title: Force Nanoscopy as a Versatile Platform for Quantifying the Activity of Antiadhesion Compounds Targeting Bacterial Pathogens.
abstract: The development of bacterial strains that are resistant to multiple antibiotics has urged the need for new antibacterial therapies. An exciting approach to fight bacterial diseases is the use of antiadhesive agents capable to block the adhesion of the pathogens to host tissues, the first step of infection. We report the use of a novel atomic force microscopy (AFM) platform for quantifying the activity of antiadhesion compounds directly on living bacteria, thus without labeling or purification. Novel fullerene-based mannoconjugates bearing 10 carbohydrate ligands and a thiol bond were efficiently prepared. The thiol functionality could be exploited as a convenient handle to graft the multimeric species onto AFM tips. Using a combination of single-molecule and single-cell AFM assays, we demonstrate that, unlike mannosidic monomers, multivalent glycofullerenes strongly block the adhesion of uropathogenic Escherichia coli bacteria to their carbohydrate receptors. We expect that the nanoscopy technique developed here will help designing new antiadhesion drugs to treat microbial infections, including those caused by multidrug resistant organisms.
authors.affiliation: Université catholique de Louvain , Institute of Life Sciences, Croix du Sud, 4-5, bte L7.07.06., B-1348 Louvain-la-Neuve, Belgium.
authors.forename: Audrey
authors.initials: A
authors.lastname: Beaussart
authors.affiliation: University of Namur , Department of Chemistry, Rue de Bruxelles 61, 5000 Namur, Belgium.
authors.forename: Marta
authors.initials: M
authors.lastname: Abellán-Flos
authors.affiliation: Université catholique de Louvain , Institute of Life Sciences, Croix du Sud, 4-5, bte L7.07.06., B-1348 Louvain-la-Neuve, Belgium.
authors.forename: Sofiane
authors.initials: S
authors.lastname: El-Kirat-Chatel
authors.affiliation: University of Namur , Department of Chemistry, Rue de Bruxelles 61, 5000 Namur, Belgium.
authors.forename: Stéphane P
authors.initials: SP
authors.lastname: Vincent
authors.affiliation: Université catholique de Louvain , Institute of Life Sciences, Croix du Sud, 4-5, bte L7.07.06., B-1348 Louvain-la-Neuve, Belgium.|Walloon Excellence in Life sciences and Biotechnology (WELBIO) 1300 Wavre, Belgium.
authors.forename: Yves F
authors.initials: YF
authors.lastname: Dufrêne
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000627:therapeutic use; D001419:Bacteria / Q000187:drug effects* / Q000472:pathogenicity; D001422:Bacterial Adhesion / Q000187:drug effects*; D024881:Drug Resistance, Bacterial / Q000187:drug effects; D006801:Humans; D018625:Microscopy, Atomic Force; D053758:Nanoparticles / Q000737:chemistry* / Q000627:therapeutic use; D013438:Sulfhydryl Compounds / Q000737:chemistry
chemical_list: D000900:Anti-Bacterial Agents; D013438:Sulfhydryl Compounds