Detection of mutations associated with isoniazid resistance in multidrug-resistant Mycobacterium tuberculosis clinical isolates

Jagielski, Tomasz; Bakuła, Zofia; Roeske, Katarzyna; Kamiński, Michał; Napiórkowska, Agnieszka; Augustynowicz–Kopeć, Ewa; Zwolska, Zofia; Bielecki, Jacek

doi:10.1093/jac/dku161

Cited by 62 publications

(51 citation statements)

References 27 publications

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“…All isolates of the LAM lineage had alteration at nucleotide 513 in the rrs gene. Several studies have reported rrs mutations in this lineage [12,32]. Based on MIRU-VNTR genotyping, the most prevalent genotype was Beijing.…”

Section: Discussionmentioning

confidence: 99%

Frequency of rrs and rpsL mutations in streptomycin-resistant Mycobacterium tuberculosis isolates from Iranian patients

Khosravi

Etemad

Hashemzadeh

et al. 2017

Journal of Global Antimicrobial Resistance

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Section: Discussionmentioning

confidence: 99%

Frequency of rrs and rpsL mutations in streptomycin-resistant Mycobacterium tuberculosis isolates from Iranian patients

Khosravi

Etemad

Hashemzadeh

et al. 2017

Journal of Global Antimicrobial Resistance

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“…The mutation-carrying genes, such as those encoding the enzymes KatG (11,12) and EthA (13,14), are associated with individual resistance to INH and ETH, respectively. Mutations at the inhA promoter region or inhA gene result in the overexpression or modification of the InhA target, causing cross-resistance to INH and ETH (8,15).…”

Section: Ethionamide (Eth) Is An Antibiotic Used For the Treatment Ofmentioning

confidence: 99%

Genotypic Analysis of Genes Associated with Independent Resistance and Cross-Resistance to Isoniazid and Ethionamide in Mycobacterium tuberculosis Clinical Isolates

Rueda

Realpe

Mejía

et al. 2015

Antimicrob Agents Chemother

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d 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. E thionamide (ETH), a structural analog of isoniazid (INH), is a second-line drug used in the treatment of multidrug-resistant tuberculosis (MDR-TB) (1). Both ETH and INH are classified as prodrugs that are activated by different mycobacterial enzymes. INH is activated by the katG-encoded catalase-peroxidase, and ETH is activated by the ethA-encoded monooxygenase (2, 3). The activated INH and ETH drugs share the same molecular target, i.e., the NADH-dependent enoyl-acyl carrier protein reductase InhA, which is involved in the long-chain mycolic acid biosynthesis pathway (4). Therefore, the cross-resistance between INH and ETH can be detected in Mycobacterium tuberculosis clinical isolates in the case of mutations affecting the common target, which may occur when patients have previously been treated with INH and not with ETH (5). The frequency of cross-resistance differs between countries: 100% in Korea (6), 95.12% in Argentina (7), 94% in Brazil (8), 62% in France (9), and 13.8% in Thailand (10).Resistance to INH and ETH is mainly due to the chromosomal mutations. The mutation-carrying genes, such as those encoding the enzymes KatG (11,12) and EthA (13,14), are associated with individual resistance to INH and ETH, respectively. Mutations at the inhA promoter region or inhA gene result in the ove...

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“…The transmission of strains resistant to both rifampin (RIF) and isoniazid (INH), i.e., multidrug-resistant (MDR) strains, remains a public health problem. These strains may harbor mutations in rpoB (2,3), katG, and inhA, among other genomic regions (4,5). The aim of this study was to evaluate the diagnostic accuracy of the GenoFlow DR-MTB array test (DiagCor Bioscience, Hong Kong) for the detection of M. tuberculosis molecular resistance to RIF and INH.…”

mentioning

confidence: 99%

Evaluation of GenoFlow DR-MTB Array Test for Detection of Rifampin and Isoniazid Resistance in Mycobacterium tuberculosis

et al. 2016

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Detection of mutations associated with isoniazid resistance in multidrug-resistant Mycobacterium tuberculosis clinical isolates

Cited by 62 publications

References 27 publications

Frequency of rrs and rpsL mutations in streptomycin-resistant Mycobacterium tuberculosis isolates from Iranian patients

Frequency of rrs and rpsL mutations in streptomycin-resistant Mycobacterium tuberculosis isolates from Iranian patients

Genotypic Analysis of Genes Associated with Independent Resistance and Cross-Resistance to Isoniazid and Ethionamide in Mycobacterium tuberculosis Clinical Isolates

Evaluation of GenoFlow DR-MTB Array Test for Detection of Rifampin and Isoniazid Resistance in Mycobacterium tuberculosis

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