Journal
NATURE MICROBIOLOGY
Volume 2, Issue 1, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nmicrobiol.2016.189
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Funding
- VIB
- Flanders Science Foundation (FWO)
- Hercules funds [UABR/09/005]
- German Centre for Infection Research, partner site Munich
- BMBFGO-Bio Program
- BMBF [01EO1002]
- Mercator Research Center Ruhr [An2012-0070]
- German Science Foundation [CRC-796, CRC-1181, Collaborative Research Center/Transregio 124]
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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.
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