Genotypic analysis of genes associated with independent resistance and cross-resistance to isoniazid and ethionamide in Mycobacterium tuberculosis clinical isolates

Johana Rueda, Teresa Realpe, Gloria Isabel Mejia, Elsa Zapata, Juan Carlos Rozo, Beatriz Eugenia Ferro, Jaime Robledo

    Resultado de la investigación: Contribución a una revistaArtículorevisión exhaustiva

    33 Citas (Scopus)

    Resumen

    Ethionamide (ETH) is an antibiotic used for the treatment of multidrug-resistant (MDR) tuberculosis (TB) (MDR-TB), and its use may be limited with the emergence of resistance in the Mycobacterium tuberculosis population. ETH resistance in M. tuberculosis is phenomenon independent or cross related when accompanied with isoniazid (INH) resistance. In most cases, resistance to INH and ETH is explained by mutations in the inhA promoter and in the following genes: katG, ethA, ethR, mshA, ndh, and inhA. We sequenced the above genes in 64 M. tuberculosis isolates (n=57 ETH-resistant MDR-TB isolates; n=3 ETH-susceptible MDR-TB isolates; and n=4 fully susceptible isolates). Each isolate was tested for susceptibility to first- and second-line drugs using the agar proportion method. Mutations were observed in ETH-resistant MDR-TB isolates at the following rates: 100% in katG, 72% in ethA, 45.6% in mshA, 8.7% in ndh, and 33.3% in inhA or its promoter. Of the three ETH-susceptible MDR-TB isolates, all showed mutations in katG; one had a mutation in ethA, and another, in mshA and inhA. Finally, of the four fully susceptible isolates, two showed no detectable mutation in the studied genes, and two had mutations in mshA gene unrelated to the resistance. Mutations not previously reported were found in the ethA, mshA, katG, and ndh genes. The concordance between the phenotypic susceptibility testing to INH and ETH and the sequencing was 1 and 0.45, respectively. Among isolates exhibiting INH resistance, the high frequency of independent resistance and cross-resistance with ETH in the M. tuberculosis isolates suggests the need to confirm the susceptibility to ETH before considering it in the treatment of patients with MDR-TB.

    Idioma originalInglés
    Páginas (desde-hasta)7805-7810
    Número de páginas6
    PublicaciónAntimicrobial Agents and Chemotherapy
    Volumen59
    N.º12
    DOI
    EstadoPublicada - 1 dic. 2015

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    Publisher Copyright:
    Copyright © 2015, American Society for Microbiology. All Rights Reserved.

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