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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Casali, Nicola Nikolayevskyy, Vladyslav Balabanova, Yanina Ignatyeva, Olga Kontsevaya, Irina Harris, Simon R. Bentley, Stephen D. Parkhill, Julian Nejentsev, Sergey Hoffner, Sven E. Horstmann, Rolf D. Brown, Timothy Drobniewski, Francis |
| Spatial Coverage | Russia |
| Description | Country affiliation: United kingdom Author Affiliation: Casali N ( National Mycobacterium Reference Laboratory, Blizard Institute, Queen Mary, University of London, London E1 2AT, United Kingdom.) |
| Abstract | Extensively drug-resistant (XDR) tuberculosis (TB), which is resistant to both first- and second-line antibiotics, is an escalating problem, particularly in the Russian Federation. Molecular fingerprinting of 2348 Mycobacterium tuberculosis isolates collected in Samara Oblast, Russia, revealed that 72% belonged to the Beijing lineage, a genotype associated with enhanced acquisition of drug resistance and increased virulence. Whole-genome sequencing of 34 Samaran isolates, plus 25 isolates representing global M. tuberculosis complex diversity, revealed that Beijing isolates originating in Eastern Europe formed a monophyletic group. Homoplasic polymorphisms within this clade were almost invariably associated with antibiotic resistance, indicating that the evolution of this population is primarily driven by drug therapy. Resistance genotypes showed a strong correlation with drug susceptibility phenotypes. A novel homoplasic mutation in rpoC, found only in isolates carrying a common rpoB rifampicin-resistance mutation, may play a role in fitness compensation. Most multidrug-resistant (MDR) isolates also had mutations in the promoter of a virulence gene, eis, which increase its expression and confer kanamycin resistance. Kanamycin therapy may thus select for mutants with increased virulence, helping preserve bacterial fitness and promoting transmission of drug-resistant TB strains. The East European clade was dominated by two MDR clusters, each disseminated across Samara. Polymorphisms conferring fluoroquinolone resistance were independently acquired multiple times within each cluster, indicating that XDR TB is currently not widely transmitted. |
| File Format | HTM / HTML |
| ISSN | 10889051 |
| e-ISSN | 15495469 |
| DOI | 10.1101/gr.128678.111 |
| Journal | Genome Research |
| Issue Number | 4 |
| Volume Number | 22 |
| Language | English |
| Publisher | Cold Spring Harbor Laboratory Press |
| Publisher Date | 2012-04-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Discipline Genetics Discipline Genomics Evolution, Molecular Extensively Drug-resistant Tuberculosis Microbiology Genome, Bacterial Genetics Mycobacterium Tuberculosis Bacterial Proteins Dna Fingerprinting Dna, Bacterial Chemistry Drug Resistance, Multiple Genotype Geography Microbial Sensitivity Tests Models, Genetic Mutation Classification Pathogenicity Phylogeny Polymorphism, Single Nucleotide Promoter Regions, Genetic Sequence Analysis, Dna Species Specificity Virulence Research Support, Non-u.s. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Genetics Genetics (clinical) |
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