(425e) Probing Cell Signaling Processes Via Biofunctionalized Mems Devices

Traditional screens for antimicrobials target processes critical to the pathogen's survival. Initial screens were simple and targeted specific pathogens ? a successful agent killed or inhibited growth at a low concentration. As the molecular details of drug action became known, screens targeted specific cellular components; these are most prevalent today. While amenable to high throughput, these screens do not probe populations nor target pathogenic phenotype. A hallmark of bacterial quorum sensing is the coordinated behavior of the population ? we hypothesize that population-based behavior will provide the most fertile ground from which next generation antimicrobials will emerge. Indeed, evidence is mounting linking the interruption of quorum sensing with the prevention of biofilm formation, a population phenotype responsible for survival of bacterial infections. This has refined the search for new antimicrobials and this population-based approach is now ripe for high-throughput analysis and combinatorial chemistry. The inhibition of biofilm formation has already been adapted by Wood and co-workers for high-throughput. This presentation will describe efforts to construct next generation devices that are "biofunctionalized" after manufacturing and packaging so that the labile nature of the biological components is accomodated. High content screening focused on population-based behavior is developed, based on a reconstruction of the biosynthesis pathway for a bacterial autoinducer, AI-2 and the incorporation of AI-2 responding reporter cells.