Extended Data Fig. 4: Validation of predicted DNA gyrase inhibitors.
From: Large-scale chemical–genetics yields new M. tuberculosis inhibitor classes
a, Actual compound performance of predicted DNA gyrase inhibitors in an agarose gel-based in vitro assay of DNA gyrase supercoiling inhibition. The ratio of imaged pixel intensities (Supplementary Fig. 1a–l) for supercoiled and relaxed bands was indicative of inhibition, shown by the ciprofloxacin control. Eight of the twenty-seven compounds with the greatest effect sizes that showed statistically significant (P < 0.05, two-sided Wald test) inhibition are shown. Open circles show the independent samples (n = 23 for ciprofloxacin and novobiocin, n = 2 for all other conditions); filled circles indicate the mean pixel intensity ratio; error bars denote the 95% confidence interval of the mean. b, Agarose gel showing increasing inhibition of Mtb DNA gyrase supercoiling activity with increasing tryptanthrin concentration. DNA gyrase catalyses supercoiling of pBR322; inhibitors prevent the accumulation of supercoiled gel bands. This experiment was repeated independently once with similar results. The uncropped version is shown in Supplementary Fig. 1m.
