Nanoscale Urinary Catheter Surface Modification to Enhance Bacterial Interference

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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.