title: 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 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.affiliation: Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München, 81675 Munich, Germany.|German Center for Infection Research, Partner Site Munich, 81675 Munich, Germany.
authors.forename: Anahita
authors.initials: A
authors.lastname: Javaheri
authors.affiliation: Imevax GmbH, 81675 Munich, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Kruse
authors.affiliation: Structural and Molecular Microbiology, Structural Biology Research Center, VIB, Pleinlaan 2, 1050 Brussels, Belgium.|Structural Biology Brussels, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium.
authors.forename: Kristof
authors.initials: K
authors.lastname: Moonens
authors.affiliation: Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München, 81675 Munich, Germany.|German Center for Infection Research, Partner Site Munich, 81675 Munich, Germany.
authors.forename: Raquel
authors.identifier: http://orcid.org/0000-0002-4602-4927
authors.initials: R
authors.lastname: Mejías-Luque
authors.affiliation: Structural and Molecular Microbiology, Structural Biology Research Center, VIB, Pleinlaan 2, 1050 Brussels, Belgium.|Structural Biology Brussels, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium.
authors.forename: Ayla
authors.initials: A
authors.lastname: Debraekeleer
authors.affiliation: Department of Biology, Division of Microbiology, Friedrich Alexander University Erlangen, 91058 Erlangen, Germany.
authors.forename: Carmen I
authors.initials: CI
authors.lastname: Asche
authors.affiliation: Department of Biology, Division of Microbiology, Friedrich Alexander University Erlangen, 91058 Erlangen, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Tegtmeyer
authors.affiliation: Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München, 81675 Munich, Germany.|Imevax GmbH, 81675 Munich, Germany.
authors.forename: Behnam
authors.initials: B
authors.lastname: Kalali
authors.affiliation: Department Chemie, Center for Integrated Protein Science Munich, Institute of Advanced Studies, Technische Universität München, 85747 Garching, Germany.
authors.forename: Nina C
authors.initials: NC
authors.lastname: Bach
authors.affiliation: Department Chemie, Center for Integrated Protein Science Munich, Institute of Advanced Studies, Technische Universität München, 85747 Garching, Germany.
authors.forename: Stephan A
authors.initials: SA
authors.lastname: Sieber
authors.affiliation: School of Cellular &Molecular Medicine, University of Bristol, Bristol BS8 1TD, UK.
authors.forename: Darryl J
authors.initials: DJ
authors.lastname: Hill
authors.affiliation: Department of Bacteriology, Max von Pettenkofer-Institut für Hygiene und Medizinische Mikrobiologie, Ludwig-Maximilians-Universität, D-80336 Munich, Germany.
authors.forename: Verena
authors.initials: V
authors.lastname: Königer
authors.affiliation: Lehrstuhl für Zellbiologie, Universität Konstanz, 78457 Konstanz, Germany.
authors.forename: Christof R
authors.initials: CR
authors.lastname: Hauck
authors.affiliation: Department of Pathology, Sumy State University, Sumy 40000, Ukraine.
authors.forename: Roman
authors.initials: R
authors.lastname: Moskalenko
authors.affiliation: Department of Bacteriology, Max von Pettenkofer-Institut für Hygiene und Medizinische Mikrobiologie, Ludwig-Maximilians-Universität, D-80336 Munich, Germany.
authors.forename: Rainer
authors.identifier: http://orcid.org/0000-0002-2761-0947
authors.initials: R
authors.lastname: Haas
authors.affiliation: Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München, 81675 Munich, Germany.
authors.forename: Dirk H
authors.initials: DH
authors.lastname: Busch
authors.affiliation: Septomics Research Centre, Jena University Hospital, 07745 Jena, Germany.|Center for Sepsis Control and Care (CSCC), Jena University Hospital, 07747 Jena, Germany.
authors.forename: Esther
authors.initials: E
authors.lastname: Klaile
authors.affiliation: Septomics Research Centre, Jena University Hospital, 07745 Jena, Germany.
authors.forename: Hortense
authors.initials: H
authors.lastname: Slevogt
authors.affiliation: Medical Faculty, Institute of Anatomy, University Duisburg-Essen, 45122 Essen, Germany.|Department of Medical Biosciences, Pathology, Umeå University, SE-901 85 Umeå, Sweden.
authors.forename: Alexej
authors.initials: A
authors.lastname: Schmidt
authors.affiliation: Department of Biology, Division of Microbiology, Friedrich Alexander University Erlangen, 91058 Erlangen, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Backert
authors.affiliation: Structural and Molecular Microbiology, Structural Biology Research Center, VIB, Pleinlaan 2, 1050 Brussels, Belgium.|Structural Biology Brussels, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium.
authors.forename: Han
authors.initials: H
authors.lastname: Remaut
authors.affiliation: Medical Faculty, Institute of Anatomy, University Duisburg-Essen, 45122 Essen, Germany.
authors.forename: Bernhard B
authors.initials: BB
authors.lastname: Singer
authors.affiliation: Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München, 81675 Munich, Germany.|German Center for Infection Research, Partner Site Munich, 81675 Munich, Germany.|Imevax GmbH, 81675 Munich, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Gerhard
mesh_terms: D018829:Adhesins, Bacterial / Q000737:chemistry / Q000378:metabolism*; D000942:Antigens, Bacterial / Q000378:metabolism; D001422:Bacterial Adhesion; D001426:Bacterial Proteins / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002460:Cell Line; D018360:Crystallography, X-Ray; D016480:Helicobacter pylori / Q000472:pathogenicity* / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D021381:Protein Transport; D014774:Virulence
chemical_list: D018829:Adhesins, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C508606:CXCL8 protein, human; D015815:Cell Adhesion Molecules; D016209:Interleukin-8; C073899:adhesin, helicobacter; C080866:cagA protein, Helicobacter pylori