Fig. 2: A screen for targeted Mtb Alr inhibitors identifies benazepril.
From: Low-cost anti-mycobacterial drug discovery using engineered E. coli
a The TESEC Mtb Alr expression strain was induced with arabinose at high (107 nM) or low (102 nM) levels and treated with the 1280-compound Prestwick library at 0.1 mM. Growth was measured by OD after 8 h and the median of three biological replicates is plotted for each drug. Hit compounds inhibit the growth of low-Alr strains but not high-Alr strains, occupying the upper-left quadrant. b SSMD scores were used to assess the statistical significance of the high- and low-induction growth levels. Hits were selected with an OD differential of 0.2 and an SSMD greater than 5. c Growth measurements for selected hits in high Alr (colored bars) and low Alr (gray bars) expression. Data are presented as the mean and individual data points for three biological replicates. d Chemical-genetic growth profiles of the TESEC Mtb Alr expression strain treated with each drug of the Prestwick library at 0.1 mM and a range of arabinose induction levels. e Selected chemical-genetic growth profiles for candidate hit compounds. Both DCS and benazepril showed growth inhibition only at low induction levels. Amlexanox, in contrast, did not show reproducible induction-specific activity. Data are presented as the mean and the standard deviation of three replicates. Source data are provided as a Source Data file.
