Abstract:
:n-Heptyl α-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 μM 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 Crohn's 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.
journal_name
Biomacromoleculesjournal_title
Biomacromoleculesauthors
Yan X,Sivignon A,Yamakawa N,Crepet A,Travelet C,Borsali R,Dumych T,Li Z,Bilyy R,Deniaud D,Fleury E,Barnich N,Darfeuille-Michaud A,Gouin SG,Bouckaert J,Bernard Jdoi
10.1021/acs.biomac.5b00413subject
Has Abstractpub_date
2015-06-08 00:00:00pages
1827-36issue
6eissn
1525-7797issn
1526-4602journal_volume
16pub_type
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