Bacteria can utilize chemical signals to coordinate the expression of group-beneficial behaviors in a mode of cell-cell communication called quorum sensing (QS). Once a quorate population of bacteria is achieved in a given environment, bacteria will work together as a group to initiate behaviors that are impossible as individual cells. The discovery that QS controls the production of virulence factors and biofilm formation in many common human pathogens has driven an explosion of research aimed at both deepening our basic understanding of these regulatory networks and developing chemical agents that can modulate QS signaling. The inherently chemical nature of QS makes studying these pathways with small molecule tools a complementary approach to traditional microbiology techniques. In fact, chemical tools are beginning to yield new insights into QS regulation and provide new strategies to inhibit QS. In this presentation, I will outline our general research approach to the design of synthetic ligands capable of blocking or activating QS in a range of Gram-negative and Gram-positive bacteria. Recent examples of how we have used these ligands to reveal new knowledge of QS biology will be highlighted.
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