title: 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 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.
  
  
  
  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.
authors.affiliation: Department of Bioengineering Sciences, Structural Biology Brussels, International Joint Research Group VUB-EPFL BioNanotechnology & NanoMedicine (NANO), Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Francesco S
authors.initials: FS
authors.lastname: Ielasi
authors.affiliation: Department of Electronics and Informatics (ETRO), AVSP Lab, International Joint Research Group VUB-EPFL BioNanotechnology and NanoMedicine (NANO), Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Mitchel
authors.initials: M
authors.lastname: Alioscha-Perez
authors.affiliation: Department of Bioengineering Sciences, Structural Biology Brussels, International Joint Research Group VUB-EPFL BioNanotechnology & NanoMedicine (NANO), Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Dagmara
authors.initials: D
authors.lastname: Donohue
authors.affiliation: Department of Microbiology and Immunology, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium.
authors.forename: Sandra
authors.initials: S
authors.lastname: Claes
authors.affiliation: Department of Electronics and Informatics (ETRO), AVSP Lab, International Joint Research Group VUB-EPFL BioNanotechnology and NanoMedicine (NANO), Vrije Universiteit Brussel, Brussels, Belgium Interuniversity Microelectronics Centre (IMEC), Leuven, Belgium.
authors.forename: Hichem
authors.initials: H
authors.lastname: Sahli
authors.affiliation: Department of Microbiology and Immunology, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium.
authors.forename: Dominique
authors.initials: D
authors.lastname: Schols
authors.affiliation: Department of Bioengineering Sciences, Structural Biology Brussels, International Joint Research Group VUB-EPFL BioNanotechnology & NanoMedicine (NANO), Vrije Universiteit Brussel, Brussels, Belgium Ronnie.Willaert@vub.ac.be.
authors.forename: Ronnie G
authors.initials: RG
authors.lastname: Willaert
mesh_terms: D018829:Adhesins, Bacterial / Q000378:metabolism*; D002460:Cell Line; D005656:Fungal Proteins / Q000378:metabolism*; D006801:Humans; D037102:Lectins / Q000378:metabolism; D011134:Polysaccharides / Q000378:metabolism; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000032:analysis*
chemical_list: D018829:Adhesins, Bacterial; D005656:Fungal Proteins; D037102:Lectins; D011134:Polysaccharides; D011956:Receptors, Cell Surface