TccP is an enterohaemorrhagic Escherichia coli O157:H7 type III effector protein that couples Tir to the actin-cytoskeleton

Garmendia, Junkal, Phillips, Alan D., Carlier, Marie-France, Chong, Yuwen, Schuller, Stephanie ORCID: https://orcid.org/0000-0003-3260-9112, Marches, Olivier, Dahan, Sivan, Oswald, Eric, Shaw, Rob K., Knutton, Stuart and Frankel, Gad (2004) TccP is an enterohaemorrhagic Escherichia coli O157:H7 type III effector protein that couples Tir to the actin-cytoskeleton. Cellular Microbiology, 6 (12). pp. 1167-1183. ISSN 1462-5814

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Abstract

Subversion of host cell actin microfilaments is the hallmark of enterohaemorrhagic (EHEC) and enteropathogenic (EPEC) Escherichia coli infections. Both pathogens translocate the trans-membrane receptor protein – translocated intimin receptor (Tir), which links the extracellular bacterium to the cell cytoskeleton. While both converge on neural Wiskott–Aldrich syndrome protein (N-WASP), Tir-mediated actin accretion by EPEC and EHEC differ in that TirEPEC requires both tyrosine phosphorylation and the host adaptor protein Nck, whereas TirEHEC is not phosphorylated and utilizes an unidentified linker. Here we report the identification of Tir-cytoskeleton coupling protein (TccP), a novel EHEC effector that displays an Nck-like coupling activity following translocation into host cells. A tccP mutant did not affect Tir translocation and focusing but failed to recruit α-actinin, Arp3, N-WASP and actin to the site of bacterial adhesion. When expressed in EPEC, bacterial-derived TccP restored actin polymerization activity following infection of an Nck-deficient cell line. TccP has a similar biological activity on infected human intestinal explants ex vivo. Purified TccP activates N-WASP stimulating, in the presence of Arp2/3, actin polymerization in vitro. These results show that EHEC translocates both its own receptor (Tir) and an Nck-like protein (TccP) to facilitate actin polymerization.

Item Type:	Article
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups:	Faculty of Medicine and Health Sciences > Research Groups > Gastroenterology and Gut Biology Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health Faculty of Medicine and Health Sciences > Research Groups > Pathogen Biology Group
Depositing User:	Rhiannon Harvey
Date Deposited:	20 Jul 2011 09:34
Last Modified:	24 Sep 2024 10:01
URI:	https://ueaeprints.uea.ac.uk/id/eprint/33956
DOI:	10.1111/j.1462-5822.2004.00459.x

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