E. coli bacteria are usually known as harmless commensals in the human gut. However, several subsets of E. coli have acquired genetic elements which make them pathogenic to humans. Research in our laboratory is focused on pathogenesis of enteropathogenic (EPEC) and enterohaemorrhagic E. coli (EHEC) both of which are important foodborne pathogens. While EPEC is a major cause of infant diarrhoea in developing countries, EHEC is associated with bloody diarrhoea and severe kidney disease (Haemolytic Uraemic Syndrome/HUS) in children in the developed world.
Both EPEC and EHEC share the ability to adhere to the human gut epithelium by forming characteristic attaching/effacing lesions. This is mediated by a type III secretion system which acts as a macromolecular syringe to inject bacterial effector proteins into the host cell. A multitude of effectors have been identified for EPEC and EHEC which interfere with a range of signal transduction pathways within the host cell and ultimately lead to the development of diarrhoea.
EHEC also release Shiga toxins (Stx) which are associated with HUS and highly cytotoxic to renal microvasculature. HUS is the leading cause of acute kidney failure in children and currently there is no treatment for this potentially fatal disease.
Research in our laboratory aims at understanding EPEC- and EHEC-mediated pathogenesis by using in vitro and ex vivo model systems that closely mimic the environment in the human gut. In collaboration with gastroenterologists at the Norfolk & Norwich University Hospital, we are using in vitro organ culture of human intestinal biopsies to investigate bacterial colonisation and gene expression, host innate immune response to infection and the use of probiotics as treatment strategies. In addition, we have established a vertical diffusion chamber (VDC) system which enables us to perform infections under microaerobic conditions similar to those in the human gut. By using the VDC system we are aiming to understand the influence of oxygen on bacterial virulence gene expression and pathogenesis, the role of Stx in intestinal pathology and the mechanism of Stx translocation across the gut barrier.
Taken together, our research should lead to a better understanding of the early events during EPEC and EHEC pathogenesis and enable the design of more efficient treatment strategies.