Effects of Mutations in GrlA of Topoisomerase IV from Staphylococcus aureus on Quinolone and Coumarin Activity

The grlA genes of Staphylococcus aureus ISP794 (wild type), MT5224c4 (grlA [Phe-80]), MT5224c2 (grlA [Pro-116]), and MT111 (grlA [Glu-116]) were cloned in pSK950, a shuttle vector, and introduced into S. aureus strains derived from strain RN4220. The mutations at position 116 of GrlA (Ala→Pro or Glu) caused an increase in the level of fluoroquinolone resistance and a decrease in the level of coumarin susceptibility, whereas the mutation at position 80 (Ser→Phe) caused only an increase in the level of fluoroquinolone resistance. In multicopy alleles, both types of mutations were codominant for fluoroquinolone resistance, and mutations at position 116 were also codominant for coumarin resistance.