Analysis of macromolecular biosynthesis to define the quinolone-induced postantibiotic effect in Escherichia coli.

Quinolones inhibit DNA gyrase, and the major effects of this inhibition are on replication and transcription of DNA. The postantibiotic effect (PAE) refers to continued inhibition of cell division, in terms of the viable count, following transient exposure to an antibiotic. Previous work has shown that quinolone-treated cells have not fully recovered by the time the classically defined PAE has ended. We describe the PAE of the quinolones CI-960, enoxacin, and ciprofloxacin on macromolecular biosynthesis in the clinical isolate Escherichia coli J96 in an attempt to relate the PAE to the time that it actually takes for the cells to recover fully. DNA synthesis was inhibited immediately upon exposure to these quinolones at 0.5x or 0.75x the MIC. This inhibition continued for several hours following quinolone removal. The effects of these quinolones on RNA and protein synthesis varied; enoxacin treatment at 0.5x the MIC resulted in an increase of over 60% in both RNA and protein synthesis per unit of cell mass, while ciprofloxacin and CI-960 at that level had no significant effects on either RNA or protein synthesis. The effects of enoxacin and ciprofloxacin on bacterial protein profiles were also distinguishable, and these changes corresponded to their PAE on DNA synthesis. Throughout the study, all measures of the physiological status of the cells returned to normal by the time DNA synthesis per unit of cell mass did so. These results suggest that DNA synthesis per unit of cell mass provides an accurate measure of the time required for quinolone-treated cells to recover fully.