title: Glycopolymers as Antiadhesives of E. coli Strains Inducing Inflammatory Bowel Diseases.
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.
authors.affiliation: §Université de Lyon, Lyon, F-69003 France.|◆INSA-Lyon, IMP, Villeurbanne, F-69621 France.|¶CNRS, UMR 5223, Ingénierie des Matériaux Polymères, Villeurbanne, F-69621, France.
authors.forename: Xibo
authors.initials: X
authors.lastname: Yan
authors.affiliation: ∥Clermont Université, UMR 1071, Inserm/Université d'Auvergne, 63000 Clermont-Ferrand, France.|⊥INRA, Unité Sous Contrat 2018, 63000, Clermont-Ferrand, France.
authors.forename: Adeline
authors.initials: A
authors.lastname: Sivignon
authors.affiliation: #Unité de Glycobiologie Structurale et Fonctionnelle (UGSF), UMR 8576, Université Lille 1, F-59655 Villeneuve d'Ascq Cedex, France.
authors.forename: Nao
authors.initials: N
authors.lastname: Yamakawa
authors.affiliation: §Université de Lyon, Lyon, F-69003 France.|◆INSA-Lyon, IMP, Villeurbanne, F-69621 France.|¶CNRS, UMR 5223, Ingénierie des Matériaux Polymères, Villeurbanne, F-69621, France.
authors.forename: Agnes
authors.initials: A
authors.lastname: Crepet
authors.affiliation: ○Centre de Recherches sur les Macromolécules Végétales (CERMAV - CNRS UPR 5301), Université de Grenoble-Alpes, ICMG - CNRS FR 2607, PolyNat Carnot Institute, Arcane LabEx, 601 rue de la Chimie, 38041 Grenoble, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Travelet
authors.affiliation: ○Centre de Recherches sur les Macromolécules Végétales (CERMAV - CNRS UPR 5301), Université de Grenoble-Alpes, ICMG - CNRS FR 2607, PolyNat Carnot Institute, Arcane LabEx, 601 rue de la Chimie, 38041 Grenoble, France.
authors.forename: Redouane
authors.initials: R
authors.lastname: Borsali
authors.affiliation: □Institute of Cell Biology, NASU, Drahomanov Street 14/16, 79005 Lviv, Ukraine.
authors.forename: Tetiana
authors.initials: T
authors.lastname: Dumych
authors.affiliation: △Division of Bacterial Diseases, State key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Maduan St. 427#, Nangang Dis, Harbin, China.
authors.forename: Zhaoli
authors.initials: Z
authors.lastname: Li
authors.affiliation: □Institute of Cell Biology, NASU, Drahomanov Street 14/16, 79005 Lviv, Ukraine.
authors.forename: Rostyslav
authors.initials: R
authors.lastname: Bilyy
authors.affiliation: ▽LUNAM Université, CEISAM, Chimie Et Interdisciplinarité, Synthèse, Analyse, Modélisation, UMR CNRS 6230, UFR des Sciences et des Techniques, 2, rue de la Houssinière, BP 92208, 44322 Nantes Cedex 3, France.
authors.forename: David
authors.initials: D
authors.lastname: Deniaud
authors.affiliation: §Université de Lyon, Lyon, F-69003 France.|◆INSA-Lyon, IMP, Villeurbanne, F-69621 France.|¶CNRS, UMR 5223, Ingénierie des Matériaux Polymères, Villeurbanne, F-69621, France.
authors.forename: Etienne
authors.initials: E
authors.lastname: Fleury
authors.affiliation: ∥Clermont Université, UMR 1071, Inserm/Université d'Auvergne, 63000 Clermont-Ferrand, France.|⊥INRA, Unité Sous Contrat 2018, 63000, Clermont-Ferrand, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Barnich
authors.affiliation: ∥Clermont Université, UMR 1071, Inserm/Université d'Auvergne, 63000 Clermont-Ferrand, France.|⊥INRA, Unité Sous Contrat 2018, 63000, Clermont-Ferrand, France.
authors.forename: Arlette
authors.initials: A
authors.lastname: Darfeuille-Michaud
authors.affiliation: ▽LUNAM Université, CEISAM, Chimie Et Interdisciplinarité, Synthèse, Analyse, Modélisation, UMR CNRS 6230, UFR des Sciences et des Techniques, 2, rue de la Houssinière, BP 92208, 44322 Nantes Cedex 3, France.
authors.forename: Sébastien G
authors.initials: SG
authors.lastname: Gouin
authors.affiliation: #Unité de Glycobiologie Structurale et Fonctionnelle (UGSF), UMR 8576, Université Lille 1, F-59655 Villeneuve d'Ascq Cedex, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Bouckaert
authors.affiliation: §Université de Lyon, Lyon, F-69003 France.|◆INSA-Lyon, IMP, Villeurbanne, F-69621 France.|¶CNRS, UMR 5223, Ingénierie des Matériaux Polymères, Villeurbanne, F-69621, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Bernard
mesh_terms: D018830:Adhesins, Escherichia coli; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D004926:Escherichia coli / Q000472:pathogenicity; D036781:Fimbriae Proteins / Q000037:antagonists & inhibitors*; D006367:HeLa Cells; D019850:Heptanol / Q000737:chemistry; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000382:microbiology; D007413:Intestinal Mucosa / Q000187:drug effects*; D008358:Mannose / Q000737:chemistry; D051379:Mice; D011135:Polysaccharides, Bacterial / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D018830:Adhesins, Escherichia coli; D011135:Polysaccharides, Bacterial; C058769:fimH protein, E coli; D036781:Fimbriae Proteins; D019850:Heptanol; D008358:Mannose