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

Antibiotics ◽  
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.

scholarly journals Genome-wide analysis of drug resistant Mycobacterium tuberculosis isolates causing pulmonary and extrapulmonary tuberculosis in Russia

2018 ◽  
Author(s):  
Ekaterina Nikolayevna Chernyaeva ◽  
Mikhail Rotkevich ◽  
Ksenia Krasheninnikova ◽  
Alla Lapidus ◽  
Dmitrii E. Polev ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Phylogenetic Analyses ◽  
Clinical Status ◽  
Extrapulmonary Tuberculosis ◽  
Point Mutations ◽  
Whole Genome Sequence ◽  
Public Health Importance ◽  
Genome Wide ◽  
Genomic Markers ◽  
Resistance Patterns

Mycobacterium tuberculosisis a highly studied pathogen due to public health importance. Despite progress in M.tuberculosis genome diversity analysis, there remain insufficient data on genome analysis of M.tuberculosis strains associated with pulmonary vs. extrapulmonary TB (PTB or XPTB respectively) tissue localization. Here we conduct comparative analysis of whole-genome sequence (WGS) for clinical M.tuberculosis strains collected from patients with PTB (n=72) and XPTB (n=73) localization. We further analyze the incidence of point mutations widely used for drug resistance detection in laboratory practice. M.tuberculosis isolates were collected from patients with varying clinical status from 2007 to 2014 in Russia. Bacterial DNA was extracted and sequenced using MiSeq platform (Illumina). WGSdata allowed identifying M.tuberculosis substrains associated with distinctions in the occurrence in PTB v.s. XPTB cases. There occurred little statistically significant specific DNA variants or genotypes diagnostic of tissue distribution, however phylogenetic analyses did reveal M.tuberculosis genetic substrains associated with TB localization. XPTB was associated with Beijing CAO, A and 4.8 groups, while PTB localization was associated with group LAM (4.3). Further, XPTB strain in some cases showed elevated drug resistance patterns relative to PTB isolates. HIV is significantly associated with the development of XPTB in the Beijing B0/W148 group and among unclustered Beijing isolates. This research analysis pinpointed genomic markers identified in XPTB and PTB with detailed characterization of drug-resistance markers of Russian M.tuberculosis isolates. We suggest that further comprehensive analysis of bacterial and human biological signatures might allow for better understanding consistent pattern of XPTB development.

scholarly journals Genomic Polymorphisms in Toxin-Antitoxin Systems and Identification of Novel Phylo-SNPs and Polymorphisms Associated with Drug Resistance/Susceptibility in Clinical Isolates of Mycobacterium tuberculosis from Mumbai, India

2019 ◽  
Author(s):  
Kayzad Nilgiriwala ◽  
Vidushi Chitalia ◽  
Sanchi Shah ◽  
Akshata Papewar
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Central Asia ◽  
Sequence Data ◽  
Drug Susceptibility ◽  
Clinical Isolates ◽  
Whole Genome Sequence ◽  
Silent Mutation ◽  
Drug Resistance Profile ◽  
Cell Arrest

ABSTRACTToxin-antitoxin (TA) modules are one of the prominent determinants that triggers a persistent state aiding Mycobacterium tuberculosis evasion to host generated stresses. The 79 characterized and putative TA systems described in M. tuberculosis are dominated by the VapBC, MazEF, HigAB, RelBE and ParDE TA families, largely involved in persistence and cell arrest. Hence, there is a need to maintain and conserve the TA loci in the chromosome of the pathogen. It is essential to study the genomic differences of the TA systems in clinical isolates along with its association to drug susceptibility patterns and lineage. In the current study, the TA loci and their promoter sequences were analysed from the whole genome sequence data of 74 clinical isolates. Mykrobe Predictor was used for lineage identification and drug resistance predictions in the clinical isolates. Polymorphisms associated with 79.8% (63/79) TA systems were observed across 72 clinical isolates. Among the TA systems, the isolates had a varying number of polymorphisms localised primarily in the toxin genes (58.7%), antitoxin genes (40.7%) and chaperones (0.6%), due to Single Nucleotide Polymorphism (SNP) resulting in transition (67.3%), transversion or frameshift mutations. Our analysis suggests the presence of novel Phylo-SNPs by establishing high confidence association of specific lineages to polymorphisms in the TA systems. Notably, association of polymorphisms in Rv1838c-1839c (VapBC13), Rv3358-3357 (YefM/YoeB) and Rv0240-0239 (VapBC24) to Delhi/Central Asia lineage. The polymorphic loci of the 3 TA systems is localised in the antitoxin gene of the Delhi/Central Asia strains, with a resultant silent mutation. The assessment of correlation between TA polymorphisms and the drug resistance profile revealed correlation of SNPs in VapBC35 with drug resistant M. tuberculosis strains and SNPs in VapBC24, VapBC13 and YefM/YoeB to drug sensitive strains.

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

2015 ◽  
Vol 19 (4) ◽  
pp. 428-433 ◽  
Author(s):  
L. Chaidir ◽  
S. Sengstake ◽  
J. de Beer ◽  
H. Krismawati ◽  
F. D. Lestari ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Resistance Patterns

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

2005 ◽  
Vol 49 (9) ◽  
pp. 3794-3802 ◽  
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.

Sign in / Sign up

Export Citation Format

Share Document