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BabA dependent binding of Helicobacter pylori to human gastric mucins cause aggregation that inhibits proliferation and is regulated via ArsS

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....

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Autores principales: Skoog, Emma C., Padra, Médea, Åberg, Anna, Gideonsson, Pär, Obi, Ikenna, Quintana-Hayashi, Macarena P., Arnqvist, Anna, Lindén, Sara K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5247751/
https://www.ncbi.nlm.nih.gov/pubmed/28106125
http://dx.doi.org/10.1038/srep40656
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author Skoog, Emma C.
Padra, Médea
Åberg, Anna
Gideonsson, Pär
Obi, Ikenna
Quintana-Hayashi, Macarena P.
Arnqvist, Anna
Lindén, Sara K.
author_facet Skoog, Emma C.
Padra, Médea
Åberg, Anna
Gideonsson, Pär
Obi, Ikenna
Quintana-Hayashi, Macarena P.
Arnqvist, Anna
Lindén, Sara K.
author_sort Skoog, Emma C.
collection PubMed
description 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 Le(b)-glycoconjugates inhibited the proliferation of the bacteria in a BabA dependent manner, similarly to the effect of mucins carrying Le(b). Furthermore, deletion of arsS lead to a decrease in binding to Le(b)-glycoconjugates and Le(b)-decorated mucins, accompanied by decreased aggregation and absence of anti-prolific effect of mucins and Le(b)-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.
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spelling pubmed-52477512017-01-23 BabA dependent binding of Helicobacter pylori to human gastric mucins cause aggregation that inhibits proliferation and is regulated via ArsS Skoog, Emma C. Padra, Médea Åberg, Anna Gideonsson, Pär Obi, Ikenna Quintana-Hayashi, Macarena P. Arnqvist, Anna Lindén, Sara K. Sci Rep Article 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 Le(b)-glycoconjugates inhibited the proliferation of the bacteria in a BabA dependent manner, similarly to the effect of mucins carrying Le(b). Furthermore, deletion of arsS lead to a decrease in binding to Le(b)-glycoconjugates and Le(b)-decorated mucins, accompanied by decreased aggregation and absence of anti-prolific effect of mucins and Le(b)-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. Nature Publishing Group 2017-01-20 /pmc/articles/PMC5247751/ /pubmed/28106125 http://dx.doi.org/10.1038/srep40656 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Skoog, Emma C.
Padra, Médea
Åberg, Anna
Gideonsson, Pär
Obi, Ikenna
Quintana-Hayashi, Macarena P.
Arnqvist, Anna
Lindén, Sara K.
BabA dependent binding of Helicobacter pylori to human gastric mucins cause aggregation that inhibits proliferation and is regulated via ArsS
title BabA dependent binding of Helicobacter pylori to human gastric mucins cause aggregation that inhibits proliferation and is regulated via ArsS
title_full BabA dependent binding of Helicobacter pylori to human gastric mucins cause aggregation that inhibits proliferation and is regulated via ArsS
title_fullStr BabA dependent binding of Helicobacter pylori to human gastric mucins cause aggregation that inhibits proliferation and is regulated via ArsS
title_full_unstemmed BabA dependent binding of Helicobacter pylori to human gastric mucins cause aggregation that inhibits proliferation and is regulated via ArsS
title_short BabA dependent binding of Helicobacter pylori to human gastric mucins cause aggregation that inhibits proliferation and is regulated via ArsS
title_sort baba dependent binding of helicobacter pylori to human gastric mucins cause aggregation that inhibits proliferation and is regulated via arss
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5247751/
https://www.ncbi.nlm.nih.gov/pubmed/28106125
http://dx.doi.org/10.1038/srep40656
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