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Microbiology 153 (2007), 959-967; DOI  10.1099/mic.0.2006/003467-0
© 2007 Society for General Microbiology

Functional studies of intimin in vivo and ex vivo: implications for host specificity and tissue tropism

Rosanna Mundy1, Stephanie Schüller2, Francis Girard1,3, John M. Fairbrother3, Alan D. Phillips2 and Gad Frankel1

1 Division of Cell and Molecular Biology, Imperial College London, London, UK
2 Centre for Paediatric Gastroenterology, Royal Free and University College Medical School, London, UK
3 Groupe de Recherche sur les Maladies Infectieuses du Porc (GREMIP), Faculté de Medicine Vétérinaire, Université de Montréal, St-Hyacinthe, Canada

Correspondence
Gad Frankel
g.frankel{at}imperial.ac.uk

Intimin is an outer-membrane adhesin that is essential for colonization of the host gastrointestinal tract by attaching and effacing pathogens including enteropathogenic Escherichia coli (EPEC), enterohaemorrhagic E. coli (EHEC) and Citrobacter rodentium (CR). The N-terminus of intimin from the different strains is highly conserved while the C-terminus, which harnesses the active receptor-binding site, shows sequence and antigenic polymorphism. This diversity was used to define a number of distinct intimin types, the most common of which are {alpha}, beta and {gamma}. Intimin binds the type III secretion system effector protein Tir. However, a large body of evidence suggests that intimin also binds a host-cell-encoded receptor(s) (Hir), and interaction of different intimin types with Hir contributes to tissue and host specificity. The aims of this study were to compare the activity of the major intimin types ({alpha}, beta and {gamma}) in vivo and ex vivo, using the CR mouse model and in vitro organ culture (IVOC), and to determine their exchangeability. The results confirm that intimin {gamma} is not functional in the CR mouse model. In the pig, intimin beta can substitute for EPEC intimin {alpha} but when placed in an EHEC O157 : H7 background it does not produce an intimin {alpha}-like tropism, although some adhesion to the small and large intestine was observed. In contrast, in human IVOC, intimin beta in an EHEC background produces small intestinal colonization in a similar manner to intimin {alpha}.

Abbreviations: A/E, attaching and effacing; CR, Citrobacter rodentium; EHEC, enterohaemorrhagic E. coli; EPEC, enteropathogenic E. coli; IVOC, in vitro organ culture; HPS, haematoxylin, phloxine and safranine; LEE, locus of enterocyte effacement; p.i., post-inoculation; SEM, scanning electron microscope/microscopy




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[Abstract] [Full Text] [PDF]


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