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Metabolic and ultrastructural effects induced by ciprofloxacin in Staphylococcus aureus during the postantibiotic
M Gottfredsson1, H Erlendsdóttir, R Kolka
1Department of Microbiology, Reykjavik City Hospital, Iceland.
Abstract:
The new quinolone antibacterial agents have been found to produce a postantibiotic effect (PAE) of 1-4 h in bacteria but the underlying mechanism is still unknown. After exposure to ciprofloxacin in concentrations of 1-16 x MIC for 1 hr the DNA synthesis in S. aureus ATCC 25923 was investigated during the PAE. Ultrastructure was also investigated by electron microscopy after exposure to a concentration of 2 x MIC. The rate of DNA synthesis per organism (measured as CPM/cfu/ml) increased progressively up to a maximum value at 1 1/2 h after drug removal. The maximal 3H-thymidine incorporation per organism at this moment correlated directly with the duration of the PAE. Bacterial swelling with scarcity and vacuole-formation of the cytoplasm characterized the majority of the staphylococci during the PAE. The physiological importance of the increased DNA synthesis is unknown, but the increased metabolic activity, coincident with increased duration of the PAE, suggests a possible common mechanism.
Insights
New quinolone antibacterials cause a postantibiotic effect (PAE) in bacteria. Increased DNA synthesis and bacterial swelling observed during PAE suggest a potential common mechanism for this effect.
Area of Science:
- Microbiology
- Pharmacology
Background:
- New quinolone antibacterial agents exhibit a postantibiotic effect (PAE) lasting 1-4 hours in bacteria.
- The precise mechanism underlying this bacterial PAE remains largely unknown.
Purpose of the Study:
- To investigate the mechanism of the postantibiotic effect (PAE) induced by ciprofloxacin in Staphylococcus aureus.
- To examine the impact of ciprofloxacin exposure on bacterial DNA synthesis and ultrastructure during the PAE.
Main Methods:
- Exposure of S. aureus ATCC 25923 to ciprofloxacin (1-16x MIC) for 1 hour.
- Measurement of DNA synthesis (3H-thymidine incorporation) post-drug removal.
- Ultrastructural analysis using electron microscopy after exposure to 2x MIC ciprofloxacin.
Main Results:
- DNA synthesis per organism increased progressively after ciprofloxacin removal, peaking at 1.5 hours.
- Maximal 3H-thymidine incorporation correlated directly with PAE duration.
- Electron microscopy revealed bacterial swelling and cytoplasmic vacuolization during the PAE.
Conclusions:
- Increased DNA synthesis and metabolic activity during the PAE suggest a potential common underlying mechanism.
- The physiological significance of enhanced DNA synthesis post-ciprofloxacin exposure requires further investigation.
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