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

Proc Natl Acad Sci U S A. 2016 Nov 29;113(48):13833-13838. doi: 10.1073/pnas.1611400113. Epub 2016 Nov 14.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Colon / metabolism
  • Colon / microbiology
  • Digestive System / metabolism
  • Epithelial Cells / metabolism
  • Epithelial Cells / microbiology
  • Glycosylation
  • Gram-Positive Bacteria / genetics*
  • Gram-Positive Bacteria / metabolism
  • Host-Pathogen Interactions / genetics
  • Lectins / genetics*
  • Lectins / metabolism
  • Membrane Proteins / genetics*
  • Mice
  • Mice, Knockout
  • Mucus / metabolism
  • Mucus / microbiology
  • Proteomics*
  • Symbiosis / genetics


  • Lectins
  • Membrane Proteins
  • ZG-16 protein, mouse