INHIBITORY ACTIVITY OF POTENTOX AGAINST DNA GYRASE OF ENTEROBACTERIACEAE

Abstract

DNA gyrase, a type II topoisomerase catalyzes the supercoiling of relaxed closed circular DNA. In this report we evaluated the in vitro inhibitory effect of non antibiotic adjuvant compounds disodium edetate and sodium citrate against supercoiling activity of bacterial DNA gyrase. Further, we assessed the effect of different drugs alone and in combination with one or more adjuvants in overcoming FQ resistance. A total of twelve DNA gyrase mutant strains three of each Escherichia coli, Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae were used in the study. MICs of drugs were determined by the agar dilution method following the Clinical and Laboratory Standards Institute (CLSI) guidelines. Potentox was the most active against all the selected mutants of with MIC values ranging 16-32 µg mL^-1. DNA gyrase showed optimum supercoiling activity at 60 mM Mg²⁺. DNA gyrase inhibition was observed with low concentrations of disodium edetate and 50 and 100% inhibition on DNA gyrase activity was noted at approximately 4.2 and 10 mM disodium edetate. On the other hand, 50 and 100% inhibition of DNA gyrase was found at 65 and 140 mM sodium citrate. Furthermore, results revealed that Potentox inhibited the supercoiling activity of DNA gyrase at half of MIC of drug whereas other comparator drugs except gatifloxacin did not inhibit significantly the supercoiling activity of mutants as well as positive control. Potentox and gatifloxacin inhibited DNA gyrase and supercoiling at lower concentration and were the most effective. Although DNA gyrase from mutants was highly resistant to quinolones but sensitive to Potentox. Based on these results, it can be concluded that Potentox is an effective solution for the treatment of infections caused by fluoroquinolone resistant organism having DNA gyrase mutation.