Lectin-Glycan Interaction Network-Based Identification of Host Receptors of Microbial Pathogenic Adhesins

ABSTRACT The first step in the infection of humans by microbial pathogens is their adherence to host tissue cells, which is frequently based on the binding of carbohydrate-binding proteins (lectin-like adhesins) to human cell receptors that expose glycans. In only a few cases have the human receptor...

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Autores principales:	Francesco S. Ielasi, Mitchel Alioscha-Perez, Dagmara Donohue, Sandra Claes, Hichem Sahli, Dominique Schols, Ronnie G. Willaert
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Lenguaje:	EN
Publicado:	American Society for Microbiology 2016
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/b23f771303964066863bc08ffeb0ab0e
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spelling	oai:doaj.org-article:b23f771303964066863bc08ffeb0ab0e2021-11-15T15:50:18ZLectin-Glycan Interaction Network-Based Identification of Host Receptors of Microbial Pathogenic Adhesins10.1128/mBio.00584-162150-7511https://doaj.org/article/b23f771303964066863bc08ffeb0ab0e2016-09-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00584-16https://doaj.org/toc/2150-7511ABSTRACT The first step in the infection of humans by microbial pathogens is their adherence to host tissue cells, which is frequently based on the binding of carbohydrate-binding proteins (lectin-like adhesins) to human cell receptors that expose glycans. In only a few cases have the human receptors of pathogenic adhesins been described. A novel strategy—based on the construction of a lectin-glycan interaction (LGI) network—to identify the potential human binding receptors for pathogenic adhesins with lectin activity was developed. The new approach is based on linking glycan array screening results of these adhesins to a human glycoprotein database via the construction of an LGI network. This strategy was used to detect human receptors for virulent Escherichia coli (FimH adhesin), and the fungal pathogens Candida albicans (Als1p and Als3p adhesins) and C. glabrata (Epa1, Epa6, and Epa7 adhesins), which cause candidiasis. This LGI network strategy allows the profiling of potential adhesin binding receptors in the host with prioritization, based on experimental binding data, of the most relevant interactions. New potential targets for the selected adhesins were predicted and experimentally confirmed. This methodology was also used to predict lectin interactions with envelope glycoproteins of human-pathogenic viruses. It was shown that this strategy was successful in revealing that the FimH adhesin has anti-HIV activity. IMPORTANCE Microbial pathogens may express a wide range of carbohydrate-specific adhesion proteins that mediate adherence to host tissues. Pathogen attachment to host cells is achieved through the binding of these lectin-like adhesins to glycans on human glycoproteins. In only a few cases have the human receptors of pathogenic adhesins been described. We developed a new strategy to predict these interacting receptors. Therefore, we developed a novel LGI network that would allow the mapping of potential adhesin binding receptors in the host with prioritization, based on the experimental binding data, of the most relevant interactions. New potential targets for the selected adhesins (bacterial uroepithelial FimH from E. coli and fungal Epa and Als adhesins from C. glabrata and C. albicans) were predicted and experimentally confirmed. This methodology was also used to predict lectin interactions with human-pathogenic viruses and to discover whether FimH adhesin has anti-HIV activity.Francesco S. IelasiMitchel Alioscha-PerezDagmara DonohueSandra ClaesHichem SahliDominique ScholsRonnie G. WillaertAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 7, Iss 4 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Francesco S. Ielasi Mitchel Alioscha-Perez Dagmara Donohue Sandra Claes Hichem Sahli Dominique Schols Ronnie G. Willaert Lectin-Glycan Interaction Network-Based Identification of Host Receptors of Microbial Pathogenic Adhesins
description	ABSTRACT The first step in the infection of humans by microbial pathogens is their adherence to host tissue cells, which is frequently based on the binding of carbohydrate-binding proteins (lectin-like adhesins) to human cell receptors that expose glycans. In only a few cases have the human receptors of pathogenic adhesins been described. A novel strategy—based on the construction of a lectin-glycan interaction (LGI) network—to identify the potential human binding receptors for pathogenic adhesins with lectin activity was developed. The new approach is based on linking glycan array screening results of these adhesins to a human glycoprotein database via the construction of an LGI network. This strategy was used to detect human receptors for virulent Escherichia coli (FimH adhesin), and the fungal pathogens Candida albicans (Als1p and Als3p adhesins) and C. glabrata (Epa1, Epa6, and Epa7 adhesins), which cause candidiasis. This LGI network strategy allows the profiling of potential adhesin binding receptors in the host with prioritization, based on experimental binding data, of the most relevant interactions. New potential targets for the selected adhesins were predicted and experimentally confirmed. This methodology was also used to predict lectin interactions with envelope glycoproteins of human-pathogenic viruses. It was shown that this strategy was successful in revealing that the FimH adhesin has anti-HIV activity. IMPORTANCE Microbial pathogens may express a wide range of carbohydrate-specific adhesion proteins that mediate adherence to host tissues. Pathogen attachment to host cells is achieved through the binding of these lectin-like adhesins to glycans on human glycoproteins. In only a few cases have the human receptors of pathogenic adhesins been described. We developed a new strategy to predict these interacting receptors. Therefore, we developed a novel LGI network that would allow the mapping of potential adhesin binding receptors in the host with prioritization, based on the experimental binding data, of the most relevant interactions. New potential targets for the selected adhesins (bacterial uroepithelial FimH from E. coli and fungal Epa and Als adhesins from C. glabrata and C. albicans) were predicted and experimentally confirmed. This methodology was also used to predict lectin interactions with human-pathogenic viruses and to discover whether FimH adhesin has anti-HIV activity.
format	article
author	Francesco S. Ielasi Mitchel Alioscha-Perez Dagmara Donohue Sandra Claes Hichem Sahli Dominique Schols Ronnie G. Willaert
author_facet	Francesco S. Ielasi Mitchel Alioscha-Perez Dagmara Donohue Sandra Claes Hichem Sahli Dominique Schols Ronnie G. Willaert
author_sort	Francesco S. Ielasi
title	Lectin-Glycan Interaction Network-Based Identification of Host Receptors of Microbial Pathogenic Adhesins
title_short	Lectin-Glycan Interaction Network-Based Identification of Host Receptors of Microbial Pathogenic Adhesins
title_full	Lectin-Glycan Interaction Network-Based Identification of Host Receptors of Microbial Pathogenic Adhesins
title_fullStr	Lectin-Glycan Interaction Network-Based Identification of Host Receptors of Microbial Pathogenic Adhesins
title_full_unstemmed	Lectin-Glycan Interaction Network-Based Identification of Host Receptors of Microbial Pathogenic Adhesins
title_sort	lectin-glycan interaction network-based identification of host receptors of microbial pathogenic adhesins
publisher	American Society for Microbiology
publishDate	2016
url	https://doaj.org/article/b23f771303964066863bc08ffeb0ab0e
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Lectin-Glycan Interaction Network-Based Identification of Host Receptors of Microbial Pathogenic Adhesins

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