Evolution of Drug Resistance in Different Sublineages of Mycobacterium tuberculosis Beijing Genotype

ABSTRACT We compared the population structure and drug resistance patterns of the Mycobacterium tuberculosis strains currently circulating in the Beijing area of China. One hundred thirteen of 123 strains belonged to the Beijing family genotypes defined by spoligotyping. The Beijing genotype strains were further subdivided into old and modern sublineages on the basis of NTF locus analysis. A stronger association with resistance to the more recently introduced antituberculosis drugs has been observed for old versus modern strains of the Beijing genotype, suggesting that its different sublineages may differ in their mechanisms of adaptation to drug selective pressure.

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Drug Resistance and Population Structure of Mycobacterium tuberculosis Beijing Strains Isolated in Poland

Polish Journal of Microbiology ◽

10.5604/17331331.1185243 ◽

2015 ◽

Vol 64 (4) ◽

pp. 399-401 ◽

Cited By ~ 1

Author(s):

Monika Kozińska ◽

Ewa Augustynowicz-Kopeć

Keyword(s):

Drug Resistance ◽

Mycobacterium Tuberculosis ◽

Population Structure ◽

Relative Risk ◽

Beijing Genotype ◽

Drug Resistant ◽

Foreign Born ◽

Resistant Strains ◽

Drug Resistant Strains ◽

Genotype Infection

In total, 1095 Mycobacterium tuberculosis clinical isolates from 282 patients with drug-resistant and 813 with drug-sensitive tuberculosis (TB) in Poland during 2007–2011 were analysed. Seventy-one (6.5%) patients were found to have strains of Beijing genotype as defined by spoligotyping. The majority of patients were Polish–born; among foreign-born a large proportion came from Chechnya and Vietnam. Analysis showed strong associations between Beijing genotype infection and MDR, pre-XDR and XDR resistance, with a considerable relative risk among new patients, suggesting that this is due to increased spread of drug-resistant strains rather than acquisition of resistance during treatment.

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Genomic Variations in Drug Resistant Mycobacterium tuberculosis Strains Collected from Patients with Different Localization of Infection

Antibiotics ◽

10.3390/antibiotics10010027 ◽

2020 ◽

Vol 10 (1) ◽

pp. 27

Author(s):

Ekaterina Chernyaeva ◽

Mikhail Rotkevich ◽

Ksenia Krasheninnikova ◽

Alla Lapidus ◽

Dmitrii E. Polev ◽

...

Keyword(s):

Drug Resistance ◽

Mycobacterium Tuberculosis ◽

Pulmonary Tuberculosis ◽

Central Asia ◽

Phylogenetic Analyses ◽

Treatment Success ◽

Point Mutations ◽

Whole Genome Sequence ◽

Public Health Importance ◽

Resistance Patterns

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.

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Mycobacterium tuberculosis genotypic drug resistance patterns and clustering in Jayapura, Papua, Indonesia

The International Journal of Tuberculosis and Lung Disease ◽

10.5588/ijtld.14.0350 ◽

2015 ◽

Vol 19 (4) ◽

pp. 428-433 ◽

Cited By ~ 6

Author(s):

L. Chaidir ◽

S. Sengstake ◽

J. de Beer ◽

H. Krismawati ◽

F. D. Lestari ◽

...

Keyword(s):

Drug Resistance ◽

Mycobacterium Tuberculosis ◽

Resistance Patterns

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Genotypes of Mycobacterium tuberculosis isolates circulating in Shaanxi Province, China

PLoS ONE ◽

10.1371/journal.pone.0242971 ◽

2020 ◽

Vol 15 (12) ◽

pp. e0242971

Author(s):

Yan Li ◽

Yu Pang ◽

Tianhua Zhang ◽

Xiaoping Xian ◽

Jian Yang ◽

...

Keyword(s):

Genetic Diversity ◽

Drug Resistance ◽

Mycobacterium Tuberculosis ◽

Multidrug Resistant ◽

Shaanxi Province ◽

Drug Resistant ◽

Beijing Family ◽

Tuberculosis Patients ◽

Smear Positive Pulmonary Tuberculosis ◽

Discriminatory Index

Objectives The prevalence of drug-resistant TB in Shaanxi Province is higher than other areas. This study was aimed to investigate the genetic diversity and epidemiology of Mycobacterium tuberculosis clinical strains in Shaanxi Province, China. Methods From January to December 2016, a total of 298 Mycobacterium tuberculosis clinical isolates from smear-positive pulmonary tuberculosis patients were genotyped by Mcspoligotyping and 15-locus VNTR. Results We found that the Beijing family strains was the most prominent family(81.54%, 243/298). Other family strains included T family(9.06%, 27/298), U family(0.67%, 2/298), LAM9 family(0.34%, 1/298) and Manu family(0.34%, 1/298). The rates of multidrug-resistant (MDR) M.Tuberculosis, age, type of case and education between Beijing and non-Beijing family strains were not statistically different, while the distribution in the three different regions among these was statistically significant. VNTR results showed that strains were classified into 280 genotypes, and 33 (11.07%) strains could be grouped into 14 clusters. 11 of the 15-VNTR loci were highly or moderately discriminative according to the Hunter-Gaston discriminatory index. Conclusions We concluded that the Beijing family genotype was the most prevalent genotype and 15-locus VNTR typing might be suitable for genotyping of M. tuberculosis in Shaanxi Province. There was less association between Beijing family genotypes and drug resistance in our study area.

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Comparison of drug resistance genotypes between Beijing and non-Beijing family strains of Mycobacterium tuberculosis in Korea

Journal of Microbiological Methods ◽

10.1016/j.mimet.2005.03.002 ◽

2005 ◽

Vol 63 (2) ◽

pp. 165-172 ◽

Cited By ~ 43

Author(s):

Young Kil Park ◽

Sonya Shin ◽

Sungweon Ryu ◽

Sang Nae Cho ◽

Won-Jung Koh ◽

...

Keyword(s):

Drug Resistance ◽

Mycobacterium Tuberculosis ◽

Beijing Family

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Role of embB Codon 306 Mutations in Mycobacterium tuberculosis Revisited: a Novel Association with Broad Drug Resistance and IS6110 Clustering Rather than Ethambutol Resistance

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.49.9.3794-3802.2005 ◽

2005 ◽

Vol 49 (9) ◽

pp. 3794-3802 ◽

Cited By ~ 79

Author(s):

Manzour Hernando Hazbón ◽

Miriam Bobadilla del Valle ◽

Marta Inírida Guerrero ◽

Mandira Varma-Basil ◽

Ingrid Filliol ◽

...

Keyword(s):

Drug Resistance ◽

Mycobacterium Tuberculosis ◽

Odds Ratio ◽

Univariate Analysis ◽

Drug Susceptibility ◽

Drug Resistant ◽

Development Of Resistance ◽

Resistance Patterns ◽

Novel Association

ABSTRACT Mutations at position 306 of embB (embB306) have been proposed as a marker for ethambutol resistance in Mycobacterium tuberculosis; however, recent reports of embB306 mutations in ethambutol-susceptible isolates caused us to question the biological role of this mutation. We tested 1,020 clinical M. tuberculosis isolates with different drug susceptibility patterns and of different geographical origins for associations between embB306 mutations, drug resistance patterns, and major genetic group. One hundred isolates (10%) contained a mutation in embB306; however, only 55 of these mutants were ethambutol resistant. Mutations in embB306 could not be uniquely associated with any particular type of drug resistance and were found in all three major genetic groups. A striking association was observed between these mutations and resistance to any drug (P < 0.001), and the association between embB306 mutations and resistance to increasing numbers of drugs was highly significant (P < 0.001 for trend). We examined the association between embB306 mutations and IS6110 clustering (as a proxy for transmission) among all drug-resistant isolates. Mutations in embB306 were significantly associated with clustering by univariate analysis (odds ratio, 2.44; P = 0.004). In a multivariate model that also included mutations in katG315, katG463, gyrA95, and kasA269, only mutations in embB306 (odds ratio, 2.14; P = 0.008) and katG315 (odds ratio, 1.99; P = 0.015) were found to be independently associated with clustering. In conclusion, embB306 mutations do not cause classical ethambutol resistance but may predispose M. tuberculosis isolates to the development of resistance to increasing numbers of antibiotics and may increase the ability of drug-resistant isolates to be transmitted between subjects.

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