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Helicobacter pylori adhesin HopQ engages in a virulence-enhancing interaction with human CEACAMs
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2017 (English)In: NATURE MICROBIOLOGY, ISSN 2058-5276, Vol. 2, no 1, 16189Article in journal (Refereed) Published
Abstract [en]

Helicobacter pylori specifically colonizes the human gastric epithelium and is the major causative agent for ulcer disease and gastric cancer development. Here, we identify members of the carcinoembryonic antigen-related cell adhesion molecule (CEACAM) family as receptors of H. pylori and show that HopQ is the surface-exposed adhesin that specifically binds human CEACAM1, CEACAM3, CEACAM5 and CEACAM6. HopQ-CEACAM binding is glycan-independent and targeted to the N-domain. H. pylori binding induces CEACAM1-mediated signalling, and the HopQ-CEACAM1 interaction enables translocation of the virulence factor CagA into host cells and enhances the release of pro-inflammatory mediators such as interleukin-8. Based on the crystal structure of HopQ, we found that a beta-hairpin insertion (HopQ-ID) in HopQ's extracellular 3+4 helix bundle domain is important for CEACAM binding. A peptide derived from this domain competitively inhibits HopQ-mediated activation of the Cag virulence pathway, as genetic or antibody-mediated abrogation of the HopQ function shows. Together, our data suggest the HopQ-CEACAM1 interaction to be a potentially promising novel therapeutic target to combat H. pylori-associated diseases.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP , 2017. Vol. 2, no 1, 16189
National Category
Immunology in the medical area Microbiology in the medical area
Identifiers
URN: urn:nbn:se:umu:diva-133381DOI: 10.1038/nmicrobiol.2016.189ISI: 000396366300008PubMedID: 27748768OAI: oai:DiVA.org:umu-133381DiVA: diva2:1090903
Available from: 2017-04-25 Created: 2017-04-25 Last updated: 2017-04-25Bibliographically approved

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CiteExportLink to record
Permanent link

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Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf