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Genotypic assessment of rifampin resistance in Mycobacterium tuberculosis isolated in Belarus

Abstract number: p1255

Slizen  V., Zaker  S., Surkova  L., Bahrmand  A., Taghikhani  M., Titov  L.

Objectives: 

The mechanism of resistance to rifampin involves missense mutations in 81-bp fragment of rpo B gene with the majority of mutations occurring at codons 531, 526, 516, 511. Profile of mutations in rpo B gene depends on geographical region. The aim of the study was to identify mutations associated with rifampin resistance in strains isolated in Belarus.

Methods: 

Susceptibility to RMP and INH in 44 clinical isolates of Mycobacterium tuberculosis was determined by internationally accepted reference technique, their rpo B gene (305 bp region) was amplified and autosequenced.

Results: 

All 44 tested strains displaying resistance to isoniazid (0.1 mg/mL) and rifampin (2 mg/mL) had point mutations in 1–4 separate codons with the prevalence of double mutations. l, 2, 3 and 4 mutations carried 11 (25%), 22(50%), 8 (18%), 4 (7%) strains respectively. Most of the mutations (80%) were located in 510, 526, 523, 531 codons accounted for resistance in 50, 45.5, 40.9, 29.5% of isolates correspondingly. The rpoB codons 531, 526, 516, 511 were reported to be the most frequently mutated codons worldwide. In Belarus, in contrast to other studies, most common codons affected by point mutations were 510 and 523. Point mutations in codons 508, 507, 512, 516, 520, 522, 521, 525 occurred in 2.3–9.1% of isolates. Most of the detected mutations led to alterations of coding aminoacids and only 7 mutations were silent. Mutations occurred in codon 510 resulted in replacement of Gln to Glu (59%) or Lys (13.6%) or generated stop codon. Mutations in codon 526 led to substitution His > Asp (85%) or His > Leu, in codon 523 there were revealed substitution Gly > Ala (78%) or silent mutations, in codon 531 – Ser > Leu (one strain displayed Ser > Lys).

Conclusion: 

It was revealed geographical variation in rpo B gene mutations profile in Mycobacterium tuberculosis isolates from Belarus, characterised by high frequency of double, triple, quadruple mutations and mutations localised in 510 and 523 codons.

Session Details

Date: 01/08/2007
Time: 00:00-00:00
Session name: XXIst ISTH Congress
Subject:
Location: Oxford, UK
Presentation type:
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