title: Gram-positive bacteria are held at a distance in the colon mucus by the lectin-like protein ZG16.
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.
authors.affiliation: Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, University of Gothenburg, Gothenburg SE-405 30, Sweden.
authors.forename: Joakim H
authors.initials: JH
authors.lastname: Bergström
authors.affiliation: Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, University of Gothenburg, Gothenburg SE-405 30, Sweden.
authors.forename: George M H
authors.identifier: 0000-0003-2283-2353
authors.initials: GM
authors.lastname: Birchenough
authors.affiliation: Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg SE-405 30, Sweden.
authors.forename: Gergely
authors.initials: G
authors.lastname: Katona
authors.affiliation: Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg, Gothenburg SE-405 30, Sweden.
authors.forename: Bjoern O
authors.identifier: 0000-0002-6716-8284
authors.initials: BO
authors.lastname: Schroeder
authors.affiliation: Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, University of Gothenburg, Gothenburg SE-405 30, Sweden.
authors.forename: André
authors.initials: A
authors.lastname: Schütte
authors.affiliation: Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, University of Gothenburg, Gothenburg SE-405 30, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Ermund
authors.affiliation: Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, University of Gothenburg, Gothenburg SE-405 30, Sweden.
authors.forename: Malin E V
authors.identifier: 0000-0002-4237-6677
authors.initials: ME
authors.lastname: Johansson
authors.affiliation: Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, University of Gothenburg, Gothenburg SE-405 30, Sweden; gunnar.hansson@medkem.gu.se.
authors.forename: Gunnar C
authors.initials: GC
authors.lastname: Hansson
mesh_terms: D000818:Animals; D003106:Colon / Q000378:metabolism / Q000382:microbiology; D004064:Digestive System / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism / Q000382:microbiology; D006031:Glycosylation; D006094:Gram-Positive Bacteria / Q000235:genetics* / Q000378:metabolism; D054884:Host-Pathogen Interactions / Q000235:genetics; D037102:Lectins / Q000235:genetics* / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D009093:Mucus / Q000378:metabolism / Q000382:microbiology; D040901:Proteomics; D013559:Symbiosis / Q000235:genetics
chemical_list: D037102:Lectins; D008565:Membrane Proteins; C487135:ZG-16 protein, mouse
keywords: colon; inflammation; mucin; obesity; peptidoglycan