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Characterization of extensively drug-resistant Mycobacterium tuberculosis isolates circulating in Siberia

BACKGROUND: The spread of multidrug-resistant (MDR) and extensively drug-resistant (XDR) Mycobacterium tuberculosis compromises effective control of tuberculosis (TB) in Siberia. Early identification of drug-resistant isolates is, therefore, crucial for effective treatment of this disease. The aim o...

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Autores principales: Dymova, Maya A, Cherednichenko, Andrey G, Alkhovik, Olga I, Khrapov, Eugeny A, Petrenko, Tatjana I, Filipenko, Maxim L
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4161839/
https://www.ncbi.nlm.nih.gov/pubmed/25186134
http://dx.doi.org/10.1186/1471-2334-14-478
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author Dymova, Maya A
Cherednichenko, Andrey G
Alkhovik, Olga I
Khrapov, Eugeny A
Petrenko, Tatjana I
Filipenko, Maxim L
author_facet Dymova, Maya A
Cherednichenko, Andrey G
Alkhovik, Olga I
Khrapov, Eugeny A
Petrenko, Tatjana I
Filipenko, Maxim L
author_sort Dymova, Maya A
collection PubMed
description BACKGROUND: The spread of multidrug-resistant (MDR) and extensively drug-resistant (XDR) Mycobacterium tuberculosis compromises effective control of tuberculosis (TB) in Siberia. Early identification of drug-resistant isolates is, therefore, crucial for effective treatment of this disease. The aim of this study was to conduct drug susceptibility testing and identify mutations in drug resistance genes in clinical isolates of M. tuberculosis from some TB patients presenting for treatment in Siberia. METHODS: Thirty randomly selected clinical isolates of M. tuberculosis were obtained from the Novosibirsk Research Institute of Tuberculosis, Russia. Isolates were screened for drug resistance and characterized by variable number of tandem repeats (VNTR)-typing using 15 standard and four additional loci. Deligotyping on multiple large sequences was performed using 10 loci. RESULTS: Twenty-nine of the isolates were assigned XDR status. Twenty-eight isolates belonged to the M. tuberculosis Beijing family, from which 11 isolates were considered the M11 type (39%), two the M2 type (7%), and one the M33 type (3%). Seventeen isolates (60.7%) from this family exhibited unique genetic patterns. The remaining two isolates belonged to the Latino-American Mediterranean family. Gene sequences (rpoB, katG, rrs, rpsL, tlyA, gidB, gyrA, gyrB) were analyzed to identify mutations that confer resistance to rifampicin, isoniazid, amikacin, kanamycin, capreomycin, and ofloxacin. The most common mutations among the XDR isolates were S531L in RpoB, S315T in KatG, various codon 94 mutations in gyrA, A90V in GyrA, K43R in RpsL, and 1401 A → G in rrs; these confer resistance to rifampicin, isoniazid, ofloxacin, streptomycin and kanamycin/capreomycin, respectively. There was high congruence between the two typing methods (VNTR typing and deligotyping) and RD105, RD149, RD152, RD181, and RD207 regions of difference were absent from the 28 Beijing family isolates. CONCLUSIONS: Deligotyping can be used for rapid and reliable screening of M. tuberculosis isolates, followed by more in-depth genotyping. Identification of Beijing family isolates with extensive drug resistance confirms that such strains have epidemiological importance in Siberia. Rapid detection of mutations that lead to drug resistance should facilitate selection of effective drug therapies, and the development of early prevention strategies to combat this infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2334-14-478) contains supplementary material, which is available to authorized users.
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spelling pubmed-41618392014-09-13 Characterization of extensively drug-resistant Mycobacterium tuberculosis isolates circulating in Siberia Dymova, Maya A Cherednichenko, Andrey G Alkhovik, Olga I Khrapov, Eugeny A Petrenko, Tatjana I Filipenko, Maxim L BMC Infect Dis Research Article BACKGROUND: The spread of multidrug-resistant (MDR) and extensively drug-resistant (XDR) Mycobacterium tuberculosis compromises effective control of tuberculosis (TB) in Siberia. Early identification of drug-resistant isolates is, therefore, crucial for effective treatment of this disease. The aim of this study was to conduct drug susceptibility testing and identify mutations in drug resistance genes in clinical isolates of M. tuberculosis from some TB patients presenting for treatment in Siberia. METHODS: Thirty randomly selected clinical isolates of M. tuberculosis were obtained from the Novosibirsk Research Institute of Tuberculosis, Russia. Isolates were screened for drug resistance and characterized by variable number of tandem repeats (VNTR)-typing using 15 standard and four additional loci. Deligotyping on multiple large sequences was performed using 10 loci. RESULTS: Twenty-nine of the isolates were assigned XDR status. Twenty-eight isolates belonged to the M. tuberculosis Beijing family, from which 11 isolates were considered the M11 type (39%), two the M2 type (7%), and one the M33 type (3%). Seventeen isolates (60.7%) from this family exhibited unique genetic patterns. The remaining two isolates belonged to the Latino-American Mediterranean family. Gene sequences (rpoB, katG, rrs, rpsL, tlyA, gidB, gyrA, gyrB) were analyzed to identify mutations that confer resistance to rifampicin, isoniazid, amikacin, kanamycin, capreomycin, and ofloxacin. The most common mutations among the XDR isolates were S531L in RpoB, S315T in KatG, various codon 94 mutations in gyrA, A90V in GyrA, K43R in RpsL, and 1401 A → G in rrs; these confer resistance to rifampicin, isoniazid, ofloxacin, streptomycin and kanamycin/capreomycin, respectively. There was high congruence between the two typing methods (VNTR typing and deligotyping) and RD105, RD149, RD152, RD181, and RD207 regions of difference were absent from the 28 Beijing family isolates. CONCLUSIONS: Deligotyping can be used for rapid and reliable screening of M. tuberculosis isolates, followed by more in-depth genotyping. Identification of Beijing family isolates with extensive drug resistance confirms that such strains have epidemiological importance in Siberia. Rapid detection of mutations that lead to drug resistance should facilitate selection of effective drug therapies, and the development of early prevention strategies to combat this infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2334-14-478) contains supplementary material, which is available to authorized users. BioMed Central 2014-09-03 /pmc/articles/PMC4161839/ /pubmed/25186134 http://dx.doi.org/10.1186/1471-2334-14-478 Text en © Dymova et al.; licensee BioMed Central Ltd. 2014 This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Dymova, Maya A
Cherednichenko, Andrey G
Alkhovik, Olga I
Khrapov, Eugeny A
Petrenko, Tatjana I
Filipenko, Maxim L
Characterization of extensively drug-resistant Mycobacterium tuberculosis isolates circulating in Siberia
title Characterization of extensively drug-resistant Mycobacterium tuberculosis isolates circulating in Siberia
title_full Characterization of extensively drug-resistant Mycobacterium tuberculosis isolates circulating in Siberia
title_fullStr Characterization of extensively drug-resistant Mycobacterium tuberculosis isolates circulating in Siberia
title_full_unstemmed Characterization of extensively drug-resistant Mycobacterium tuberculosis isolates circulating in Siberia
title_short Characterization of extensively drug-resistant Mycobacterium tuberculosis isolates circulating in Siberia
title_sort characterization of extensively drug-resistant mycobacterium tuberculosis isolates circulating in siberia
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4161839/
https://www.ncbi.nlm.nih.gov/pubmed/25186134
http://dx.doi.org/10.1186/1471-2334-14-478
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