Cysteine Residues in Helicobacter pylori Adhesin HopQ Are Required for CEACAM-HopQ Interaction and Subsequent CagA Translocation

Hamway, Youssef; Taxauer, Karin; Moonens, Kristof; Neumeyer, Victoria; Fischer, Wolfgang; Schmitt, Verena; Singer, Bernhard B.; Remaut, Han; Gerhard, Markus und Mejias-Luque, Raquel (2020): Cysteine Residues in Helicobacter pylori Adhesin HopQ Are Required for CEACAM-HopQ Interaction and Subsequent CagA Translocation. In: Microorganisms, Bd. 8, Nr. 4, 465

Abstract

Attachment to the host gastric mucosa is a key step in Helicobacter pylori infection. Recently, a novel adhesin, HopQ, was shown to bind distinct host CEACAM proteins-an interaction that was found to be essential for the translocation of CagA, a key virulence factor of H. pylori. The HopQ-CEACAM1 co-crystal structure revealed a binding mode dependent on loops in HopQ that are clasped by disulfide bonds. In this study, we investigated the importance of these cysteine residues for CEACAM1 engagement by H. pylori. We observed a loss of CEACAM1 binding and CagA translocation upon disruption of the disulfide bond in loop CL1 (connecting C103 to C132 in HopQ). Deletion of the Dsb-like oxidoreductase HP0231 did not affect cell surface expression of HopQ or alter the interaction of H. pylori with target cells. Although HP0231 deletion was previously described to impede CagA translocation, our results indicate that this occurs through a HopQ-independent mechanism. Together, our results open up new avenues to therapeutically target the HopQ-CEACAM1 interaction and reduce the burden of pathogenic H. pylori.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Sprache: Englisch