Microevolution of extensively drug-resistant tuberculosis in Russia

Nicola Casali, Vladyslav Nikolayevskyy, Yanina Balabanova, Olga Ignatyeva, Irina Kontsevaya, Simon R Harris, Stephen D Bentley, Julian Parkhill, Sergey Nejentsev, Sven E Hoffner, Rolf D Horstmann, Timothy Brown, Francis Drobniewski

Research output: Contribution to journalArticleAcademicpeer-review

164 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)735-45
Number of pages11
JournalGenome Research
Issue number4
Publication statusPublished - Apr 2012
Externally publishedYes


  • Bacterial Proteins/genetics
  • DNA Fingerprinting
  • DNA, Bacterial/chemistry
  • Drug Resistance, Multiple/genetics
  • Evolution, Molecular
  • Extensively Drug-Resistant Tuberculosis/microbiology
  • Genome, Bacterial/genetics
  • Genotype
  • Geography
  • Humans
  • Microbial Sensitivity Tests
  • Models, Genetic
  • Mutation
  • Mycobacterium tuberculosis/classification
  • Phylogeny
  • Polymorphism, Single Nucleotide
  • Promoter Regions, Genetic/genetics
  • Russia
  • Sequence Analysis, DNA
  • Species Specificity
  • Virulence/genetics

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