Fig. 4: Identification of a QcrB inhibitor from an unbiased library. | Nature Communications

Fig. 4: Identification of a QcrB inhibitor from an unbiased library.

From: Reference-based chemical-genetic interaction profiling to elucidate small molecule mechanism of action in Mycobacterium tuberculosis

Fig. 4

a Structures of screening hit BRD4310 and a synthesized analog, BRD4310a, with improved activity. b The chemical-genetic interaction (CGI) profiles for BRD4310 tested in dose-response, with Dxr (red) and IspD (blue) hypomorphs highlighted. Wild-type (WT) H37Rv strains are highlighted in black. c Sensitization of cydA::Tn upon BRD4310a treatment. d Mutations in BRD4310a-resistant H37Rv mutants identified by whole-genome sequencing. e The transcriptional responses of respiration-related genes in H37Rv to BRD4310a exposure at 6 and 24 h are similar to those observed with Q203 exposure at 6 h. The color scale indicates differential regulation as log2-fold change (L2fc) of H37Rv with compound condition relative to time-matched vehicle controls. Upregulation is indicated in red, downregulation is in blue. Data are from two independent RNAseq experiments each with 3 replicates (n = 3). f BRD4310a triggers the depletion of ATP levels of Mtb grown in aerobic conditions; Q203 was used as a control. Data from three independent experiments are presented as the mean ± s.d. Source data are provided as a Source Data file.

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