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

Francesco S Ielasi,Dagmara Donohue,Mitchel Alioscha-Perez,Ronnie G Willaert,Dominique Schols,Sandra Claes,Hichem Sahli,Peter N Lipke,Judith Berman

doi:10.1128/mbio.00584-16

Francesco S Ielasi, Dagmara Donohue + Show 7 more

Open Access

https://doi.org/10.1128/mbio.00584-16

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Abstract

ABSTRACTThe 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.

Highlights

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 to human cell receptors that expose glycans
The proposed lectin-glycan interaction (LGI) network has been modeled as a weighted, undirected graph composed of a set of nodes and a set of edges connecting the pair of nodes
We developed and successfully employed a novel LGI network in which the carbohydrate-binding properties of the E. coli adhesin FimH and Candida adhesins from the Epa and Als adhesin families were explored

Summary

Introduction

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. 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 (Epa, Epa, and Epa adhesins), which cause candidiasis. 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 used to predict lectin interactions with human-pathogenic viruses and to discover whether FimH adhesin has anti-HIV activity. We recently demonstrated that wild-type N-Epa1p binds to FN from human plasma [29], no experimental data on the potential host glycoprotein binding receptors of Epa1p or other C. glabrata adhesins are available

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