Structure activity relationship of zosteric acid analogues as inhibitors of biofilm formation by Escherichia coli

Biofilm is defined as a complex microbial community characterized by adhesion to a solid surface and by production of a matrix, which surrounds the bacterial cells and includes extracellular polysaccharides (EPS), proteins and DNA. Biofilm plays a pivotal role in healthcare-associated infections, especially those related to the implant of medical devices, such as vascular and urinary catheters and orthopedic implants. Attempt to use conventional antibiotics to retard the formation of bacterial films on implanted medical devices suffer from the problem of the emergence and increasing prevalence of microbial strains in form of biofilm that are resistant to available antimicrobial-based therapies. [1] The new approach consists in using sublethal doses of bio-inspired molecules to interfere with the key-steps that orchestrate biofilm formation (like surface sensing process and/or cell-to-cell signalling pathways), thus infection cascade might be hampered. In addition, as these approaches do not directly kill cells or prevent their growth, there is presumably less evolutionary pressure for the development of resistance than with traditional antimicrobial agents. In this contest, zosteric acid or p-(sulfo-oxy) cinnamic acid, a secondary metabolite produced by the seagrass Zostera marina, might be suitable for implementation as a preventive or integrative approach against device-related infections. In this project supported by Cariplo Fundation a series of zosteric acid derivatives was synthesized and tested as inhibitors of biofilm formation by Escherichia coli. The results will be reported in the poster.