Function of the SOS Process in Repair of DNA Damage Induced by Modern 4-Quinolones

Abstract

The recA13 mutant of Escherichia coli strain K-12, which lacks recombination and SOS error-prone DNA repair is hypersensitive to nalidixic acid and to the newer 4-quinolones ciprofloxacin, norfloxacin and ofloxacin. However, whereas recombination-proficient but SOS repair-deficient strains, such as those carrying the lexA3 or recA430 alleles are no more sensitive to nalidixic than the lexA+ recA+ parent, they are more sensitive to the newer quinolones, although not as sensitive as the recA13 derivative. Nalidixic acid possesses only bactericidal mechanism A (which requires RNA and protein synthesis and is only effective on actively dividing cells), whereas the newer 4-quinolones exhibit additional mechanisms B (which does not require RNA and protein synthesis and is effective on bacteria unable to multiply) and C (which requires RNA and protein synthesis but does not depend on cell division). Results obtained with bacteria suspended in phosphate-buffered saline, which inhibits mechanism A, and with bacteria suspended in nutrient broth plus rifampicin, which inhibits mechanisms A and C, showed that the lexA3 mutant was still more sensitive than the lexA+ parent under these conditions. The results suggest that, unlike bactericidal mechanism A, DNA damage that results from bactericidal mechanisms B and C of the newer 4-quinolones is subject to SOS error-prone (mutagenic) repair.