|Title||Helicobacter pylori adhesin HopQ engages in a virulence-enhancing interaction with human CEACAMs.|
|Publication Type||Journal Article|
|Year of Publication||2016|
|Authors||Javaheri, A., T. Kruse, K. Moonens, R. Mejías-Luque, A. Debraekeleer, C. I. Asche, N. Tegtmeyer, B. Kalali, N. C. Bach, S. A. Sieber, D. J. Hill, V. Königer, C. R. Hauck, R. Moskalenko, R. Haas, D. H. Busch, E. Klaile, H. Slevogt, A. Schmidt, S. Backert, H. Remaut, B. B. Singer, and M. Gerhard|
|Date Published||2016 Oct 17|
|Keywords||Adhesins, Bacterial, Antigens, Bacterial, Bacterial Adhesion, Bacterial Proteins, Cell Adhesion Molecules, Cell Line, Crystallography, X-Ray, Helicobacter pylori, Host-Pathogen Interactions, Humans, Interleukin-8, Protein Binding, Protein Conformation, Protein Transport, Virulence|
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 β-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.
|Alternate Journal||Nat Microbiol|
Helicobacter pylori adhesin HopQ engages in a virulence-enhancing interaction with human CEACAMs.