A Toxic Environment: a Growing Understanding of How Microbial Communities Affect Escherichia coli O157:H7 Shiga Toxin Expression

Abstract

Enterohemorrhagic E. coli (EHEC), including E. coli O157:H7, cause severe illness in humans due to production of Shiga toxin (Stx) and other virulence factors. Because Stx is coregulated with lambdoid prophage induction, its expression is especially susceptible to environmental cues. Infections with Stx-producing E. coli can be difficult to model due to the wide range of disease outcomes—some infections are relatively mild, while others have serious complications. Probiotic organisms, members of the gut microbiome, and organic acids can depress Stx production, in many cases by inhibiting the growth of EHEC strains. On the other hand, the factors currently known to amplify Stx act via their effect on the stx-converting phage. Here, we characterize two interactive mechanisms that increase Stx production by O157:H7 strains: first, direct interactions with phage-susceptible E. coli; and second, indirect amplification by secreted factors. Infection of susceptible strains by the stx-converting phage can expand the Stx-producing population in a human or animal host, and phage infection has been shown to modulate virulence in vitro and in vivo. Acellular factors, particularly colicins and microcins, can kill O157:H7 cells but may also trigger Stx expression in the process. Colicins, microcins, and other bacteriocins have diverse cellular targets, and many such molecules remain uncharacterized. Identification of additional Stx-amplifying microbial interactions will improve our understanding of E. coli O157:H7 infections and help elucidate the intricate regulation of pathogenicity in EHEC strains.

The Escherichia coli SOS Response: Much More than DNA Damage Repair

“…Pathogenic strains are broadly classified into two major groups, with regard to their virulence factors and diseases they provoke, the nondiarrheagenic and diarrheagenic. The nondiarrheagenic are designated extraintestinal pathogenic E. coli (ExPEC) while diarrheagenic provoke diarrhea and include the Shiga toxin (Stx) producing E. coli (STEC) as well as enterohemorrhagic E. coli (EHEC) [37].…”

“…All EHEC strains, including the notorius serotype O157;H7, produce Stx the main virulence factor associated with hemorrhagic colitis [37].…”

AB5 Enterotoxin-Mediated Pathogenesis: Perspectives Gleaned from Shiga Toxins

“…Butyrate is also known to upregulate the receptor for Stx, Gb 3 , in renal tissue and the colonic epithelium [122], and increases adhesion and microcolony formation to epithelial cells [123]. Additionally, secreted molecules, such as bacteriocins (proteinaceous toxins that target closely related bacteria), released by commensal E. coli strains, induce the SOS response and stimulate phage induction and Stx release via DNA damage [124][125][126]. Human-derived microbiome metabolites, such as 4-methyl benzoic acid, 3,4-dimethyl benzoic acid, hexanoic acid, and heptanoic acid, may also promote HUS pathogenesis by preferentially enhancing the motility of E. coli O157:H7 via the induction of flagellin expression, although Stx expression and E. coli O157:H7 colonization are not affected [127].…”

Biocontrol Approaches against Escherichia coli O157:H7 in Foods

“…Shiga-toxigenic Escherichia coli (STEC), also known as verotoxigenic (VTEC) or enterohemorragic (EHEC) E. coli , comprise an important group of bacterial pathogens. STEC is a common cause of foodborne infections, accounting for more than 265,000 illnesses per year in the United States [ 1 ]. E. coli O157:H7 is the most notable STEC serotype with a low infectious dose (50–100 colony-forming units (CFU/g or mL)) and it has been shown to cause a variety of human diseases, such as mild diarrhea, hemorrhagic colitis, hemolytic uremic syndrome, and thrombotic thrombocytopenic purpura [ 2 ].…”