Investigation of Smith's quinolone killing mechanisms during the PAE of ciprofloxacin on Escherichia coli
| Autor: | R. J. Pinney, Hayley J Wickens |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Protein Synthesis Inhibitors
Programmed cell death Cell division Cell Survival medicine.drug_class DNA repair Chloramphenicol Pharmaceutical Science Biology medicine.disease_cause Quinolone DNA gyrase Microbiology Anti-Infective Agents Ciprofloxacin Escherichia coli medicine Protein biosynthesis Drug Interactions Rifampin Cells Cultured medicine.drug |
| Zdroj: | International Journal of Pharmaceutics. 227:149-156 |
| ISSN: | 0378-5173 |
| DOI: | 10.1016/s0378-5173(01)00793-1 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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