ChiA, a major player in the pathogenicity of adherent and invasive E. coli bacteria (AIEC) associated with Crohn's disease.

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Fargeas, Margot | Faure, Frédéric | Douadi, Clara | Chevarin, Caroline | Sivignon, Adeline | Denizot, Jérémy | Billard, Elisabeth | Buisson, Anthony | Barnich, Nicolas

Edité par CCSD -

International audience. In patients with Crohn Disease (CD), the prevalence of adherent and invasive E. coli (AIEC) is increased. These bacteria have the ability to adhere to and invade intestinal epithelial cells (IEC), as well as replicate and survive in intestinal macrophages. Nowadays, the pathogenic capacities of AIEC bacteria are incompletely described. A metagenomic study demonstrates that chiA gene is significatively more abundant in the microbiota of CD patients compared to other digestive pathologies as ulcerative colitis or colorectal cancer. The aim of this work is to characterize the role of the virulence factor ChiA in the invasion of AIEC bacteria into the intestinal mucosa. In vivo experiments showed that deletion of the chiA gene significantly reduced colonization of the LF82, AIEC reference strain, in the intestinal mucosa of mice. Further studies performed in mice model combined with in vitro experiments revealed that ChiA plays a role in 1) the mucus degradation, enabling AIEC bacteria to gain better access to IECs; 2) the adhesion of AIEC bacteria to IECs via the eukaryotic transmembrane protein CHI3L1; 3) the crossing the epithelial barrier; and 4) the macrophage entry and the innate immune uptake of AIEC bacteria. ChiA is thus a major player in the pathogenicity of these bacteria. Therefore, blocking the ChiA-CHI3L1 interaction could be a promising way for targeting AIEC bacteria in CD patients, and thus preventing chronic inflammation.

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