Journal
NANO LETTERS
Volume 16, Issue 2, Pages 1299-1307Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.nanolett.5b04689
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Funding
- National Fund for Scientific Research (FNRS)
- FNRS-WELBIO [WELBIO-CR-2015A-05]
- Universite catholique de Louvain (Fonds Speciaux de Recherche)
- Federal Office for Scientific, Technical and Cultural Affairs (Interuniversity Poles of Attraction Programme)
- Research Department of the Communaute francaise de Belgique (Concerted Research Action)
- People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme DyNano under REA [289033]
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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.
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