The long-term goal of this project is to expand the range of therapies for bacterial infections that: 1) can effectively treat even antibiotic-resistan organisms; and 2) do not contribute to the further development of antibiotic resistance. This project will explore a new approach using photodynamic therapy for urinary tract infections in people who use catheters for medical purposes. Over a million cases of urinary tract infections are diagnosed each year in this population, and the repeated use of antibiotics to treat these infections is contributing to the spread of drug-resistant organisms. This new approach combines two common and inexpensive drugs (methylene blue, MB and potassium iodide, KI) that will be delivered to the bladder of infected patients and then will be activated by a fiber-opic light source introduced into the bladder. This newly discovered drug combination is synergistic and KI enhances killing by up to 1000-fold compared to the killing using light and MB alone. The light treatment should be applied almost immediately after drug treatment to spare the normal bladder tissue. This approach may enable the eradication of urinary tract infections without the use of antibiotics and without the potential to encourage development of additional treatment resistant in target organisms. Only initial bench studies have been done on the use of photodynamic therapy to treat urinary tract infections. Therefore, the specific aims of this projec are to show that the specific drug combination activated by light can effectively kill a range of bacteria that cause urinary tract infections, including those that are antibiotic-resistant; and tht this photodynamic therapy can be used to eradicate bacterial infections without causing significant damage to the bladder. In the first phase of this project studies will be done with an already-identified drug combination, testing it in bacterial cultures and in small animal models. I the second phase of the project, studies will be done to identify new second generation drug combinations and less expensive LED light sources in order to make treatment more effective and less expensive. Finally, an optimized treatment combination will be tested in a pig model, where the bladder is similar to a human bladder, to show that the photodynamic therapy can eradicate the same kind of bacteria that infect people who have urinary tract infections caused by catheter use.