Thioloxidoreductase HP0231 of Helicobacter pylori impacts HopQ-dependent CagA translocation

Int J Med Microbiol. 2018 Dec;308(8):977-985. doi: 10.1016/j.ijmm.2018.08.002. Epub 2018 Aug 7.


Thioloxidoreductase HP0231 of Helicobacter pylori plays essential roles in gastric colonization and related gastric pathology. Comparative proteomics and analysis of complexes between HP0231 and its protein substrates suggested that several Hop proteins are its targets. HP0231 is a dimeric oxidoreductase that functions in an oxidizing Dsb (disulfide bonds) pathway of H. pylori. H. pylori HopQ possesses six cysteine residues, which generate three consecutive disulfide bridges. Comparison of the redox state of HopQ in wild-type cells to that in hp0231-mutated cells clearly indicated that HopQ is a substrate of HP0231. HopQ binds CEACAM1, 3, 5 and 6 (carcinoembryonic antigen-related cell adhesion molecules). This interaction enables T4SS-mediated translocation of CagA into host cells and induces host signaling. Site directed mutagenesis of HopQ (changing cysteine residues into serine) and analysis of the functioning of HopQ variants showed that HP0231 influences the delivery of CagA into host cells, in part through its impact on HopQ redox state. Introduction of a C382S mutation into HopQ significantly affects its reaction with CEACAM receptors, which disturbs T4SS functioning and CagA delivery. An additional effect of HP0231 on other adhesins and their redox state, resulting in their functional impairment, cannot be excluded.

Keywords: CagA; HP0231; Helicobacter pylori; HopQ; Thioloxidoreductases.

Publication types

  • Comparative Study

MeSH terms

  • Antigens, Bacterial / genetics
  • Antigens, Bacterial / metabolism*
  • Antigens, CD / genetics
  • Antigens, CD / metabolism
  • Bacterial Adhesion
  • Bacterial Outer Membrane Proteins / genetics
  • Bacterial Outer Membrane Proteins / metabolism*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Bacterial Translocation*
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism
  • Cell Line
  • Helicobacter Infections / microbiology*
  • Helicobacter pylori / enzymology*
  • Helicobacter pylori / genetics
  • Helicobacter pylori / pathogenicity*
  • Humans
  • Mutagenesis, Site-Directed
  • Oxidoreductases / genetics
  • Oxidoreductases / metabolism*
  • Protein Transport
  • Virulence


  • Antigens, Bacterial
  • Antigens, CD
  • Bacterial Outer Membrane Proteins
  • Bacterial Proteins
  • CD66 antigens
  • Cell Adhesion Molecules
  • cagA protein, Helicobacter pylori
  • Oxidoreductases