Design and synthesis of non-native ligands for the interception of quorum sensing in Gram-negative bacteria: New methods to attenuate pathogenesis and symbiosis

ORGN 632

Grant D. Geske, geske@chem.wisc.edu, Jennifer C. O'Neill, oneill2@wisc.edu, Qi Lin, Margrith E. Mattmann, mattmann@wisc.edu, and Helen E. Blackwell, blackwell@chem.wisc.edu. Department of Chemistry, University of Wisconsin-Madison, 1101 University Avenue, Madison, WI 53706-1322
This poster will report the development of synthetic ligands that can modulate cell-cell communication pathways in Gram-negative bacteria. The ability of bacteria to communicate with themselves and function as a group is central in both pathogenesis and symbiosis. Gram-negative bacteria communicate using small molecule signals and their cognate protein receptors to monitor their local population density in a phenomenon known as ‘quorum sensing'. The development of methods to attenuate bacterial quorum sensing represents a new anti-infective strategy. We have designed and synthesized a library of synthetic ligands using computational, synthetic organic, and combinatorial chemistry techniques. Evaluation of this library in a series of different Gram-negative reporter strains revealed a set of potent quorum sensing antagonists and agonists. This poster will present our on-going studies on these compounds, including pertinent in vitro and in vivo assays.