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编码 colibactin、细胞毒性坏死因子和细胞毒性扩张毒素的细胞毒性大肠杆菌菌株定植于实验室普通狨猴(Callithrix jacchus)。

Cytotoxic Escherichia coli strains encoding colibactin, cytotoxic necrotizing factor, and cytolethal distending toxin colonize laboratory common marmosets (Callithrix jacchus).

机构信息

Division of Comparative Medicine, Massachusetts Institute of Technology, Building 16-825, 77 Massachusetts Avenue, Cambridge, MA, 02139, USA.

Merck Research Laboratories, Merck, South San Francisco, CA, 94080, USA.

出版信息

Sci Rep. 2021 Jan 27;11(1):2309. doi: 10.1038/s41598-020-80000-1.

DOI:10.1038/s41598-020-80000-1
PMID:33504843
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7841143/
Abstract

Cyclomodulins are virulence factors that modulate cellular differentiation, apoptosis, and proliferation. These include colibactin (pks), cytotoxic necrotizing factor (cnf), and cytolethal distending toxin (cdt). Pathogenic pks+, cnf+, and cdt+ E. coli strains are associated with inflammatory bowel disease (IBD) and colorectal cancer in humans and animals. Captive marmosets are frequently afflicted with IBD-like disease, and its association with cyclomodulins is unknown. Cyclomodulin-encoding E. coli rectal isolates were characterized using PCR-based assays in healthy and clinically affected marmosets originating from three different captive sources. 139 E. coli isolates were cultured from 122 of 143 marmosets. The pks gene was detected in 56 isolates (40%), cnf in 47 isolates (34%), and cdt in 1 isolate (0.7%). The prevalences of pks+ and cnf+ E. coli isolates were significantly different between the three marmoset colonies. 98% of cyclomodulin-positive E. coli belonged to phylogenetic group B2. Representative isolates demonstrated cyclomodulin cytotoxicity, and serotyping and whole genome sequencing were consistent with pathogenic E. coli strains. However, the presence of pks+, cnf+, or cdt+ E. coli did not correlate with clinical gastrointestinal disease in marmosets. Cyclomodulin-encoding E. coli colonize laboratory common marmosets in a manner dependent on the source, potentially impacting reproducibility in marmoset models.

摘要

环调节素是调节细胞分化、凋亡和增殖的毒力因子。这些包括 colibactin (pks)、细胞毒性坏死因子 (cnf) 和细胞致死性扩张毒素 (cdt)。致病性 pks+、cnf+ 和 cdt+大肠杆菌菌株与人类和动物的炎症性肠病 (IBD) 和结直肠癌有关。圈养狨猴经常患有类似 IBD 的疾病,但其与环调节素的关系尚不清楚。使用基于 PCR 的检测方法对来自三个不同圈养来源的健康和临床受影响的狨猴直肠环调节素编码大肠杆菌分离株进行了特征描述。从 143 只狨猴中培养了 139 株大肠杆菌。在 56 株(40%)分离株中检测到 pks 基因,在 47 株(34%)分离株中检测到 cnf,在 1 株(0.7%)分离株中检测到 cdt。三种狨猴群体中 pks+和 cnf+大肠杆菌分离株的流行率存在显著差异。98%的环调节素阳性大肠杆菌属于 B2 型进化群。代表性分离株显示出环调节素细胞毒性,血清分型和全基因组测序与致病性大肠杆菌菌株一致。然而,pks+、cnf+或 cdt+大肠杆菌的存在与狨猴的临床胃肠道疾病无关。编码环调节素的大肠杆菌以依赖来源的方式定植于实验室普通狨猴,这可能会影响狨猴模型的可重复性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5128/7841143/e25d6ba2f0ff/41598_2020_80000_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5128/7841143/3c8cd6ef62b6/41598_2020_80000_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5128/7841143/a15602bbb550/41598_2020_80000_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5128/7841143/e25d6ba2f0ff/41598_2020_80000_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5128/7841143/3c8cd6ef62b6/41598_2020_80000_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5128/7841143/a15602bbb550/41598_2020_80000_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5128/7841143/e25d6ba2f0ff/41598_2020_80000_Fig3_HTML.jpg

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