Saranya PhunpruchSaradee WaritRungaroon SuksamranPamaree BillamasSarinya JaitrongPrasit PalittapongarnpimTherdsak PrammanananKing Mongkut's Institute of Technology LadkrabangThailand National Center for Genetic Engineering and BiotechnologyMahidol University2018-10-192018-10-192013-06-01International Journal of Antimicrobial Agents. Vol.41, No.6 (2013), 548-55118727913092485792-s2.0-84877712222https://repository.li.mahidol.ac.th/handle/20.500.14594/32315The emergence of extensively drug-resistant tuberculosis (XDR-TB) makes the control of tuberculosis (TB) difficult. As a result, there is an urgent need to develop new anti-TB drugs. Alternatively, drugs that have already been used in humans as anti-infectives and later found to have antitubercular activity might be useful as anti-TB drugs, particularly against drug-resistant TB. Clarithromycin (CLR), a 14-membered macrolide and protein synthesis inhibitor, has potent activity against most mycobacterial infections, except Mycobacterium tuberculosis. Mycobacterium tuberculosis is naturally resistant to CLR [minimum inhibitory concentration (MIC) of 8-16 μg/mL] owing to the presence of inducible erm methylase (ErmMT). With a view to gaining further insight into the mechanisms of innate CLR resistance in M. tuberculosis, CLR-susceptible M. tuberculosis H37Rv mutants were generated by transposon mutagenesis. One mutant, designated as Tn-196, was further investigated and it was found that ksgA (Rv1010) was inactivated by the transposon. The ksgA gene encodes a 16S rRNA adenine dimethyltransferase that methylates A1518 and A1519 (Escherichia coli numbering) of 16S rRNA and plays an important role in ribosome biogenesis. Complementation of the Tn-196 mutant with a wild-type ksgA gene restored the resistant phenotype (MIC of 8-16 μg/mL), corroborating the association of ksgA with intrinsic CLR resistance in M. tuberculosis. © 2013 Elsevier B.V. and the International Society of Chemotherapy.Mahidol UniversityMedicineArticleSCOPUS10.1016/j.ijantimicag.2013.02.011