This Article Full Text Full Text (PDF) Other Versions of this Article: IAI.01199-07v1 76/1/361    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Bai, L. Articles by Frankel, G. Search for Related Content PubMed PubMed Citation Articles by Bai, L. Articles by Frankel, G.

 Previous Article  |  Next Article 

Infection and Immunity, January 2008, p. 361-368, Vol. 76, No. 1
0019-9567/08/$08.00+0     doi:10.1128/IAI.01199-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Enteropathogenic Escherichia coli O125:H6 Triggers Attaching and Effacing Lesions on Human Intestinal Biopsy Specimens Independently of Nck and TccP/TccP2

Li Bai,^1, Stephanie Schüller,^2, Andrew Whale,³ Aurelie Mousnier,³ Olivier Marches,³ Lei Wang,¹ Tadasuke Ooka,⁴ Robert Heuschkel,² Franco Torrente,² James B. Kaper,⁵ Tânia A. T. Gomes,⁶ Jianguo Xu,¹ Alan D. Phillips,² and Gad Frankel^3*

State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Diseases Control and Prevention, China CDC, Beijing, China,¹ Centre for Paediatric Gastroenterology, Royal Free and University College Medical School, London, United Kingdom,² Division of Cell and Molecular Biology, Imperial College London, London, United Kingdom,³ Division of Bioenvironmental Science, Frontier Science Research Center, University of Miyazaki, 5200 Kiyotake, Miyazaki 889-1692, Japan,⁴ Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland,⁵ Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo, São Paulo, Brazil⁶

Received 31 August 2007/ Returned for modification 7 October 2007/ Accepted 24 October 2007

Typical enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic E. coli (EHEC) employ either Nck, TccP/TccP2, or Nck and TccP/TccP2 pathways to activate the neuronal Wiskott-Aldrich syndrome protein (N-WASP) and to trigger actin polymerization in cultured cells. This phenotype is used as a marker for the pathogenic potential of EPEC and EHEC strains. In this paper we report that EPEC O125:H6, which represents a large category of strains, lacks the ability to utilize either Nck or TccP/TccP2 and hence triggers actin polymerization in vitro only inefficiently. However, we show that infection of human intestinal biopsies with EPEC O125:H6 results in formation of typical attaching and effacing lesions. Expression of TccP in EPEC O125:H6, which harbors an EHEC O157-like Tir, resulted in efficient actin polymerization in vitro and enhanced colonization of human intestinal in vitro organ cultures with detectable N-WASP and electron-dense material at the site of bacterial adhesion. These results show the existence of a natural category of EPEC that colonizes the gut mucosa using Nck- and TccP-independent mechanisms. Importantly, the results highlight yet again the fact that conclusions made on the basis of in vitro cell culture models cannot be extrapolated wholesale to infection of mucosal surfaces and that the ability to induce actin polymerization on cultured cells should not be used as a definitive marker for EPEC and EHEC virulence.

Published ahead of print on 5 November 2007.

Editor: J. B. Bliska

L.B. and S.S. are equal contributors.