Identification of MRSA Inhibitors by C. elegans Screening

The five compounds: (4,4′,4″-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol, PPT; (1S,2S)-2-[2-[[3-(1H-benzimidazol-2-yl)propyl]methylamino]ethyl]-6-fluoro-1,2,3,4-tetrahydro-1-(1-methylethyl)-2- naphthalenyl cyclopropanecarboxylate dihydrochloride, NNC; 4,5,6,7-tetrabromobenzotriazole, TBB; 3-[2-[2-chloro-4-[3-(2,6-dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methoxy]phenyl] ethenyl] benzoic acid, GW4064; and N-(cyclopropylmethoxy)-3,4,5-trifluoro-2-[(4-iodo-2-methylphenyl)amino] benzamide, PD198306) were purchased from Tocris Bioscience at the following levels of purity: PPT: >99.7%, NNC: >98%, TBB: >99%, GW4064: >97%, and PD198306: 98.8%. These compounds are members of a set of 185 hits identified previously in a C. elegans–MRSA-MW2 screen of 82,000 synthetic, low molecular weight compounds that block the ability of MRSA to kill nematodes [5 (link),9 (link)]. Hits were identified based on Z-scores. Z-scores are calculated from the ratio of alive versus dead worms after treatment with test compounds and represents the number of standard deviations (SD) the test compound differs from the mean using the formula Z = (x − μ)/σ; where x is the raw sample score, μ is the mean of the population and σ is the standard deviation of the population. Samples with Z > 2σ are considered hits [5 (link)].