Fig. 4: Studies to explore the cellular mechanism of action.

a A resistant mutant was isolated against 7, resistance was confirmed by looking at sensitivity over a concentration range compared to parental H37Rv for both 7 and the unrelated drug isoniazid. b Impact of TetON overexpression of either wild-type (WT) LysRS or mutant LysRS.491 on sensitivity to 8 ± anhydrotetracycline (ATc), for comparison the impact of 8 on H37Rv is also shown. For a, b, graphs are representative data from one of two independent experiments each run in triplicate presented as mean values ± standard deviation. c Metabolomic analysis of cells treated with three active and one inactive members of the LysRS inhibitor series (5× MIC) for 18 h. Metabolites related to the lysine biosynthetic pathway are shown. Drug concentrations were evaluated in triplicate per experiment, and the results are representative of at least two independent experiments. Data are depicted on a log₂ transformed ratio of ion intensity of metabolite abundance in treated vs untreated M. tuberculosis and displayed using the image generation program treeview (http://jtreeview.sourceforge.net/). Source data are provided as a Source Data file.