Neisserial Opa Protein-CEACAM Interactions: Competition for Receptors as a Means of Bacterial Invasion and Pathogenesis

Biochemistry. 2016 Aug 9;55(31):4286-94. doi: 10.1021/acs.biochem.6b00124. Epub 2016 Aug 1.

Abstract

Carcino-embryonic antigen-like cellular adhesion molecules (CEACAMs), members of the immunoglobulin superfamily, are responsible for cell-cell interactions and cellular signaling events. Extracellular interactions with CEACAMs have the potential to induce phagocytosis, as is the case with pathogenic Neisseria bacteria. Pathogenic Neisseria species express opacity-associated (Opa) proteins, which interact with a subset of CEACAMs on human cells, and initiate the engulfment of the bacterium. We demonstrate that recombinant Opa proteins reconstituted into liposomes retain the ability to recognize and interact with CEACAMs in vitro but do not maintain receptor specificity compared to that of Opa proteins natively expressed by Neisseria gonorrhoeae. We report that two Opa proteins interact with CEACAMs with nanomolar affinity, and we hypothesize that this high affinity is necessary to compete with the native CEACAM homo- and heterotypic interactions in the host. Understanding the mechanisms of Opa protein-receptor recognition and engulfment enhances our understanding of Neisserial pathogenesis. Additionally, these mechanisms provide insight into how human cells that are typically nonphagocytic can utilize CEACAM receptors to internalize exogenous matter, with implications for the targeted delivery of therapeutics and development of imaging agents.

Publication types

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

MeSH terms

  • Antigens, CD / chemistry
  • Antigens, CD / metabolism*
  • Bacterial Outer Membrane Proteins / chemistry
  • Bacterial Outer Membrane Proteins / genetics
  • Bacterial Outer Membrane Proteins / metabolism*
  • Carcinoembryonic Antigen / chemistry
  • Carcinoembryonic Antigen / metabolism*
  • Cell Adhesion Molecules / chemistry
  • Cell Adhesion Molecules / metabolism*
  • Host-Pathogen Interactions
  • Humans
  • Immunoglobulin Domains
  • Liposomes
  • Models, Molecular
  • Neisseria / genetics
  • Neisseria / metabolism*
  • Neisseria / pathogenicity
  • Neisseria gonorrhoeae / genetics
  • Neisseria gonorrhoeae / metabolism
  • Neisseria gonorrhoeae / pathogenicity
  • Protein Interaction Domains and Motifs
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism

Substances

  • Antigens, CD
  • Bacterial Outer Membrane Proteins
  • CD66 antigens
  • CEACAM3 protein, human
  • Carcinoembryonic Antigen
  • Cell Adhesion Molecules
  • Liposomes
  • Recombinant Proteins
  • Opa protein, Neisseria