Open Access
BMC Genomics, volume 19, issue 1, publication number 762
New epidemic cluster of pre-extensively drug resistant isolates of Mycobacterium tuberculosis Ural family emerging in Eastern Europe
2
Irkutsk State Medical Academy of Continuing Education, Irkutsk, Russia
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6
Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, USA
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Publication type: Journal Article
Publication date: 2018-10-22
PubMed ID:
30348088
Genetics
Biotechnology
Abstract
Ural genetic family is a part of the Euro-American lineage of Mycobacterium tuberculosis and is endemic in Northern Eurasia (former Soviet Union [FSU]). These strains were long described as drug susceptible and of low virulence, but recent studies reported an increasing circulation of the multidrug-resistant (MDR) and extensively drug-resistant (XDR) Ural strains. Here, we analyzed all publicly available whole genome sequence data of Ural genotype isolates, in order to elucidate their phylogenomic diversity with a special focus on MDR and potentially epidemic clones. A total of 149 M. tuberculosis genomes of Ural isolates from FSU countries were mined from the GMTV database and TB-ARC project. We identified 6002 variable amino acid positions that were assessed for functional significance and used to build ML, NJ trees and for Bayesian TMRCA estimation. Three robust monophyletic clades were identified: Clade A (31 isolates from Russia, Belarus, Moldova), Clade B (52 isolates from Russia), and Clade C (37 isolates from Moldova, 2 from Belarus). Clade C was significantly associated with XDR or pre-XDR status compared to the pooled Clades A and B (33/39 versus 5/83, P < 0.0001). Time of origin was estimated for Clade A at 77.7–137 years ago and for Clade B at 56.3–99.2 years ago compared to the significantly more recent origin for Clade C. in silico spoligotyping identified signatures specific of the Clade A (spoligotype SIT35), and Clades B and C (both SIT262). A genetically compact and evolutionarily young Ural Clade C, likely originated after collapse of the Soviet Union, and reached epidemic proportions in Moldova in the last 20 years. This epidemic pre-XDR clone (mostly rifampin, isoniazid and kanamycin resistant) is characterized by a specific combination of mutations: KatG Ser315Thr, fabG1 -15C > T, RpoB Ser450Leu, RpsL Lys88Arg, eis -12G > A and EmbB Ser297Ala/T > G. Its further dissemination may occur towards both Russia and European Union and should be taken into consideration by health authorities. The identified spoligotyping signatures can serve for rapid preliminary detection and surveillance of the more hazardous pre-XDR associated strains of the Ural family, both in populations from countries of their endemic circulation and migrant communities.
Citations by journals
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Citations by publishers
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- We do not take into account publications that without a DOI.
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- Statistics recalculated weekly.
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Sinkov V. et al. New epidemic cluster of pre-extensively drug resistant isolates of Mycobacterium tuberculosis Ural family emerging in Eastern Europe // BMC Genomics. 2018. Vol. 19. No. 1. 762
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Sinkov V., Ogarkov O., Mokrousov I. V., Bukin Y., Zhdanova S., Heysell S. K. New epidemic cluster of pre-extensively drug resistant isolates of Mycobacterium tuberculosis Ural family emerging in Eastern Europe // BMC Genomics. 2018. Vol. 19. No. 1. 762
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TY - JOUR
DO - 10.1186/s12864-018-5162-3
UR - https://doi.org/10.1186%2Fs12864-018-5162-3
TI - New epidemic cluster of pre-extensively drug resistant isolates of Mycobacterium tuberculosis Ural family emerging in Eastern Europe
T2 - BMC Genomics
AU - Sinkov, Viacheslav
AU - Ogarkov, Oleg
AU - Mokrousov, I. V.
AU - Bukin, Yuri
AU - Zhdanova, Svetlana
AU - Heysell, Scott K.
PY - 2018
DA - 2018/10/22 00:00:00
PB - Springer Nature
IS - 1
VL - 19
PMID - 30348088
SN - 1471-2164
ER -
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@article{2018_Sinkov,
author = {Viacheslav Sinkov and Oleg Ogarkov and I. V. Mokrousov and Yuri Bukin and Svetlana Zhdanova and Scott K. Heysell},
title = {New epidemic cluster of pre-extensively drug resistant isolates of Mycobacterium tuberculosis Ural family emerging in Eastern Europe},
journal = {BMC Genomics},
year = {2018},
volume = {19},
publisher = {Springer Nature},
month = {oct},
url = {https://doi.org/10.1186%2Fs12864-018-5162-3},
number = {1},
doi = {10.1186/s12864-018-5162-3}
}
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