Genetic characterisation of a whiB7 mutant of a Mycobacterium tuberculosis clinical strain

Saradee Warit; Saranya Phunpruch; Chaitas Jityam; Sarinya Jaitrong; Pamaree Billamas; Angkana Chaiprasert; Prasit Palittapongarnpim; Therdsak Prammananan

doi:10.1016/j.jgar.2015.07.004

Genetic characterisation of a whiB7 mutant of a Mycobacterium tuberculosis clinical strain

J Glob Antimicrob Resist. 2015 Dec;3(4):262-266. doi: 10.1016/j.jgar.2015.07.004. Epub 2015 Aug 11.

Authors

Saradee Warit¹, Saranya Phunpruch², Chaitas Jityam³, Sarinya Jaitrong¹, Pamaree Billamas¹, Angkana Chaiprasert⁴, Prasit Palittapongarnpim⁵, Therdsak Prammananan⁶

Affiliations

¹ Tuberculosis Research Laboratory, National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), Thailand Science Park, Pathum Thani 12120, Thailand.
² Department of Biology, Faculty of Science, King Mongkut's Institute of Technology Ladkrabang, Bangkok 10520, Thailand; Bioenergy Research Unit, Faculty of Science, King Mongkut's Institute of Technology Ladkrabang, Bangkok 10520, Thailand.
³ Department of Biology, Faculty of Science, King Mongkut's Institute of Technology Ladkrabang, Bangkok 10520, Thailand.
⁴ Department of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
⁵ Tuberculosis Research Laboratory, National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), Thailand Science Park, Pathum Thani 12120, Thailand; Department of Microbiology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand.
⁶ Tuberculosis Research Laboratory, National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), Thailand Science Park, Pathum Thani 12120, Thailand. Electronic address: therdsak@biotec.or.th.

PMID: 27842870
DOI: 10.1016/j.jgar.2015.07.004

Abstract

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.

Keywords: Macrolide; Methyltransferase; Mycobacterium; Resistance mechanism.