Glycopolymers as Antiadhesives of E. coil Strains Inducing Inflammatory Bowel Diseases

文献类型： 外文期刊

第一作者： Yan, Xibo

作者： Yan, Xibo;Crepet, Agnes;Feury, Etienne;Bernard, Julien;Yan, Xibo;Crepet, Agnes;Feury, Etienne;Bernard, Julien;Yan, Xibo;Crepet, Agnes;Feury, Etienne;Bernard, Julien;Sivignon, Adeline;Barnich, Nicolas;Darfeuille-Michaud, Arlette;Sivignon, Adeline;Barnich, Nicolas;Darfeuille-Michaud, Arlette;Yamakawa, Nao;Bouckaert, Julie;Travelet, Christophe;Borsali, Redouane;Dumych, Tetiana;Bilyy, Rostyslav;Li, Zhaoli;Deniaud, David;Gouin, Sebastien G.

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期刊名称：BIOMACROMOLECULES （ 影响因子：6.988； 五年影响因子：6.813 ）

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收录情况： SCI

摘要： n-Heptyl alpha-D-mannose (HM) is a nanomolar antagonist of FimH, a virulence factor of E. coli. Herein we report on the construction of multivalent HM-based glycopolymers as potent antiadhesives of type 1 piliated E. coli. We investigate glycopolymer/FimH and glycopolymer/bacteria interactions and show that HM-based glycopolymers efficiently inhibit bacterial adhesion and disrupt established cell-bacteria interactions in vitro at very low concentration (0.1 mu M on a mannose unit basis). On a valency-corrected basis, HM-based glycopolymers are, respectively, 10(2) and 10(6) times more potent than HM and D-mannose for their capacity to disrupt the binding of adherent-invasive E. coli to T84 intestinal epithelial cells. Finally, we demonstrate that the antiadhesive capacities of HM-based glycopolymers are preserved ex vivo in the colonic loop of a transgenic mouse model of Crohns disease. All together, these results underline the promising scope of HM-based macromolecular ligands for the antiadhesive treatment of E. coli induced inflammatory bowel diseases.

分类号： Q7

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