Helicobacter pylori exploits human CEACAMs via HopQ for adherence and translocation of CagA View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2016-10-17

AUTHORS

Verena Königer, Lea Holsten, Ute Harrison, Benjamin Busch, Eva Loell, Qing Zhao, Daniel A. Bonsor, Alexandra Roth, Arnaud Kengmo-Tchoupa, Stella I. Smith, Susanna Mueller, Eric J. Sundberg, Wolfgang Zimmermann, Wolfgang Fischer, Christof R. Hauck, Rainer Haas

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 (KD from 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. More... »

PAGES

16188

Journal

TITLE

Nature Microbiology

ISSUE

1

VOLUME

2

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nmicrobiol.2016.188

DOI

http://dx.doi.org/10.1038/nmicrobiol.2016.188

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1033284979

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/27748756


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