Molecular characterization of rpoB gene mutations in rifampicine‐resistant Mycobacterium tuberculosis isolates from tuberculosis patients in Belarus

Abstract

The aim of this study was to investigate the frequency, location and type of rpoB mutations in Mycobacterium tuberculosis isolated from patients in Belarus. Tuberculosis cases are increasing every year in Belarus. Moreover, resistance to anti-tuberculosis drugs, especially to rifampicine, has increased. In this study, 44 rifampicine-resistance M. tuberculosis clinical isolates (including multidrug-resistant isolates) were subjected to DNA sequencing analysis of the hypervariable region (hot-spot) of the rpoB gene originating from different geographical regions in Belarus. Sixteen different types of mutations were identified. The most common point mutations were in codons 510 (47.7%), 526 (45.5%), 523 (40.86%) and 531 (29.5%). Eleven isolates (27.7%) carried one mutation and 23 (52%), 7 (16%), 3 (7%) of isolates carried 2, 3 and 4 mutations, respectively. A characteristic, prominent finding of this study was high frequency of multiple mutations in different codons of the rpoB gene (27.7%) and also the detection of unusual types of mutations in the 510 codon, comprising CAG mutations (deletion or changing, to CTG, CAC or CAT). In our study, the change TTG in codon 531 was found in 92% of isolates and the change TGC in 8% of isolates. A TAC change in codon 526 was not found, but the GAC change was found in all isolates. Isolates of M. tuberculosis isolated in Belarus were characterized by the wide spectrum of the important mutations and might belong to the epidemic widespread clones.

Extremely high prevalence of multidrug resistant tuberculosis in Murmansk, Russia: a population-based study

“…Based on the fingerprinting data, no indication of dual infection was found in these isolates. Dual or multiple mutations in the rpoB have been reported Kazakhstan [37], Turkey [39] Belarus [40] and South Korea [41] to mention a few.…”

High-Level Rifampin Resistance Correlates with Multiple Mutations in the rpoB Gene of Pulmonary Tuberculosis Isolates from the Afghanistan Border of Iran

“…The higher frequencies of mutation-bearing sites found in our data in codons 531, 526 and 523 can be partially compared with those isolates reported from other countries (6,9,13,20,24). Other authors have reported additional variations of nucleotide changes in codon 531 (in India, TCG3TGG or TTG; in Russia, TCG3TGG, CAG, or TGT; in China, TCG3TTG; in Japan, TCG3TTG; in Korea, TCG3TTG; and in Taiwan, TCG3TTG) and in codon 526 (in India, CAC3CTC, TAC, GAC, CGC, or ACC; in Russia, CAC3CTC, GAC, CAA, CAG, TGC, AAC, CGC, or CCC; in China, CAC3TAC; in Japan, CAC3TAC; in Taiwan, CAC3TAC and CGC; in Korea, CAC3TAC; and in Brazil, TCG3TTG) (6,7,13,17,20,30,31). In this study, we observed two nucleotide polymorphism changes in codon 531 among 12 isolates: 7 isolates (15.22%) changed from TCG3TTG (Ser3Leu), and 5 changed from TCG3TTC (Ser3Phe).…”

Detection of mutation in isoniazid-resistant <i> Mycobacterium tuberculosis</i> isolates from tuberculosis patients in Belarus

“…[1][2][3][4][5] Belarus is in southern endemic region of Europe with 20 to 30% multiple-drug resistant (MDR) isolates among 50.6 tuberculosis cases per 100,000 population. [6] Resistance to isoniazid is increasing in Belarus because 88% of hospitalized patients with drug resistant tuberculosis in Institute of Pulmonology and Tuberculosis (Belarus-Minsk, Magilev, Brest, Gomel, Horodna and Vitebsk] demonstrated resistance to at least isoniazid and rifampicine. [6,7] In United States, approximately 13% of isolates from new tuberculosis cases are resistant to one or more of the Þ rst-line anti tuberculosis chemotherapy and 1.6% of cases are resistant to both isoniazid and rifampicin, deÞ ned as MDR tuberculosis.…”

“…[6] Resistance to isoniazid is increasing in Belarus because 88% of hospitalized patients with drug resistant tuberculosis in Institute of Pulmonology and Tuberculosis (Belarus-Minsk, Magilev, Brest, Gomel, Horodna and Vitebsk] demonstrated resistance to at least isoniazid and rifampicine. [6,7] In United States, approximately 13% of isolates from new tuberculosis cases are resistant to one or more of the Þ rst-line anti tuberculosis chemotherapy and 1.6% of cases are resistant to both isoniazid and rifampicin, deÞ ned as MDR tuberculosis. [3,8,9] Recent worldwide surveillance has demonstrated that drug-resistant strains are now widespread and are reaching alarmingly high levels in certain countries.…”