title: BabA dependent binding of Helicobacter pylori to human gastric mucins cause aggregation that inhibits proliferation and is regulated via ArsS.
abstract: Mucins in the gastric mucus layer carry a range of glycan structures, which vary between individuals, can have antimicrobial effect or act as ligands for Helicobacter pylori. Mucins from various individuals and disease states modulate H. pylori proliferation and adhesin gene expression differently. Here we investigate the relationship between adhesin mediated binding, aggregation, proliferation and adhesin gene expression using human gastric mucins and synthetic adhesin ligand conjugates. By combining measurements of optical density, bacterial metabolic activity and live/dead stains, we could distinguish bacterial aggregation from viability changes, enabling elucidation of mechanisms behind the anti-prolific effects that mucins can have. Binding of H. pylori to Leb-glycoconjugates inhibited the proliferation of the bacteria in a BabA dependent manner, similarly to the effect of mucins carrying Leb. Furthermore, deletion of arsS lead to a decrease in binding to Leb-glycoconjugates and Leb-decorated mucins, accompanied by decreased aggregation and absence of anti-prolific effect of mucins and Leb-glycoconjugates. Inhibition of proliferation caused by adhesin dependent binding to mucins, and the subsequent aggregation suggests a new role of mucins in the host defense against H. pylori. This aggregating trait of mucins may be useful to incorporate into the design of adhesin inhibitors and other disease intervention molecules.
authors.affiliation: Department of Biomedical Chemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Emma C
authors.initials: EC
authors.lastname: Skoog
authors.affiliation: Department of Biomedical Chemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Médea
authors.initials: M
authors.lastname: Padra
authors.affiliation: Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Åberg
authors.affiliation: Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden.
authors.forename: Pär
authors.initials: P
authors.lastname: Gideonsson
authors.affiliation: Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden.
authors.forename: Ikenna
authors.initials: I
authors.lastname: Obi
authors.affiliation: Department of Biomedical Chemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Macarena P
authors.initials: MP
authors.lastname: Quintana-Hayashi
authors.affiliation: Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Arnqvist
authors.affiliation: Department of Biomedical Chemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Sara K
authors.initials: SK
authors.lastname: Lindén
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics / Q000378:metabolism*; D001422:Bacterial Adhesion; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism; D005752:Gastric Mucins / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism / Q000382:microbiology; D015964:Gene Expression Regulation, Bacterial; D006001:Glycoconjugates / Q000378:metabolism; D016481:Helicobacter Infections / Q000378:metabolism* / Q000382:microbiology*; D016480:Helicobacter pylori / Q000502:physiology*; D006801:Humans; D050296:Microbial Viability; D011485:Protein Binding; D017384:Sequence Deletion
chemical_list: D018829:Adhesins, Bacterial; C400429:BabA protein, Helicobacter pylori; C451032:BabB protein, Helicobacter pylori; D001425:Bacterial Outer Membrane Proteins; D005752:Gastric Mucins; D006001:Glycoconjugates