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Small Molecules Disrupting Bacterial Cell Membranes

Antibiotic resistance continues to be an increasingly important issue to combat as bacteria develop new mechanisms of resistance and current antibiotics become less effective. We have synthesized/studied small molecules and related analogs, some of which have been made in collaboration with the Mylonakis lab group at Brown University. These molecules have been shown to kill bacteria through disruption of bacterial membranes, specifically in methicillin-resistant Staphylococcus aureus (MRSA). Investigation is ongoing regarding the mechanisms of action of these molecules and their interactions with bacterial membranes.

Kim, W.; Steele, A.D.; Zhu, W.; Csatary, E.E.; Fricke, N.; Dekarske, M.M.; Jayamani, E.; Pan, W.; Kwon, B.; Sinitsa, I.F.; Rosen, J.; Conery, A.L.; Fuchs, B.B.; Vlahovska, P.M.; Ausubel, F.M.; Gao, H.; Wuest, W.M.*; Mylonakis, E. “Discovery and Optimization of nTZDpa as an Antibiotic Effective Against Bacterial Persisters” ACS Infectious Diseases 2018 4, 1540 DOI: 10.1021/acsinfecdis.8b00161

Kim, W.; Zhu, W.; Hendricks, G.L.; Van Tyne, D.; Steele, A.D.; Keohane, C.E.; Fricke, N.; Conery, A.L.; Shen, S.; Pan, W.; Lee, K.; Rajamuthiah, R.; Fuchs, B.B.; Vlahovska, P.M.; Wuest, W.M.; Gilmore, M.S.; Gao, H.; Ausubel, F.M.; Mylonakis, E. “A new class of synthetic retinoid antibiotics effective against bacterial persisters” Nature 2018 556, 103.  DOI: 10.1038/nature26157