Identification and characterisation of novel virulence genes in attaching and effacing strains of Escherichia coli

几个不同变种的大肠杆菌(E.)大肠杆菌是无害的细菌，生活在健康的肠道中，而其他细菌则会导致腹泻。这些引起腹泻的大肠杆菌包括所谓的致病性大肠杆菌(EPEC)，它是欠发达国家婴幼儿腹泻的主要原因，以及肠出血性大肠杆菌(EHEC)，它是汉堡病的原因。这些细菌之所以能够致病，是因为它们拥有无害的各种大肠杆菌所不具备的特定遗传信息。虽然这些疾病相关基因中的许多已经被确定，但其中许多的具体作用尚不清楚。此外，似乎还有更多这种类型的基因有待发现。EPEC是宿主特有的事实意味着这些细菌致病的机制只能在人类身上进行研究。这对可以进行的调查的数量和类型是极其有限的。然而，有一些兔特有的EPEC菌株会导致兔子患上一种疾病，而这种疾病与EPEC在儿童中引起的疾病难以区分。本研究的目的是通过建立兔腹泻模型，进一步了解EPEC的某些特定因子在疾病发生中的作用，并发现新的致病因子。这将通过三个相辅相成的策略来实现：(1)调查兔大肠杆菌的毒力基因，并确定它们是否存在于人类菌株中；(2)检测这些基因的失活对大肠杆菌引起兔腹泻能力的影响；以及(3)用突变的大肠杆菌菌株池感染兔，以确定细菌在兔体内生存所需的因素。这些研究的结果将提高对大肠杆菌致病机制的了解，并可能为开发诊断、治疗和预防大肠杆菌相关性腹泻的新工具提供机会。

Some varieties of Escherichia (E.) coli are harmless bacteria that live in the healthy intestinal tract, whereas others can cause diarrhoea. Those varieties of E. coli which cause diarrhoea include so-called enteropathogenic E. coli (EPEC), which is a leading cause of life- diarrhoea in infants and young children in less developed countries, and enterohaemorrhagic E. coli (EHEC) the cause of hamburger disease. These bacteria are able to cause disease because they possess specific genetic information that is absent from harmless varieties of E. coli. Although many of these disease-associated genes have been identified, the specific role of many of them is not known. In addition, it seems likely that many more genes of this type remain to be discovered. The fact that EPEC is host specific means that the mechanisms by which these bacteria cause disease can only be investigated in humans. This is extremely limiting for the number and type of investigations that can be performed. However, there are rabbit-specific strains of EPEC which cause a disease in rabbits that is indistinguishable from that caused by EPEC in children. The aims of this study are to use the rabbit model of diarrhoea to learn more about the contribution of certain specific factors of EPEC to disease causation and to discover new factors of this type. This will be achieved by three complementary strategies: (1) investigating rabbit E. coli for virulence genes and determining if they are present in human strains; (2) examining the effect of inactivating these genes on the ability of E. coli to cause diarrhoea in rabbits; and (3) infecting rabbits with pools of mutant E. coli strains to identify factors that the bacteria require to survive in rabbits. The results of these studies will improve understanding of the mechanisms by which E. coli cause disease and may provide opportunities for the development of novel tools to diagnose, treat and prevent E. coli-associated diarrhoea.