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

GOMEZ FERNANDO D; SCALISE MARÍA LUJÁN; IBARRA CRISTINA; GARIMANO NICOLÁS; AMARAL MARÍA MARTA

Frontiers in Cellular and Infection Microbiology-

Frontiers

Lugar: Lausana; Año: 2022

The human colonic mucus is mainly composed of mucins, which are highly glycosylatedproteins. The normal commensal colonic microbiota has mucolytic activity and iscapable of releasing the monosaccharides contained in mucins, which can then be used as carbon sources by pathogens such as Enterohemorrhagic Escherichia coli (EHEC). EHEC can regulate the expression of some of its virulence factors through environmental sensing of mucus-derived sugars, but its implications regarding its mainvirulence factor,  Shiga toxin type 2 (Stx2), among others, remain unknown. Inthe present work, we have studied the effects of five of the most abundantmucolytic activity-derived sugars, Fucose(L-Fucose), Galactose (D-Galactose), N-Gal (N-acetyl-galactosamine), NANA(N-Acetyl-Neuraminic Acid) and NAG (N-Acetyl-D-Glucosamine) 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 NANA compared to Galactose, Fucose or N-Gal, and that EHEC adhesion was inhibited regardless of the metabolite used. On the other hand, Stx2 production was enhanced when using NAG and inhibited with the restof the metabolites, whilst Stx2 translocation was only enhanced when using NANA, and this increase occurred only through the transcellular route. Overall, this study provides insights on the influence of the commensalmicrobiota on the pathogenicity of E.coli O157:H7, helping to identify favorable intestinal environments for the development of severe disease.@font-face{font-family:"Cambria Math";panose-1:2 4 5 3 5 4 6 3 2 4;mso-font-charset:0;mso-generic-font-family:roman;mso-font-pitch:variable;mso-font-signature:-536870145 1107305727 0 0 415 0;}@font-face{font-family:Calibri;panose-1:2 15 5 2 2 2 4 3 2 4;mso-font-charset:0;mso-generic-font-family:swiss;mso-font-pitch:variable;mso-font-signature:-520082689 -1073697537 9 0 511 0;}p.MsoNormal, li.MsoNormal, div.MsoNormal{mso-style-unhide:no;mso-style-qformat:yes;mso-style-parent:"";margin-top:6.0pt;margin-right:0cm;margin-bottom:12.0pt;margin-left:0cm;mso-pagination:widow-orphan;font-size:12.0pt;mso-bidi-font-size:11.0pt;font-family:"Times New Roman",serif;mso-fareast-font-family:Calibri;mso-fareast-theme-font:minor-latin;mso-bidi-font-family:"Times New Roman";mso-bidi-theme-font:minor-bidi;mso-ansi-language:EN-US;mso-fareast-language:EN-US;}.MsoChpDefault{mso-style-type:export-only;mso-default-props:yes;font-size:11.0pt;mso-ansi-font-size:11.0pt;mso-bidi-font-size:11.0pt;font-family:"Cambria",serif;mso-ascii-font-family:Cambria;mso-ascii-theme-font:major-latin;mso-fareast-font-family:Calibri;mso-fareast-theme-font:minor-latin;mso-hansi-font-family:Cambria;mso-hansi-theme-font:major-latin;mso-bidi-font-family:"Times New Roman";mso-bidi-theme-font:minor-bidi;mso-ansi-language:EN-US;mso-fareast-language:EN-US;}.MsoPapDefault{mso-style-type:export-only;margin-bottom:10.0pt;line-height:115%;}div.WordSection1{page:WordSection1;}