Pathogenesis and prevention of Shiga toxigenic Escherichia coli infections [ 2002 - 2003 ]

Research Grant

Researchers: Prof James Paton (Principal investigator) ,  Prof Adrienne Paton

Brief description Shiga toxin (Stx)-producing strains of Escherichia coli (STEC) are known to cause diarrhoea and haemorrhagic colitis in humans. In a proportion of cases, this leads to potentially fatal systemic complications, such as haemolytic uraemic syndrome (HUS), which is the commonest cause of acute renal failure in children. HUS has a high mortality rate in spite of intensive supportive therapy. Morbidity is also substantial, as permanent renal damage and neurological sequelae occur in a significant proportion of survivors. Large outbreaks of STEC infection are becoming increasingly common, and highlight the threat to public health posed by these bacteria. The serious systemic complications of STEC disease, as well as much of the intestinal pathology, are directly attributable to Stx. However, pathogenesis is multifactorial and capacity of the bacteria to colonize the gut is a crucial virulence trait. STEC infections can now be diagnosed very early in the course of disease, but currently no effective therapeutic intervention is possible. We are addressing this deficiency by developing a novel therapy for STEC infections based on a genetically modified harmless bacterium capable of binding toxin in the gut. Vaccines capable of preventing transmission of STEC disease in the community are also needed, but development of these demands a full understanding of the mechanisms whereby diverse STEC strains adhere to intestinal epithelium and colonize the human gut. We are therefore also examining the interaction between STEC and gut epithelial cells at the cellular and molecular level, with a view to identifying and assessing the vaccine potential of key determinants of adherence.

Funding Amount $AUD 341,320.00

Funding Scheme NHMRC Project Grants

Notes Standard Project Grant