TY - JOUR

T1 - Genomic variations in drug resistant Mycobacterium tuberculosis strains collected from patients with different localization of infection

AU - Chernyaeva, Ekaterina

AU - Rotkevich, Mikhail

AU - Krasheninnikova, Ksenia

AU - Lapidus, Alla

AU - Polev, Dmitrii E.

AU - Solovieva, Natalia

AU - Zhuravlev, Viacheslav

AU - Yablonsky, Piotr

AU - O’Brien, Stephen J.

N1 - Funding Information: Funding: The authors acknowledge the contribution of CARE Consortium funded by the European Union’s Horizon 2020 program and the Ministry of Science and Higher Education of the Russian Federation (unique project identifier RFMEFI61019X0020). AL was supported by St. Petersburg State University grant (No 51555639). Publisher Copyright: © 2020 by the authors. Licensee MDPI, Basel, Switzerland. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/1

Y1 - 2021/1

N2 - Mycobacterium tuberculosis is a highly studied pathogen due to public health importance. Despite this, problems like early drug resistance, diagnostics and treatment success prediction are still not fully resolved. Here, we analyze the incidence of point mutations widely used for drug resistance detection in laboratory practice and conduct comparative analysis of whole-genome sequence (WGS) for clinical M. tuberculosis strains collected from patients with pulmonary tuberculosis (PTB) and extra-pulmonary tuberculosis (XPTB) localization. A total of 72 pulmonary and 73 extrapulmonary microbiologically characterized M. tuberculosis isolates were collected from patients from 2007 to 2014 in Russia. Genomic DNA was used for WGS and obtained data allowed identifying major mutations known to be associated with drug resistance to first-line and second-line antituberculous drugs. In some cases previously described mutations were not identified. Using genome-based phylogenetic analysis we identified M. tuberculosis substrains associated with distinctions in the occurrence in PTB vs. XPTB cases. Phylogenetic analyses did reveal M. tuberculosis genetic substrains associated with TB localization. XPTB was associated with Beijing sublineages Central Asia (Beijing CAO), Central Asia Clade A (Beijing A) and 4.8 groups, while PTB localization was associated with group LAM (4.3). Further, the XPTB strain in some cases showed elevated drug resistance patterns relative to PTB isolates. HIV was significantly associated with the development of XPTB in the Beijing B0/W148 group and among unclustered Beijing isolates.

AB - Mycobacterium tuberculosis is a highly studied pathogen due to public health importance. Despite this, problems like early drug resistance, diagnostics and treatment success prediction are still not fully resolved. Here, we analyze the incidence of point mutations widely used for drug resistance detection in laboratory practice and conduct comparative analysis of whole-genome sequence (WGS) for clinical M. tuberculosis strains collected from patients with pulmonary tuberculosis (PTB) and extra-pulmonary tuberculosis (XPTB) localization. A total of 72 pulmonary and 73 extrapulmonary microbiologically characterized M. tuberculosis isolates were collected from patients from 2007 to 2014 in Russia. Genomic DNA was used for WGS and obtained data allowed identifying major mutations known to be associated with drug resistance to first-line and second-line antituberculous drugs. In some cases previously described mutations were not identified. Using genome-based phylogenetic analysis we identified M. tuberculosis substrains associated with distinctions in the occurrence in PTB vs. XPTB cases. Phylogenetic analyses did reveal M. tuberculosis genetic substrains associated with TB localization. XPTB was associated with Beijing sublineages Central Asia (Beijing CAO), Central Asia Clade A (Beijing A) and 4.8 groups, while PTB localization was associated with group LAM (4.3). Further, the XPTB strain in some cases showed elevated drug resistance patterns relative to PTB isolates. HIV was significantly associated with the development of XPTB in the Beijing B0/W148 group and among unclustered Beijing isolates.

KW - Drug resistance

KW - Extrapulmonary tuberculosis

KW - Mycobacterium tuberculosis

KW - Pulmonary tuberculosis

KW - Whole-genome sequencing

UR - http://www.scopus.com/inward/record.url?scp=85099056897&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/6efe8c2d-c889-398f-9362-a42007bb69e4/

U2 - 10.3390/antibiotics10010027

DO - 10.3390/antibiotics10010027

M3 - Article

AN - SCOPUS:85099056897

VL - 10

SP - 1

EP - 12

JO - Antibiotics

JF - Antibiotics

SN - 2079-6382

IS - 1

M1 - 27

ER -