title: The role of eis mutations in the development of kanamycin resistance in Mycobacterium tuberculosis isolates from the Moscow region.
abstract: OBJECTIVE
  Kanamycin is an important second-line drug used to treat multidrug-resistant (MDR) tuberculosis (TB). Molecular analysis of the rrs gene seems to be not enough to identify every case of kanamycin resistance. In the present study we evaluated the incidence of eis mutations in kanamycin-resistant Mycobacterium tuberculosis isolates.
  
  
  METHODS
  We analysed 70 MDR M. tuberculosis clinical isolates. All isolates were screened for rrs and eis mutations using single-strand conformation polymorphism and sequencing. Phenotypic drug susceptibility testing was performed using Bactec MGIT 960 and the absolute concentration method on Lowenstein-Jensen medium.
  
  
  RESULTS
  eis mutations were found in 10 isolates. The most prevalent mutations were the A1401G substitution in the rrs gene and the C14T substitution in the eis promoter region.
  
  
  CONCLUSIONS
  Our study shows that the eis promoter region is a useful molecular marker of kanamycin resistance in the Moscow region. Complex analysis of rrs and eis mutations will significantly reduce the time to diagnose kanamycin resistance in TB patients, compared with phenotypic drug resistance testing.
authors.affiliation: Moscow Scientific and Clinical Antituberculosis Center, Department of Health of Moscow, Moscow, 107014 Stromynka 10, Russia. m.gikalo@gmail.com
authors.forename: Marina B
authors.initials: MB
authors.lastname: Gikalo
authors.forename: Elena Y
authors.initials: EY
authors.lastname: Nosova
authors.forename: Ludmila Y
authors.initials: LY
authors.lastname: Krylova
authors.forename: Arkadyi M
authors.initials: AM
authors.lastname: Moroz
mesh_terms: D000123:Acetyltransferases; D000942:Antigens, Bacterial / Q000235:genetics* / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D007613:Kanamycin Resistance; D008826:Microbial Sensitivity Tests; D009031:Moscow; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D018807:Polymorphism, Single-Stranded Conformational; D011401:Promoter Regions, Genetic; D017422:Sequence Analysis, DNA; D018088:Tuberculosis, Multidrug-Resistant / Q000382:microbiology*
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D050505:Mutant Proteins; D000123:Acetyltransferases; C430563:Eis protein, Mycobacterium tuberculosis