Aspergillus fumigatus is a major human pathogen. In contrast, Aspergillus fischeri and the recently described Aspergillus oerlinghausenensis, the two species most closely related to A. fumigatus, are not known to be pathogenic. Some of the genetic determinants of virulence (or "cards of virulence") that A. fumigatus possesses are secondary metabolites that impair the host immune system, protect from host immune cell attacks, or acquire key nutrients. To examine whether secondary metabolism-associated cards of virulence vary between these species, we conducted extensive genomic and secondary metabolite profiling analyses of multiple A. fumigatus, one A. oerlinghausenensis, and multiple A. fischeri strains. We identified two cards of virulence (gliotoxin and fumitremorgin) shared by all three species and three cards of virulence (trypacidin, pseurotin, and fumagillin) that are variable. For example, we found that all species and strains examined biosynthesized gliotoxin, which is known to contribute to virulence, consistent with the conservation of the gliotoxin biosynthetic gene cluster (BGC) across genomes. For other secondary metabolites, such as fumitremorgin, a modulator of host biology, we found that all species produced the metabolite but that there was strain heterogeneity in its production within species. Finally, species differed in their biosynthesis of fumagillin and pseurotin, both contributors to host tissue damage during invasive aspergillosis. A. fumigatus biosynthesized fumagillin and pseurotin, while A. oerlinghausenensis biosynthesized fumagillin and A. fischeri biosynthesized neither. These biochemical differences were reflected in sequence divergence of the intertwined fumagillin/pseurotin BGCs across genomes. These results delineate the similarities and differences in secondary metabolism-associated cards of virulence between a major fungal pathogen and its nonpathogenic closest relatives, shedding light onto the genetic and phenotypic changes associated with the evolution of fungal pathogenicity.

中文翻译：

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曲霉属物种的生物合成基因簇、次级代谢物谱和毒力卡之间的变异。

烟曲霉是一种主要的人类病原体。相比之下，费氏曲霉和最近描述的奥林豪森曲霉这两个与烟曲霉关系最密切的物种尚不知道是否具有致病性。一些毒力的遗传决定因素（或“毒力卡”）是 A . 烟曲霉拥有的是损害宿主免疫系统、保护宿主免疫细胞免受攻击或获取关键营养物质的次级代谢产物。为了检查这些物种之间与次级代谢相关的毒力是否存在差异，我们对多种烟曲霉、一种奥林豪森曲霉和多种费氏曲霉菌株进行了广泛的基因组和次级代谢物分析。我们确定了所有三个物种共有的两张毒力卡（胶霉毒素和烟曲霉素）以及三种可变的毒力卡（锥虫素、伪丁和夫马洁林）。例如，我们发现所有物种和菌株都检测了生物合成的胶霉毒素，已知胶霉毒素有助于毒力，这与基因组中胶霉毒素生物合成基因簇（BGC）的保守性一致。对于其他次生代谢物，例如宿主生物学调节剂Fumitremorgin，我们发现所有物种都产生该代谢物，但物种内其产生存在菌株异质性。最后，不同物种对夫马洁林和伪丁的生物合成存在差异，这两种物质在侵袭性曲霉病期间都会造成宿主组织损伤。A. fumigatus生物合成夫马洁林和伪丁，而A. oerlinghausenensis生物合成烟曲霉素，而A. fischeri则两者均不生物合成。这些生化差异反映在基因组中相互缠绕的夫马洁林/伪丁 BGC 的序列差异上。这些结果描绘了主要真菌病原体与其非致病性近亲之间次生代谢相关毒力卡的相似性和差异，揭示了与真菌致病性进化相关的遗传和表型变化。