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[文章]

利用全基因组测序揭示临床和环境烟曲霉菌株的毒力潜力-2019.11-4.259

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关键词Fungi,Draft Genome,virulence

中文题目:利用全基因组测序揭示临床和环境烟曲霉菌株的毒力潜力

英文题目:Revealing the Virulence Potential of Clinical and Environmental Aspergillus fumigatus Isolates Using Whole-Genome Sequencing

 

  名:Frontiers in Microbiology    发表时间:2019.9   IF4.259

作者单位格罗宁根大学

测序产品:真菌基因组             

样品来源:烟曲霉

文章类型:报告类

DOL10.3389/fmicb.2019.01970. eCollection 2019

 

英文摘要

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 (T andem 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.

 

中文摘要

烟曲霉被认为是人类真菌感染的常见致病菌。一定数量的毒力因子已被研究过,但没有导致不同菌株之间毒力水平的分化。先前已经报道了取决于分离物来源的毒力表型的变化,该变化以在动物感染模型中的存活百分比来衡量。在这项研究中,我们分析了从临床和环境来源分离的烟曲霉菌株的全基因组序列,以确定其毒力基因含量。样本包括在格罗宁根大学医学中心(UMCG)测序的四个分离株、三个临床分离株(其中两个分离自同一病人)和实验菌株B5233,以及从公共数据库获得的一个参考菌株、两个环境分离株和两个临床分离株的基因组草图。使用与耐热性、抗免疫应答、细胞壁形成、营养吸收、信号和调节、以及毒素和次级代谢物和变应原产生的244个基因的内部数据库筛选毒力相关基因(VRGS)的存在。此外,我们还进行了变量调用分析,以比较在UMCG上测序的分离菌株,并使用TRESP(位于表面蛋白编码基因外显子内的Tm重复序列)基因分型法研究它们的遗传相关性。我们既未观察到引起侵袭性感染的临床分离株和定植性临床分离株之间的毒力基因含量差异,也未观察到来自临床和环境来源的分离株之间的毒力基因含量差异。这四个新的烟曲霉序列具有不同的TRESP基因型和48590-68352个遗传变异。此外,比较基因组学分析显示,VRG中存在单核苷酸多态性,VRG组附近存在重复的基因元件,这可能影响这些基因的调控。总之,我们的基因组分析显示,环境和临床烟曲霉分离株之间以及同一患者的临床分离株之间存在高度的遗传多样性,表明在后一种情况下感染人群是混合的。然而,所有分离株都具有相似的毒力基因含量,至少在基因组水平上显示了它们的致病潜力。

阿布魏 2019-11-14 09:54:45

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