Unravelling the TccP and Nck actin remodelling pathways of attaching and effacing E coli (AEEC). (360G-Wellcome-079541_Z_06_Z)

£198,436

Enteropathogenic (EPEC) and enterohaemorrhagic E. coli (EHEC) are human pathogens that translocate the Tir protein into the plasma membrane of the host cell. Through interaction with the outer membrane adhesion molecule intimin Tir connects the extracellular bacterium to the host cell actin cytoskeleton. Intimin-Tir interaction focuses Tir and triggers actin polymerisation at the site of bacterial adhesion. While both converge on N-WASP, Tir-mediated actin accretion by EPECE2348/69 requires Tir tyrosine (TirY474) phosphorylation and the host adaptor Nck, whereas TirEHECO157 is not phosphorylated and utilises TccP, a bacterial effector that binds, albeit indirectly, Tir and activates N-WASP. While screening for tccP among a large collection of EPEC and non-O157 EHEC we found that many strains carry tccP and a TirY474 equivalent. Preliminary results showed that the TccP/TirY474 strains simultaneously utilise the Nck and TccP pathways during infection, defining a new class of versatile and potentially more virulent diarrhoeagenic E. coli. The main goals of this project are to characterise the signalling pathways used by the TccP/TirY474 strains, to determine their role, synergy or redundancy during infection and colonisation using in vitro and in vivo models and to find the host cell adaptor protein(s) that links TccP to Tir.

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Grant Details

Amount Awarded 198436
Applicant Surname Frankel
Approval Committee Immunology and Infectious Disease Funding Committee
Award Date 2006-04-24T00:00:00+00:00
Financial Year 2005/06
Grant Programme: Title Project Grant
Internal ID 079541/Z/06/Z
Lead Applicant Prof Gad Frankel
Partnership Value 198436
Planned Dates: End Date 2011-06-30T00:00:00+00:00
Planned Dates: Start Date 2006-08-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region Greater London