Aberg Veronica, Fällman Erik, Axner Ove, Uhlin Bernt Eric, Hultgren Scott J, Almqvist Fredrik
Organic Chemistry, Umeå University, SE-90187 Umeå, Sweden.
Mol Biosyst. 2007 Mar;3(3):214-8. doi: 10.1039/b613441f. Epub 2007 Jan 19.
The infectious ability of uropathogenic Escherichia coli relies on adhesive fibers, termed pili or fimbriae, that are expressed on the bacterial surface. Pili are multi-protein structures that are formed via a highly preserved assembly and secretion system called the chaperone-usher pathway. We have earlier reported that small synthetic compounds, referred to as pilicides, disrupt both type 1 and P pilus biogenesis in E. coli. In this study, we show that the pilicides do not affect the structure, dynamics or function of the pilus rod. This was demonstrated by first suppressing the expression of P pili in E. coli by pilicide treatment and, next, measuring the biophysical properties of the pilus rod. The reduced abundance of pili was assessed with hemagglutination, atomic force microscopy and Western immunoblot analysis. The biodynamic properties of the pili fibers were determined by optical tweezers force measurements on individual pili and were found to be intact. The presented results establish a potential use of pilicides as chemical tools to study important biological processes e.g. adhesion, pilus biogenesis and the role of pili in infections and biofilm formation.
尿路致病性大肠杆菌的感染能力依赖于细菌表面表达的称为菌毛或纤毛的粘附纤维。菌毛是通过一种高度保守的组装和分泌系统形成的多蛋白结构，该系统称为伴侣-分泌途径。我们之前报道过，被称为菌毛抑制剂的小合成化合物会破坏大肠杆菌中1型菌毛和P菌毛的生物合成。在这项研究中，我们表明菌毛抑制剂不会影响菌毛杆的结构、动力学或功能。这首先通过菌毛抑制剂处理抑制大肠杆菌中P菌毛的表达，然后测量菌毛杆的生物物理特性得到了证明。通过血凝试验、原子力显微镜和Western免疫印迹分析评估菌毛丰度的降低。通过对单个菌毛进行光镊力测量来确定菌毛纤维的生物动力学特性，发现其是完整的。所呈现的结果确立了菌毛抑制剂作为化学工具在研究重要生物学过程（如粘附、菌毛生物合成以及菌毛在感染和生物膜形成中的作用）方面的潜在用途。
