PRJNA522257
Mycobacterium tuberculosis
1H-benzo[d]imidazole derivatives exhibit antitubercular activity in vitro as well as in vivo in human monocyte-derived macrophages in a nanomolar range of concentrations and are not toxic for human cells. The mode of action of 5-Bromo-2-(2-cyclohexylethyl)-1H-benzo[d]imidazole (EJMCh4) and 2-(2-cyclohexylethyl)-5,6-dimethyl-1H-benzo[d]imidazole (EJMCh6) compounds was identified by selection of resistant Mycobacterium tuberculosis mutants followed by whole genome sequencing as well as observed inhibition of mycolylation of arabinogalactan and synthesis of TDM indicated MmpL3 as a molecular target for their antitubercular activity.Bacterial strains:1. Mycobacterium tuberculosis H37Rv strain, IBMPAN stock2. 4/1 MmpL3 (V285A) mutant selected on EJMCh4 of Mycobacterium tuberculosis H37Rv strain, IBMPAN3. 4/3 MmpL3 (V195A) mutant selected on EJMCh4 of Mycobacterium tuberculosis H37Rv strain, IBMPAN4. 6A MmpL3 (V684A) mutant selected on EJMCh6 of Mycobacterium tuberculosis H37Rv strain, IBMPAN5. 6B MmpL3 (V240A) mutant selected on EJMCh6 of Mycobacterium tuberculosis H37Rv strain, IBMPAN6. 6C MmpL3 (G253E) mutant selected on EJMCh6 of Mycobacterium tuberculosis H37Rv strain, IBMPAN