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| 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 |
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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