Chemical Biology

In addition to chemical synthesis, we desire to understand how our molecules exert their antimicrobial activity. We do this through in-house biological assays and collaborations with experts in the field. For example, promysalin’s mechanism of action and molecular target was probed with many different assays such as metal binding, resistance selection, and proteomics. In addition, our lab has expertise with molecules that perturb bacterial membranes and have used varies fluorometric and absorbance-based probes to understand how these molecules work. We can also study how a bacteria responds to a molecule by imaging biofilm and quantifying it along with other virulence factors. Together, these tools give us a deeper understanding of our molecules and help advance our knowledge of bacteria’s response to antimicrobial compounds.

Publications

1. Steele, A.D.; Keohane, C.E.; Knouse, K.W.; Rossiter, S.E.; Williams, S.J.; Wuest, W.M.* “Diverted Total Synthesis of Promysalin Analogs Demonstrates that an Iron-Binding Motif is Responsible for its Narrow-spectrum Antibacterial Activity” J. Am. Chem. Soc. 2016 138, 5833. DOI: 10.1021/jacs.6b03373

2. Solinski, A.E.; Scharnow, A.M.; Fraboni, A.J., Wuest, W.M.* “Synthetic Simplification of Carolacton Enables Chemical Genetic Studies in Streptococcus mutans” ACS Infectious Diseases 2019 5, 1480 DOI:10.1021/acsinfecdis.9b00213

3. Keohane, C.E.; Steele, A.D.; Fetzer, C.; Khowsathit, J.; Van Tyne, D.; Moynie, L.; Gilmore, M.S.; Karanicolas, J.; Sieber, S.A.; Wuest, W.M.* “Promysalin Elicits Species-Selective Inhibition of Pseudomonas aeruginosa by Targeting Succinate Dehydrogenase” J. Am. Chem. Soc. 2018 140, 1774 DOI: 10.1021/jacs.7b11212