کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3358879 1591794 2013 4 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
A role for 16S rRNA dimethyltransferase (ksgA) in intrinsic clarithromycin resistance in Mycobacterium tuberculosis
موضوعات مرتبط
علوم زیستی و بیوفناوری ایمنی شناسی و میکروب شناسی میکروبیولوژی و بیوتکنولوژی کاربردی
پیش نمایش صفحه اول مقاله
A role for 16S rRNA dimethyltransferase (ksgA) in intrinsic clarithromycin resistance in Mycobacterium tuberculosis
چکیده انگلیسی

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.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: International Journal of Antimicrobial Agents - Volume 41, Issue 6, June 2013, Pages 548–551
نویسندگان
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