Influence of lineage-specific amino acid dimorphisms in GyrA on Mycobacterium tuberculosis resistance to fluoroquinolones.

We conducted in vitro DNA supercoiling assays, utilizing recombinant DNA gyrases, to elucidate the influence of the lineage-specific serine or threonine residue at position 95 of GyrA on fluoroquinolone resistance in Mycobacterium tuberculosis. There was little effect of the GyrA-Ala74Ser amino acid substitution on activity of the GyrA-Ser95 gyrase, while activity of the GyrA-Asp94Gly-Ser95 gyrase was reduced. These findings were in striking contrast to previous reports analyzing GyrA with Thr95 and suggest an important impact of the amino acid in the development of fluoroquinolone resistance.