Cortactin recruitment by enterohemorrhagic Escherichia coli O157:H7 during infection in vitro and ex vivo

Mousnier, Aurelie, Whale, Andrew, Schuller, Stephanie ORCID: https://orcid.org/0000-0003-3260-9112, Leong, John M., Phillips, Alan D. and Frankel, Gad (2008) Cortactin recruitment by enterohemorrhagic Escherichia coli O157:H7 during infection in vitro and ex vivo. Infection and Immunity, 76 (10). pp. 4669-4676. ISSN 0019-9567

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Abstract

Enterohemorrhagic Escherichia coli (EHEC) O157:H7 is an important human pathogen that colonizes the gut mucosa via attaching and effacing (A/E) lesions; A/E lesion formation in vivo and ex vivo is dependent on the type III secretion system (T3SS) effector Tir. Infection of cultured cells by EHEC leads to induction of localized actin polymerization, which is dependent on Tir and a second T3SS effector protein, TccP, also known as EspFU. Recently, cortactin was shown to bind both the N terminus of Tir and TccP via its SH3 domain and to play a role in EHEC-triggered actin polymerization in vitro. In this study, we investigated the recruitment of cortactin to the site of EHEC adhesion during infection of in vitro-cultured cells and mucosal surfaces ex vivo (using human terminal ileal in vitro organ cultures [IVOC]). We have shown that cortactin is recruited to the site of EHEC adhesion in vitro downstream of TccP and N-WASP. Deletion of the entire N terminus of Tir or replacing the N-terminal polyproline region with alanines did not abrogate actin polymerization or cortactin recruitment. In contrast, recruitment of cortactin to the site of EHEC adhesion in IVOC is TccP independent. These results imply that cortactin is recruited to the site of EHEC adhesion in vitro and ex vivo by different mechanisms and suggest that cortactin might have a role during EHEC infection of mucosal surfaces.

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:	22 Mar 2011 16:53
Last Modified:	24 Sep 2024 09:34
URI:	https://ueaeprints.uea.ac.uk/id/eprint/26930
DOI:	10.1128/IAI.00140-08

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