Relationship between gyrA gene mutation in Mycobacterium tuberculosis and the minimum inhibitory concentration of fluoroquinolones in vitro

  Objective  To explore the relationship between gyrA gene mutation in Mycobacterium tuberculosis and the minimum inhibitory concentration (MIC) of fluoroquinolones in vitro.

  Methods  Clinical isolated positive strains of Mycobacterium tuberculosis in 640 patients were collected. The probe solubility curve was used to screen strains with mutation of gyrA gene in the drug resistance determining region, and sequencing of the drug resistance determining region was performed. The MICs of ofloxacin, levofloxacin, moxifloxacin and gatifloxacin for strains with mutations at different loci were detected, and the differences were analyzed.

  Results  A total of 45 strains (7.03%) with gyrA gene mutation were screened out by the probe solubility curve, including 15(33.33%) with the codon 90 mutation, 26(57.78%) with the codon 94 mutation, and 4(8.89%) with the codon 91 mutation. Among strains with the codon 90 mutation, 2 strains showed high resistance to ofloxacin, no levofloxacin-resistant strains were found, 3 showed low resistance to moxifloxacin, 2 showed high resistance to moxifloxacin, and 3 showed high resistance to gatifloxacin. Among strains with the codon 91 mutation, no ofloxacin or levofloxacin-resistant strains were found.Two strains showed high resistance to moxifloxacin, and 1 showed high resistance to gatifloxacin. Among strains with the codon 94 mutation, 4 strains showed low resistance and 7 showed highly resistant to ofloxacin, 7 showed low resistance to levofloxacin, 2 showed low resistance and 13 showed high resistance to moxifloxacin, 3 showed low resistance and 14 showed high resistance to gatifloxacin.For strains with the codon 90 mutation, except for levofloxacin, they were all highly resistant to the other drugs.Strains with the codon 91 mutation were prone to have high resistance to moxifloxacin, and strains with the codon 94 mutation were mostly highly resistant to moxifloxacin and gatifloxacin, especially those with Aspartic acid (Asp)→Asparagine (Asn) and Asp→Glycine (Gly).

  Conclusion  The type of gyrA gene mutation in Mycobacterium tuberculosis is related to the MICs of fluoroquinolones, which provides important reference for clinical medication.