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Abstract
Most multidrug-resistant (MDR) Mycobacterium tuberculosis isolates in Russia belong to the Beijing or
Latino-American and Mediterranean (LAM) spoligotype families. The objective of this study was to
investigate possible associations between genotype and the frequencies of mutations that confer drug
resistance in a population that has two large families of circulating strains. Spoligotyping, IS6110
restriction fragment length polymorphism typing, and sequencing of the katG and rpoB genes, were
performed for 217 consecutive MDR M. tuberculosis isolates from patients. The rpsL and rrs genes were
also sequenced for selected streptomycin-resistant isolates. Of the 217 MDR isolates, 99 (46%) belonged
to the LAM family, 92 (42%) to the Beijing family, 21 (10%) to the Haarlem family and four (2%) to the T
family. There was one unique spoligotype. Mutations in the katG gene were identi“ed in 207 (95%)
isolates, all of which had mutations in codon 315. Mutations in the rpoB gene were identi“ed in 200
(92%) isolates; 75% of LAM isolates carried a mutation in codon 516, whereas 71% of Beijing isolates
carried a mutation in codon 531. In the 33 isolates resistant to streptomycin 50 mg⁄ L, the 43AGG rpsL
mutation was found in 27%of Haarlem, 75%of Beijing and 0%of LAM isolates, and rrs mutations were
found in 17% (516C fi T) of Beijing and 100% (513A fi C) of LAM isolates. Overall, there appeared to
be a correlation between the genotype and speci“c mutations conferring resistance to rifampicin or
streptomycin in the Beijing and LAM families. The biological implications of this correlation remain to
be explored. |
