Description:

Bacterial biofilms have been estimated to cost society in excess of $200 billion/yr, affecting everything from human health to water purification and are increasingly resistant to antibiotic treatment and responsible for persistent infections. Our group looks to Nature for inspiring chemical scaffolds and identifies promising candidates that perturb bacterial biofilms. The talk will highlight two projects from hypotheses conceptualization to synthesis and evaluation of each class of analogs to utilizing each set of molecules as chemical probes to better understand the chemical biology of bacterial biofilms.

Species-specific, “narrow-spectrum” antibiotics is of potential interest to medical and environmental communities as these compounds can serve as novel therapeutics and chemical probes. Promysalin, a secondary metabolite of P. putida isolated from the rhizosphere microbiome, possesses unique species-specific activity against a range of Pseudomonads. We have completed the first total synthesis of the natural product, established the relative and absolute stereochemistry, and identified previously unknown anti-virulence properties.

Broad-spectrum antibiofilm agents are of great need and of significant interest to industrial and healthcare partners. Inspired by reports indicating that polyamine norspermidine possessed interesting antibiofilm activity, our group expanded these findings to a class of quaternary ammonium compounds (QAC). We have synthesized and evaluated over 200 synthetic analogs and identified some of the most potent biofilm-eradicating compounds to date. Furthermore, we utilized these tool compounds to better understand how QAC-resistance protects pathogenic bacteria from society’s most ubiquitous antiseptics (i.e. Lysol).