title: Inhibition profiles of mono- and polyvalent FimH antagonists against 10 different Escherichia coli strains.
abstract: Mono- and polyvalent ligands with strong affinities for the mannose-binding adhesin FimH were synthesised, and their anti-adhesive properties against ten E. coli strains were compared in two cell-based assays. The compounds were assessed against the non-pathogenic E. coli K12 and nine strains isolated by coproculture or from patients with osteoarticular infections (OIs), Crohn's disease (CD) and urinary tract infections (UTIs). The results showed that the compounds could inhibit the whole set of bacterial strains but with marked differences in terms of effective concentrations. The relative inhibitory potency of the monovalent compounds was also conserved for the ten strains and in the two assays. These results clearly suggest that a potent monovalent anti-adhesive assessed on a single E. coli strain will probably be effective on a broad range of strains and may treat diverse E. coli infections (OIs, CD and UTIs). In contrast, the polyvalent compounds showed a significant strain-dependancy in preventing E. coli attachment to intestinal cells. The multivalent antiadhesive effect may therefore vary depending on the E. coli strain tested.
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. sebastien.gouin@univ-nantes.fr.
authors.forename: T
authors.initials: T
authors.lastname: Chalopin
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. sebastien.gouin@univ-nantes.fr.
authors.forename: Y
authors.initials: Y
authors.lastname: Brissonnet
authors.affiliation: Clermont Université, UMR 1071 Inserm/Université d'Auvergne, 63000 Clermont-Ferrand, France and INRA, Unité Sous Contrat 2018, 63000 Clermont-Ferrand, France.
authors.forename: A
authors.initials: A
authors.lastname: Sivignon
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. sebastien.gouin@univ-nantes.fr.
authors.forename: D
authors.initials: D
authors.lastname: Deniaud
authors.affiliation: Université de Nantes, UFR de Médecine, EA3826, Thérapeutiques cliniques et expérimentales des infections, 1 rue G. Veil, 44000 Nantes, France.
authors.forename: L
authors.initials: L
authors.lastname: Cremet
authors.affiliation: Clermont Université, UMR 1071 Inserm/Université d'Auvergne, 63000 Clermont-Ferrand, France and INRA, Unité Sous Contrat 2018, 63000 Clermont-Ferrand, France.
authors.forename: N
authors.initials: N
authors.lastname: Barnich
authors.affiliation: Unité de Glycobiologie Structurale et Fonctionnelle (UGSF), UMR 8576 du CNRS, Université de Lille 1, F-59655 Villeneuve d'Ascq Cedex, France.
authors.forename: J
authors.initials: J
authors.lastname: Bouckaert
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. sebastien.gouin@univ-nantes.fr.
authors.forename: S G
authors.initials: SG
authors.lastname: Gouin
mesh_terms: D018830:Adhesins, Escherichia coli / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D001422:Bacterial Adhesion / Q000187:drug effects*; D004926:Escherichia coli / Q000145:classification / Q000187:drug effects* / Q000378:metabolism; D004927:Escherichia coli Infections / Q000188:drug therapy* / Q000382:microbiology; D036781:Fimbriae Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D008024:Ligands
chemical_list: D018830:Adhesins, Escherichia coli; D000900:Anti-Bacterial Agents; D008024:Ligands; C058769:fimH protein, E coli; D036781:Fimbriae Proteins