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Infection and Immunity, February 2009, p. 783-790, Vol. 77, No. 2
0019-9567/09/$08.00+0     doi:10.1128/IAI.01048-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Human Microbiota-Secreted Factors Inhibit Shiga Toxin Synthesis by Enterohemorrhagic Escherichia coli O157:H7{triangledown}

Thibaut de Sablet,{dagger} Christophe Chassard,{ddagger} Annick Bernalier-Donadille, Marjolaine Vareille, Alain P. Gobert, and Christine Martin*

INRA, Institut National de la Recherche Agronomique, UR454 Unité de Microbiologie, Centre de Recherche de Clermont-Ferrand/Theix, 63122 Saint-Genès-Champanelle, France

Received 22 August 2008/ Returned for modification 1 October 2008/ Accepted 6 November 2008

Escherichia coli O157:H7 is a food-borne pathogen causing hemorrhagic colitis and hemolytic-uremic syndrome, especially in children. The main virulence factor responsible for the more serious disease is the Shiga toxin 2 (Stx2), which is released in the gut after oral ingestion of the organism. Although it is accepted that the amount of Stx2 produced by E. coli O157:H7 in the gut is critical for the development of disease, the eukaryotic or prokaryotic gut factors that modulate Stx2 synthesis are largely unknown. In this study, we examined the influence of prokaryotic molecules released by a complex human microbiota on Stx2 synthesis by E. coli O157:H7. Stx2 synthesis was assessed after growth of E. coli O157:H7 in cecal contents of gnotobiotic rats colonized with human microbiota or in conditioned medium having supported the growth of complex human microbiota. Extracellular prokaryotic molecules produced by the commensal microbiota repress stx2 mRNA expression and Stx2 production by inhibiting the spontaneous and induced lytic cycle mediated by RecA. These molecules, with a molecular mass of below 3 kDa, are produced in part by Bacteroides thetaiotaomicron, a predominant species of the normal human intestinal microbiota. The microbiota-induced stx2 repression is independent of the known quorum-sensing pathways described in E. coli O157:H7 involving SdiA, QseA, QseC, or autoinducer 3. Our findings demonstrate for the first time the regulatory activity of a soluble factor produced by the complex human digestive microbiota on a bacterial virulence factor in a physiologically relevant context.


* Corresponding author. Mailing address: INRA, Centre de Theix, Unité de Microbiologie, 63122 Saint-Genès-Champanelle, France. Phone: 33 4 73 62 42 47. Fax: 33 4 73 62 45 81. E-mail: cmartin{at}clermont.inra.fr

{triangledown} Published ahead of print on 8 December 2008.

Editor: S. R. Blanke

{dagger} Present address: Department of Medicine, Division of Gastroenterology, Vanderbilt University Medical Center, 2215B Garland Avenue, 1015A MRB IV, Nashville, TN 37232-0252.

{ddagger} Present address: Institute of Food Science and Nutrition, Schmelzbergstrasse 7, ETH Zentrum LFV, CH-8092 Zürich, Switzerland.


Infection and Immunity, February 2009, p. 783-790, Vol. 77, No. 2
0019-9567/09/$08.00+0     doi:10.1128/IAI.01048-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.




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