Intestinal mucus-derived metabolites modulate virulence of a clade 8 enterohemorrhagic Escherichia coli O157:H7

GARIMANO, NICOLAS; SCALISE, MARÍA L.; GÓMEZ, FERNANDO; AMARAL, MARIA MARTA; IBARRA, CRISTINA

Frontiers in Cellular and Infection microbiology

Frontiers Media S.A

Año: 2022

The human colonic mucus is mainly composed of mucins, which are highlyglycosylated proteins. The normal commensal colonic microbiota hasmucolytic activity and is capable of releasing the monosaccharides containedin mucins, which can then be used as carbon sources by pathogens such asEnterohemorrhagic Escherichia coli (EHEC). EHEC can regulate the expressionof some of its virulence factors through environmental sensing of mucusderivedsugars, but its implications regarding its main virulence factor, Shigatoxin type 2 (Stx2), among others, remain unknown. In the present work, wehave studied the effects of five of the most abundant mucolytic activity-derivedsugars, Fucose (L-Fucose), Galactose (D-Galactose), N-Gal (N-acetylgalactosamine),NANA (N-Acetyl-Neuraminic Acid) and NAG (N-Acetyl-DGlucosamine)on EHEC growth, adhesion to epithelial colonic cells (HCT-8),and Stx2 production and translocation across a polarized HCT-8 monolayer.We found that bacterial growth was maximum when using NAG and NANAcompared to Galactose, Fucose or N-Gal, and that EHEC adhesion wasinhibited regardless of the metabolite used. On the other hand, Stx2production was enhanced when using NAG and inhibited with the rest of themetabolites, whilst Stx2 translocation was only enhanced when using NANA,and this increase occurred only through the transcellular route. Overall, thisstudy provides insights on the influence of the commensal microbiota on thepathogenicity of E. coli O157:H7, helping to identify favorable intestinalenvironments for the development of severe disease.