Titre :

The Antiadhesive Strategy in Crohn's Disease: Orally Active Mannosides to Decolonize Pathogenic Escherichia coli from the Gut

Auteur(s) :

Alvarez Dorta, Dimitri [Auteur]
Chimie Et Interdisciplinarité : Synthèse, Analyse, Modélisation [CEISAM]
Sivignon, Adeline [Auteur]
Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte [M2iSH]
Chalopin, Thibaut [Auteur]
Chimie Et Interdisciplinarité : Synthèse, Analyse, Modélisation [CEISAM]
Dumych, Tetiana [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Roos, Goedele [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Bilyy, Rostyslav [Auteur]
Danylo Halytsky Lviv National Medical University [Lviv, Ukraine]
Deniaud, David [Auteur]
Chimie Et Interdisciplinarité : Synthèse, Analyse, Modélisation [CEISAM]
Krammer, Eva-Maria [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
De Ruyck, Jerome [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Lensink, Marc [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Bouckaert, Julie [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Barnich, Nicolas [Auteur]
Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte [M2iSH]
Gouin, Sébastien G. [Auteur]
Chimie Et Interdisciplinarité : Synthèse, Analyse, Modélisation [CEISAM]

Titre de la revue :

Chembiochem. A European Journal of Chemical Biology

Nom court de la revue :

Chembiochem

Numéro :

17

Pagination :

936-952

Date de publication :

2016

ISSN :

1439-7633

Mot(s)-clé(s) en anglais :

Intestinal Mucosa
inhibitors
Fimbriae Proteins
Mannosides
Body Weight
Enzyme-Linked Immunosorbent Assay
Adhesins, Escherichia coli
X-ray Crystallography
Cell Survival
Humans
Escherichia coli
Crohn Disease
Biological Availability
Mice, Transgenic
Crohn's disease
Cell Adhesion
Bacterial Adhesion
Animals
Protein Binding
Protein Domains
Lectins
Mice
Disease Models, Animal
FimH

Discipline(s) HAL :

Chimie/Chimie théorique et/ou physique

Résumé en anglais : [en]

Blocking the adherence of bacteria to cells is an attractive complementary approach to current antibiotic treatments, which are faced with increasing resistance. This strategy has been particularly studied in the context ...
Lire la suite >Blocking the adherence of bacteria to cells is an attractive complementary approach to current antibiotic treatments, which are faced with increasing resistance. This strategy has been particularly studied in the context of urinary tract infections (UTIs), in which the adhesion of pathogenic Escherichia coli strains to uroepithelial cells is prevented by blocking the FimH adhesin expressed at the tips of bacteria organelles called fimbriae. Recently, we extended the antiadhesive concept, showing that potent FimH antagonists can block the attachment of adherent-invasive E. coli (AIEC) colonizing the intestinal mucosa of patients with Crohn's disease (CD). In this work, we designed a small library of analogues of heptyl mannoside (HM), a previously identified nanomolar FimH inhibitor, but one that displays poor antiadhesive effects in vivo. The anomeric oxygen atom was replaced by a sulfur or a methylene group to prevent hydrolysis by intestinal glycosidases, and chemical groups were attached at the end of the alkyl tail. Importantly, a lead compound was shown to reduce AIEC levels in the feces and in the colonic and ileal mucosa after oral administration (10 mg kg(-1) ) in a transgenic mouse model of CD. The compound showed a low bioavailability, preferable in this instance, thus suggesting the possibility of setting up an innovative antiadhesive therapy, based on the water-soluble and non-cytotoxic FimH antagonists developed here, for the CD subpopulation in which AIEC plays a key role.Lire moins >

Langue :

Anglais

Audience :

Non spécifiée

Établissement(s) :

CNRS
Université de Lille

Collections :

• Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576

Équipe(s) de recherche :

Computational Molecular Systems Biology

Date de dépôt :

2020-02-12T15:11:19Z
2021-03-18T08:34:33Z