Surface-attached molecules control Staphylococcus aureus quorum sensing and biofilm development

Bacteria use a process called quorum sensing to communicate and orchestrate collective behaviours, including virulence factor secretion and biofilm formation. Quorum sensing relies on the production, release, accumulation and population-wide detection of signal molecules called autoinducers. Here, we develop concepts to coat surfaces with quorum-sensing-manipulation molecules as a method to control collective behaviours. We probe this strategy using Staphylococcus aureus. Pro- and anti-quorum-sensing molecules can be covalently attached to surfaces using click chemistry, where they retain their abilities to influence bacterial behaviours. We investigate key features of the compounds, linkers and surfaces necessary to appropriately position molecules to interact with cognate receptors and the ability of modified surfaces to resist long-term storage, repeated infections, host plasma components and flow-generated stresses. Our studies highlight how this surface approach can be used to make colonization-resistant materials against S. aureus and other pathogens and how the approach can be adapted to promote beneficial behaviours of bacteria on surfaces. Covalent attachment of quorum-modulating peptides to surfaces can regulate Staphyloccocus aureus biofilm formation.