MECHANISMS OF FLUOROQUINOLONE RESISTANCE IN GENETICALLY RELATED STRAINS OF STAPHYLOCOCCUS-AUREUS

Fluoroquinolone resistance in Staphylococcus aureus results from amino acid substitutions at particular locations in the DNA gyrase A and B subunits as well as in the topoisomerase TV A subunit and from NorA-me diated efflux. More than one resistance mechanism may be present in a single strain, Fluoroquinolone-resistant derivatives of SA-1199, a met hicillin-susceptible S. aureus strain, were selected in vivo or in vit ro, and their mechanisms of fluoroquinolone resistance were identified , We found that many of the resistance mechanisms described above can develop in derivatives of a single parent strain, either singly or in combination, and can arise in a single step. Variances in MICs for str ains with the same apparent resistance mechanisms likely are due to th e presence of new or undetected but established means of fluoroquinolo ne resistance, NorA-mediated resistance can occur in the apparent abse nce of topoisomerase mutations and in some strains may be the result o f a promoter region mutation causing increased expression of norA. How ever, increased expression of norA can occur independently of this mut ation, suggesting that a regulatory locus for this gene exists elsewhe re on the chromosome.