%0 Journal Article
%T Association of mutation patterns in gyrA/B genes and ofloxacin resistance levels in Mycobacterium tuberculosis isolates from East China in 2009
%A Zhenling Cui
%A Jie Wang
%A Junmei Lu
%A Xiaochen Huang
%A Zhongyi Hu
%J BMC Infectious Diseases
%D 2011
%I BioMed Central
%R 10.1186/1471-2334-11-78
%X The quinolone resistance-determining region of gyrA/B were sequenced in 192 M. tuberculosis clinical isolates and the minimal inhibitory concentrations (MICs) of 95 ofloxacin-resistant M. tuberculosis isolates were determined by using microplate nitrate reductase assays.Mutations in gyrA (codons 90, 91 and 94) and in gyrB (G551R, D500N, T539N, R485C/L) were observed in 89.5% (85/95) and 11.6% (11/95) of ofloxacin-resistant strains, respectively. The gyrB mutations G551R and G549D were observed in 4.1% (4/97) of ofloxacin-susceptible strains and no mutation was found in gyrA in ofloxacin-susceptible strains. The MICs of all ofloxacin-resistant strains showed no significant difference among strains with mutations at codons 90, 91 or 94 in gyrA (F = 1.268, p = 0.287). No differences were detected among strains with different amino acid mutations in the quinolone resistance-determining region of gyrA (F = 1.877, p = 0.123). The difference in MICs between ofloxacin-resistant strains with mutations in gyrA only and ofloxacin-resistant strains with mutations in both gyrA and gyrB genes was not statistically significant (F = 0.549, p = 0.461).Although gyrA/B mutations can lead to ofloxacin resistance in M. tuberculosis, there were no associations of different mutation patterns in gyrA/B and the level of ofloxacin resistance in M. tuberculosis isolates from East China in 2009.Fluoroquinolones (FQs), such as ofloxacin (OFX), levofloxacin and moxifloxacin, are widely used anti-tubercular therapeutic agents for the treatment of multidrug-resistant tuberculosis (MTB) [1]. In mycobacteria, FQs bind to DNA gyrase and inhibit DNA replication [2]. This mechanism has been verified by the structural analysis and functional analysis of enzymes of M. tuberculosis (MTB), including DNA gyrase [3,4]. These studies showed that the MTB strains with wild-type gyrA/B genes were highly susceptible to FQs. Moreover, a murine model study showed that low-level FQ resistance could be overcome with
%U http://www.biomedcentral.com/1471-2334/11/78