Howard B M, Pinney R J, Smith J T
Department of Pharmaceutics, School of Pharmacy, University of London, UK.
J Pharm Pharmacol. 1993 Jul;45(7):658-62. doi: 10.1111/j.2042-7158.1993.tb05673.x.
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.
大肠杆菌K - 12的recA13突变体缺乏重组能力且存在SOS易错DNA修复缺陷，对萘啶酸以及新型4 - 喹诺酮类药物环丙沙星、诺氟沙星和氧氟沙星高度敏感。然而，尽管重组功能正常但SOS修复缺陷的菌株，如携带lexA3或recA430等位基因的菌株，对萘啶酸的敏感性并不比lexA + recA +亲本更高，但它们对新型喹诺酮类药物更敏感，不过不如recA13衍生物敏感。萘啶酸仅具有杀菌机制A（需要RNA和蛋白质合成，且仅对活跃分裂的细胞有效），而新型4 - 喹诺酮类药物还具有额外的机制B（不需要RNA和蛋白质合成，对无法繁殖的细菌有效）和机制C（需要RNA和蛋白质合成，但不依赖细胞分裂）。用悬浮于抑制机制A的磷酸盐缓冲盐水中的细菌，以及悬浮于抑制机制A和C的营养肉汤加利福平中的细菌所得到的结果表明，在这些条件下，lexA3突变体仍然比lexA +亲本更敏感。结果表明，与杀菌机制A不同，新型4 - 喹诺酮类药物的杀菌机制B和C所导致的DNA损伤会受到SOS易错（诱变）修复。
