pathogenic success relies on tight coordination between growth, metabolism and environmental adaptation. Secondary metabolites (SMs) contribute to virulence and ecological fitness but impose substantial metabolic costs. Here, we identify the histone deacetylase HosA as a chromatin-level regulator that promotes fungal growth and virulence while repressing secondary metabolism. Genome-wide ChIP-seq revealed no significant global changes in acetylation upon hosA deletion, but revealed locus-specific increases across the fumagillin/pseurotin supercluster and the Velvet complex genes. Transcriptomic analyses at 28°C and 37°C demonstrated temperature-dependent regulation of SM clusters that correlates with reduced hosA expression at lower temperature. Loss of HosA further enhanced fumagillin-dependent inhibition of Gram-positive bacteria, highlighting a trade-off between growth and chemical defense. Together, our findings uncover a chromatin-based regulatory mechanism that coordinates fungal growth, virulence and secondary metabolism, providing insights into A. fumigatus pathogenic fitness and potential antifungal target development.