Phylogenetically Defined Isoforms of Listeria monocytogenes Invasion Factor InlB Differently Activate Intracellular Signaling Pathways and Interact with the Receptor gC1q-R

Int J Mol Sci. 2019 Aug 24;20(17):4138. doi: 10.3390/ijms20174138.


The pathogenic Gram-positive bacterium Listeria monocytogenes has been evolving into a few phylogenetic lineages. Phylogenetically defined substitutions were described in the L. monocytogenes virulence factor InlB, which mediates active invasion into mammalian cells via interactions with surface receptors c-Met and gC1q-R. InlB internalin domain (idInlB) is central to interactions with c-Met. Here we compared activity of purified recombinant idInlB isoforms characteristic for L. monocytogenes phylogenetic lineage I and II. Size exclusion chromatography and intrinsic fluorescence were used to characterize idInlBs. Western blotting was used to study activation of c-Met-dependent MAPK- and PI3K/Akt-pathways. Solid-phase microplate binding and competition assay was used to quantify interactions with gCq1-R. Isogenic recombinant L. monocytogenes strains were used to elucidate the input of idInlB isoforms in HEp-2 cell invasion. Physicochemical parameters of idInlB isoforms were similar but not identical. Kinetics of Erk1/2 and Akt phosphorylation in response to purified idInlBs was lineage specific. Lineage I but not lineage II idInlB specifically bound gC1q-R. Antibody against gC1q-R amino acids 221-249 inhibited invasion of L. monocytogenes carrying lineage I but not lineage II idInlB. Taken together, obtained results suggested that phylogenetically defined substitutions in idInlB provide functional distinctions and might be involved in phylogenetically determined differences in virulence potential.

Keywords: InlB; Listeria; Virulence; bacterial virulence factors; c-Met; evolution; gC1q-R; host-parasite interactions; mammalian surface receptors.

MeSH terms

  • Amino Acid Sequence
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / genetics*
  • Bacterial Proteins / metabolism*
  • Carrier Proteins / metabolism*
  • Cell Line
  • Humans
  • Listeria monocytogenes / classification*
  • Listeria monocytogenes / pathogenicity
  • Listeria monocytogenes / physiology*
  • Membrane Proteins / chemistry
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism*
  • Mitochondrial Proteins / metabolism*
  • Mitogen-Activated Protein Kinases / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phylogeny*
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • Protein Isoforms
  • Signal Transduction*
  • Virulence Factors


  • Bacterial Proteins
  • C1QBP protein, human
  • Carrier Proteins
  • Membrane Proteins
  • Mitochondrial Proteins
  • Protein Isoforms
  • Virulence Factors
  • inlB protein, Listeria monocytogenes
  • Mitogen-Activated Protein Kinases