Mutation characterization of gyrA and gyrB genes in levofloxacin-resistant Mycobacterium tuberculosis clinical isolates from Guangdong Province in China

Summary 

Objective

Fluoroquinolone (FQ)-resistant Mycobacterium tuberculosis (MTB) clinical isolates have emerged in many areas of the world. The aim of this study was to observe the molecular characterization of gyrA and gyrB genes in FQ-resistant MTB clinical isolates from Guangdong Province in China.

Materials and methods

A total of 62 MTB clinical strains were originally isolated from patients with pulmonary tuberculosis. The phenotype of susceptibility of each strain was determined by the absolute concentration method and the sequences of the QRDR in gyrA and gyrB genes were detected with DNA direct sequencing technique.

Results

44 of 60 (73.3%) levofloxacin-resistant MTB clinical isolates, including 17 of 18 (94.4%) high-level resistant strains and 27 of 42 (64.3%) low-level resistant strains, had mutation in QRDR of gyrA gene. The mutation patterns involved six patterns of single codon mutation (H70R, A90V, S91A, D94G, D94A or D94N) and one pattern of double codons mutation (A90V with D94A). Of 60 levofloxacin-resistant MTB clinical isolates, only one (1.6%) mutated in gyrB gene (T511N).

Conclusions

These findings confirm that mutations of gyrA codons 90, 91 and 94 constitute the primary mechanism of FQ resistance in MTB. Furthermore, our findings indicate that the regional investigations are necessary for the comprehensive understanding of FQ resistance of MTB.

Keywords: GyrA, GyrB, Levofloxacin, Mycobacterium tuberculosis