PDF(Pubmed)
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 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.
摘要：
真菌病原体表现出广泛的菌株异质性，包括毒力的变化。密切相关的非致病性物种是否也表现出菌株异质性仍然未知。这里,我们全面地表征了致病潜力(即，引起发病率和死亡率的能力)16种不同的费氏曲霉菌株，主要病原菌烟曲霉的非致病性近亲。使用肺曲霉病小鼠模型的体外免疫应答测定和体内毒力测定表明，费氏曲霉菌株的致病潜力差异很大。此外，pangenome分析表明，费氏酵母的基因组和表型多样性甚至更大。基因组，转录组，代谢组学分析确定了与毒力变化相关的几种途径和次生代谢产物。值得注意的是,菌株的毒力与同时存在的次级代谢产物六氢echrome和神经胶质毒素有关。我们认为，检查非致病性近亲的致病性潜力是了解真菌致病性起源的关键。
