MECHANISM OF ACTION OF NALIDIXIC ACID ON ESCHERICHIA COLI

Abstract

Nalidixic-acid was lethal for proliferating cultures of E. coli. Associated with this lethal effect was the formation of elongated serpentine forms. Cultures treated with nalidixic-acid were osmotically stable; lethality was observed in the presence of stabilizers. Although it was possible to demonstrate leakage of intracellular components from treated cells, this effect occurred only after 99% of the cells were nonviable. Nalidixic-acid had little or no effect on respiration with glucose as substrate. If cellular growth was restricted by suboptimal temperature or nutritional deficiencies, the drug was not lethal. Chemical analysis of cellular constituents revealed that lipid, protein and ribonucleic-acid levels were of the same order of magnitude in control and drug-treated cells. Only deoxyribonucleic-acid (DNA) levels were markedly lowered in drug-treated cells. These facts are consistent with the view that nalidixic-acid interferes with the synthesis of E. coli DNA.