title: Investigation of Smith's quinolone killing mechanisms during the PAE of ciprofloxacin on Escherichia coli.
abstract: Quinolone antibacterials interact with the DNA-DNA gyrase complex, but subsequent events that lead to cell death are unresolved. Three distinct mechanisms of quinolone lethality have been identified by Smith and co-workers: Mechanism A, which requires RNA and protein synthesis and cell division for expression; Mechanism B, which remains active when these functions are precluded; and Mechanism C, which is active on non-dividing cells. Exposure to 4x MIC ciprofloxacin (Cip) in nutrient broth (NB) for 3 h reduced the viability of Escherichia coli AB1157 to 0.25%. Addition of rifampicin (Rif) or chloramphenicol (Cm), to inhibit RNA or protein synthesis, respectively, increased survival 70-fold. Treatment of cells with Cip in phosphate-buffered saline (PBS), to inhibit cell division, increased survival 20-fold. No further cell death occurred once the various drug combinations or PBS had been washed out and cells resuspended in drug-free nutrient broth. These latter conditions allow expression of the post-antibiotic effect (PAE). PAE was lengthened in cells exposed to Cip in the presence of Rif or Cm, probably as a result of delay in the initiation of inducible DNA repair.
authors.affiliation: Microbiology Section, Department of Pharmaceutics, The School of Pharmacy, University of London, Brunswick Square, London WC1N 1AX, UK.
authors.forename: H J
authors.initials: HJ
authors.lastname: Wickens
authors.forename: R J
authors.initials: RJ
authors.lastname: Pinney
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002701:Chloramphenicol / Q000494:pharmacology*; D002939:Ciprofloxacin / Q000494:pharmacology*; D004347:Drug Interactions; D004926:Escherichia coli / Q000187:drug effects*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D012293:Rifampin / Q000494:pharmacology*
chemical_list: D000890:Anti-Infective Agents; D011500:Protein Synthesis Inhibitors; D002939:Ciprofloxacin; D002701:Chloramphenicol; D012293:Rifampin