Helicobacter pylori adhesin HopQ engages in a virulence-enhancing interaction with human CEACAMs

Anahita Javaheri; Tobias Kruse; Kristof Moones; Raquel Mejías-Luque; Ayla Debraekeleer; Isabell Asche; Nicole Tegtmeyer; Behnam Kalali; Nina Bach; Stephan A. Sieber; Darryl Hill; Verena Königer; Christof R. Hauck; Roman Moskalenko; Rainer Haas; Dirk H. Busch; Esther Klaile; Hortense Slevogt; Alexej Schmidt; Steffen Backert; Han Remaut; Bernhard B. Singer; Markus Gerhard

doi:10.1038/nmicrobiol.2016.189

Helicobacter pylori adhesin HopQ engages in a virulence-enhancing interaction with human CEACAMs

Anahita Javaheri, Tobias Kruse, Kristof Moones, Raquel Mejías-Luque, Ayla Debraekeleer, Isabell Asche, Nicole Tegtmeyer, Behnam Kalali, Nina Bach, Stephan A. Sieber, Darryl Hill, Verena Königer, Christof R. Hauck, Roman Moskalenko, Rainer Haas, Dirk H. Busch, Esther Klaile, Hortense Slevogt, Alexej Schmidt, Steffen BackertHan Remaut, Bernhard B. Singer, Markus Gerhard

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Abstract

Helicobacter pylori specifically colonizes the human gastric epithelium and is the major causative agent for ulcer disease and gastric cancer development. Here we identified 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 signaling, 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 imply the HopQ-CEACAM1 interaction as potentially promising novel therapeutic target to combat H. pylori-associated diseases.

Original language	English
Article number	16189
Journal	Nature Microbiology
Volume	2
DOIs	https://doi.org/10.1038/nmicrobiol.2016.189
Publication status	Published - 17 Oct 2016

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Javaheri, A., Kruse, T., Moones, K., Mejías-Luque, R., Debraekeleer, A., Asche, I., Tegtmeyer, N., Kalali, B., Bach, N., Sieber, S. A., Hill, D., Königer, V., Hauck, C. R., Moskalenko, R., Haas, R., Busch, D. H., Klaile, E., Slevogt, H., Schmidt, A., ... Gerhard, M. (2016). Helicobacter pylori adhesin HopQ engages in a virulence-enhancing interaction with human CEACAMs. Nature Microbiology, 2, Article 16189. https://doi.org/10.1038/nmicrobiol.2016.189

@article{7af2dd1affb24e2f986a1ec10f5606c1,

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 identified 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 signaling, 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{\textquoteright}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 imply the HopQ-CEACAM1 interaction as potentially promising novel therapeutic target to combat H. pylori-associated diseases. ",

author = "Anahita Javaheri and Tobias Kruse and Kristof Moones and Raquel Mej{\'i}as-Luque and Ayla Debraekeleer and Isabell Asche and Nicole Tegtmeyer and Behnam Kalali and Nina Bach and Sieber, {Stephan A.} and Darryl Hill and Verena K{\"o}niger and Hauck, {Christof R.} and Roman Moskalenko and Rainer Haas and Busch, {Dirk H.} and Esther Klaile and Hortense Slevogt and Alexej Schmidt and Steffen Backert and Han Remaut and Singer, {Bernhard B.} and Markus Gerhard",

year = "2016",

month = oct,

day = "17",

doi = "10.1038/nmicrobiol.2016.189",

language = "English",

volume = "2",

journal = "Nature Microbiology",

issn = "2058-5276",

publisher = "Springer Nature",

}

Javaheri, A, Kruse, T, Moones, K, Mejías-Luque, R, Debraekeleer, A, Asche, I, Tegtmeyer, N, Kalali, B, Bach, N, Sieber, SA, Hill, D, Königer, V, Hauck, CR, Moskalenko, R, Haas, R, Busch, DH, Klaile, E, Slevogt, H, Schmidt, A, Backert, S, Remaut, H, Singer, BB & Gerhard, M 2016, 'Helicobacter pylori adhesin HopQ engages in a virulence-enhancing interaction with human CEACAMs', Nature Microbiology, vol. 2, 16189. https://doi.org/10.1038/nmicrobiol.2016.189

TY - JOUR

T1 - Helicobacter pylori adhesin HopQ engages in a virulence-enhancing interaction with human CEACAMs

AU - Javaheri, Anahita

AU - Kruse, Tobias

AU - Moones, Kristof

AU - Mejías-Luque, Raquel

AU - Debraekeleer, Ayla

AU - Asche, Isabell

AU - Tegtmeyer, Nicole

AU - Kalali, Behnam

AU - Bach, Nina

AU - Sieber, Stephan A.

AU - Hill, Darryl

AU - Königer, Verena

AU - Hauck, Christof R.

AU - Moskalenko, Roman

AU - Haas, Rainer

AU - Busch, Dirk H.

AU - Klaile, Esther

AU - Slevogt, Hortense

AU - Schmidt, Alexej

AU - Backert, Steffen

AU - Remaut, Han

AU - Singer, Bernhard B.

AU - Gerhard, Markus

PY - 2016/10/17

Y1 - 2016/10/17

N2 - Helicobacter pylori specifically colonizes the human gastric epithelium and is the major causative agent for ulcer disease and gastric cancer development. Here we identified 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 signaling, 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 imply the HopQ-CEACAM1 interaction as potentially promising novel therapeutic target to combat H. pylori-associated diseases.

AB - Helicobacter pylori specifically colonizes the human gastric epithelium and is the major causative agent for ulcer disease and gastric cancer development. Here we identified 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 signaling, 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 imply the HopQ-CEACAM1 interaction as potentially promising novel therapeutic target to combat H. pylori-associated diseases.

U2 - 10.1038/nmicrobiol.2016.189

DO - 10.1038/nmicrobiol.2016.189

M3 - Article (Academic Journal)

C2 - 27748768

SN - 2058-5276

VL - 2

JO - Nature Microbiology

JF - Nature Microbiology

M1 - 16189

ER -

Helicobacter pylori adhesin HopQ engages in a virulence-enhancing interaction with human CEACAMs

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