Molecular analysis of regulation of virulence gene expression in pathogenic E. coli strains (ETEC and atypical EPEC)

致病性大肠杆菌菌株（ETEC 和非典型 EPEC）毒力基因表达调控的分子分析

• 批准号: nhmrc : 400029
• 负责人: Dr Ji Yang
• 金额: $ 19.29万
• 依托单位: The University of Melbourne
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2006
• 资助国家: 澳大利亚
• 起止时间: 2006-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/molecular-analysis-regulation-atypical-epec/77253
• 关键词: Molecular; analysis; regulation; virulence; gene

Infectious diarrhoea is one of the commonest human afflictions worldwide, and is responsible for the deaths of millions of children each year. One of the principal causes of diarrhoea is pathogenic E. coli, which are classified into several groups according to the factors they employ to cause disease. One type of pathogenic E. coli, known as enterotoxigenic E. coli (ETEC), causes diarrhoea resembling cholera in children in less developed countries and in adult travellers to those countries. Another type is enteropathogenic E. coli (EPEC), which causes acute and persistent diarrhoea in children worldwide. Recent studies in Melbourne and Darwin have shown that EPEC are a particularly common cause of diarrhoea in children living in those cities. Individual groups of E. coli use different strategies to cause infection. In the case of ETEC, the key step in infection is the injection of bacterial toxins into intestinal cells. These toxins perturb the ability of these cells to transport water and electrolytes across their membrane. In contrast, infection with EPEC is characterised by intimate adherence of the bacteria to the lining of the intestine, causing structural damage to intestinal cells. Because the synthesis of virulence factors is an energy-costly process for bacteria, pathogenic varieties of E. coli have evolved sophisticated mechanisms to control the production of these factors, so that they are made only when needed, e.g., under environmental conditions like those in the gut. In this project, we will investigate the ways by which ETEC and EPEC sense and respond to environmental signals to produce their virulence determinants. The identification of specific control genes and proteins of these bacteria may lead to the development of novel diagnostic tools for EPEC and help us to devise new treatment strategies to block the production of virulence factors by pathogenic E. coli.

传染性腹泻是全世界最常见的人类疾病之一，每年造成数百万儿童死亡。腹泻的主要原因之一是致病性大肠杆菌。大肠杆菌，根据致病因素分为几类。一种致病性E.大肠埃希菌（enterocardiogenic E. coli）。大肠杆菌（ETEC），在欠发达国家的儿童和前往这些国家的成年旅行者中引起类似霍乱的腹泻。另一种是肠致病性E.大肠杆菌（EPEC），导致全球儿童急性和持续性腹泻。最近在墨尔本和达尔文的研究表明，EPEC是生活在这些城市的儿童腹泻的一个特别常见的原因。E.大肠杆菌使用不同的策略来引起感染。在ETEC的情况下，感染的关键步骤是将细菌毒素注射到肠细胞中。这些毒素扰乱了这些细胞跨膜运输水和电解质的能力。相比之下，EPEC感染的特征是细菌紧密粘附在肠道内壁，导致肠细胞结构损伤。由于毒力因子的合成对细菌来说是一个消耗能量的过程，因此致病性大肠杆菌的变种。大肠杆菌已经进化出复杂的机制来控制这些因子的产生，使得它们仅在需要时产生，例如，在肠道环境条件下。在这个项目中，我们将研究ETEC和EPEC感知和响应环境信号以产生其毒力决定因子的方式。这些细菌的特定控制基因和蛋白质的鉴定可能导致开发新的诊断工具EPEC，并帮助我们设计新的治疗策略，以阻止致病性E.杆菌