Glycointeractome of <named-content content-type="genus-species">Neisseria gonorrhoeae</named-content>: Identification of Host Glycans Targeted by the Gonococcus To Facilitate Adherence to Cervical and Urethral Epithelial Cells

ABSTRACT Neisseria gonorrhoeae is a significant threat to global health for which a vaccine and novel treatment options are urgently needed. Glycans expressed by human cells are commonly targeted by pathogens to facilitate interactions with the host, and thus characterization of these interactions c...

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Autores principales:	Evgeny A. Semchenko, Arun V. Everest-Dass, Freda E.-C. Jen, Tsitsi D. Mubaiwa, Christopher J. Day, Kate L. Seib
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	Neisseria gonorrhoeae adherence carbohydrate epithelial cells glycobiology gonorrhea Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/5cba5c16fa0040759a91090679c8b607
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spelling	oai:doaj.org-article:5cba5c16fa0040759a91090679c8b6072021-11-15T16:22:10ZGlycointeractome of <named-content content-type="genus-species">Neisseria gonorrhoeae</named-content>: Identification of Host Glycans Targeted by the Gonococcus To Facilitate Adherence to Cervical and Urethral Epithelial Cells10.1128/mBio.01339-192150-7511https://doaj.org/article/5cba5c16fa0040759a91090679c8b6072019-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01339-19https://doaj.org/toc/2150-7511ABSTRACT Neisseria gonorrhoeae is a significant threat to global health for which a vaccine and novel treatment options are urgently needed. Glycans expressed by human cells are commonly targeted by pathogens to facilitate interactions with the host, and thus characterization of these interactions can aid identification of bacterial receptors that can be exploited as vaccine and/or drug targets. Using glycan array analysis, we identified 247 specific interactions between N. gonorrhoeae and glycans representative of those found on human cells. Interactions included those with mannosylated, fucosylated, and sialylated glycans, glycosaminoglycans (GAGs), and glycans terminating with galactose (Gal), N-acetylgalactosamine (GalNAc), and N-acetylglucosamine (GlcNAc). By investigating the kinetics of interactions with selected glycans, we demonstrate that whole-cell N. gonorrhoeae has a high affinity for mannosylated glycans (dissociation constant [KD], 0.14 to 0.59 μM), which are expressed on the surface of cervical and urethral epithelial cells. Using chromatography coupled with mass spectrometric (MS) analysis, we identified potential mannose-binding proteins in N. gonorrhoeae. Pretreatment of cells with mannose-specific lectin (concanavalin A) or free mannose competitor (α-methyl-d-mannopyranoside) substantially reduced gonococcal adherence to epithelial cells. This suggests that N. gonorrhoeae targets mannosyl glycans to facilitate adherence to host cells and that mannosides or similar compounds have the potential to be used as a novel treatment option for N. gonorrhoeae. IMPORTANCE Multidrug-resistant strains of Neisseria gonorrhoeae are emerging worldwide, and novel treatment and prevention strategies are needed. Glycans are ubiquitously expressed by all human cells and can be specifically targeted by pathogens to facilitate association with host cells. Here we identify and characterize the N. gonorrhoeae host-glycan binding profile (glycointeractome), which revealed numerous interactions, including high-affinity binding to mannosyl glycans. We identify gonococcal potential mannose-binding proteins and show that N. gonorrhoeae uses mannosyl glycans expressed on the surface of cervical and urethral epithelia to facilitate adherence. Furthermore, a mannose-binding lectin or a mannoside compound was able to reduce this adherence. By characterizing the glycointeractome of N. gonorrhoeae, we were able to elucidate a novel mechanism used by this important pathogen to interact with human cells, and this interaction could be exploited to develop novel therapeutics to treat antibiotic-resistant gonorrhea.Evgeny A. SemchenkoArun V. Everest-DassFreda E.-C. JenTsitsi D. MubaiwaChristopher J. DayKate L. SeibAmerican Society for MicrobiologyarticleNeisseria gonorrhoeaeadherencecarbohydrateepithelial cellsglycobiologygonorrheaMicrobiologyQR1-502ENmBio, Vol 10, Iss 4 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neisseria gonorrhoeae adherence carbohydrate epithelial cells glycobiology gonorrhea Microbiology QR1-502
spellingShingle	Neisseria gonorrhoeae adherence carbohydrate epithelial cells glycobiology gonorrhea Microbiology QR1-502 Evgeny A. Semchenko Arun V. Everest-Dass Freda E.-C. Jen Tsitsi D. Mubaiwa Christopher J. Day Kate L. Seib Glycointeractome of <named-content content-type="genus-species">Neisseria gonorrhoeae</named-content>: Identification of Host Glycans Targeted by the Gonococcus To Facilitate Adherence to Cervical and Urethral Epithelial Cells
description	ABSTRACT Neisseria gonorrhoeae is a significant threat to global health for which a vaccine and novel treatment options are urgently needed. Glycans expressed by human cells are commonly targeted by pathogens to facilitate interactions with the host, and thus characterization of these interactions can aid identification of bacterial receptors that can be exploited as vaccine and/or drug targets. Using glycan array analysis, we identified 247 specific interactions between N. gonorrhoeae and glycans representative of those found on human cells. Interactions included those with mannosylated, fucosylated, and sialylated glycans, glycosaminoglycans (GAGs), and glycans terminating with galactose (Gal), N-acetylgalactosamine (GalNAc), and N-acetylglucosamine (GlcNAc). By investigating the kinetics of interactions with selected glycans, we demonstrate that whole-cell N. gonorrhoeae has a high affinity for mannosylated glycans (dissociation constant [KD], 0.14 to 0.59 μM), which are expressed on the surface of cervical and urethral epithelial cells. Using chromatography coupled with mass spectrometric (MS) analysis, we identified potential mannose-binding proteins in N. gonorrhoeae. Pretreatment of cells with mannose-specific lectin (concanavalin A) or free mannose competitor (α-methyl-d-mannopyranoside) substantially reduced gonococcal adherence to epithelial cells. This suggests that N. gonorrhoeae targets mannosyl glycans to facilitate adherence to host cells and that mannosides or similar compounds have the potential to be used as a novel treatment option for N. gonorrhoeae. IMPORTANCE Multidrug-resistant strains of Neisseria gonorrhoeae are emerging worldwide, and novel treatment and prevention strategies are needed. Glycans are ubiquitously expressed by all human cells and can be specifically targeted by pathogens to facilitate association with host cells. Here we identify and characterize the N. gonorrhoeae host-glycan binding profile (glycointeractome), which revealed numerous interactions, including high-affinity binding to mannosyl glycans. We identify gonococcal potential mannose-binding proteins and show that N. gonorrhoeae uses mannosyl glycans expressed on the surface of cervical and urethral epithelia to facilitate adherence. Furthermore, a mannose-binding lectin or a mannoside compound was able to reduce this adherence. By characterizing the glycointeractome of N. gonorrhoeae, we were able to elucidate a novel mechanism used by this important pathogen to interact with human cells, and this interaction could be exploited to develop novel therapeutics to treat antibiotic-resistant gonorrhea.
format	article
author	Evgeny A. Semchenko Arun V. Everest-Dass Freda E.-C. Jen Tsitsi D. Mubaiwa Christopher J. Day Kate L. Seib
author_facet	Evgeny A. Semchenko Arun V. Everest-Dass Freda E.-C. Jen Tsitsi D. Mubaiwa Christopher J. Day Kate L. Seib
author_sort	Evgeny A. Semchenko
title	Glycointeractome of <named-content content-type="genus-species">Neisseria gonorrhoeae</named-content>: Identification of Host Glycans Targeted by the Gonococcus To Facilitate Adherence to Cervical and Urethral Epithelial Cells
title_short	Glycointeractome of <named-content content-type="genus-species">Neisseria gonorrhoeae</named-content>: Identification of Host Glycans Targeted by the Gonococcus To Facilitate Adherence to Cervical and Urethral Epithelial Cells
title_full	Glycointeractome of <named-content content-type="genus-species">Neisseria gonorrhoeae</named-content>: Identification of Host Glycans Targeted by the Gonococcus To Facilitate Adherence to Cervical and Urethral Epithelial Cells
title_fullStr	Glycointeractome of <named-content content-type="genus-species">Neisseria gonorrhoeae</named-content>: Identification of Host Glycans Targeted by the Gonococcus To Facilitate Adherence to Cervical and Urethral Epithelial Cells
title_full_unstemmed	Glycointeractome of <named-content content-type="genus-species">Neisseria gonorrhoeae</named-content>: Identification of Host Glycans Targeted by the Gonococcus To Facilitate Adherence to Cervical and Urethral Epithelial Cells
title_sort	glycointeractome of <named-content content-type="genus-species">neisseria gonorrhoeae</named-content>: identification of host glycans targeted by the gonococcus to facilitate adherence to cervical and urethral epithelial cells
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/5cba5c16fa0040759a91090679c8b607
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Glycointeractome of <named-content content-type="genus-species">Neisseria gonorrhoeae</named-content>: Identification of Host Glycans Targeted by the Gonococcus To Facilitate Adherence to Cervical and Urethral Epithelial Cells

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