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

Abstract

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.

Role of Host Xanthine Oxidase in Infection Due to Enteropathogenic and Shiga-Toxigenic Escherichia coli

“…4C). The anaerobic microbiota of the gut, and of B. thetaiotaomicron in particular, secretes soluble factors that inhibit Stx production (31). Elimination of anaerobic microbes via H 2 O 2 would be another mechanism by which XO regulates virulence.…”

Coculture of Escherichia coli O157:H7 with a Nonpathogenic E. coli Strain Increases Toxin Production and Virulence in a Germfree Mouse Model

“…A further exploration of the interactions between E. coli O157:H7 and the plethora of bacterial species present in the gut is needed to appreciate how the gut microbiome affects the virulence of this foodborne pathogen. It was also shown previously that fecal Bacteroides thetaiotaomicron alters Stx2 expression (40)(41)(42), although two studies (40,42) report decreases while one (41) report shows Hematoxylin-and eosin-stained renal sections from mice infected with either C600 or PA2 and PA2 plus C600. The mice were scored as described in Materials and Methods.…”

Differential Expression of Virulence and Stress Fitness Genes during Interaction betweenListeria monocytogenesandBifidobacterium longum

“…Various studies have suggested that probiotics or their secreted factors such as organic acids downregulate the transcriptional levels of virulence genes in E. coli O157:H7, 5,9,10,24) but the specific role of probiotics in L. monocytogenes virulence-related gene expression has not been well described.…”