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Infect. Immun. doi:10.1128/IAI.00446-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Escherichia coli O157:H7 survives within human macrophages: Global gene expression profile and involvement of the Shiga toxins

Department of Microbiology and Immunology, University of Montreal, C.P. 6128 Succursale Centre-Ville, Montréal, Québec, Canada, H3C 3J7; Department of Microbiology, Columbia University Medical Center, New York, NY 10032, USA; Biotechnology Research Institute, National Research Council of Canada, 6100 Royalmount Ave., Montreal, Quebec, Canada H4P 2R2; Laboratory for Foodborne Zoonoses, Public Health Agency of Canada, Lethbridge, Alberta, Canada T1J 3Z4; Institut National de la Recherche Agronomique, UR454 Unité de Microbiologie, Centre de Theix, 63122 Saint-Genès-Champanelle, France; Département de pathologie et microbiologie, Université de Montréal, C. P. 5000. St-Hyacinthe, QC, Canada, J2S 7C6

^* To whom correspondence should be addressed. Email: france.daigle{at}umontreal.ca.

	Abstract

Escherichia coli O157:H7 is an important food borne pathogen that specifically binds to the follicle associated epithelium in the intestine, which rapidly brings this bacterial pathogen in contact with underlying human macrophages. Very little information is available about the interaction between E. coli O157:H7 and human macrophages. We evaluated the uptake and survival of strain EDL933 during infection of human macrophages. Surprisingly, EDL933 survived and multiplied in human macrophages 24 h post-infection. The global gene expression profile of this pathogen during macrophage infection was determined. Inside human macrophages, up-regulation of E. coli O157:H7 genes encoded on O islands was observed, such as pagC, both of the Shiga toxins and two iron transport systems, fit and chu. Genes involved in acid resistance and in SOS response were up-regulated. However, genes of the locus of enterocyte effacement or genes involved in peroxide resistance were not differentially expressed. Many genes with putative or unknown function were up-regulated inside human macrophages and may be newly discovered virulence factors. As the Shiga toxin genes were up-regulated in macrophages, survival and cytotoxicity assay were performed with isogenic Shiga toxin mutants. Initial uptake of Shiga toxins mutants was higher than that of the wild-type, however the survival rates were significantly lower 24 h post-infection. Thus, Shiga toxins are implicated in the interaction between E. coli O157:H7 and human macrophages. Understanding the molecular mechanisms used by E. coli to survive within macrophages may help in the identification of targets for new therapeutic agents.