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Whole genome sequence analysis of multidrug-resistant Mycobacterium tuberculosis Beijing isolates from an outbreak in Thailand

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Abstract

The Mycobacterium tuberculosis Beijing family is often associated with multidrug resistance and large outbreaks. Conventional genotyping study of a community outbreak of multidrug-resistant tuberculosis (MDR-TB) that occurred in Kanchanaburi Province, Thailand was carried out. The study revealed that the outbreak was clonal and the strain was identified as a member of Beijing family. Although, the outbreak isolates showed identical spoligotyping and mycobacterial interspersed repetitive units-variable number tandem repeats patterns, a discrepancy regarding ethambutol resistance was observed. In-depth characterization of the isolates through whole genome sequencing of the first and the last three isolates from our culture collection showed them to belong to principal genetic group 1, single nucleotide polymorphism (SNP) cluster group 2, sequence type 10. Compared with the M. tuberculosis H37Rv reference genome, 1242 SNPs were commonly found in all isolates. The genomes of these isolates were shown to be clonal and highly stable over a 5-year period and two or three unique SNPs were identified in each of the last three isolates. Genes known to be associated with drug resistance and their promoter regions, where applicable, were analyzed. The presence of low or no fitness cost mutations for drug resistance and an additional L731P SNP in the rpoB gene was observed in all isolates. These findings might account for the successful transmission of this MDR-TB strain.

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Acknowledgments

This work was jointly supported by Japan Science and Technology Agency (JST), National Science and Technology Development Agency (NSTDA), and Mahidol University Research Fund grants P-12-01777 and MU-PD_2014_03. AC was supported by a Chalermprakiat grant, Faculty of Medicine Siriraj Hospital, Mahidol University. SM was supported by a Siriraj Graduate Scholarship and Siriraj Graduate Thesis Scholarship.

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Authors and Affiliations

  1. Department of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Wanglang Road, Bangkok-Noi, Bangkok, 10700, Thailand

    Sanjib Mani Regmi, Angkana Chaiprasert, Olabisi Oluwabukola Coker & Iyarit Thaipisuttikul

  2. National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathum Thani, 12120, Thailand

    Supasak Kulawonganunchai, Sissades Tongsima, Therdsak Prammananan & Wasna Viratyosin

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  1. Sanjib Mani Regmi
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Correspondence to Angkana Chaiprasert.

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Regmi, S.M., Chaiprasert, A., Kulawonganunchai, S. et al. Whole genome sequence analysis of multidrug-resistant Mycobacterium tuberculosis Beijing isolates from an outbreak in Thailand. Mol Genet Genomics 290, 1933–1941 (2015). https://doi.org/10.1007/s00438-015-1048-0

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