Atrans-translation inhibitor killsMycobacterium tuberculosisby targeting ribosomal protein bL12

New antibiotics with novel mechanisms of action are needed to treat infections by multidrug-resistant strains ofMycobacterium tuberculosis. Here, we show that KKL-1005, an anti-tubercular triazole-based molecule, binds to ribosomal protein bL12 and specifically inhibits thetrans-translation ribosome rescue pathway, a process essential for the survival ofM. tuberculosis.Our data demonstrate that KKL-1005 binds to the N terminal domain of bL12, bothin vitroand in bacterial cells, and specifically inhibitstrans-translation and not normal translation. These results suggest that tmRNA-SmpB interacts with bL12 differently from tRNA, and raise the possibility of developing antibiotics targeting bL12.