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Author: search.filters.author.Palittapongarnpim, PrasitSubject: search.filters.subject.Methyltransferase

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    Item type:Publication,
    Genetic characterisation of a whiB7 mutant of a Mycobacterium tuberculosis clinical strain
    (2015-12-01)
    Warit, Saradee
    ;
    Phunpruch, Saranya
    ;
    Jityam, Chaitas
    ;
    Jaitrong, Sarinya
    ;
    Billamas, Pamaree
    Mycobacterium tuberculosis is naturally resistant to clarithromycin (CLR). The genes Rv3197A (whiB7) and Rv1988 (ermMT) have been shown to be involved in the resistant phenotype. In this study, a CLR-susceptible M. tuberculosis clinical strain was identified, designated as DS3214, and the nucleotide sequences and expression profiles of whiB7 and ermMT were investigated. The results revealed that strain DS3214 contained a one nucleotide deletion in whiB7, leading to a truncated peptide. Expression of whiB7 was low, whereas comparable expression of ermMT was determined compared with the reference strain M. tuberculosis H37Rv. Overexpression of the mutant whiB7 in M. tuberculosis H37Ra did not increase the minimum inhibitory concentration (MIC) to CLR or kanamycin, indicating the defect of the mutant WhiB7. The CLR-susceptible M. tuberculosis clinical strain, whose whiB7 is naturally mutated, was first described in this study and whiB7 has been shown to play a role in the CLR-susceptible phenotype.
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    A role for 16S rRNA dimethyltransferase (ksgA) in intrinsic clarithromycin resistance in Mycobacterium tuberculosis
    (2013-06-01)
    Phunpruch, Saranya
    ;
    Warit, Saradee
    ;
    Suksamran, Rungaroon
    ;
    Billamas, Pamaree
    ;
    Jaitrong, Sarinya
    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.