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Gram-positive bacteria are held at a distance in the colon mucus by the lectin-like protein ZG16.

Journal article
Authors Joakim H. Bergström
George M. H. Birchenough
Gergely Katona
Björn O. Schröder
André Schütte
Anna Ermund
Malin E V Johansson
Gunnar C. Hansson
Published in Proceedings of the National Academy of Sciences of the United States of America
Volume 113
Issue 48
Pages 13833-13838
ISSN 1091-6490
Publication year 2016
Published at Department of Chemistry and Molecular Biology
Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
Institute of Medicine, Department of Molecular and Clinical Medicine
Pages 13833-13838
Language en
Links dx.doi.org/10.1073/pnas.1611400113
www.ncbi.nlm.nih.gov/entrez/query.f...
Subject categories Cell and Molecular Biology

Abstract

The distal colon functions as a bioreactor and harbors an enormous amount of bacteria in a mutualistic relationship with the host. The microbiota have to be kept at a safe distance to prevent inflammation, something that is achieved by a dense inner mucus layer that lines the epithelial cells. The large polymeric nets made up by the heavily O-glycosylated MUC2 mucin forms this physical barrier. Proteomic analyses of mucus have identified the lectin-like protein ZG16 (zymogen granulae protein 16) as an abundant mucus component. To elucidate the function of ZG16, we generated recombinant ZG16 and studied Zg16(-/-) mice. ZG16 bound to and aggregated Gram-positive bacteria via binding to the bacterial cell wall peptidoglycan. Zg16(-/-) mice have a distal colon mucus layer with normal thickness, but with bacteria closer to the epithelium. Using distal colon explants mounted in a horizontal perfusion chamber we demonstrated that treatment of bacteria with recombinant ZG16 hindered bacterial penetration into the mucus. The inner colon mucus of Zg16(-/-) animals had a higher load of Gram-positive bacteria and showed bacteria with higher motility in the mucus close to the host epithelium compared with cohoused littermate Zg16(+/+) The more penetrable Zg16(-/-) mucus allowed Gram-positive bacteria to translocate to systemic tissues. Viable bacteria were found in spleen and were associated with increased abdominal fat pad mass in Zg16(-/-) animals. The function of ZG16 reveals a mechanism for keeping bacteria further away from the host colon epithelium.

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http://gu.se/english/research/publication/?publicationId=246326
Utskriftsdatum: 2019-12-11