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空肠弯曲菌NCTC 11168在人类和小鼠宿主基因组中的比较变异。

Comparative variation within the genome of Campylobacter jejuni NCTC 11168 in human and murine hosts.

作者信息

Thomas Dallas K, Lone Abdul G, Selinger L Brent, Taboada Eduardo N, Uwiera Richard R E, Abbott D Wade, Inglis G Douglas

机构信息

Agriculture and Agri-Food Canada Research Centre, Lethbridge, Alberta, Canada.

Agriculture and Agri-Food Canada Research Centre, Lethbridge, Alberta, Canada ; Department of Biological Sciences, University of Lethbridge, Lethbridge, Alberta, Canada.

出版信息

PLoS One. 2014 Feb 7;9(2):e88229. doi: 10.1371/journal.pone.0088229. eCollection 2014.

Abstract

Campylobacteriosis incited by C. jejuni is a significant enteric disease of human beings. A person working with two reference strains of C. jejuni National Collection of Type Cultures (NCTC) 11168 developed symptoms of severe enteritis including bloody diarrhea. The worker was determined to be infected by C. jejuni. In excess of 50 isolates were recovered from the worker's stool. All of the recovered isolates and the two reference strains were indistinguishable from each other based on comparative genomic fingerprint subtyping. Whole genome sequence analysis indicated that the worker was infected with a C. jejuni NCTC 11168 obtained from the American Type Culture Collection; this strain (NCTC 11168-GSv) is the genome sequence reference. After passage through the human host, major genetic changes including indel mutations within twelve contingency loci conferring phase variations were detected in the genome of C. jejuni. Specific and robust single nucleotide polymorphism (SNP) changes in the human host were also observed in two loci (Cj0144c, Cj1564). In mice inoculated with an isolate of C. jejuni NCTC 11168-GSv from the infected person, the isolate underwent further genetic variation. At nine loci, mutations specific to inoculated mice including five SNP changes were observed. The two predominant SNPs observed in the human host reverted in mice. Genetic variations occurring in the genome of C. jejuni in mice corresponded to increased densities of C. jejuni cells associated with cecal mucosa. In conclusion, C. jejuni NCTC 11168-GSv was found to be highly virulent in a human being inciting severe enteritis. Host-specific mutations in the person with enteritis occurred/were selected for in the genome of C. jejuni, and many were not maintained in mice. Information obtained in the current study provides new information on host-specific genetic adaptation by C. jejuni.

摘要

空肠弯曲菌引发的弯曲菌病是一种严重的人类肠道疾病。一名接触空肠弯曲菌国家典型培养物保藏中心(NCTC)11168两个参考菌株的工作人员出现了严重肠炎症状,包括血性腹泻。该工作人员被确定为空肠弯曲菌感染。从该工作人员的粪便中分离出了50多个菌株。基于比较基因组指纹亚型分析,所有分离出的菌株与两个参考菌株无法区分。全基因组序列分析表明,该工作人员感染的是空肠弯曲菌NCTC 11168,此菌株来自美国模式培养物保藏所;该菌株(NCTC 11168-GSv)是基因组序列参考菌株。在通过人类宿主后,在空肠弯曲菌基因组中检测到主要的基因变化,包括1个2个赋予相变异的应急位点内的插入缺失突变。在两个位点(Cj0144c、Cj1564)也观察到人类宿主中特异性且强烈的单核苷酸多态性(SNP)变化。在用从感染者分离出的空肠弯曲菌NCTC 11168-GSv菌株接种的小鼠中,该菌株发生了进一步的基因变异。在9个位点观察到接种小鼠特有的突变,包括5个SNP变化。在人类宿主中观察到的两个主要SNP在小鼠中发生了回复。空肠弯曲菌在小鼠基因组中发生的基因变异与盲肠黏膜相关的空肠弯曲菌细胞密度增加相对应。总之,发现空肠弯曲菌NCTC 11168-GSv对人类具有高度毒性,可引发严重肠炎。肠炎患者体内空肠弯曲菌基因组中出现/被选择出宿主特异性突变,其中许多在小鼠中未保留。本研究获得的信息为空肠弯曲菌宿主特异性基因适应提供了新信息。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b9e/3917866/e07d28ee7600/pone.0088229.g001.jpg

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