Nalidixic Acid and the Metabolism of Escherichia coli

Nalidixic acid (NAL) is bactericidal for E. coli B. Synthesis of deoxyribonucleic acid (DNA), ribonucleic acid and protein was necessary to initiate the lethal effect, but only protein synthesis was necessary to sustain it. NAL inhibited DNA synthesis specifically, but this inhibition occurred even under conditions that were not lethal to the bacteria. In contrast to other inhibitors of DNA synthesis, NAL did not cause the solubilization of cellular DNA even when bacteria were exposed to it for 2 hr. A bacterial mutant deficient in DNA polymerase was much more sensitive to the lethal action of NAL than its parent strain. Moreover, inhibition of protein synthesis did not protect this mutant from NAL-induced killing. NAL inhibited neither DNA polymerase, nor thymidine or thymidylate kinases. The data are interpretated as suggesting that NAL altered the structure of DNA or a protein attached to nascent DNA and that this lesion can be partially repaired by DNA polymerase.