Correlation of <i>gyr</i> Mutations with the Minimum Inhibitory Concentrations of Fluoroquinolones among Multidrug-Resistant <i>Mycobacterium tuberculosis</i> Isolates in Bangladesh
Fluoroquinolone (FQ) compounds—moxifloxacin (MOX), levofloxacin (LEV), and ofloxacin (OFL)—are used to treat multidrug-resistant tuberculosis (MDR-TB) globally. In this study, we investigated the correlation of <i>gyr</i> mutations among <i>Mtb</i> isolates with the MICs of M...
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| Autores principales: | , , , , , , , |
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| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
MDPI AG
2021
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/20fdd82a7c5a4297a4525a2fb71cce86 |
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| Sumario: | Fluoroquinolone (FQ) compounds—moxifloxacin (MOX), levofloxacin (LEV), and ofloxacin (OFL)—are used to treat multidrug-resistant tuberculosis (MDR-TB) globally. In this study, we investigated the correlation of <i>gyr</i> mutations among <i>Mtb</i> isolates with the MICs of MOX, LEV, and OFL in Bangladesh. A total of 50 MDR-TB isolates with <i>gyr</i> mutations, detected by the GenoType MTBDR<i>sl</i> assay, were subjected to drug susceptibility testing to determine the MICs of the FQs. Spoligotyping was performed to correlate the genetic diversity of the gyr mutant isolates with different MIC distributions. Among the 50 isolates, 44 (88%) had mutations in the <i>gyrA</i> gene, one (2%) had a mutation in the <i>gyrB</i> gene, and five (10%) isolates had unidentified mutations. The substitutions in the <i>gyrA</i> region were at A90V (<i>n</i> = 19, 38%), D94G (<i>n</i> = 16, 32%), D94A (<i>n</i> = 4, 8%), D94N/D94Y (<i>n</i> = 4, 8%), and S91P (<i>n</i> = 1, 2%), compared to the <i>gyrB</i> gene at N538D (<i>n</i> = 1.2%). D94G mutations showed the highest MICs for MOX, LEV, and OFL, ranging between 4.0 and 8.0 μg/mL, 4.0 and 16.0 μg/mL, and 16.0 and 32.0 μg/mL, respectively; while the most common substitution of A90V showed the lowest ranges of MICs (1.0–4.0 μg/mL, 2.0–8.0 μg/mL, and 4.0–32.0 μg/mL, respectively). Spoligotyping lineages demonstrated no significant differences regarding the prevalence of different <i>gyr</i> mutations. In conclusion, the substitutions of codon A90V and D94G in the <i>gyr</i> genes were mostly responsible for the FQs’ resistance among <i>Mtb</i> isolates in Bangladesh. Low levels of resistance were associated with the substitutions of A90V, while the D94G substitutions were associated with a high level of resistance to all FQs. |
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