Function of the SOS process in repair of DNA damage induced by modern 4-quinolones.
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.
Howard
B M
BM
Department of Pharmaceutics, School of Pharmacy, University of London, UK.
Pinney
R J
RJ
Smith
J T
JT
D000890:Anti-Infective Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002939:Ciprofloxacin / Q000494:pharmacology; D004249:DNA Damage; D004260:DNA Repair; D004269:DNA, Bacterial / Q000378:metabolism; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics; D009154:Mutation; D009268:Nalidixic Acid / Q000494:pharmacology; D009643:Norfloxacin / Q000494:pharmacology; D015242:Ofloxacin / Q000494:pharmacology; D012329:RNA, Bacterial / Q000096:biosynthesis; D013014:SOS Response, Genetics
D000890:Anti-Infective Agents; D004269:DNA, Bacterial; D012329:RNA, Bacterial; D009268:Nalidixic Acid; D002939:Ciprofloxacin; D015242:Ofloxacin; D009643:Norfloxacin