Fig. 3: Mechanism of action (MOA) assignments from the GSK set.

a Perturbagen Class (PCL) MOA predictions for GlaxoSmithKline (GSK) set. b Distribution of high-confidence PCL MOA assignments. c MOA-specific sensitization of strains in PCL clusters from respiration inhibitors. y-axis = mean strain standardized growth rate (sGR) across all conditions in the PCL cluster, x-axis = average strain rank. QcrB:#25 has 29 chemical-genetic interaction (CGI) profiles from 4 unique compounds; Phenazine-like:#3 has 24 CGI profiles from 4 unique compounds. Cytochrome bcc components are highlighted in blue, isoprenoid synthetic enzymes in solid red, open red circles show additional strains linked to menaquinone and heme synthesis, solid black circles are wild-type controls, and the rest of the hypomorphs are gray circles. d Confirmation of activity of predicted novel QcrB inhibitors. Heatmap of minimum inhibitory concentration (MIC) shifts against cydA::Tn and QcrB A317T mutants relative to wild-type (WT) H37Rv. PCL predictions shown in column 1. In column 2, compounds with MIC-shift-based confirmation of QcrB MOA in green; red indicates MIC shifts do not support QcrB as the target. Column 4 shows the scaffold class: napthalene carboximides (NC); triazolothiadiazoles (TTDZ); diphenylamines (DPA); anilopyridines (2-AP). In columns 5-7, the log2-fold change (L2fc) in MIC for the two mutants relative to the wild-type MIC is shown with blue showing sensitization and red showing resistance, along with the wild-type MIC. MIC values are curve fits to average of 2 replicates. e–h Scaffolds of clusters of novel respiration inhibitors. e NC inhibitors of QcrB. f TTDZ inhibitors of QcrB. g 2-APs displaying phenazine-like activity. h DPAs displaying phenazine-like activity. Source data are provided as a Source Data file.