Mechanism of Action of Nalidixic Acid on Escherichia coli III. Conditions Required for Lethality

Deitz, William H. (Sterling-Winthrop Research Institute, Rensselaer, N.Y.),Thomas M. Cook, and William A. Goss . Mechanism of action of nalidixic acid onEscherichia coli . III. Conditions required for lethality. J. Bacteriol.91: 768–773. 1966.—Nalidixic acid selectively inhibited deoxyribonucleic acid (DNA) synthesis in cultures ofEscherichia coli 15TAU. Protein and ribonucleic acid synthesis were shown to be a prerequisite for the bactericidal action of the drug. This action can be prevented by means of inhibitors at bacteriostatic concentrations. Both chloramphenicol, which inhibits protein synthesis, and dinitrophenol, which uncouples oxidative phosphorylation, effectively prevented the bactericidal action of nalidixic acid onE. coli . The lethal action of nalidixic acid also was controlled by transfer of treated cells to drug-free medium. DNA synthesis resumed immediately upon removal of the drug and was halted immediately by retreatment. These studies indicate that nalidixic acid acts directly on the replication of DNA rather than on the “initiator” of DNA synthesis. The entry of nalidixic acid into cells ofE. coli was not dependent upon protein synthesis. Even in the presence of an inhibiting concentration of chloramphenicol, nalidixic acid prevented DNA synthesis byE. coli 15TAU.