[Molecular genetic characteristics of rifampicin-resistant Mycobacterium tuberculosis isolates in Novosibirsk].

: Forty rifampicin-resistant clinical isolates from patients living in Novosibirsk were studied. Six alleles earlier described in the literature were identified by the sequencing technique. The frequency of mutations in the studied samples slightly differs from that earlier reported for other geographic regions: 21 (52.5%) strains carried the mutated codon TTG in position 531 (Ser-->Leu), 7 (17.5%) had GTC in position 516 (Asp-->Val) and 2 (5%) had the GAC substitution in position 526 (His-->Asp), which is prevalent elsewhere. Sequence analysis revealed no mitations in 5 (12.5%) of the 40 isolates although this isolate was repeatedly resistant to rifampicin. VNTR-typing targeted to tandem repeats (ETR A, B, C, D, and E) was carried out to establish a genetic relationship for rifampicin-resistant isolates. Nine genetic types with VNTR-profiles termed as 12322, 32122, 32123, 32124, 32125, 32522, 23524, 12223, 22222, 33433 were revealed. There was no strict correlation between the type of mutation in the rpoB gene and the VNTR-type, which reflects different rates of evolution and the level of selective pressure on these genetic targets. The isolates of VNTR-types 32123 and 32125 with mutations in codon 531, and type 32122 in codons 531, 526, 516 showed a high clustering. This is likely to reflect the recent transmission and clonal dissemination of the epidemic strains of Mycobacterium tuberculosis. Thus, mutations in the rpoB gene did not reduce the virulence and transmissivity of these clones. Twenty-six of 27 clinical isolates selected by rifampicin-resistance were also resistant to isoniazid, which confirms the known fact that rifampicin-resistance may be used as a marker of isoniazid-resistance.