Enteropathogenic Escherichia coli (EPEC) and enterohaemorrhagic Escherichia coli (EHEC) are closely related diarrheagenic pathogens that are important causes of morbidity and mortality worldwide, especially in young children. EPEC and EHEC are known as attaching and effacing pathogens because they intimately adhere to gut enterocytes and instigate effacement of brush border microvilli. Injection of bacterial effector proteins via a type III secretion system (T3SS) is an integral part of the EPEC and EHEC infection strategy. One such effector, EspF, binds and induces degradation of the anti-apoptotic protein AbcF2, however, although infected cells show early apoptotic symptoms, they do not present late apoptosis signs. The T3SS effectors NleH1 and NleH2 were recently found to have a broad range anti-apoptotic activity which may neutralise the effect of EspF and promote cell survival.<P>
In this proposal we wish to investigate the anti-apoptotic activity of NleH, in particular its binding to the endoplasmic reticulum (ER) anti-apoptotic protein Bax inhibitor-1 (BI-1) and to PDZ domain-containing protein/s.
Funded under 7th FWP (Seventh Framework Programme)