N-glycosylated proteins and distinct lipooligosaccharide glycoforms of Campylobacter jejuni target the human C-type lectin receptor MGL

Cell Microbiol. 2009 Dec;11(12):1768-81. doi: 10.1111/j.1462-5822.2009.01370.x. Epub 2009 Aug 13.

Abstract

An increasing number of bacterial pathogens produce an array of glycoproteins of unknown function. Here we report that Campylobacter jejuni proteins that are modified by the N-linked glycosylation machinery encoded by the pgl locus bind the human Macrophage Galactose-type lectin (MGL). MGL receptor binding was abrogated by EDTA and N-acetylgalactosamine (GalNAc) and was successfully transferred to Escherichia coli by introducing the C. jejuni pgl locus together with a glycan acceptor protein. In addition to glycoproteins, C. jejuni lipooligosaccharide with a terminal GalNAc residue was recognized by MGL. Recombinant E. coli expressing the C. jejuni pgl locus in the absence of a suitable glycan acceptor protein produced altered lipopolysaccharide glycoforms that gained MGL reactivity. Infection assays demonstrated high levels of GalNAc-dependent interaction of the recombinant E. coli with MGL-transfected mammalian cells. In addition, interleukin-6 production by human dendritic cells was enhanced by C. jejuni lacking N-linked glycans compared with wild-type bacteria. Collectively, our results provide evidence that both N-linked glycoproteins and distinct lipooligosaccharide glycoforms of C. jejuni are ligands for the human C-type lectin MGL and that the C. jejuni N-glycosylation machinery can be exploited to target recombinant bacteria to MGL-expressing eukaryotic cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylgalactosamine / metabolism
  • Acetylgalactosamine / pharmacology
  • Animals
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • CHO Cells
  • Campylobacter Infections / metabolism*
  • Campylobacter Infections / microbiology
  • Campylobacter jejuni / drug effects
  • Campylobacter jejuni / genetics
  • Campylobacter jejuni / metabolism*
  • Chelating Agents / pharmacology
  • Cricetinae
  • Cricetulus
  • Dendritic Cells / metabolism
  • Edetic Acid / pharmacology
  • Escherichia coli / metabolism
  • Glycoproteins / metabolism*
  • Glycosylation
  • Host-Pathogen Interactions / drug effects
  • Humans
  • Interleukin-6 / biosynthesis
  • Lectins, C-Type / metabolism*
  • Lipopolysaccharides / metabolism*
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Substrate Specificity

Substances

  • Bacterial Proteins
  • Chelating Agents
  • Glycoproteins
  • Interleukin-6
  • Lectins, C-Type
  • Lipopolysaccharides
  • MGL lectin, human
  • Recombinant Proteins
  • lipid-linked oligosaccharides
  • Edetic Acid
  • Acetylgalactosamine