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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.

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.

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