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嗜粒细胞无形体 HF 株基因组的比较分析,一种研究致命性人类埃立克体病的模式细菌。

Comparative Analysis of Genome of Ehrlichia sp. HF, a Model Bacterium to Study Fatal Human Ehrlichiosis.

机构信息

Department of Veterinary Biosciences, The Ohio State University, 1925 Coffey Road, Columbus, OH, 43210, USA.

Institute for Genome Sciences, University of Maryland School of Medicine, 801 W. Baltimore St, Baltimore, MD, 21201, USA.

出版信息

BMC Genomics. 2021 Jan 6;22(1):11. doi: 10.1186/s12864-020-07309-z.

Abstract

BACKGROUND

The genus Ehrlichia consists of tick-borne obligatory intracellular bacteria that can cause deadly diseases of medical and agricultural importance. Ehrlichia sp. HF, isolated from Ixodes ovatus ticks in Japan [also referred to as I. ovatus Ehrlichia (IOE) agent], causes acute fatal infection in laboratory mice that resembles acute fatal human monocytic ehrlichiosis caused by Ehrlichia chaffeensis. As there is no small laboratory animal model to study fatal human ehrlichiosis, Ehrlichia sp. HF provides a needed disease model. However, the inability to culture Ehrlichia sp. HF and the lack of genomic information have been a barrier to advance this animal model. In addition, Ehrlichia sp. HF has several designations in the literature as it lacks a taxonomically recognized name.

RESULTS

We stably cultured Ehrlichia sp. HF in canine histiocytic leukemia DH82 cells from the HF strain-infected mice, and determined its complete genome sequence. Ehrlichia sp. HF has a single double-stranded circular chromosome of 1,148,904 bp, which encodes 866 proteins with a similar metabolic potential as E. chaffeensis. Ehrlichia sp. HF encodes homologs of all virulence factors identified in E. chaffeensis, including 23 paralogs of P28/OMP-1 family outer membrane proteins, type IV secretion system apparatus and effector proteins, two-component systems, ankyrin-repeat proteins, and tandem repeat proteins. Ehrlichia sp. HF is a novel species in the genus Ehrlichia, as demonstrated through whole genome comparisons with six representative Ehrlichia species, subspecies, and strains, using average nucleotide identity, digital DNA-DNA hybridization, and core genome alignment sequence identity.

CONCLUSIONS

The genome of Ehrlichia sp. HF encodes all known virulence factors found in E. chaffeensis, substantiating it as a model Ehrlichia species to study fatal human ehrlichiosis. Comparisons between Ehrlichia sp. HF and E. chaffeensis will enable identification of in vivo virulence factors that are related to host specificity, disease severity, and host inflammatory responses. We propose to name Ehrlichia sp. HF as Ehrlichia japonica sp. nov. (type strain HF), to denote the geographic region where this bacterium was initially isolated.

摘要

背景

埃立克体属是蜱传专性细胞内细菌,可引起具有医学和农业重要性的致命疾病。从日本的硬蜱中分离到的埃立克体 sp. HF(也称为硬蜱埃立克体(IOE)剂),在实验室小鼠中引起急性致命感染,类似于由查菲埃立克体引起的急性致命人类单核细胞埃立克体病。由于没有小型实验室动物模型来研究致命的人类埃立克体病,因此埃立克体 sp. HF 提供了一种必要的疾病模型。然而,无法培养埃立克体 sp. HF 以及缺乏基因组信息一直是推进该动物模型的障碍。此外,由于埃立克体 sp. HF 缺乏分类学上公认的名称,因此在文献中有几个名称。

结果

我们从 HF 株感染的小鼠的犬组织细胞白血病 DH82 细胞中稳定培养了埃立克体 sp. HF,并确定了其完整的基因组序列。埃立克体 sp. HF 具有一个 1,148,904 bp 的单链双链环状染色体,它编码 866 种蛋白质,具有与查菲埃立克体相似的代谢潜力。埃立克体 sp. HF 编码了在查菲埃立克体中发现的所有毒力因子的同源物,包括 23 种 P28/OMP-1 家族外膜蛋白、IV 型分泌系统装置和效应蛋白、双组分系统、锚蛋白重复蛋白和串联重复蛋白的同工型。通过与六种代表埃立克体种、亚种和菌株的全基因组比较,使用平均核苷酸同一性、数字 DNA-DNA 杂交和核心基因组比对序列同一性,表明埃立克体 sp. HF 是埃立克体属的一个新种。

结论

埃立克体 sp. HF 的基因组编码了在查菲埃立克体中发现的所有已知毒力因子,证明它是研究致命人类埃立克体病的模型埃立克体种。埃立克体 sp. HF 与查菲埃立克体之间的比较将能够确定与宿主特异性、疾病严重程度和宿主炎症反应相关的体内毒力因子。我们建议将埃立克体 sp. HF 命名为埃立克体日本亚种(HF 株),以表示该细菌最初分离的地理区域。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ad7/7789307/5e11fad012d4/12864_2020_7309_Fig1_HTML.jpg

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