1. Gram-positive bacteria are held at a distance in the colon mucus by the lectin-like protein ZG16
- Author
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Bjoern O. Schroeder, Joakim H. Bergström, Gunnar C. Hansson, Anna Ermund, George M. H. Birchenough, André Schütte, Gergely Katona, and Malin E. V. Johansson
- Subjects
Proteomics ,0301 basic medicine ,Glycosylation ,Colon ,Gram-positive bacteria ,Motility ,Biology ,Gram-Positive Bacteria ,Bacterial cell structure ,Microbiology ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Lectins ,medicine ,Animals ,Symbiosis ,Inner mucus layer ,Mice, Knockout ,Multidisciplinary ,Membrane Proteins ,Epithelial Cells ,Biological Sciences ,biology.organism_classification ,Mucus ,Epithelium ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,030220 oncology & carcinogenesis ,Host-Pathogen Interactions ,Peptidoglycan ,Digestive System ,Bacteria - 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.
- Published
- 2016