Seven nalidixic acid-resistant clinical isolates of Escherichia coli were shown to carry resistance mutations in their gyrase A proteins. Six had serine-83 to leucine or tryptophan changes; the seventh had an aspartate-87 to valine substitution. The frequent occurrence of a mutation at serine-83 implies a key role for this residue in quinolone action.Antimicrobial 4-quinolones exert their potent antagonistic effects on bacterial DNA replication by inhibiting DNA gyrase, an A2B2 tetrameric enzyme that catalyzes ATPdependent DNA supercoiling (4, 6-8, 10, 13, 23). Gyrase promotes the negative supercoiling of DNA and the formation and resolution of interlocked DNA circles and knotted DNA by passing a DNA duplex through a transient enzymebridged double-strand break in DNA (22). Studies with purified Escherichia coli DNA gyrase have shown that quinolones interfere with DNA breakage and reunion mediated by Tyr-122 of the 875-residue gyrase A subunits (6, 12).

The gyrA genes isolated from three ciprofloxacin-resistant clinical isolates of Staphylococcus aureus carried codon 84 (serine-leucine) and/or codon 85 (serine-*proline) mutations that were absent in pretreatment susceptible strains. These substitutions occur in a region of the gyrase A protein wherein directly analogous mutations of serine 83-*leucine and alanine 84->proline in Escherichia coli confer quinolone resistance. Thus, DNA gyrase A subunit mutations are implicated in resistance to ciprofloxacin in S. aureus.