Structural Studies into E. coli SslE and its role in Diarrhoeal Diseases

大肠杆菌 SslE 的结构研究及其在腹泻病中的作用

• 批准号: MR/W000814/1
• 负责人: James Garnett
• 金额: $ 77.89万
• 依托单位: King's College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FW000814%2F1
• 关键词: Structural; Studies; into; E.; coli

Bacteria are single cell organisms that inhabit a wide range of environments and can have both a positive and negative impact on human health. The gastrointestinal tract in humans is covered by a layer of mucus and this acts as a barrier to separate host cells from "good bacteria" but also from invading pathogens. However, dangerous bacteria have developed ways to bind and break down host mucus, which releases nutrients to help the bacteria grow but also allows them to access host tissues so they can bind and initiate infection. In this application, we propose a number of experiments that will help us to understand how some dangerous bacteria are able to cause disease in humans through interactions with mucus. We will specifically be studying Escherichia coli, which is commonly found in the human intestines and is often beneficial to the host. However, infectious strains cause severe diarrhoeal diseases, urinary tract infections, blood infections (sepsis) and meningitis. For example, enterotoxigenic E. coli (ETEC) is a strain which is responsible for up to 400 million cases of diarrhoea each year in the developing world, results in the death of at least 300,000 children and is the most frequent cause of traveller's diarrhoea.E. coli use a 'type II secretion system' (T2SS), a syringe-like mechanism to transport proteins into their surroundings and many of these secreted proteins help the bacteria to cause disease. One such protein, SslE, is secreted by many infectious and some beneficial E. coli strains. Once exported it can break down mucus in the intestines but also allows E. coli to form biofilms, where bacteria clump together and are protected from the local environment. In pathogenic strains, SslE has a major role in promoting bacterial disease. We have been studying SslE from both a harmless and an enterotoxigenic strain and we have begun to unravel how SslE is able to perform these two different functions. Understanding the details of how this protein functions and how it interacts with host mucus will be crucial to further our knowledge of E. coli infection in diarrhoeal and other diseases. Furthermore, this secreted protein has shown great promise as a target to develop new vaccines for a range of different types of disease-causing E. coli strains, so providing a better understanding here will also aid future vaccine development. These studies may also reveal common pathways for infectious disease used by other bacteria, which may in turn help us design compounds which disarm E. coli and other dangerous pathogens.

细菌是一种单细胞生物，存在于各种环境中，对人类健康既有积极的影响，也有消极的影响。人类的胃肠道被一层粘液覆盖，这是将宿主细胞与“好细菌”分开的屏障，也是将入侵的病原体分开的屏障。然而，危险的细菌已经找到了结合和分解宿主粘液的方法，这些粘液释放出营养物质来帮助细菌生长，但也允许它们进入宿主组织，这样它们就可以结合并引发感染。在这个应用程序中，我们提出了一些实验，这些实验将帮助我们了解一些危险的细菌是如何通过与粘液的相互作用而导致人类疾病的。我们将专门研究大肠杆菌，它常见于人类肠道，通常对宿主有益。然而，传染性菌株引起严重的腹泻病、尿路感染、血液感染（败血症）和脑膜炎。例如，产肠毒素大肠杆菌（ETEC）是一种菌株，每年在发展中国家造成多达4亿例腹泻病例，导致至少30万儿童死亡，是旅行者腹泻的最常见原因。大肠杆菌使用“II型分泌系统”（T2SS），这是一种类似注射器的机制，可以将蛋白质输送到周围环境中，许多这些分泌的蛋白质帮助细菌引起疾病。其中一种蛋白质，SslE，是由许多传染性和一些有益的大肠杆菌菌株分泌的。一旦出口，它可以分解肠内的粘液，但也允许大肠杆菌形成生物膜，细菌聚集在一起，免受当地环境的影响。在致病性菌株中，SslE在促进细菌性疾病中起主要作用。我们一直在从无害菌株和产肠毒素菌株中研究SslE，我们已经开始揭示SslE如何能够执行这两种不同的功能。了解这种蛋白质如何发挥作用以及它如何与宿主黏液相互作用的细节，对于进一步了解腹泻和其他疾病中的大肠杆菌感染至关重要。此外，这种分泌蛋白已经显示出巨大的希望，可以作为针对一系列不同类型的致病性大肠杆菌菌株开发新疫苗的靶点，因此在这方面提供更好的了解也将有助于未来的疫苗开发。这些研究还可能揭示其他细菌感染传染病的共同途径，这可能反过来帮助我们设计出能够消除大肠杆菌和其他危险病原体的化合物。

项目成果

How to study biofilms: technological advancements in clinical biofilm research.

• DOI: 10.3389/fcimb.2023.1335389
• 发表时间: 2023
• 期刊: Frontiers in cellular and infection microbiology
• 影响因子: 5.7