Abstract: A major hurdle in the treatment of bacterial infections is the rapid emergence of microbial resistance to antibiotics. Bacteria communicate using specific chemical molecules called ‘autoinducers’ to exhibit virulence that includes the formation of biofilms. As bacterial cells divide, the concentration of autoinducers in the environment increases proportionately. When autoinducers reach a threshold concentration, they begin to diffuse away and bind to the receptors of neighboring bacteria. This process helps bacteria to keep a census count of their nearest neighbors (quorum sensing), which induces them to cluster and change their lifestyle to a communal mode, paving the way to the formation, development and maturation of biofilms. Bacterial infections are very difficult to treat in this biofilm mode because a thick polysaccharide matrix encapsulates bacteria, protecting them from antibiotic attack. During the first half of my talk, I will discuss couple of examples from past research where chemical mutagenesis was used to shed light on the structure and function of enzymes that are pharmacological targets. In the second half of my talk, I will discuss our current work at Skidmore on developing chemical tools to understand substrate specificity of an enzyme that makes ‘autoinducers’ in Pseudomonas aeruginosa bacteria. The knowledge gained from this work will be utilized to design small molecules that curb the ability of bacteria to form biofilms. Molecules that interrupt interbacterial communication have the potential to become the next generation of antibiotics to treat bacterial infections in the future.