Department of Chemistry, University of Houston, Houston, Texas 77204, United States.
College of Materials Science and Engineering, Qingdao University of Science and Technology, Qingdao, Shandong 266042, China.
ACS Appl Mater Interfaces. 2020 May 13;12(19):21300-21310. doi: 10.1021/acsami.9b17868. Epub 2020 Feb 28.
Prevention of catheter-associated urinary tract infection (CAUTI) over long-term usage of urinary catheters remains a great challenge. Bacterial interference using nonpathogenic bacteria, such as 83972, have been investigated in many pilot-scale clinical studies as a potentially nonantibiotic based strategy for CAUTI prevention. We have demonstrated that preforming a dense and stable biofilm of the nonpathogenic greatly enhances their capability to prevent pathogen colonization. Such nonpathogenic biofilms were formed by 83972 expressing type 1 fimbriae () on mannoside-presenting surfaces. In this work, we report the synthesis of a series of mannoside derivatives with a wide range of binding affinities, all being equipped with a handle for covalent attachment to silicone surfaces. We established a high-throughput competitive assay based on mannoside-modified particles and flow-cytometry to directly measure the binding affinity between the mannoside ligands and 83972. We demonstrated that the bacterial adhesion and biofilm formation were strongly correlated to the binding affinity of the immobilized mannoside ligands. Mass spectrometry based proteomic analysis indicated a substantial difference in the proteome of the extracellular polymeric substance (EPS) secreted by biofilms on different mannoside surfaces, which might be related to the biofilm stability.
预防长期留置导尿管相关尿路感染（CAUTI）仍然是一个巨大的挑战。使用非致病性细菌（如 83972）进行细菌干扰已在许多试点临床研究中进行了研究，作为一种潜在的非抗生素策略来预防 CAUTI。我们已经证明，形成非致病性 83972 的密集且稳定的生物膜极大地增强了它们预防病原体定植的能力。这种非致病性生物膜是由在甘露糖存在的表面上表达 I 型菌毛的 83972 形成的。在这项工作中，我们报告了一系列具有广泛结合亲和力的甘露糖衍生物的合成，所有这些衍生物都配备了用于与硅树脂表面共价连接的接头。我们建立了一种基于甘露糖修饰颗粒和流式细胞术的高通量竞争测定法，以直接测量甘露糖配体与 83972 之间的结合亲和力。我们证明了细菌粘附和生物膜形成与固定化甘露糖配体的结合亲和力强烈相关。基于质谱的蛋白质组学分析表明，在不同甘露糖表面上形成的生物膜分泌的细胞外聚合物物质（EPS）的蛋白质组有很大差异，这可能与生物膜稳定性有关。
