ChiA: a major player in the virulence of Crohn's disease-associated adherent and invasive (AIEC).

We investigated the role of ChiA and its associated polymorphisms in the interaction between Crohn's disease (CD)-associated adherent-invasive (AIEC) and intestinal mucosa. We observed a higher abundance of among the metagenome of CD patients compared to healthy subjects. In dextran sulfate sodium-induced colitis mice model, AIEC-LF82∆ colonization was reduced in ileal, colonic and fecal samples compared to wild-type LF82. The binding of ChiA to recombinant human CHI3L1 or mucus was higher with the pathogenic polymorphism. The strength of ChiA-mucin interaction was 300-fold stronger than ChiA-rhCHI3L1. ChiA was able to degrade mucin to promote its growth and enabled LF82 to get closer to epithelial cells. The pathogenic polymorphism of ChiA had a stronger impact on mucus degradation than on the binding capability of AIEC to adhere to the intestinal epithelium. We observed that ChiA could favor an efficient bacterial invasion of intestinal crypts, and that ChiA, especially its pathogenic polymorphism, gives LF82 an advantage to uptake within Peyer's patches, macrophages and mesenteric lymph nodes. All together, these data support the role of ChiA in the virulence of AIEC and show that it could be a promising target to reduce AIEC colonization in patients with CD.