Strain heterogeneity in a non-pathogenic fungus highlights factors contributing to virulence

Abstract

ABSTRACTFungal pathogens exhibit extensive strain heterogeneity, including variation in virulence. Whether closely related non-pathogenic species also exhibit strain heterogeneity remains unknown. Here, we comprehensively characterized the pathogenic potentials (i.e., the ability to cause morbidity and mortality) of 16 diverse strains ofAspergillus fischeri, a non-pathogenic close relative of the major pathogenAspergillus fumigatus.In vitroimmune response assays andin vivovirulence assays using a mouse model of pulmonary aspergillosis showed thatA. fischeristrains varied widely in their pathogenic potential. Furthermore, pangenome analyses suggest thatA. fischerigenomic and phenotypic diversity is even greater. Genomic, transcriptomic, and metabolomic profiling identified several pathways and secondary metabolites associated with variation in virulence. Notably, strain virulence was associated with the simultaneous presence of the secondary metabolites hexadehydroastechrome and gliotoxin. We submit that examining the pathogenic potentials of non-pathogenic close relatives is key for understanding the origins of fungal pathogenicity.