ANTIFOULING AGENTS: FUNCTIONALIZATION OF SURFACES TO OBTAIN NOVEL MEDICAL DEVICES MATERIALS INHIBITING BIOFILM FORMATION

Vascular and urinary catheters are the most frequently used indwelling medical devices in the intensive care units and, in general, in medical wards. Despite drug/device combination products and antimicrobial therapies (including systemic antibiotic prophylaxis), device-related infections are difficult to eradicate and pose a severe threat to human health and excess of medical costs. The most important factor in the pathogenesis of catheter-related infections is the formation of an adherent functional heterogenic microbial consortium, embedded in a self-produced matrix of extracellular polymeric substance (EPS), called biofilm. Biofilm formation is an important cause of illness since the biofilm lifestyle is associated with the chronic nature of infections, the evasion to the host immune-response and the enhanced resistance to medical treatments. Indeed, after bacteria become established in a biofilm, the individual cells exhibit tolerance up to 1000 folds more than their planktonic counterparts and often do not respond to antimicrobial agents. Given the less innovation in the discovery and the development of novel antimicrobial compounds over the past 20 years and the alarming incidence of recalcitrant device-related infections, the need for an innovative anti-infective material is becoming imperative. Bio-inspired molecules able to disarm microorganisms without affecting their existence, offer an elegant way to interfere with specific key-steps that orchestrate biofilm formation sidestepping drug resistance and extending the efficacy of the current antimicrobial agents. The general goal of this applied research project is to develop an innovative antibiotic-free functionalized material able to hold out against infections of vascular and urinary catheters by means of compounds with known anti-biofilm activities. Initially, it was necessary to prepare chemically modified anti-biofilm derivatives related to zosteric acid, a natural preventive compound against device-related infections, in order to improve their affinity and retention on a surface. The antifouling performance was tested against Escherichia coli, selected as the model system for bacterial infections. Furthermore, affinity purification experiments of proteins from E. coli extracts allowed the identification of targets directly interacting with these antibiofilm compounds. Then, the methodology for grafting the modified agents to materials was developed and optimized. The new materials efficacy and their ability to increase the susceptibility of microorganisms to traditional antibiotics were tested in biofilm reactors using chemical and molecular techniques combined with microscopic investigations.