Correlation of gyr Mutations with the Minimum Inhibitory Concentrations of Fluoroquinolones among Multidrug-Resistant Mycobacterium tuberculosis 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 gyr mutations among Mtb isolates with the MICs of M...

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Autores principales:	Mohammad Khaja Mafij Uddin, Md. Fahim Ather, Rumana Nasrin, Tanjina Rahman, A. S. M. Iftekhairul Islam, S. M. Mazidur Rahman, Shahriar Ahmed, Sayera Banu
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	<i>gyr</i> mutations fluoroquinolones minimum inhibitory concentrations <i>Mycobacterium tuberculosis</i> Medicine R
Acceso en línea:	https://doaj.org/article/20fdd82a7c5a4297a4525a2fb71cce86
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spelling	oai:doaj.org-article:20fdd82a7c5a4297a4525a2fb71cce862021-11-25T18:38:09ZCorrelation of <i>gyr</i> Mutations with the Minimum Inhibitory Concentrations of Fluoroquinolones among Multidrug-Resistant <i>Mycobacterium tuberculosis</i> Isolates in Bangladesh10.3390/pathogens101114222076-0817https://doaj.org/article/20fdd82a7c5a4297a4525a2fb71cce862021-11-01T00:00:00Zhttps://www.mdpi.com/2076-0817/10/11/1422https://doaj.org/toc/2076-0817Fluoroquinolone (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.Mohammad Khaja Mafij UddinMd. Fahim AtherRumana NasrinTanjina RahmanA. S. M. Iftekhairul IslamS. M. Mazidur RahmanShahriar AhmedSayera BanuMDPI AGarticle<i>gyr</i> mutationsfluoroquinolonesminimum inhibitory concentrations<i>Mycobacterium tuberculosis</i>MedicineRENPathogens, Vol 10, Iss 1422, p 1422 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	<i>gyr</i> mutations fluoroquinolones minimum inhibitory concentrations <i>Mycobacterium tuberculosis</i> Medicine R
spellingShingle	<i>gyr</i> mutations fluoroquinolones minimum inhibitory concentrations <i>Mycobacterium tuberculosis</i> Medicine R Mohammad Khaja Mafij Uddin Md. Fahim Ather Rumana Nasrin Tanjina Rahman A. S. M. Iftekhairul Islam S. M. Mazidur Rahman Shahriar Ahmed Sayera Banu Correlation of <i>gyr</i> Mutations with the Minimum Inhibitory Concentrations of Fluoroquinolones among Multidrug-Resistant <i>Mycobacterium tuberculosis</i> Isolates in Bangladesh
description	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.
format	article
author	Mohammad Khaja Mafij Uddin Md. Fahim Ather Rumana Nasrin Tanjina Rahman A. S. M. Iftekhairul Islam S. M. Mazidur Rahman Shahriar Ahmed Sayera Banu
author_facet	Mohammad Khaja Mafij Uddin Md. Fahim Ather Rumana Nasrin Tanjina Rahman A. S. M. Iftekhairul Islam S. M. Mazidur Rahman Shahriar Ahmed Sayera Banu
author_sort	Mohammad Khaja Mafij Uddin
title	Correlation of <i>gyr</i> Mutations with the Minimum Inhibitory Concentrations of Fluoroquinolones among Multidrug-Resistant <i>Mycobacterium tuberculosis</i> Isolates in Bangladesh
title_short	Correlation of <i>gyr</i> Mutations with the Minimum Inhibitory Concentrations of Fluoroquinolones among Multidrug-Resistant <i>Mycobacterium tuberculosis</i> Isolates in Bangladesh
title_full	Correlation of <i>gyr</i> Mutations with the Minimum Inhibitory Concentrations of Fluoroquinolones among Multidrug-Resistant <i>Mycobacterium tuberculosis</i> Isolates in Bangladesh
title_fullStr	Correlation of <i>gyr</i> Mutations with the Minimum Inhibitory Concentrations of Fluoroquinolones among Multidrug-Resistant <i>Mycobacterium tuberculosis</i> Isolates in Bangladesh
title_full_unstemmed	Correlation of <i>gyr</i> Mutations with the Minimum Inhibitory Concentrations of Fluoroquinolones among Multidrug-Resistant <i>Mycobacterium tuberculosis</i> Isolates in Bangladesh
title_sort	correlation of <i>gyr</i> mutations with the minimum inhibitory concentrations of fluoroquinolones among multidrug-resistant <i>mycobacterium tuberculosis</i> isolates in bangladesh
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/20fdd82a7c5a4297a4525a2fb71cce86
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Correlation of <i>gyr</i> Mutations with the Minimum Inhibitory Concentrations of Fluoroquinolones among Multidrug-Resistant <i>Mycobacterium tuberculosis</i> Isolates in Bangladesh

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