Abstract
Gut dysbiosis associated with intestinal inflammation is characterized by the blooming of particular bacteria such as adherent-invasive E. coli (AIEC). However, the precise mechanisms by which AIEC impact on colitis remain largely unknown. Here we show that antibiotic-induced dysbiosis worsened chemically-induced colitis in IL-22-deficient mice, but not in wild-type mice. The increase in intestinal inflammation was associated with the expansion of E. coli strains with genetic and functional features of AIEC. These E. coli isolates exhibited high ability to out compete related bacteria via colicins and resistance to the host complement system in vitro. Mutation of wzy, the lipopolysaccharide O polymerase gene, rendered AIEC more sensitive to the complement system and more susceptible to engulfment and killing by phagocytes while retaining its ability to outcompete related bacteria in vitro. The wzy AIEC mutant showed impaired fitness to colonize the intestine under colitic conditions, but protected mice from chemically-induced colitis. Importantly, the ability of the wzy mutant to protect from colitis was blocked by depletion of complement C3 which was associated with impaired intestinal eradication of AIEC in colitic mice. These studies link surface lipopolysaccharide O-antigen structure to the regulation of colitic activity in commensal AIEC via interactions with the complement system.
Highlights
The surface of bacterial symbionts and pathogens is important for the interaction of these microorganisms with their hosts
A common change is the increased abundance of adherent-invasive Escherichia coli (AIEC), a bacterial population that is associated with the development of inflammatory bowel disease
Extraintestinal pathogenic Escherichia coli (ExPEC) strains produce specific K or O serotypes and are often resistant to host systemic immunity [7, 8], while intestinal pathogenic E. coli (InPEC) strains can cause or promote colitis, diarrhea and inflammatory bowel disease (IBD) through their ability to interact with intestinal cells [9]
Summary
The surface of bacterial symbionts and pathogens is important for the interaction of these microorganisms with their hosts. Extraintestinal pathogenic Escherichia coli (ExPEC) strains produce specific K or O serotypes and are often resistant to host systemic immunity [7, 8], while intestinal pathogenic E. coli (InPEC) strains can cause or promote colitis, diarrhea and inflammatory bowel disease (IBD) through their ability to interact with intestinal cells [9]. These host/bacterial interactions are primarily mediated by bacterial adhesive molecules and toxins, but the role of surface polysaccharides in the regulation of intestinal inflammation remains largely unknown
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