Rifampicin and isoniazid resistance mutations in Mycobacterium tuberculosis strains isolated from patients in Kazakhstan.

Objective: To analyse possible associations of specific mutations conferring rifampicin (RMP) and isoniazid (INH) resistance with Beijing and non Beijing genotype strains of Mycobacterium tuberculosis from Kazakhstan.

Method: Genotypic analysis of 92 multidrug-resistant (MDR), 50 INH but not RMP-resistant (INHr/RMPs) and 10 fully susceptible strains of M. tuberculosis from Kazakhstan was performed. In the MDR group, 59 strains (64.1%), and within the INHr/RMPs group, 32 strains (64.0%) were classified as Beijing genotype.

Results: Analysis of the rpoB gene of the MDR strains revealed 10 different mutations in five codons, with rpoB codons 531 (65.2%), 526 (23.9%) and 516 (7.6%) most frequently affected. A significantly higher proportion of the rpoB S531L mutation was found among Beijing genotype strains compared with non Beijing strains (71.2% vs. 46.2%, P = 0.027). All 92 MDR isolates (100%), irrespective of their genotype, carried a mutation in codon 315 of the katG gene (S315T). However, in the INHr/RMPS control group, the S315T mutation was significantly more prevalent in the Beijing than in the non Beijing group (96.9% vs. 71.4%, P = 0.012).

Conclusion: The high similarity of mutations supports the assumption that transmission of resistant strains is a major reason for the emergence of drug resistance in this region.