Enzyme-Activated Nitric Oxide-Releasing Composite Material for Antibacterial Activity Against Escherichia coli

Bacterial infections occurring on medical devices are incredibly difficult to treat, highlighting the urgency for progress in developing antibiotics and antibacterial materials. This work describes the preparation of an antibacterial prodrug polymer composite material for use as an antibacterial coating for medical devices to prevent infections. Polyvinyl chloride and polyurethane films are prepared containing a bacterial nitroreductase enzyme-activated diazeniumdiolate that releases nitric oxide (NO), a known potent antimicrobial agent. Characterization of the surface of the composite materials by scanning electron microscopy (SEM) and energy-dispersive X-ray analysis (EDS) reveals that the surface of the materials is composed of high amounts of nitrogen due to incorporation of the NO donor compound, up to 13.2% nitrogen on the surface of the 2.5% w/v diazeniumdiolate composite. NO release from the composite films is observed only after metabolism by a bacterial nitroreductase enzyme isolated from E. coli, demonstrating the prodrug nature of the polymer composite materials. Antibacterial efficacy experiments resulted in up to a 66% reduction in E. coli after exposure to the diazeniumdiolate-composite materials. This work details the first illustration of an antibacterial enzyme-activated NO-releasing polymer, a material with potential application as a medical device coating to prevent device-associated infections and improve patient outcomes.