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比较基因组学揭示了鸽子作为导致人类疾病的产志贺毒素大肠杆菌(stx-carrying Escherichia coli)主要来源的证据不足,同时也揭示了产志贺毒素和肠致病性大肠杆菌混合流行的现象。

Comparative genomics reveals a lack of evidence for pigeons as a main source of stx-carrying Escherichia coli causing disease in humans and the common existence of hybrid Shiga toxin-producing and enteropathogenic E. coli pathotypes.

机构信息

Centre for Infectious Disease Control (CIb), National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.

Department of Medical Microbiology and Infection Prevention, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

出版信息

BMC Genomics. 2019 Apr 5;20(1):271. doi: 10.1186/s12864-019-5635-z.

Abstract

BACKGROUND

Wild birds, in particular pigeons are considered a natural reservoir for stx-carrying E. coli. An extensive comparison of isolates from pigeons and humans from the same region is lacking, which hampers justifiable conclusions on the epidemiology of these pathogens. Over two hundred human and pigeon stx-carrying E. coli isolates predominantly from the Netherlands were analysed by whole genome sequencing and comparative genomic analysis including in silico MLST, serotyping, virulence genes typing and whole genome MLST (wgMLST).

RESULTS

Serotypes and sequence types of stx-carrying E. coli showed a strong non-random distribution among the human and pigeon isolates with O63:H6/ST583, O113:H6/ST121 and O125:H6/ST583 overrepresented among the human isolates and not found among pigeons. Pigeon isolates were characterized by an overrepresentation of O4:H2/ST20 and O45:H2/ST20. Nearly all isolates harboured the locus of enterocyte effacement (LEE) but different eae and tir subtypes were non-randomly distributed among human and pigeon isolates. Phylogenetic core genome comparison demonstrated that the pigeon isolates and clinical isolates largely occurred in separated clusters. In addition, serotypes/STs exclusively found among humans generally were characterized by high level of clonality, smaller genome sizes and lack of several non-LEE-encoded virulence genes. A bundle-forming pilus operon, including bfpA, indicative for typical enteropathogenic E. coli (tEPEC) was demonstrated in 72.0% of the stx-carrying serotypes but with distinct operon types between the main pigeon and human isolate clusters.

CONCLUSIONS

Comparative genomics revealed that isolates from mild human disease are dominated by serotypes not encountered in the pigeon reservoir. It is therefore unlikely that zoonotic transmission from this reservoir plays an important role in the contribution to the majority of human disease associated with stx-producing E. coli in the Netherlands. Unexpectedly, this study identified the common occurrence of STEC/tEPEC hybrid pathotype in various serotypes and STs. Further research should focus on the possible role of human-to-human transmission of Stx2f-producing E. coli.

摘要

背景

野生鸟类,尤其是鸽子,被认为是携带 stx 的大肠杆菌的天然宿主。缺乏对来自同一地区的鸽子和人类分离株的广泛比较,这阻碍了对这些病原体流行病学的合理结论。对来自荷兰的 200 多株主要来自人类和鸽子的 stx 携带大肠杆菌分离株进行了全基因组测序和比较基因组分析,包括体外 MLST、血清型、毒力基因分型和全基因组 MLST(wgMLST)。

结果

stx 携带大肠杆菌的血清型和序列型在人类和鸽子分离株中分布不均,O63:H6/ST583、O113:H6/ST121 和 O125:H6/ST583 在人类分离株中过度表达,而在鸽子中未发现。鸽子分离株的特点是 O4:H2/ST20 和 O45:H2/ST20 的过度表达。几乎所有的分离株都携带肠上皮细胞侵袭(LEE)基因座,但不同的 eae 和 tir 亚型在人类和鸽子分离株中的分布不均。系统发育核心基因组比较表明,鸽子分离株和临床分离株主要发生在分离的集群中。此外,仅在人群中发现的血清型/ST 通常具有高克隆性、较小的基因组大小和缺乏几个非 LEE 编码的毒力基因。在 72.0%的 stx 携带血清型中证实了包括 bfpA 在内的束形成菌毛操纵子,这表明典型的肠致病性大肠杆菌(tEPEC)的存在,但在主要的鸽子和人类分离株集群之间存在不同的操纵子类型。

结论

比较基因组学显示,轻度人类疾病的分离株主要由在鸽子储层中未遇到的血清型组成。因此,从这个储层中发生的人畜共患传播不太可能在对荷兰与stx 产生大肠杆菌相关的大多数人类疾病的贡献中发挥重要作用。出乎意料的是,本研究发现各种血清型和 ST 中 STEC/tEPEC 混合表型的常见发生。进一步的研究应集中在stx2f 产生大肠杆菌的人与人之间传播的可能作用上。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c275/6451237/386066ded4e7/12864_2019_5635_Fig1_HTML.jpg

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