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志贺毒素阴性的大肠杆菌O157:H7是肠致病性大肠杆菌还是肠出血性大肠杆菌?使用全基因组测序的综合分子分析

Is Shiga Toxin-Negative Escherichia coli O157:H7 Enteropathogenic or Enterohemorrhagic Escherichia coli? Comprehensive Molecular Analysis Using Whole-Genome Sequencing.

作者信息

Ferdous Mithila, Zhou Kai, Mellmann Alexander, Morabito Stefano, Croughs Peter D, de Boer Richard F, Kooistra-Smid Anna M D, Rossen John W A, Friedrich Alexander W

机构信息

Department of Medical Microbiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

Institute of Hygiene, University Hospital Münster, Münster, Germany.

出版信息

J Clin Microbiol. 2015 Nov;53(11):3530-8. doi: 10.1128/JCM.01899-15. Epub 2015 Aug 26.

Abstract

The ability of Escherichia coli O157:H7 to induce cellular damage leading to disease in humans is related to numerous virulence factors, most notably the stx gene, encoding Shiga toxin (Stx) and carried by a bacteriophage. Loss of the Stx-encoding bacteriophage may occur during infection or culturing of the strain. Here, we collected stx-positive and stx-negative variants of E. coli O157:H7/NM (nonmotile) isolates from patients with gastrointestinal complaints. Isolates were characterized by whole-genome sequencing (WGS), and their virulence properties and phylogenetic relationship were determined. Because of the presence of the eae gene but lack of the bfpA gene, the stx-negative isolates were considered atypical enteropathogenic E. coli (aEPEC). However, they had phenotypic characteristics similar to those of the Shiga toxin-producing E. coli (STEC) isolates and belonged to the same sequence type, ST11. Furthermore, EPEC and STEC isolates shared similar virulence genes, the locus of enterocyte effacement region, and plasmids. Core genome phylogenetic analysis using a gene-by-gene typing approach showed that the sorbitol-fermenting (SF) stx-negative isolates clustered together with an SF STEC isolate and that one non-sorbitol-fermenting (NSF) stx-negative isolate clustered together with NSF STEC isolates. Therefore, these stx-negative isolates were thought either to have lost the Stx phage or to be a progenitor of STEC O157:H7/NM. As detection of STEC infections is often based solely on the identification of the presence of stx genes, these may be misdiagnosed in routine laboratories. Therefore, an improved diagnostic approach is required to manage identification, strategies for treatment, and prevention of transmission of these potentially pathogenic strains.

摘要

大肠杆菌O157:H7诱导细胞损伤并导致人类疾病的能力与众多毒力因子有关,其中最显著的是stx基因,该基因编码志贺毒素(Stx)并由噬菌体携带。在该菌株感染或培养过程中,编码Stx的噬菌体可能会丢失。在这里,我们从有胃肠道不适症状的患者中收集了大肠杆菌O157:H7/NM(无动力)分离株的stx阳性和stx阴性变体。通过全基因组测序(WGS)对分离株进行了表征,并确定了它们的毒力特性和系统发育关系。由于存在eae基因但缺乏bfpA基因,stx阴性分离株被认为是非典型肠致病性大肠杆菌(aEPEC)。然而,它们具有与产志贺毒素大肠杆菌(STEC)分离株相似的表型特征,并且属于同一序列类型ST11。此外,EPEC和STEC分离株共享相似的毒力基因、肠细胞脱落区域位点和质粒。使用逐个基因分型方法进行的核心基因组系统发育分析表明,发酵山梨醇(SF)的stx阴性分离株与一株SF STEC分离株聚集在一起,一株不发酵山梨醇(NSF)的stx阴性分离株与NSF STEC分离株聚集在一起。因此,这些stx阴性分离株被认为要么已经失去了Stx噬菌体,要么是STEC O157:H7/NM的祖先。由于STEC感染的检测通常仅基于stx基因存在的鉴定,这些菌株在常规实验室中可能会被误诊。因此,需要一种改进的诊断方法来管理这些潜在致病菌株的鉴定、治疗策略和传播预防。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed4c/4609726/49ed9d170a9d/zjm9990945720001.jpg

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