Characterizing the gene mutations associated with resistance to gatifloxacin in Mycobacterium tuberculosis through whole-genome sequencing

ABSTRACT: Objectives: Gatifloxacin (GAT), a fourth-generation fluoroquinolone (FQ), is used to treat drug-resistant tuberculosis. Although DNA gyrase mutations are the leading cause of FQ resistance, mutations conferring resistance to GAT remain inadequately characterized. Methods: GAT-resistant mu...

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Autores principales:	Jing Bi, Qinglong Guo, Xiangdong Fu, Juan Liang, Lidong Zeng, Min Ou, Juanjuan Zhang, Zhaoqin Wang, Yicheng Sun, Lei Liu, Guoliang Zhang
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Mycobacterium tuberculosis Fluoroquinolones Gatifloxacinresistance gyrA (Rv0005) gyrB (Rv0006) Infectious and parasitic diseases RC109-216
Acceso en línea:	https://doaj.org/article/405b5d381a1b449b815947176ecf4040
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spelling	oai:doaj.org-article:405b5d381a1b449b815947176ecf40402021-11-30T04:14:15ZCharacterizing the gene mutations associated with resistance to gatifloxacin in Mycobacterium tuberculosis through whole-genome sequencing1201-971210.1016/j.ijid.2021.09.028https://doaj.org/article/405b5d381a1b449b815947176ecf40402021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S1201971221007359https://doaj.org/toc/1201-9712ABSTRACT: Objectives: Gatifloxacin (GAT), a fourth-generation fluoroquinolone (FQ), is used to treat drug-resistant tuberculosis. Although DNA gyrase mutations are the leading cause of FQ resistance, mutations conferring resistance to GAT remain inadequately characterized. Methods: GAT-resistant mutants were selected from 7H10 agar plates containing 0.5 mg/L GAT (critical concentration). Mutations involved in GAT resistance were identified through whole-genome sequencing. Results: In total, 123 isolates demonstrated resistance to GAT. Among these isolates, 55.3% (68/123) had gyrA gene mutations [G280A (D94N), A281G (D94G), G280T (D94Y) and G262T (G88C)]. The remainder (44.7%, 55/123) harboured gyrB gene mutations [A1495G (N499D), C1497A (N499K), C1497G (N499K) and A1503C (E501D)]. Conclusions: Mutations in the gyrA and gyrB genes are the main mechanisms of GAT resistance. These findings provide new insight into GAT resistance, and contribute to molecular diagnosis of GAT resistance in the clinical setting.Jing BiQinglong GuoXiangdong FuJuan LiangLidong ZengMin OuJuanjuan ZhangZhaoqin WangYicheng SunLei LiuGuoliang ZhangElsevierarticleMycobacterium tuberculosisFluoroquinolonesGatifloxacinresistancegyrA (Rv0005)gyrB (Rv0006)Infectious and parasitic diseasesRC109-216ENInternational Journal of Infectious Diseases, Vol 112, Iss , Pp 189-194 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Mycobacterium tuberculosis Fluoroquinolones Gatifloxacinresistance gyrA (Rv0005) gyrB (Rv0006) Infectious and parasitic diseases RC109-216
spellingShingle	Mycobacterium tuberculosis Fluoroquinolones Gatifloxacinresistance gyrA (Rv0005) gyrB (Rv0006) Infectious and parasitic diseases RC109-216 Jing Bi Qinglong Guo Xiangdong Fu Juan Liang Lidong Zeng Min Ou Juanjuan Zhang Zhaoqin Wang Yicheng Sun Lei Liu Guoliang Zhang Characterizing the gene mutations associated with resistance to gatifloxacin in Mycobacterium tuberculosis through whole-genome sequencing
description	ABSTRACT: Objectives: Gatifloxacin (GAT), a fourth-generation fluoroquinolone (FQ), is used to treat drug-resistant tuberculosis. Although DNA gyrase mutations are the leading cause of FQ resistance, mutations conferring resistance to GAT remain inadequately characterized. Methods: GAT-resistant mutants were selected from 7H10 agar plates containing 0.5 mg/L GAT (critical concentration). Mutations involved in GAT resistance were identified through whole-genome sequencing. Results: In total, 123 isolates demonstrated resistance to GAT. Among these isolates, 55.3% (68/123) had gyrA gene mutations [G280A (D94N), A281G (D94G), G280T (D94Y) and G262T (G88C)]. The remainder (44.7%, 55/123) harboured gyrB gene mutations [A1495G (N499D), C1497A (N499K), C1497G (N499K) and A1503C (E501D)]. Conclusions: Mutations in the gyrA and gyrB genes are the main mechanisms of GAT resistance. These findings provide new insight into GAT resistance, and contribute to molecular diagnosis of GAT resistance in the clinical setting.
format	article
author	Jing Bi Qinglong Guo Xiangdong Fu Juan Liang Lidong Zeng Min Ou Juanjuan Zhang Zhaoqin Wang Yicheng Sun Lei Liu Guoliang Zhang
author_facet	Jing Bi Qinglong Guo Xiangdong Fu Juan Liang Lidong Zeng Min Ou Juanjuan Zhang Zhaoqin Wang Yicheng Sun Lei Liu Guoliang Zhang
author_sort	Jing Bi
title	Characterizing the gene mutations associated with resistance to gatifloxacin in Mycobacterium tuberculosis through whole-genome sequencing
title_short	Characterizing the gene mutations associated with resistance to gatifloxacin in Mycobacterium tuberculosis through whole-genome sequencing
title_full	Characterizing the gene mutations associated with resistance to gatifloxacin in Mycobacterium tuberculosis through whole-genome sequencing
title_fullStr	Characterizing the gene mutations associated with resistance to gatifloxacin in Mycobacterium tuberculosis through whole-genome sequencing
title_full_unstemmed	Characterizing the gene mutations associated with resistance to gatifloxacin in Mycobacterium tuberculosis through whole-genome sequencing
title_sort	characterizing the gene mutations associated with resistance to gatifloxacin in mycobacterium tuberculosis through whole-genome sequencing
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/405b5d381a1b449b815947176ecf4040
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Characterizing the gene mutations associated with resistance to gatifloxacin in Mycobacterium tuberculosis through whole-genome sequencing

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