FUNCTION OF THE SOS PROCESS IN REPAIR OF DNA-DAMAGE INDUCED BY MODERN4-QUINOLONES

The recA13 mutant of Escherichia coli strain K-12, which lacks recombi nation and SOS error-prone DNA repair is hypersensitive to nalidixic a cid and to the newer 4-quinolones ciprofloxacin, norfloxacin and oflox acin. However, whereas recombination-proficient but SOS repair-deficie nt strains, such as those carrying the lexA3 or recA430 alleles are no more sensitive to nalidixic than the lexA+ recA+ parent, they are mor e sensitive to the newer quinolones, although not as sensitive as the recA13 derivative. Nalidixic acid possesses only bactericidal mechanis m A (which requires RNA and protein synthesis and is only effective on actively dividing cells), whereas the newer 4-quinolones exhibit addi tional 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). Resu lts obtained with bacteria suspended in phosphate-buffered saline, whi ch inhibits mechanism A, and with bacteria suspended in nutrient broth plus rifampicin, which inhibits mechanisms A and C, showed that the l exA3 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.