title: Helicobacter pylori exploits human CEACAMs via HopQ for adherence and translocation of CagA.
abstract: Helicobacter pylori (Hp) strains that carry the cag type IV secretion system (cag-T4SS) to inject the cytotoxin-associated antigen A (CagA) into host cells are associated with peptic ulcer disease and gastric adenocarcinoma. CagA translocation by Hp is mediated by β1 integrin interaction of the cag-T4SS. However, other cellular receptors or bacterial outer membrane adhesins essential for this process are unknown. Here, we identify the HopQ protein as a genuine Hp adhesin, exploiting defined members of the carcinoembryonic antigen-related cell adhesion molecule family (CEACAMs) as host cell receptors. HopQ binds the amino-terminal IgV-like domain of human CEACAM1, CEACAM3, CEACAM5 or CEACAM6 proteins, thereby enabling translocation of the major pathogenicity factor CagA into host cells. The HopQ-CEACAM interaction is characterized by a remarkably high affinity (KDfrom 23 to 268 nM), which is independent of CEACAM glycosylation, identifying CEACAMs as bona fide protein receptors for Hp. Our data suggest that the HopQ-CEACAM interaction contributes to gastric colonization or Hp-induced pathologies, although the precise role and functional consequences of this interaction in vivo remain to be determined.
authors.affiliation: Max von Pettenkofer-Institut für Hygiene und Medizinische Mikrobiologie, Ludwig-Maximilians-Universität, Pettenkoferstraße 9a, München D-80336, Germany.
authors.forename: Verena
authors.initials: V
authors.lastname: Königer
authors.affiliation: Max von Pettenkofer-Institut für Hygiene und Medizinische Mikrobiologie, Ludwig-Maximilians-Universität, Pettenkoferstraße 9a, München D-80336, Germany.
authors.forename: Lea
authors.initials: L
authors.lastname: Holsten
authors.affiliation: Max von Pettenkofer-Institut für Hygiene und Medizinische Mikrobiologie, Ludwig-Maximilians-Universität, Pettenkoferstraße 9a, München D-80336, Germany.
authors.forename: Ute
authors.initials: U
authors.lastname: Harrison
authors.affiliation: Max von Pettenkofer-Institut für Hygiene und Medizinische Mikrobiologie, Ludwig-Maximilians-Universität, Pettenkoferstraße 9a, München D-80336, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Busch
authors.affiliation: Max von Pettenkofer-Institut für Hygiene und Medizinische Mikrobiologie, Ludwig-Maximilians-Universität, Pettenkoferstraße 9a, München D-80336, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Loell
authors.affiliation: Max von Pettenkofer-Institut für Hygiene und Medizinische Mikrobiologie, Ludwig-Maximilians-Universität, Pettenkoferstraße 9a, München D-80336, Germany.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Institute of Human Virology, University of Maryland School of Medicine, University of Maryland, Baltimore, Maryland 21201.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Bonsor
authors.affiliation: Lehrstuhl Zellbiologie, Fachbereich Biologie, Universität Konstanz, D-78457 Konstanz, Germany.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Roth
authors.affiliation: Lehrstuhl Zellbiologie, Fachbereich Biologie, Universität Konstanz, D-78457 Konstanz, Germany.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Kengmo-Tchoupa
authors.affiliation: Molecular Biology and Biotechnology Division, Nigerian Institute of Medical Research, 6 Edmond Crescent, Yaba, PMB 2013 Lagos, Nigeria.
authors.forename: Stella I
authors.initials: SI
authors.lastname: Smith
authors.affiliation: Institut für Pathologie, Ludwig-Maximilians-Universität, D-80337 München, Germany.
authors.forename: Susanna
authors.initials: S
authors.lastname: Mueller
authors.affiliation: Institute of Human Virology, University of Maryland School of Medicine, University of Maryland, Baltimore, Maryland 21201, USA.|Department of Medicine, University of Maryland School of Medicine, University of Maryland, Baltimore, Maryland 21201, USA.|Department of Microbiology and Immunology, University of Maryland School of Medicine, University of Maryland, Baltimore, Maryland 21201, USA.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Sundberg
authors.affiliation: Tumor Immunology Laboratory, LIFE Center, Ludwig-Maximilians-Universität, Feodor-Lynen-Str. 19, D-81377 München, Germany.|German Center for Infection Research (DZIF), partner site LMU München, München, Germany.
authors.forename: Wolfgang
authors.identifier: 0000-0003-4773-5517
authors.initials: W
authors.lastname: Zimmermann
authors.affiliation: Max von Pettenkofer-Institut für Hygiene und Medizinische Mikrobiologie, Ludwig-Maximilians-Universität, Pettenkoferstraße 9a, München D-80336, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Fischer
authors.affiliation: Lehrstuhl Zellbiologie, Fachbereich Biologie, Universität Konstanz, D-78457 Konstanz, Germany.
authors.forename: Christof R
authors.initials: CR
authors.lastname: Hauck
authors.affiliation: Max von Pettenkofer-Institut für Hygiene und Medizinische Mikrobiologie, Ludwig-Maximilians-Universität, Pettenkoferstraße 9a, München D-80336, Germany.|German Center for Infection Research (DZIF), partner site LMU München, München, Germany.
authors.forename: Rainer
authors.identifier: 0000-0002-2761-0947
authors.initials: R
authors.lastname: Haas
mesh_terms: D018829:Adhesins, Bacterial / Q000378:metabolism*; D000942:Antigens, Bacterial / Q000378:metabolism*; D001422:Bacterial Adhesion; D001426:Bacterial Proteins / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002460:Cell Line; D016480:Helicobacter pylori / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D011485:Protein Binding; D021381:Protein Transport
chemical_list: D018829:Adhesins, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D015815:Cell Adhesion Molecules; C073899:adhesin, helicobacter; C080866:cagA protein, Helicobacter pylori