Mechanism of Action of Nalidixic Acid on Escherichia coli V. Possible Mutagenic Effect.

Cook, Thomas M., (Sterling-Winthrop Research Institute, Rensselaer, N.Y.), William A. Goss, and William H. Deitz. Mechanism of action of nalidixic acid on Escherichia coli. V. Possible mutagenic effect. J. Bacteriol. 91:780-783. 1966.-With a streptomycin-dependent organism, Escherichia coli ATCC 11143, it has been shown that exposure to nalidixic acid, under conditions permitting some bactericidal action, results in an increased number of streptomycin-independent bacteria among the survivors. This effect is evident only with proliferating cultures, and is related to the concentration of nalidixic acid and the duration of exposure.

Mechanism of action of nalidixic acid on Escherichia coli. 3. 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 on Escherichia coli. III. Conditions required for lethality. J. Bacteriol. 91:768-773. 1966.-Nalidixic acid selectively inhibited deoxyribonucleic acid (DNA) synthesis in cultures of Escherichia 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 on E. 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 of E. coli was not dependent upon protein synthesis. Even in the presence of an inhibiting concentration of chloramphenicol, nalidixic acid prevented DNA synthesis by E. coli 15TAU.

Mechanism of action of nalidixic acid on Escherichia coli. IV. Effects on the stability of cellular constituents.

Cook, Thomas M. (Sterling-Winthrop Research Institute, Rensselaer, N.Y.), William H. Deitz, and William A. Goss. Mechanism of action of nalidixic acid on Escherichia coli. IV. Effects on the stability of cellular constituents. J. Bacteriol. 91:774-779. 1996.-Treatment of Escherichia coli 15TAU with nalidixic acid resulted in degradation of the nucleic acids of the cells, whereas protein was unaffected. Deoxyribonucleic acid (DNA) degradation appeared to be more extensive than ribonucleic acid degradation during periods of comparable bactericidal action. The onset of DNA degradation was evident prior to a measurable bactericidal effect. However, within the range of 2 to 20%, DNA degradation was accompanied by a decrease in viable cell numbers. Degradation of DNA to acid-soluble material occurred only under conditions permitting the bactericidal action of nalidixic acid. Arrest of the bactericidal action of nalidixic acid by the addition of dinitrophenol or chloramphenicol also inhibited DNA degradation. The acid-soluble products, which were excreted into the medium, have not been characterized completely, but probably were not phosphorylated.