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

传染性腹泻是世界上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，根据它们致病的因素可将其分为几类。一种致病性大肠杆菌，称为产肠毒素大肠杆菌（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。另一种类型是肠致病性大肠杆菌（EPEC），在世界各地的儿童中引起急性和持续性腹泻。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。不同的大肠杆菌群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在细胞膜上运输水和电解质的能力。相反，EPEC感染的特征是细菌与肠道内壁的紧密粘附，导致肠细胞的结构性损伤。由于毒力因子的合成对细菌来说是一个消耗能量的过程，致病性大肠杆菌品种已经进化出复杂的机制来控制这些因子的产生，因此它们只在需要时才会产生，例如在肠道等环境条件下。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素的方式。这些细菌的特异性控制基因和蛋白质的鉴定可能会导致新的EPEC诊断工具的发展，并帮助我们设计新的治疗策略来阻止致病性大肠杆菌产生毒力因子。

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.