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Infectious disease

Crohn's disease

Bacterial fimbrial adhesin (fimH)

Cell culture and ex vivo studies suggest thiazolylaminomannosides could help treat Crohn's disease. Adherent-invasive Escherichia coli (AIEC), which are associated with Crohn's disease, use fimH to bind to oligomannosides on the surface of intestinal epithelial cells, leading to inflammation. In cultured human intestinal cells expressing the fimH receptor carcinoembryonic antigen related cell adhesion molecule 6 (CEACAM6; NCA; CD66c), a thiazole-modified N-mannoside decreased AIEC attachment compared with no treatment. In colonic explants from a mouse model for AIEC colonization, the thiazole-modified N-mannoside inhibited AIEC from binding to the mucosal surface with 10- to 100-fold higher potency than previously published D-mannosides. Next steps include testing the specificity of N-mannosides to different pathogenic fimH variants and determining
in vivo treatment efficacy in a mouse model to assess preventive and curative effects.

SciBX 6(27); doi:10.1038/scibx.2013.685
Published online July 18, 2013

Patent application filed; available for licensing from France Scientific Innovation and Transfer SA

Brument, S. et al. J. Med. Chem.; published online June 12, 2013;
Contact: Sébastien G. Gouin, University of Nantes Angers Le Mans (L'UNAM), Nantes, France
Contact: Rostyslav O. Bilyy, Rostyslav O. Bilyy, Institute of Cell Biology, National Academy of Sciences of Ukraine, Lviv, Ukraine
Contact: Arlette Darfeuille-Michaud, French National Institute for Agricultural Research (INRA),
Clermont-Ferrand, France
Contact: Julie Bouckaert, Lille 1 University, Lille, France