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

详细信息    查看全文

• 作者：Audrey Beaussart ; Marta Abellán-Flos ; Sofiane El-Kirat-Chatel ; Stéphane P. Vincent ; Yves F. Dufrêne
• 刊名：Nano Letters
• 出版年：2016
• 出版时间：February 10, 2016
• 年：2016
• 卷：16
• 期：2
• 页码：1299-1307
• 全文大小：623K
• ISSN：1530-6992

文摘

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.