Force Nanoscopy as a Versatile Platform for Quantifying the Activity of Antiadhesion Compounds Targeting Bacterial Pathogens

Nano Letters
Audrey BeaussartYves F Dufrêne

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.

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Citations

Oct 27, 2016·Nature Microbiology·Jie Xiao, Yves F Dufrêne
Jul 5, 2016·Chemistry : a European Journal·Marta Abellán FlosStéphane P Vincent
Sep 27, 2018·Chemistry, an Asian Journal·Jing HuJian Yin
Jan 10, 2020·Molecular Microbiology·Felipe VielaYves F Dufrêne
Apr 8, 2020·Journal of Bacteriology·Albertus ViljoenYves F Dufrêne
Jul 17, 2020·Frontiers in Microbiology·Yves F Dufrêne, Albertus Viljoen
Dec 9, 2020·Nanoscale·Audrey BeaussartSofiane El-Kirat-Chatel
Feb 23, 2021·Bioactive Materials·Ying HanHongyu Zhang
Mar 13, 2021·Cellular Microbiology·Yves F DufrêneMarion Mathelié-Guinlet
May 25, 2021·Frontiers in Cellular and Infection Microbiology·Supriya V BhatTanya E S Dahms

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