Institut de Recherche Interdisciplinaire-IRI, USR CNRS 3078, Université Lille 1, Parc de la Haute Borne, 50 Avenue de Halley, BP 70478, 59658 Villeneuve d'Ascq, France.
Nanoscale. 2013 Mar 21;5(6):2307-16. doi: 10.1039/c3nr33826f.
Bacterial attachment and subsequent biofilm formation on biotic surfaces or medical devices is an increasing source of infections in clinical settings. A large proportion of these biofilm-related infections are caused by Escherichia coli, a major nosocomial pathogen, in which the major adhesion factor is the FimH adhesin located at the tip of type 1 fimbriae. Inhibition of FimH-mediated adhesion has been identified as an efficient antibiotic-alternative strategy to potentially reduce E. coli-related infections. In this article we demonstrate that nanodiamond particles, covently modified with mannose moieties by a "click" chemistry approach, are able to efficiently inhibit E. coli type 1 fimbriae-mediated adhesion to eukaryotic cells with relative inhibitory potency (RIP) of as high as 9259 (bladder cell adhesion assay), which is unprecedented when compared with RIP values previously reported for alternate multivalent mannose-functionalized nanostructures designed to inhibit E. coli adhesion. Also remarkable is that these novel mannose-modified NDs reduce E. coli biofilm formation, a property previously not observed for multivalent glyco-nanoparticles and rarely demonstrated for other multivalent or monovalent mannose glycans. This work sets the stage for the further evaluation of these novel NDs as an anti-adhesive therapeutic strategy against E. coli-derived infections.
细菌附着在生物表面或医疗设备上,随后形成生物膜,这是临床环境中感染不断增加的一个来源。这些生物膜相关感染的很大一部分是由大肠杆菌引起的,大肠杆菌是一种主要的医院病原体,其主要粘附因子是位于 1 型菌毛顶端的 FimH 粘附素。抑制 FimH 介导的粘附已被确定为一种有效的抗生素替代策略,有可能减少大肠杆菌相关感染。在本文中,我们证明了通过“点击”化学方法用甘露糖修饰的纳米金刚石颗粒能够有效地抑制大肠杆菌 1 型菌毛介导的对真核细胞的粘附,相对抑制效力(RIP)高达 9259(膀胱细胞粘附试验),与以前报道的用于抑制大肠杆菌粘附的替代多价甘露糖功能化纳米结构的 RIP 值相比,这是前所未有的。同样值得注意的是,这些新型甘露糖修饰的 ND 减少了大肠杆菌生物膜的形成,这是以前多价糖纳米颗粒所没有观察到的,而且对于其他多价或单价甘露糖糖也很少有报道。这项工作为进一步评估这些新型 ND 作为一种针对大肠杆菌衍生感染的抗粘附治疗策略奠定了基础。