Nanoscale Urinary Catheter Surface Modification to Enhance Bacterial Interference

描述（由申请人提供）：在美国，每年插入超过3000万根导尿管，导致超过100万例导管相关性尿路感染（CANTI）。名义上收购的CITTI的成本超过4.51亿美元/年。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，利用纳米级表面改性的导尿管表面作为一种手段，以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产生关于细菌与表面相互作用的有价值的见解。粘附微生物的导管相关生物膜加上分泌的多糖基质是CIMTI发病机制的核心。通过认识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形成以实现我们自己的目标。我们建议在导尿管上建立一个良性的、潜在保护性的植物群生物膜，将病原体从导尿管表面排除，从而预防尿路感染。在分子水平上驱动表面上生物膜形成的因素定义不清。特别是，配体呈递的模式和密度可能是细菌识别的重要组成部分。我们将在导尿管上进行表面配体的纳米图案化实验，以创建具有最佳保护能力的坚固耐用的生物膜。目的1是开发将甘露糖栓系到硅胶导管上的方法，从而促进E。coli 83972中表达甘露糖结合1型菌毛。目的二是证明提高E. coli 83972通过导管修饰提高了E. coli 83972，以阻止病原体粘附到导管表面。该项目的总体目标是创造一种具有优化的、保护性的E.大肠杆菌，这将适合于最终的临床试验。在此过程中，我们将获得有关细菌与表面相互作用的知识，这些知识将与整个医疗器械生物膜感染领域相关。创伤性脊柱炎是一个共同的问题，直接影响到许多人，并通过对我们的保健系统施加的重大财政负担间接影响到所有公民。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如何粘附在表面上，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.