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Strain heterogeneity in a non-pathogenic Aspergillus fungus highlights factors associated with virulence
David C Rinker1, Thomas J C Sauters1, Karin Steffen1
1Department of Biological Sciences and Evolutionary Studies Initiative, Vanderbilt University, Nashville, TN, USA.
Abstract:
Fungal 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 of Aspergillus fischeri, a non-pathogenic close relative of the major pathogen Aspergillus fumigatus. In vitro immune response assays and in vivo virulence assays using a mouse model of pulmonary aspergillosis showed that A. fischeri strains varied widely in their pathogenic potential. Furthermore, pangenome analyses suggest that A. fischeri genomic and phenotypic diversity is even greater. Genomic, transcriptomic, and metabolic 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.
Insights
Even non-pathogenic fungi like Aspergillus fischeri show significant variation in disease-causing potential. This fungal strain heterogeneity, linked to specific metabolites, offers insights into the evolution of pathogenicity.
Area of Science:
- Mycology
- Pathogen Evolution
- Fungal Genetics
Background:
- Fungal pathogens display considerable strain variation in virulence.
- The heterogeneity of closely related non-pathogenic fungal species is largely unexplored.
Purpose of the Study:
- To investigate the pathogenic potential and strain heterogeneity within Aspergillus fischeri, a non-pathogenic relative of Aspergillus fumigatus.
- To identify genomic and metabolic factors contributing to virulence variation in A. fischeri.
Main Methods:
- In vitro immune response assays.
- In vivo virulence assays using a mouse model of pulmonary aspergillosis.
- Pangenome, genomic, transcriptomic, and metabolic profiling.
Main Results:
- Aspergillus fischeri strains exhibited wide-ranging pathogenic potential.
- Pangenome analysis indicated extensive genomic and phenotypic diversity.
- Virulence variation correlated with specific pathways and the co-occurrence of hexadehydroastechrome and gliotoxin.
Conclusions:
- Non-pathogenic fungal relatives can possess significant pathogenic potential and strain heterogeneity.
- Understanding virulence in non-pathogenic species is crucial for deciphering the origins of fungal pathogenicity.
- Specific secondary metabolites may play a role in modulating fungal virulence.
