Studies on the Mode of Action of Nalidixic Acid

Nalidixic acid, a very specific inhibitor of bacterial DNA synthesis, has been studied for its action on purified enzymes acting on DNA and in subcellular DNA‐synthesizing systems. The drug does not inhibit the following enzymes: DNA polymerase I, endonuclease I, exonuclease I, II and III from Escherichia coli , polynucleotide‐ligase and DNA methyl‐transferase from T 4‐ infected E. coli , DNA polymerase from Bacillus subtilis. A significant inhibition of ATP‐dependent DNA synthesis is observed in cells of a strain of E. coli lacking DNA polymerase I after short treatments with toluene (2 min); longer treatments reduce the rate of synthesis and abolish its sensitivity to nalidixic acid. Equally insensitive are the ATP‐dependent DNA synthesizing systems bound to membrane fractions of E. coli and B. subtilis. The results suggest a mode of action through a still unidentified physiological component of the growing point apparatus, and supply a new criterion of physiological integrity of subcellular DNA‐synthesizing systems, namely their sensitivity to nalidixic acid.