Nanoscale Urinary Catheter Surface Modification to Enhance Bacterial Interference

描述（由申请人提供）：在美国，每年有超过3000万的导尿管被插入，导致超过100万的导尿管相关性尿路感染（CAUTI）。医院获得性CAUTI的费用每年超过4.51亿美元。然而，有效的预防策略是有限的。我们提出了一种创新的方法，利用纳米级表面修饰的尿导管表面作为一种手段，鼓励形成一个保护性的生物膜，干扰导管定植的病原体。此外，该项目将在分子水平上对细菌与表面的相互作用产生有价值的见解。附着生物的导管相关生物膜加上分泌的多糖基质是CAUTI发病机制的核心。通过认识到生物膜形成在这种疾病发病中的作用，我们可以操纵生物膜的形成来实现我们自己的目标。我们建议在导尿管上建立一层良性的、潜在的保护性菌群生物膜，将病原体从导尿管表面排除，从而预防CAUTI。在分子水平上驱动表面生物膜形成的因素定义不清。特别是，配体呈现的模式和密度可能是细菌识别的重要组成部分。我们将对尿导管表面配体的纳米图案进行实验，以创造一种具有最佳保护能力的坚固耐用的生物膜。目的1是开发将甘露糖拴在硅胶导管上的方法，从而促进表达甘露糖结合型1型菌毛的大肠杆菌83972的粘附。目的2：通过导管修饰增强大肠杆菌83972的表面粘附，提高大肠杆菌83972阻断病原菌粘附导管表面的能力。该项目的总体目标是制造一种具有优化的保护性大肠杆菌生物膜的导尿管，该生物膜将适用于最终的临床试验。在这个过程中，我们将获得关于细菌与表面的相互作用的知识，这将与整个医疗设备的生物膜感染领域相关。CAUTI是一个普遍的问题，通过对我们的医疗保健系统施加重大的经济负担，直接和间接地影响到许多人和所有公民。我们希望开发一种带有良性细菌保护涂层的导尿管，以阻止有害细菌感染导尿管。通过这个项目，我们将更多地了解细菌是如何附着在表面的，这些知识可以指导未来预防医疗设备感染的策略。

DESCRIPTION (provided by applicant): Over 30 million urinary catheters are inserted per year in the United States, resulting in over 1 million catheter-associated urinary tract infections (CAUTI). The costs of nosocomially- acquired CAUTI are in excess of $451 million dollars/year. However, effective preventative strategies for CAUTI are limited. We propose an innovative approach utilizing nanoscale surface modification of the urinary catheter surface as a means to encourage formation of a protective biofilm that interferes with catheter colonization by pathogens. In addition, this project will yield valuable insights about the interaction of bacteria with surfaces on a molecular level. The catheter-associated biofilm of adherent organisms plus secreted polysaccharide matrix is central to the pathogenesis of CAUTI. By recognizing the role of biofilm formation in onset of this illness, we can manipulate biofilm formation to achieve our own goals. We propose that establishing a biofilm of benign, potentially protective flora on the urinary catheter will exclude pathogens from the catheter surface and thus prevent CAUTI. The factors that drive biofilm formation on surfaces on a molecular level are poorly defined. In particular, the pattern and density of ligand presentation may be essential components in bacterial recognition. We will experiment with nanopatterning of surface ligands on the urinary catheter in order to create a robust and durable biofilm with optimal protective capability. Aim 1 is to develop methodology to tether mannose to silicone catheters and thus promote adherence of E. coli 83972 expressing mannose-binding type 1 fimbriae. Aim 2 is to demonstrate that enhancing surface adherence of E. coli 83972 through catheter modification improves the ability of E. coli 83972 to block pathogen adherence to the catheter surface. The overall goal of this project is to create a urinary catheter with an optimized, protective biofilm of E. coli that will be suitable for eventual clinical trials. In the process, we will gain knowledge about the interaction of bacteria with surfaces that will be relevant to the entire field of biofilm infections of medical devices. CAUTI is a common problem that affects many persons directly and all citizens indirectly through the significant financial burden imposed upon our health care system. We hope to develop a urinary catheter with a protective coating of benign bacteria that will discourage harmful bacteria from infecting the catheter. Through this project we will learn more about how bacteria stick to surfaces, and this knowledge can guide future strategies to prevent infections of medical devices.