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Novel approach to bind and specifically detect FimH-expressing E. coli using heptylmannose-functionalized cellulose
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International audience. Adherent-Invasive Escherichia coli (AIEC) strains isolated from Crohn’s disease (CD) patients are able to adhere to and to invade intestinal epithelial cells in vitro. CEACAM6 glycoprotein was shown to be abnormally expressed at ileal mucosa of CD patients and to act as a receptor for AIEC (Barnich et al., JCI, 2007). Moreover, gut colonization of AIEC LF82 reference strain was associated to severe colitis in CEABAC10 transgenic mice, which express human CEACAM6 (Carvalho et al., J. Exp. Med., 2009). Interestingly, AIEC pathobiont shows specific allelic variants in fimH gene, which encodes for the mannose-binding FimH adhesin, increasing AIEC adhesion capacity (Dreux et al., Plos Pathog, 2013). Previously, we demonstrated that synthetic derivatives of heptylmannoside (HMan), a nanomolar FimH antagonist, were able to decrease AIEC adhesion to intestinal epithelial cells in vitro and to lower intestinal bacterial loads as well as colitis signs in CEABAC10 mice (Sivignon et al., mBio, 2015). In this project, we evaluated the efficiency of HMan grafted by click chemistry techniques onto cellulose nanofibers (CN) for its anti-adhesive effect against AIEC bacteria (therapeutic strategy) and HMan grafted onto cellulose paper (CP) for its ability to trap and accumulate AIEC bacteria in solution (detection strategy). The aim is to develop a rapid and sensitive diagnostic system to identify CD patients carrying AIEC in order to improve disease management by proposing personnalized therapies targeting these bacteria.
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