Helicobacter pylori exploits human CEACAMs via HopQ for adherence and translocation of CagA

Nat Microbiol. 2016 Oct 17:2:16188. doi: 10.1038/nmicrobiol.2016.188.

Abstract

Helicobacter pylori (Hp) strains that carry the cag type IV secretion system (cag-T4SS) to inject the cytotoxin-associated antigen A (CagA) into host cells are associated with peptic ulcer disease and gastric adenocarcinoma. CagA translocation by Hp is mediated by β1 integrin interaction of the cag-T4SS. However, other cellular receptors or bacterial outer membrane adhesins essential for this process are unknown. Here, we identify the HopQ protein as a genuine Hp adhesin, exploiting defined members of the carcinoembryonic antigen-related cell adhesion molecule family (CEACAMs) as host cell receptors. HopQ binds the amino-terminal IgV-like domain of human CEACAM1, CEACAM3, CEACAM5 or CEACAM6 proteins, thereby enabling translocation of the major pathogenicity factor CagA into host cells. The HopQ-CEACAM interaction is characterized by a remarkably high affinity (KD from 23 to 268 nM), which is independent of CEACAM glycosylation, identifying CEACAMs as bona fide protein receptors for Hp. Our data suggest that the HopQ-CEACAM interaction contributes to gastric colonization or Hp-induced pathologies, although the precise role and functional consequences of this interaction in vivo remain to be determined.

MeSH terms

  • Adhesins, Bacterial / metabolism*
  • Antigens, Bacterial / metabolism*
  • Bacterial Adhesion*
  • Bacterial Proteins / metabolism*
  • Cell Adhesion Molecules / metabolism*
  • Cell Line
  • Helicobacter pylori / physiology*
  • Host-Pathogen Interactions*
  • Humans
  • Protein Binding
  • Protein Transport*

Substances

  • Adhesins, Bacterial
  • Antigens, Bacterial
  • Bacterial Proteins
  • Cell Adhesion Molecules
  • adhesin, helicobacter
  • cagA protein, Helicobacter pylori