CORRELATION OF QUINOLONE MIC AND INHIBITION OF DNA, RNA, AND PROTEIN-SYNTHESIS AND INDUCTION OF THE SOS RESPONSE IN ESCHERICHIA-COLI
CORRELATION OF QUINOLONE MIC AND INHIBITION OF DNA, RNA, AND PROTEIN-SYNTHESIS AND INDUCTION OF THE SOS RESPONSE IN ESCHERICHIA-COLI
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DOI：
10.1128/aac.34.12.2331
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发表时间：
1990-12-01
影响因子：
4.9
通讯作者：
DIVER, JM
中科院分区：
文献类型：
--
作者：
PIDDOCK, LJV;WALTERS, RN;DIVER, JM
通过比较20 mg/L氯霉素和4种氟喹诺酮类药物在大肠杆菌中诱导recA的杀伤动力学、最低抑菌浓度、形态反应和最大诱导浓度，研究了它们对DNA、RNA和蛋白质合成的影响。所有药剂均表现出自相矛盾的杀菌动力学，在最适浓度以上，杀菌作用速度较慢。所有喹诺酮类药物对大肠杆菌AB1157均呈丝状生长，达到最适杀菌浓度。氯霉素的加入降低了杀菌活性，抑制了丝状化，取消了recA的诱导，但对任何一种药物对DNA合成的抑制都没有影响。抑制DNA合成50%所需浓度、最低抑菌浓度、诱导recA的最大浓度和最适杀菌浓度之间具有良好的相关性。这项研究和以前发表的数据表明，喹诺酮类药物的主要作用机制独立于SOS反应，不需要活性蛋白质合成；然而，诱导recA和SOS反应是必然的，并增强细胞死亡。
The effects of nalidixic acid and four fluoroquinolones on DNA, RNA, and protein synthesis in the presence and absence of 20 mg of chloramphenicol per liter were examined by comparing the killing kinetics, MIC, morphological response, and maximum concentration to induce recA in Escherichia coli. All agents demonstrated paradoxical killing kinetics, in that above an optimum concentration the rate of bactericidal action was slower. Filamentation of E. coli AB1157 was observed with all quinolones up to the optimum bactericidal concentration. Addition of chloramphenicol reduced the bactericidal activity, inhibited filamentation, and abolished recA induction, but it had no effect on DNA synthesis inhibition by any of the agents. Excellent correlation was obtained between the concentration required to inhibit DNA synthesis by 50%, the MIC, the maximum concentration to induce recA, and the optimum bactericidal concentration. Evidence from this study and previously published data suggest that the primary mechanism of action of quinolones is independent of the SOS response and does not require active protein synthesis; however, induction of recA and SOS responses is consequential and enhances cell death.