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Induction of the SOS response by new 4-quinolones
I Phillips1, E Culebras, F Moreno
1Department of Microbiology, Hospital Ramon y Cajal, Madrid, Spain.
Abstract:
The 4-quinolones ciprofloxacin, difloxacin, enoxacin, norfloxacin, ofloxacin, and nalidixic acid were found to induce the SOS response in qualitative and quantitative tests on Escherichia coli K12 containing the sfiA::lacZ gene fusion. Maximum induction of the SOS-response was observed with the quinolone concentrations that produced the most killing. There was also a modest increase in the rate of mutation in the lactose and galactose operons in a GalE- background, provided there was a functioning SOS system.
Insights
Certain 4-quinolones, including ciprofloxacin and norfloxacin, trigger the SOS response in Escherichia coli. This response, linked to bacterial killing, also moderately increased mutation rates in specific operons.
Area of Science:
- Microbiology
- Molecular Biology
- Bacteriology
Background:
- The SOS response is a global genetic system in bacteria activated by DNA damage.
- Quinolone antibiotics are known to inhibit bacterial DNA replication and repair mechanisms.
Purpose of the Study:
- To investigate the ability of various 4-quinolone antibiotics to induce the SOS response in Escherichia coli.
- To correlate SOS induction with antibiotic-induced bacterial killing and mutagenesis.
Main Methods:
- Utilized qualitative and quantitative assays on Escherichia coli K12 strains with an sfiA::lacZ gene fusion.
- Measured SOS response induction across a range of quinolone concentrations.
- Assessed mutation rates in lactose and galactose operons in a GalE- background.
Main Results:
- Several 4-quinolones (ciprofloxacin, difloxacin, enoxacin, norfloxacin, ofloxacin, nalidixic acid) induced the SOS response.
- Maximum SOS induction correlated with quinolone concentrations causing the highest bacterial killing.
- A functioning SOS system was necessary for a modest increase in mutation rates in the lactose and galactose operons.
Conclusions:
- 4-quinolones are potent inducers of the bacterial SOS response.
- The SOS response plays a role in mediating quinolone-induced mutagenesis.
- Understanding this mechanism is crucial for antibiotic development and resistance studies.