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

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...

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Autores principales: Hamway, Youssef, Taxauer, Karin, Moonens, Kristof, Neumeyer, Victoria, Fischer, Wolfgang, Schmitt, Verena, Singer, Bernhard B., Remaut, Han, Gerhard, Markus, Mejías-Luque, Raquel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7232459/
https://www.ncbi.nlm.nih.gov/pubmed/32218315
http://dx.doi.org/10.3390/microorganisms8040465
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author Hamway, Youssef
Taxauer, Karin
Moonens, Kristof
Neumeyer, Victoria
Fischer, Wolfgang
Schmitt, Verena
Singer, Bernhard B.
Remaut, Han
Gerhard, Markus
Mejías-Luque, Raquel
author_facet Hamway, Youssef
Taxauer, Karin
Moonens, Kristof
Neumeyer, Victoria
Fischer, Wolfgang
Schmitt, Verena
Singer, Bernhard B.
Remaut, Han
Gerhard, Markus
Mejías-Luque, Raquel
author_sort Hamway, Youssef
collection PubMed
description 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.
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spelling pubmed-72324592020-05-22 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 Mejías-Luque, Raquel Microorganisms Article 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. MDPI 2020-03-25 /pmc/articles/PMC7232459/ /pubmed/32218315 http://dx.doi.org/10.3390/microorganisms8040465 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hamway, Youssef
Taxauer, Karin
Moonens, Kristof
Neumeyer, Victoria
Fischer, Wolfgang
Schmitt, Verena
Singer, Bernhard B.
Remaut, Han
Gerhard, Markus
Mejías-Luque, Raquel
Cysteine Residues in Helicobacter pylori Adhesin HopQ Are Required for CEACAM–HopQ Interaction and Subsequent CagA Translocation
title Cysteine Residues in Helicobacter pylori Adhesin HopQ Are Required for CEACAM–HopQ Interaction and Subsequent CagA Translocation
title_full Cysteine Residues in Helicobacter pylori Adhesin HopQ Are Required for CEACAM–HopQ Interaction and Subsequent CagA Translocation
title_fullStr Cysteine Residues in Helicobacter pylori Adhesin HopQ Are Required for CEACAM–HopQ Interaction and Subsequent CagA Translocation
title_full_unstemmed Cysteine Residues in Helicobacter pylori Adhesin HopQ Are Required for CEACAM–HopQ Interaction and Subsequent CagA Translocation
title_short Cysteine Residues in Helicobacter pylori Adhesin HopQ Are Required for CEACAM–HopQ Interaction and Subsequent CagA Translocation
title_sort cysteine residues in helicobacter pylori adhesin hopq are required for ceacam–hopq interaction and subsequent caga translocation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7232459/
https://www.ncbi.nlm.nih.gov/pubmed/32218315
http://dx.doi.org/10.3390/microorganisms8040465
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