Correlation of quinolone MIC and inhibition of DNA, RNA, and protein synthesis and induction of the SOS response in Escherichia coli.
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.
Piddock
L J
LJ
Department of Medical Microbiology, Medical School, University of Birmingham, United Kingdom.
Walters
R N
RN
Diver
J M
JM
D000890:Anti-Infective Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000096:biosynthesis*; D002701:Chloramphenicol / Q000494:pharmacology; D003470:Culture Media; D004269:DNA, Bacterial / Q000096:biosynthesis*; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D007700:Kinetics; D008826:Microbial Sensitivity Tests; D009268:Nalidixic Acid / Q000494:pharmacology; D012329:RNA, Bacterial / Q000096:biosynthesis*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D013014:SOS Response, Genetics / Q000187:drug effects*
D000890:Anti-Infective Agents; D001426:Bacterial Proteins; D003470:Culture Media; D004269:DNA, Bacterial; D012329:RNA, Bacterial; D011994:Recombinant Proteins; D009268:Nalidixic Acid; D002701:Chloramphenicol