Microbiology

In the Wuest lab, we use our chemical knowledge to study bacterial processes. Towards this goal, we possess hundreds of bacterial strains and have had research projects focusing extensively on bacterial pathogens such as Streptococcus mutans, Staphylococcus aureus, Acinetobacter baumannii, and Pseudomonas aeruginosa. Historically, we have used different classes of chemical compounds to interrogate biological systems.

As a lab focusing primarily on organic synthesis, our synthetic targets typically are of biological interest to us. Using our resources in-house and with collaborators, we have been able to perform target identification studies on narrow-spectrum antibiotics, explore bacterial iron-transport systems, and inhibit biofilm growth-specific development phases.

Furthermore, we have been engaged in a longstanding collaboration with the Minbiole Lab at Villanova University in Pennsylvania towards the development of novel disinfectants. Common antibacterial products contain simple quaternary ammonium compounds (QACs) that are losing their effectiveness in the home and helping to strengthen resistance as they spread through groundwater and soil. It is our goal to design smarter QACs that do not encourage resistance mechanisms and will degrade in nature to be harmless to our environment. Together, we have synthesized and analyzed hundreds of compounds that are active against bacterial pathogens. We also completed a detailed investigation that suggests the commonly accepted mechanisms of action and resistance for QACs are not the full story, which encourages us to continue to dive deeper into this field.

Publications
1.  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
2. Kaplan, A.R.; Musaev, D.G.; Wuest, W.M.* “Pyochelin Biosynthetic Metabolites Bind Iron and Promote Growth in Pseudomonas Demonstrating Siderophore-like Activity” ACS Infectious Diseases 2021 7, 544 DOI: 10.1021/acsinfecdis.0c00897
3.  Solinski, A.E.#; Koval, A.B.#; Brzozowski, R.S.#; Morrison, K.R.; Fraboni, A.J.; Carson, C.E.; Eshraghi A.R.; Zhou, G.; Quivey, R.G.; Voelz, V.A.; Buttaro, B.A.; Wuest. W.M.* “Diverted Total Synthesis of Carolacton-Inspired Analogs Yields Three Distinct Phenotypes in Streptococcus mutans Biofilms” J. Am. Chem. Soc. 2017 139, 7188. DOI: 10.1021/jacs.7b03879
4. Michaud, M.E.; Allen, R.A.; Morrison-Lewis. K.R.; Sanchez, C.A.; Minbiole, K.P.C.*; Post, S.J.*; Wuest, W.M.* “Quaternary Phosphonium Compound Unveiled as a Potent Disinfectant against Highly Resistant Acinetobacter baumannii Clinical Isolates” ACS Infectious Diseases 2022 8, 2307-2314 DOI: 10.1021/acsinfecdis.2c00382