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.


METHODS
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).


CONCLUSIONS
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.
Hillemann
D
D
National Reference Center for Mycobacteria, Forschungszentrum Borstel, Borstel, Germany. dhillemann@fz-borstel.de
Kubica
T
T
Agzamova
R
R
Venera
B
B
Rüsch-Gerdes
S
S
Niemann
S
S
D000995:Antitubercular Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics*; D003062:Codon; D005838:Genotype; D006801:Humans; D007538:Isoniazid / Q000494:pharmacology*; D007623:Kazakhstan / Q000453:epidemiology; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics*; D012293:Rifampin / Q000494:pharmacology*; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy* / Q000453:epidemiology
D000995:Antitubercular Agents; D001426:Bacterial Proteins; D003062:Codon; D007538:Isoniazid; D012293:Rifampin