Function of the SOS process in repair of DNA damage induced by modern 4-quinolones

B M Howard1, R J Pinney, J T Smith

  • 1Department of Pharmaceutics, School of Pharmacy, University of London, UK.

Insights

The recA13 mutant Escherichia coli is hypersensitive to nalidixic acid and newer 4-quinolones. DNA damage from newer quinolones

Area of Science:

  • Microbiology
  • Molecular Biology
  • Genetics

Background:

  • The recA13 mutant of Escherichia coli strain K-12 lacks recombination and SOS error-prone DNA repair.
  • This mutant exhibits hypersensitivity to nalidixic acid and newer 4-quinolones like ciprofloxacin, norfloxacin, and ofloxacin.

Purpose of the Study:

  • To investigate the differential sensitivity of Escherichia coli mutants to nalidixic acid and newer 4-quinolones.
  • To elucidate the role of SOS error-prone DNA repair in the bactericidal mechanisms of these antibiotics.

Main Methods:

  • Comparative analysis of bacterial sensitivity across different mutant strains (recA13, lexA3, recA430, lexA+ recA+).
  • Assessment of antibiotic efficacy under conditions inhibiting specific bactericidal mechanisms (phosphate-buffered saline, nutrient broth plus rifampicin).

Main Results:

  • While recA13 mutants are hypersensitive to all tested quinolones, SOS repair-deficient strains (lexA3, recA430) show increased sensitivity to newer quinolones but not nalidixic acid.
  • Nalidixic acid utilizes bactericidal mechanism A (dependent on RNA/protein synthesis and cell division).
  • Newer 4-quinolones employ additional mechanisms B (independent of RNA/protein synthesis and cell division) and C (dependent on RNA/protein synthesis but not cell division).
  • Experimental conditions inhibiting mechanism A still showed increased sensitivity in lexA3 mutants to newer quinolones, indicating SOS repair's role.

Conclusions:

  • DNA damage induced by bactericidal mechanisms B and C of newer 4-quinolones is subject to SOS error-prone (mutagenic) repair.
  • SOS error-prone repair plays a significant role in the response of Escherichia coli to newer fluoroquinolones, but not nalidixic acid.

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