Elucidating the Molecular Mechanisms of Action and Resistance of Microbes to Anti-biofilm Lactam Technology

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Delivering hygiene solutions around the home and in diverse commercial settings is increasingly problematic, particularly where surfaces are continuously challenged by microbial contamination and particularly by biofilm formation. This problem is usually addressed using traditional biocidal antimicrobials which include heavy metals and quaternary ammonium compounds, however these present environmental and toxicological hazards and may contribute to the emergence of antimicrobial resistance. In nature, the red seaweed Delisea pulchra avoids contamination and infection by producing furanones that have anti-biofilm properties and block certain bacterial quorum sensing (QS) pathways involved in biofilm development. Unilever has developed a library of bioinspired lactams based on these furanone structures that have been shown to have anti-biofilm properties and an overall 'greener' profile. Data from a previous Unilever/Nottingham collaboration suggests that lactams exhibit multiple mechanisms of action and interact with different molecular targets in different bacterial species. This project will investigate the major putative lactam target in Staphylococcus aureus and other bacteria, focussing on elucidating the mode of action and whether lactam resistance is selected following prolonged exposure to specific lactams.