title: The lacdiNAc-specific adhesin LabA mediates adhesion of Helicobacter pylori to human gastric mucosa.
abstract: Adhesion of Helicobacter pylori to the gastric mucosa is a necessary prerequisite for the pathogenesis of H. pylori-related diseases. In this study, we investigated the GalNAcβ1-4GlcNAc motif (also known as N,N'-diacetyllactosediamine [lacdiNAc]) carried by MUC5AC gastric mucins as the target for bacterial binding to the human gastric mucosa. The expression of LacdiNAc carried by gastric mucins was correlated with H. pylori localization, and all strains tested adhered significantly to this motif. Proteomic analysis and mutant construction allowed the identification of a yet uncharacterized bacterial adhesin, LabA, which specifically recognizes lacdiNAc. These findings unravel a target of adhesion for H. pylori in addition to moieties recognized by the well-characterized adhesins BabA and SabA. Localization of the LabA target, restricted to the gastric mucosa, suggests a plausible explanation for the tissue tropism of these bacteria. These results pave the way for the development of alternative strategies against H. pylori infection, using adherence inhibitors.
authors.affiliation: Univ Lille Nord de France USTL, UGSF, IFR 147 CNRS, UMR 8576.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Rossez
authors.affiliation: Univ Lille Nord de France UCLille Groupe Hospitalier de l'Institut Catholique Lillois/Faculté Libre de Médecine, Lille Service d'Anatomie Pathologie.
authors.forename: Pierre
authors.initials: P
authors.lastname: Gosset
authors.affiliation: Institut Pasteur INSERM, Equipe Avenir, Groupe Biologie et génétique de la paroi bactérienne.
authors.forename: Ivo G
authors.initials: IG
authors.lastname: Boneca
authors.affiliation: Instituto de Patologia e Imunologia Molecular da Universidade do Porto.
authors.forename: Ana
authors.initials: A
authors.lastname: Magalhães
authors.affiliation: Institut Pasteur INSERM, Equipe Avenir, Groupe Biologie et génétique de la paroi bactérienne.
authors.forename: Chantal
authors.initials: C
authors.lastname: Ecobichon
authors.affiliation: Instituto de Patologia e Imunologia Molecular da Universidade do Porto Institute of Biomedical Sciences Abel Salazar and Medical Faculty of the University of Porto, Portugal.
authors.forename: Celso A
authors.initials: CA
authors.lastname: Reis
authors.affiliation: Univ Lille Nord de France EA 4488, Laboratoire d'Activité Physique, Muscle et Santé
authors.forename: Caroline
authors.initials: C
authors.lastname: Cieniewski-Bernard
authors.affiliation: Univ Lille Nord de France USTL, UGSF, IFR 147 CNRS, UMR 8576.
authors.forename: Marie
authors.initials: M
authors.lastname: Joncquel Chevalier Curt
authors.affiliation: Univ Lille Nord de France USTL, UGSF, IFR 147 CNRS, UMR 8576.
authors.forename: Renaud
authors.initials: R
authors.lastname: Léonard
authors.affiliation: Univ Lille Nord de France USTL, UGSF, IFR 147 CNRS, UMR 8576.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Maes
authors.affiliation: Unité de Pathogénie Microbienne Moléculaire et Unité INSERM 786, Institut Pasteur.
authors.forename: Brice
authors.initials: B
authors.lastname: Sperandio
authors.affiliation: Univ Lille Nord de France Laboratoire de Physiologie Cellulaire, INSERM U 1003, Université des Sciences et Technologies de Lille, Villeneuve d'Ascq.
authors.forename: Christian
authors.initials: C
authors.lastname: Slomianny
authors.affiliation: Unité de Pathogénie Microbienne Moléculaire et Unité INSERM 786, Institut Pasteur Chaire de Microbiologie et Maladies Infectieuses, Collège de France.
authors.forename: Philippe J
authors.initials: PJ
authors.lastname: Sansonetti
authors.affiliation: Univ Lille Nord de France USTL, UGSF, IFR 147 CNRS, UMR 8576.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Michalski
authors.affiliation: Univ Lille Nord de France USTL, UGSF, IFR 147 CNRS, UMR 8576.
authors.forename: Catherine
authors.initials: C
authors.lastname: Robbe-Masselot
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001422:Bacterial Adhesion / Q000502:physiology*; D005753:Gastric Mucosa / Q000382:microbiology*; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology*; D016480:Helicobacter pylori / Q000502:physiology*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018829:Adhesins, Bacterial
keywords: Helicobacter pylori; adhesin; gastric mucins; lacdiNAc; tropism