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Evolution and transmission of drug-resistant tuberculosis in a Russian population

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TLDR
The combination of drug resistance and compensatory mutations displayed by the major clades confers clinical resistance without compromising fitness and transmissibility, showing that, in addition to weaknesses in the tuberculosis control program, biological factors drive the persistence and spread of MDR and XDR tuberculosis in Russia and beyond.
Abstract
The molecular mechanisms determining the transmissibility and prevalence of drug-resistant tuberculosis in a population were investigated through whole-genome sequencing of 1,000 prospectively obtained patient isolates from Russia. Two-thirds belonged to the Beijing lineage, which was dominated by two homogeneous clades. Multidrug-resistant (MDR) genotypes were found in 48% of isolates overall and in 87% of the major clades. The most common rpoB mutation was associated with fitness-compensatory mutations in rpoA or rpoC, and a new intragenic compensatory substitution was identified. The proportion of MDR cases with extensively drug-resistant (XDR) tuberculosis was 16% overall, with 65% of MDR isolates harboring eis mutations, selected by kanamycin therapy, which may drive the expansion of strains with enhanced virulence. The combination of drug resistance and compensatory mutations displayed by the major clades confers clinical resistance without compromising fitness and transmissibility, showing that, in addition to weaknesses in the tuberculosis control program, biological factors drive the persistence and spread of MDR and XDR tuberculosis in Russia and beyond.

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Convergent evolution and adaptation of Pseudomonas aeruginosa within patients with cystic fibrosis

TL;DR: The analysis of 36 P. aeruginosa lineages identified convergent molecular evolution in 52 genes that suggest a role in host adaptation for remodeling of regulatory networks and central metabolism, acquisition of antibiotic resistance and loss of extracellular virulence factors.
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A robust SNP barcode for typing Mycobacterium tuberculosis complex strains.

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The epidemiology, pathogenesis, transmission, diagnosis, and management of multidrug-resistant, extensively drug-resistant, and incurable tuberculosis

TL;DR: Several lines of evidence suggest that alternative mechanisms-including pharmacokinetic variability, induction of efflux pumps that transport the drug out of cells, and suboptimal drug penetration into tuberculosis lesions-are likely crucial to the pathogenesis of drug-resistant tuberculosis.
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Evolutionary history and global spread of the Mycobacterium tuberculosis Beijing lineage

TL;DR: It is shown that this lineage of mycobacterium tuberculosis strains of the Beijing lineage initially originated in the Far East, from where it radiated worldwide in several waves and detected successive increases in population size over the last 200 years.
References
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The Sequence Alignment/Map format and SAMtools

TL;DR: SAMtools as discussed by the authors implements various utilities for post-processing alignments in the SAM format, such as indexing, variant caller and alignment viewer, and thus provides universal tools for processing read alignments.
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Meta-Analysis: A Constantly Evolving Research Integration Tool

TL;DR: The four articles in this special section onMeta-analysis illustrate some of the complexities entailed in meta-analysis methods and contributes both to advancing this methodology and to the increasing complexities that can befuddle researchers.
Book

Molecular Evolutionary Genetics

Masatoshi Nei
TL;DR: Recent developments of statistical methods in molecular phylogenetics are reviewed and it is shown that the mathematical foundations of these methods are not well established, but computer simulations and empirical data indicate that currently used methods produce reasonably good phylogenetic trees when a sufficiently large number of nucleotides or amino acids are used.
Journal ArticleDOI

PAML 4: Phylogenetic Analysis by Maximum Likelihood

TL;DR: PAML, currently in version 4, is a package of programs for phylogenetic analyses of DNA and protein sequences using maximum likelihood (ML), which can be used to estimate parameters in models of sequence evolution and to test interesting biological hypotheses.
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