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Proc Natl Acad Sci U S A. 2016 Nov 29;113(48):13833-13838. Epub 2016 Nov 14.

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

Author information

1
Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, University of Gothenburg, Gothenburg SE-405 30, Sweden.
2
Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg SE-405 30, Sweden.
3
Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg, Gothenburg SE-405 30, Sweden.
4
Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, University of Gothenburg, Gothenburg SE-405 30, Sweden; gunnar.hansson@medkem.gu.se.

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.

KEYWORDS:

colon; inflammation; mucin; obesity; peptidoglycan

PMID:
27849619
PMCID:
PMC5137749
DOI:
10.1073/pnas.1611400113
[Indexed for MEDLINE]
Free PMC Article

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