Vitamin B12 Uptake by the Gut Commensal Bacteria Bacteroides thetaiotaomicron Limits the Production of Shiga Toxin by Enterohemorrhagic Escherichia coli

Abstract

Enterohemorrhagic Escherichia coli (EHEC) are foodborne pathogens responsible for the development of bloody diarrhea and renal failure in humans. Many environmental factors have been shown to regulate the production of Shiga toxin 2 (Stx2), the main virulence factor of EHEC. Among them, soluble factors produced by human gut microbiota and in particular, by the predominant species Bacteroides thetaiotaomicron (B. thetaiotaomicron), inhibit Stx2 gene expression. In this study, we investigated the molecular mechanisms underlying the B. thetaiotaomicron-dependent inhibition of Stx2 production by EHEC. We determined that Stx2-regulating molecules are resistant to heat treatment but do not correspond to propionate and acetate, two short-chain fatty acids produced by B. thetaiotaomicron. Moreover, screening of a B. thetaiotaomicron mutant library identified seven mutants that do not inhibit Stx2 synthesis by EHEC. One mutant has impaired production of BtuB, an outer membrane receptor for vitamin B12. Together with restoration of Stx2 level after vitamin B12 supplementation, these data highlight vitamin B12 as a molecule produced by gut microbiota that modulates production of a key virulence factor of EHEC and consequently may affect the outcome of an infection.

Gut microbiota of newborn piglets with intrauterine growth restriction have lower diversity and different taxonomic abundances

“…In the present study, the lower relative abundance of Bacteroidetes and Firmicutes in IUGR piglets than controls suggests that IUGR piglets are less efficient at extracting energy from their diet and consequently gain less weight (Matheson et al ). In addition, Proteobacteria , which includes a wide variety of pathogens (such as Escherichia , Salmonella , Vibrio , Helicobacter and Yersinia ), is associated with inflammation (Cordonnier et al ; Wang et al ). In the present study, the IUGR piglets had a higher proportion of Proteobacteria, which increased continuously with age and negatively correlated with BW.…”

Nutrition meets the microbiome: micronutrients and the microbiota

“…The authors further showed that the degradation products of the B vitamins, attached to the surface of infected cells, may act as antigens that activate T and B cells of the immune system. Recently, it has been documented that B. thetaiotaomicron synthesizes vitamin B 12 , which reduces the activity of the main virulence factor, the Shiga toxin 2 of enterohemorrhagic Escherichia coli (EHEC) . These data indicate that the synthesis of different water‐soluble vitamins may help to affect the outcome of infections.…”

Enterotoxigenic and Enterohemorrhagic <i>Escherichia coli</i>: Survival and Modulation of Virulence in the Human Gastrointestinal Tract

“…De Sablet et al [77] have shown, in cecal contents of gnotobiotic rats colonized with human microbiota, that small molecules produced in part by Bacteroides thetaiotaomicron, a predominant species of the normal human intestinal microbiota, repressed stx2 mRNA expression. Mutants of B. thetaiotaomicron with impaired production of a specific transporter of vitamin B12 were no longer able to inhibit the production of Stx2 [78]. This work suggests that concentration of vitamin B12 in the gut and by extension, activities of commensal bacterial species producing and/or consuming vitamin B12, may modulate the production of the main virulence factor of EHEC.…”

“…A higher number of studies have evaluated how EHEC may sense SCFAs. Acetate (10-40 mM) and propionate (2-10 mM) had no effect on Stx2 production levels in vitro [78] while acetate production by Bifidobacterium strains was associated with an antiinfectious activity through the inhibition of Stx production and translocation [82]. Low SCFA concentrations (particularly of butyrate-from 6.25 to 25 mM), more typical of the distal ileum, enhanced the expression of EHEC virulence genes involved in motility, adhesion, and induction of A/E lesion formation [51,52].…”