Publication: A role for 16S rRNA dimethyltransferase (ksgA) in intrinsic clarithromycin resistance in Mycobacterium tuberculosis
Issued Date
2013-06-01
Resource Type
ISSN
18727913
09248579
09248579
Other identifier(s)
2-s2.0-84877712222
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Mahidol University
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SCOPUS
Bibliographic Citation
International Journal of Antimicrobial Agents. Vol.41, No.6 (2013), 548-551
Suggested Citation
Saranya Phunpruch, Saradee Warit, Rungaroon Suksamran, Pamaree Billamas, Sarinya Jaitrong, Prasit Palittapongarnpim, Therdsak Prammananan A role for 16S rRNA dimethyltransferase (ksgA) in intrinsic clarithromycin resistance in Mycobacterium tuberculosis. International Journal of Antimicrobial Agents. Vol.41, No.6 (2013), 548-551. doi:10.1016/j.ijantimicag.2013.02.011 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/32315
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Title
A role for 16S rRNA dimethyltransferase (ksgA) in intrinsic clarithromycin resistance in Mycobacterium tuberculosis
Abstract
The 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.