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嗜热双口虫(Naegleria lovaniensis)基因组,为解析人类致病阿米巴福氏耐格里虫(N. fowleri)致病因子的比较方法提供了基础。

The genome of Naegleria lovaniensis, the basis for a comparative approach to unravel pathogenicity factors of the human pathogenic amoeba N. fowleri.

机构信息

Interfaculty Bioinformatics Unit, University of Bern, Bern, Switzerland.

Biology Division, Spiez Laboratory, Federal Office for Civil Protection, Austrasse, Spiez, Switzerland.

出版信息

BMC Genomics. 2018 Sep 5;19(1):654. doi: 10.1186/s12864-018-4994-1.

Abstract

BACKGROUND

Members of the genus Naegleria are free-living eukaryotes with the capability to transform from the amoeboid form into resting cysts or moving flagellates in response to environmental conditions. More than 40 species have been characterized, but only Naegleria fowleri (N. fowleri) is known as a human pathogen causing primary amoebic meningoencephalitis (PAM), a fast progressing and mostly fatal disease of the central nervous system. Several studies report an involvement of phospholipases and other molecular factors, but the mechanisms involved in pathogenesis are still poorly understood. To gain a better understanding of the relationships within the genus of Naegleria and to investigate pathogenicity factors of N. fowleri, we characterized the genome of its closest non-pathogenic relative N. lovaniensis.

RESULTS

To gain insights into the taxonomy of Naegleria, we sequenced the genome of N. lovaniensis using long read sequencing technology. The assembly of the data resulted in a 30 Mb genome including the circular mitochondrial sequence. Unravelling the phylogenetic relationship using OrthoMCL protein clustering and maximum likelihood methods confirms the close relationship of N. lovaniensis and N. fowleri. To achieve an overview of the diversity of Naegleria proteins and to assess characteristics of the human pathogen N. fowleri, OrthoMCL protein clustering including data of N. fowleri, N. lovaniensis and N. gruberi was performed. GO enrichment analysis shows an association of N. fowleri specific proteins to the GO terms "Membrane" and "Protein Secretion."

CONCLUSION

In this study, we characterize the hitherto unknown genome of N. lovaniensis. With the description of the 30 Mb genome, a further piece is added to reveal the complex taxonomic relationship of Naegleria. Further, the whole genome sequencing data confirms the hypothesis of the close relationship between N. fowleri and N. lovaniensis. Therefore, the genome of N. lovaniensis provides the basis for further comparative approaches on the molecular and genomic level to unravel pathogenicity factors of its closest human pathogenic relative N. fowleri and possible treatment options for the rare but mostly fatal primary meningoencephalitis.

摘要

背景

纳格尔里亚属的成员是自由生活的真核生物,能够根据环境条件从变形虫形式转变为休眠囊或游动鞭毛。已经鉴定出超过 40 种,但只有福氏纳格尔里亚(N. fowleri)被认为是一种引起原发性阿米巴脑膜脑炎(PAM)的人类病原体,这是一种快速进展且大多数致命的中枢神经系统疾病。一些研究报告表明磷脂酶和其他分子因素的参与,但发病机制涉及的机制仍知之甚少。为了更好地了解纳格尔里亚属内的关系,并研究 N. fowleri 的致病因素,我们对其最接近的非致病亲缘种 N. lovaniensis 的基因组进行了表征。

结果

为了深入了解纳格尔里亚的分类学,我们使用长读测序技术对 N. lovaniensis 的基因组进行了测序。数据组装得到了一个 30 Mb 的基因组,包括圆形线粒体序列。使用 OrthoMCL 蛋白聚类和最大似然方法揭示系统发育关系,证实了 N. lovaniensis 和 N. fowleri 的密切关系。为了全面了解纳格尔里亚蛋白的多样性,并评估人类病原体 N. fowleri 的特征,进行了 OrthoMCL 蛋白聚类,包括 N. fowleri、N. lovaniensis 和 N. gruberi 的数据。GO 富集分析表明,N. fowleri 特异蛋白与“膜”和“蛋白质分泌”GO 术语相关。

结论

在这项研究中,我们对 N. lovaniensis 迄今未知的基因组进行了描述。通过描述 30 Mb 的基因组,进一步揭示了纳格尔里亚复杂的分类关系。此外,全基因组测序数据证实了 N. fowleri 和 N. lovaniensis 之间密切关系的假设。因此,N. lovaniensis 的基因组为进一步进行分子和基因组水平的比较研究提供了基础,以揭示其最接近的人类病原体 N. fowleri 的致病因素和可能的治疗方案,因为原发性脑膜脑炎很少见但大多数是致命的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6005/6125883/b803a2734825/12864_2018_4994_Fig1_HTML.jpg

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