Synthetic ligands that disrupt bacterial quorum sensing pathways and outcomes

ORGN 539

Helen E. Blackwell, blackwell@chem.wisc.edu, Department of Chemistry, University of Wisconsin-Madison, 1101 University Avenue, Madison, WI 53706-1322
We are developing chemical tools that attenuate cell-cell communication pathways in bacteria. Bacteria communicate using small organic molecules and peptides to monitor their population densities in a process called “quorum sensing.” At high cell densities, bacteria use this signaling network to switch from an isolated, nomadic existence to that of a multicellular community. This lifestyle switch is significant; only in groups will pathogenic bacteria turn on virulence pathways and grow into drug-impervious communities called biofilms that are the basis of myriad chronic infections. In turn, certain symbiotic bacteria will only colonize their hosts and initiate beneficial behaviors at high population densities. The molecular mechanisms of these processes are only now being delineated. Our research is focused broadly on the design of non-native ligands that can intercept quorum sensing and provide new insights into its role in host/microbe interactions. This talk will introduce our research approach and highlight recent results.