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

JH Bergström, GMH Birchenough… - Proceedings of the …, 2016 - National Acad Sciences
JH Bergström, GMH Birchenough, G Katona, BO Schroeder, A Schütte, A Ermund…
Proceedings of the National Academy of Sciences, 2016National Acad Sciences
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 …
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.
National Acad Sciences