Data_Sheet_1_Revealing the Virulence Potential of Clinical and Environmental Aspergillus fumigatus Isolates Using Whole-Genome Sequencing.ZIP

Aspergillus fumigatus is considered a common causative agent of human fungal infections. A restricted number of virulence factors have been described, and none of them lead to a differentiation in the virulence level among different strains. Variations in the virulence phenotype depending on the isolate origin, measured as survival percentage in animal infection models, have been previously reported. In this study, we analyzed the whole-genome sequence of A. fumigatus isolates from clinical and environmental origins to determine their virulence genetic content. The sample included four isolates sequenced at the University Medical Center Groningen (UMCG), three clinical (two of them isolated from the same patient) and the experimental strain B5233, and the draft genomes of one reference strain, two environmental and two clinical isolates obtained from a public database. The fungal genomes were screened for the presence of virulence-related genes (VRGs) using an in-house database of 244 genes related to thermotolerance, resistance to immune responses, cell wall formation, nutrient uptake, signaling and regulation, and production of toxins and secondary metabolites and allergens. In addition, we performed a variant calling analysis to compare the isolates sequenced at the UMCG and investigated their genetic relatedness using the TRESP (Tandem Repeats located within Exons of Surface Protein coding genes) genotyping method. We neither observed a difference in the virulence genetic content between the clinical isolates causing an invasive infection and a colonizing clinical isolate nor between isolates from the clinical and environmental origin. The four novel A. fumigatus sequences had a different TRESP genotype and a total number of genetic variants ranging from 48,590 to 68,352. In addition, a comparative genomics analysis showed the presence of single nucleotide polymorphisms in VRGs and repetitive genetic elements located next to VRG groups, which could influence the regulation of these genes. In conclusion, our genomic analysis revealed a high genetic diversity between environmental and clinical A. fumigatus isolates, as well as between clinical isolates from the same patient, indicating an infection with a mixed-population in the latter case. However, all isolates had a similar virulence genetic content, demonstrating their pathogenic potential at least at the genomic level.

烟曲霉被视为人类真菌感染的常见致病菌。目前已描述的致病性因子数量有限，且它们之间并未导致不同菌株在致病性水平上的分化。已有研究表明，根据分离物的来源，致病性表型的变化，以动物感染模型中的存活率百分比来衡量，已被广泛报道。在本研究中，我们分析了来自临床和环境来源的烟曲霉分离物的全基因组序列，以确定其致病性遗传组成。样本包括在格罗宁根大学医学中心（UMCG）测序的四个分离物，其中三个临床分离物（其中两个来自同一患者）和实验菌株B5233，以及从公共数据库中获得的一个参考菌株、两个环境分离物和两个临床分离物的草图基因组。通过使用包含244个与耐热性、免疫反应抵抗、细胞壁形成、营养摄取、信号传导和调控、毒素和次生代谢产物以及过敏原相关的基因的内部数据库，对真菌基因组进行了筛查，以检测是否存在与致病性相关的基因（VRGs）。此外，我们还进行了变异调用分析，以比较在UMCG测序的分离物，并使用TRESP（位于表面蛋白编码基因外显子中的串联重复序列）基因分型方法研究它们的遗传相关性。我们并未观察到引起侵袭性感染的临床分离物与定植性临床分离物之间，以及临床来源和环境来源的分离物之间的致病性遗传内容的差异。四个新的烟曲霉序列具有不同的TRESP基因型和48,590至68,352个遗传变异的总数。此外，比较基因组学分析显示VRGs和位于VRG组附近的重复遗传元素中存在单核苷酸多态性，这些可能影响这些基因的调控。总之，我们的基因组分析揭示了环境来源和临床来源的烟曲霉分离物之间，以及同一患者临床分离物之间的高度遗传多样性，这表明在后者情况下感染了混合种群。然而，所有分离物都具有相似的致病性遗传内容，至少在基因组水平上显示出它们的致病潜力。