Abstract
BackgroundThis study aimed to analyze the association of mutation patterns in gyrA and gyrB genes and the ofloxacin resistance levels in clinical Mycobacterium tuberculosis isolates sampled in 2009 from East China.MethodsThe 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.ResultsMutations 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).ConclusionsAlthough 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.
Highlights
This study aimed to analyze the association of mutation patterns in gyrA and gyrB genes and the ofloxacin resistance levels in clinical Mycobacterium tuberculosis isolates sampled in 2009 from East China
Reports show that the majority of FQ-resistant multidrugresistant tuberculosis (MTB) isolates carry mutations in the quinolone resistance-determining region (QRDR) of the gyrA gene [2,10,11,12,13,14,15], and that a small number have mutations in the gyrB gene [16,17]
This study aimed to investigate whether different mutations in gyrA/gyrB could lead to different levels of FQ-resistance in MTB strains
Summary
This study aimed to analyze the association of mutation patterns in gyrA and gyrB genes and the ofloxacin resistance levels in clinical Mycobacterium tuberculosis isolates sampled in 2009 from East China. 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. a murine model study showed that low-level FQ resistance could be overcome with the use of high dose moxifloxacin [5]. We analyzed the association of OFX resistance levels and the characterization of different mutations in gyrA/gyrB related to this resistance in clinical MTB isolates from East China
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