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人胃肠道中肠出血性大肠杆菌生存及毒力的调控

Modulation of Enterohaemorrhagic Survival and Virulence in the Human Gastrointestinal Tract.

作者信息

Jubelin Grégory, Desvaux Mickaël, Schüller Stephanie, Etienne-Mesmin Lucie, Muniesa Maite, Blanquet-Diot Stéphanie

机构信息

UMR454 MEDIS, Université Clermont Auvergne/INRA, 63000 Clermont-Ferrand, France.

Norwich Medical School, University of East Anglia, Norwich NR4 7TJ, UK.

出版信息

Microorganisms. 2018 Nov 19;6(4):115. doi: 10.3390/microorganisms6040115.

Abstract

Enterohaemorrhagic (EHEC) is a major foodborne pathogen responsible for human diseases ranging from diarrhoea to life-threatening complications. Survival of the pathogen and modulation of virulence gene expression along the human gastrointestinal tract (GIT) are key features in bacterial pathogenesis, but remain poorly described, due to a paucity of relevant model systems. This review will provide an overview of the in vitro and in vivo studies investigating the effect of abiotic (e.g., gastric acid, bile, low oxygen concentration or fluid shear) and biotic (e.g., gut microbiota, short chain fatty acids or host hormones) parameters of the human gut on EHEC survival and/or virulence (especially in relation with motility, adhesion and toxin production). Despite their relevance, these studies display important limitations considering the complexity of the human digestive environment. These include the evaluation of only one single digestive parameter at a time, lack of dynamic flux and compartmentalization, and the absence of a complex human gut microbiota. In a last part of the review, we will discuss how dynamic multi-compartmental in vitro models of the human gut represent a novel platform for elucidating spatial and temporal modulation of EHEC survival and virulence along the GIT, and provide new insights into EHEC pathogenesis.

摘要

肠出血性大肠杆菌(EHEC)是一种主要的食源性病原体,可导致从腹泻到危及生命的并发症等多种人类疾病。该病原体在人类胃肠道(GIT)中的存活以及毒力基因表达的调控是细菌致病机制的关键特征,但由于缺乏相关模型系统,目前对此仍知之甚少。本综述将概述体外和体内研究,这些研究探讨了人类肠道的非生物参数(如胃酸、胆汁、低氧浓度或流体剪切力)和生物参数(如肠道微生物群、短链脂肪酸或宿主激素)对EHEC存活和/或毒力的影响(特别是与运动性、黏附性和毒素产生的关系)。尽管这些研究具有相关性,但考虑到人类消化环境的复杂性,它们存在重要局限性。这些局限性包括一次仅评估一个单一的消化参数、缺乏动态通量和区室化,以及缺乏复杂的人类肠道微生物群。在综述的最后一部分,我们将讨论人类肠道的动态多区室体外模型如何代表一个新的平台,用于阐明EHEC在胃肠道中的存活和毒力的时空调控,并为EHEC致病机制提供新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c792/6313751/eed1f8c4b0f4/microorganisms-06-00115-g001.jpg

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