Human microbiota-secreted factors inhibit shiga toxin synthesis by enterohemorrhagic Escherichia coli O157:H7.
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 stx(2) 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 stx(2) 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.
de Sablet
Thibaut
T
INRA, Institut National de la Recherche Agronomique, UR454 Unité de Microbiologie, Centre de Recherche de Clermont-Ferrand/Theix, 63122 Saint-Genès-Champanelle, France.
Chassard
Christophe
C
Bernalier-Donadille
Annick
A
Vareille
Marjolaine
M
Gobert
Alain P
AP
Martin
Christine
C
D000293:Adolescent; D000328:Adult; D000818:Animals; D001439:Bacteroides / Q000378:metabolism*; D002432:Cecum / Q000382:microbiology; D002648:Child; D002675:Child, Preschool; D015536:Down-Regulation; D019453:Escherichia coli O157 / Q000378:metabolism*; D005243:Feces / Q000382:microbiology; D005260:Female; D005766:Gastrointestinal Contents / Q000382:microbiology; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D006801:Humans; D008297:Male; D053038:Quorum Sensing; D051381:Rats; D011916:Rats, Inbred F344; D013014:SOS Response, Genetics; D022641:Shiga Toxin 2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D014158:Transcription, Genetic; D014774:Virulence; D055815:Young Adult
D022641:Shiga Toxin 2