title: Molecular characterization of rpoB gene mutations in rifampicine-resistant Mycobacterium tuberculosis isolates from tuberculosis patients in Belarus.
abstract: The aim of this study was to investigate the frequency, location and type of rpoB mutations in Mycobacterium tuberculosis isolated from patients in Belarus. Tuberculosis cases are increasing every year in Belarus. Moreover, resistance to anti-tuberculosis drugs, especially to rifampicine, has increased. In this study, 44 rifampicine-resistance M. tuberculosis clinical isolates (including multidrug-resistant isolates) were subjected to DNA sequencing analysis of the hypervariable region (hot-spot) of the rpoB gene originating from different geographical regions in Belarus. Sixteen different types of mutations were identified. The most common point mutations were in codons 510 (47.7%), 526 (45.5%), 523 (40.86%) and 531 (29.5%). Eleven isolates (27.7%) carried one mutation and 23 (52%), 7 (16%), 3 (7%) of isolates carried 2, 3 and 4 mutations, respectively. A characteristic, prominent finding of this study was high frequency of multiple mutations in different codons of the rpoB gene (27.7%) and also the detection of unusual types of mutations in the 510 codon, comprising CAG mutations (deletion or changing, to CTG, CAC or CAT). In our study, the change TTG in codon 531 was found in 92% of isolates and the change TGC in 8% of isolates. A TAC change in codon 526 was not found, but the GAC change was found in all isolates. Isolates of M. tuberculosis isolated in Belarus were characterized by the wide spectrum of the important mutations and might belong to the epidemic widespread clones.
authors.affiliation: Belarusian Research Institute for Epidemiology and Microbiology, Minsk, Belarus.
authors.forename: Leonid P
authors.initials: LP
authors.lastname: Titov
authors.forename: Saeed
authors.initials: S
authors.lastname: Zakerbostanabad
authors.forename: Veranika
authors.initials: V
authors.lastname: Slizen
authors.forename: Larisa
authors.initials: L
authors.lastname: Surkova
authors.forename: Mohammad
authors.initials: M
authors.lastname: Taghikhani
authors.forename: Ahmadreza
authors.initials: A
authors.lastname: Bahrmand
mesh_terms: D000995:Antitubercular Agents / Q000627:therapeutic use; D001426:Bacterial Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D012321:DNA-Directed RNA Polymerases; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D006801:Humans; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000235:genetics*; D015995:Prevalence; D002094:Republic of Belarus / Q000453:epidemiology; D012293:Rifampin / Q000627:therapeutic use; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors; D014376:Tuberculosis / Q000188:drug therapy / Q000453:epidemiology* / Q000235:genetics* / Q000382:microbiology; D018088:Tuberculosis, Multidrug-Resistant
chemical_list: D000995:Antitubercular Agents; D001426:Bacterial Proteins; C505805:rpoB protein, Mycobacterium tuberculosis; D012321:DNA-Directed RNA Polymerases; D012293:Rifampin