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The spectrum of mutations in genes associated with resistance to rifampicin, isoniazid, and fluoroquinolones in the clinical strains of M. tuberculosis reflects the transmissibility of mutant clones

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Abstract

To study the transmissibility of drug resistant mutant clones, M. tuberculosis samples were isolated from the patients of the clinical department and the polyclinic of the Central TB Research Institute (n = 1455) for 2011–2014. A number of clones were phenotypically resistant to rifampicin (n = 829), isoniazid (n = 968), and fluoroquinolones (n = 220). We have detected 21 resistance-associated variants in eight codons of rpoB, six variants in three codons of katG, three variants in two positions of inhA, four variants in four positions of ahpC, and nine variants in five codons of gyrA, which were represented in the analyzed samples with varied frequencies. Most common mutations were rpoB 531 Ser→Leu (77.93%), katG 315 (Ser→Thr) (94.11%), and gyrA 94 (Asp→Gly) (45.45%). We found that the mutations at position 15 of inhA (C→T) (frequency of 25.72%) are commonly associated with katG 315 (Ser→Thr). This association of two DNA variants may arise due to the double selection by coexposure of M. tuberculosis to isoniazid and ethionamide. The high transmissibility of mutated strains was observed, which may be explained by the minimal influence of the resistance determinants on strain viability. The high transmissibility of resistant variants may also explain the large populational prevalence of drug-resistant TB strains.

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Abbreviations

MTB:

Mycobacterium tuberculosis

SNP:

single-nucleotide polymorphism

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Authors and Affiliations

  1. Central Tuberculosis Research Institute, Moscow, 107564, Russia

    A. Ergeshov, S. N. Andreevskaya, E. E. Larionova, T. G. Smirnova & L. N. Chernousova

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  1. A. Ergeshov
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  2. S. N. Andreevskaya
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  3. E. E. Larionova
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  4. T. G. Smirnova
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  5. L. N. Chernousova
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Correspondence to S. N. Andreevskaya.

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Original Russian Text © A. Ergeshov, S.N. Andreevskaya, E.E. Larionova, T.G. Smirnova, L.N. Chernousova, 2017, published in Molekulyarnaya Biologiya, 2017, Vol. 51, No. 4, pp. 595–602.

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Ergeshov, A., Andreevskaya, S.N., Larionova, E.E. et al. The spectrum of mutations in genes associated with resistance to rifampicin, isoniazid, and fluoroquinolones in the clinical strains of M. tuberculosis reflects the transmissibility of mutant clones. Mol Biol 51, 526–532 (2017). https://doi.org/10.1134/S0026893317030049

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