Department of Biological Sciences and Evolutionary Studies Initiative, Vanderbilt University, Nashville, TN, USA.
Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, NC, USA.
Commun Biol. 2024 Sep 4;7(1):1082. doi: 10.1038/s42003-024-06756-8.
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.
真菌病原体表现出广泛的菌株异质性，包括毒力的变异。亲缘关系密切的非致病性物种是否也表现出菌株异质性尚不清楚。在这里，我们全面描述了 16 种不同的 Aspergillus fischeri 菌株的致病潜力（即引起发病率和死亡率的能力），Aspergillus fischeri 是主要病原体 Aspergillus fumigatus 的一种非致病性近缘种。体外免疫反应测定和使用肺部曲霉病小鼠模型的体内毒力测定表明，A. fischeri 菌株在致病潜力方面差异很大。此外，泛基因组分析表明，A. fischeri 的基因组和表型多样性更大。基因组、转录组和代谢组学分析确定了与毒力变异相关的几个途径和次生代谢物。值得注意的是，菌株的毒力与同时存在的次生代谢物十六氢阿斯特罗奇和gliotoxin 有关。我们认为，研究非致病性近缘种的致病潜力对于理解真菌致病性的起源至关重要。
