The C. elegans-based assays can advance drug discovery using model organisms and decrease the need for mammalian testing. Hits identified through our screens have indicated opportunities for “repurposing” (a drug already used in the clinic for other therapies) and we have identified several compounds that have the potential for being developed as antimicrobial agents. The evaluation of these hits for efficacy, toxicity and MOA are important parts of our work. In addition to the papers described above (under A. Personal Statement), these studies describe new chemotypes suitable for further development.

Select Publications

a) Kim W, Zhu W, Hendricks GL, Van Tyne D, Steele AD, Keohane CE, Fricke N, Conery AL, Shen S, Pan W, Lee K, Rajamuthiah R, Fuchs BB, Vlahovska PM, Wuest WM, Gilmore MS, Gao H, Ausubel FM, Mylonakis E. A new class of synthetic retinoid antibiotics effective against bacterial persisters. Nature 2018 Apr 5;556(7699):103-107. doi: 10.1038/nature26157. Epub 2018 Mar 28. PMID: 29590091.

b) Kim W, Steele AD, Zhu W; Csatary, EE; Fricke N; Dekarske MM, Jayamani E; Pan W, Kwon B, Sinitsa IF, Rosen JL, Conery AL, Fuchs BB, Vlahovska PM, Ausubel FM, Gao H, Wuest WM, Mylonakis E. Discovery and optimization of nTZDpa as an antibiotic effective against bacterial persisters. ACS Infect Dis 2018 Aug 28. doi: 10.1021/acsinfecdis.8b00161. PMID: 30132650

c) Tharmalingam N, Jayamani E, Rajamuthiah R, Castillo D, Fuchs BB, Kelso MJ, Mylonakis E. Activity of a novel protonophore against methicillin-resistant Staphylococcus aureus. Future Med Chem. 2017;9(12):1401-1411. PMID: 28771026. PMCID: PMC5941710

d) Johnston T, Van Tyne D, Chen RF, Fawzi NL, Kwon B, Kelso MJ, Gilmore MS, Mylonakis, E. Propyl-5-hydroxy-3-methyl-1-phenyl-1H-pyrazole-4-carbodithioate (HMPC): a new bacteriostatic agent against methicillin—resistant Staphylococcus aureus. Sci Rep 2018 May 4;8(1):7062. doi: 10.1038/s41598-018-25571-w. PMID: 29728636. PMCID: PMC5935714