title: Association of gyrA/B mutations and resistance levels to fluoroquinolones in clinical isolates of Mycobacterium tuberculosis.
abstract: To evaluate the association between mutations in the genes gyrA/B and resistance levels to fluoroquinolones in clinical isolates of Mycobacterium tuberculosis, a total of 80 ofloxacin-resistant isolates collected in 2009 by the Shanghai Municipal Centers for Disease Control and Prevention were studied. The minimum inhibitory concentration (MIC) of ofloxacin, moxifloxacin and gatifloxacin for each isolate was determined using the microscopic observation drug susceptibility assay. Sequencing was used to identify mutations in the quinolone resistance-determining region (QRDR) of the gyrA and gyrB genes. In total, 68 isolates had mutations in gyrA, three isolates had mutations in gyrB, six isolates had mutations in both gyrA and gyrB, and three isolates had no mutations. Two common mutations in gyrA, the D94G and D94N mutations, were associated with higher-level resistance to all three fluoroquinolones than two other common mutations (A90V and D94A). Understanding the relationship between MICs and mutations in ofloxacin-resistant isolates will facilitate the optimization of the use of new-generation fluoroquinolones to treat patients with ofloxacin-resistant tuberculosis (TB).
authors.affiliation: The Department of TB Control, Shanghai Municipal Centers for Disease Control and Prevention , Shanghai 200336, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Key Laboratory of Medical Molecular Virology of the Ministries of Education and Health, Institutes of Biomedical Sciences and the Institute of Medical Microbiology, School of Basic Medical Sciences, Fudan University , Shanghai 200032, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Gao
authors.affiliation: Key Laboratory of Medical Molecular Virology of the Ministries of Education and Health, Institutes of Biomedical Sciences and the Institute of Medical Microbiology, School of Basic Medical Sciences, Fudan University , Shanghai 200032, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Luo
authors.affiliation: The Department of TB Control, Shanghai Municipal Centers for Disease Control and Prevention , Shanghai 200336, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Wu
authors.affiliation: Key Laboratory of Medical Molecular Virology of the Ministries of Education and Health, Institutes of Biomedical Sciences and the Institute of Medical Microbiology, School of Basic Medical Sciences, Fudan University , Shanghai 200032, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Sun
authors.affiliation: Key Laboratory of Medical Molecular Virology of the Ministries of Education and Health, Institutes of Biomedical Sciences and the Institute of Medical Microbiology, School of Basic Medical Sciences, Fudan University , Shanghai 200032, China.
authors.forename: Qingyun
authors.initials: Q
authors.lastname: Liu
authors.affiliation: The Department of TB Control, Shanghai Municipal Centers for Disease Control and Prevention , Shanghai 200336, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: The Department of TB Control, Shanghai Municipal Centers for Disease Control and Prevention , Shanghai 200336, China.
authors.forename: Yangyi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: The Department of TB Control, Shanghai Municipal Centers for Disease Control and Prevention , Shanghai 200336, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Mei
authors.affiliation: Key Laboratory of Medical Molecular Virology of the Ministries of Education and Health, Institutes of Biomedical Sciences and the Institute of Medical Microbiology, School of Basic Medical Sciences, Fudan University , Shanghai 200032, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Gao
keywords: M. tuberculosis; MICs; fluoroquinolones; mutations