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

Javaheri A, Kruse T, Moonens K, Mejias-Luque R, Debraekeleer A, Asche CI, Tegtmeyer-Backert N, Kalali B, Bach NC, Sieber SA, Hill DJ, Koeniger V, Hauck CR, Moskalenko R, Haas R, Busch DH, Klaile E, Slevogt H, Schmidt A, Backert S, Remaut H, Singer BB, Gerhard M (2016)

Publication Type: Journal article

Publication year: 2016

Journal

Nature Microbiology Nature Research

Book Volume: 2

Article Number: 16189

DOI: 10.1038/nmicrobiol.2016.189

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 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.

Authors with CRIS profile

Nicole Tegtmeyer-Backert Lehrstuhl für Mikrobiologie Steffen Backert Lehrstuhl für Mikrobiologie

Involved external institutions

Technische Universität München (TUM) DE Germany (DE) Sumy State University / Сумський державний університет UA Ukraine (UA) Ludwig-Maximilians-Universität (LMU) DE Germany (DE) Universität Konstanz DE Germany (DE) Universitätsklinikum Jena DE Germany (DE) Universität Duisburg-Essen (UDE) DE Germany (DE) Flanders Institute for Biotechnology / Vlaams Instituut voor Biotechnologie (VIB) BE Belgium (BE) ImevaX GmbH DE Germany (DE) University of Bristol GB United Kingdom (GB)

How to cite

APA:

Javaheri, A., Kruse, T., Moonens, K., Mejias-Luque, R., Debraekeleer, A., Asche, C.I.,... Gerhard, M. (2016). Helicobacter pylori adhesin HopQ engages in a virulence-enhancing interaction with human CEACAMs. Nature Microbiology, 2. https://dx.doi.org/10.1038/nmicrobiol.2016.189

MLA:

Javaheri, Anahita, et al. "Helicobacter pylori adhesin HopQ engages in a virulence-enhancing interaction with human CEACAMs." Nature Microbiology 2 (2016).

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