Helicobacter pylori adhesin HopQ engages in a virulence-enhancing interaction with human CEACAMs.

Abstract:

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.

SEEK ID: https://funginet.hki-jena.de/publications/84

PubMed ID: 27748768

Projects: A5

Journal: Nat Microbiol

Citation: Nat Microbiol. 2016 Oct 17;2:16189. doi: 10.1038/nmicrobiol.2016.189.

Date Published: 18th Oct 2016

Authors: A. Javaheri, T. Kruse, K. Moonens, R. Mejias-Luque, A. Debraekeleer, C. I. Asche, N. Tegtmeyer, B. Kalali, N. C. Bach, S. A. Sieber, D. J. Hill, V. Koniger, C. R. Hauck, R. Moskalenko, R. Haas, D. H. Busch, Esther Klaile, Hortense Slevogt, A. Schmidt, S. Backert, H. Remaut, B. B. Singer, M. Gerhard

help Creator
Activity

Views: 517

Created: 12th Sep 2017 at 09:01

help Attributions

None

Related items

Powered by
Seek new full
(v.1.6.2)
Copyright © 2008 - 2018 The University of Manchester and HITS gGmbH