Effect of Nalidixic Acid and Hydroxyurea on Division Ability ofEscherichia coli fil+andlon−Strains

Abstract

Short periods of incubation in medium containing nalidixic acid or hydroxyurea, followed by a return to normal growth conditions, induced filament formation inEscherichia coliB (fil⁺) and AB1899NM (lon⁻) but not in B/r (fil⁻) and AB1157 (lon⁺). These drugs reversibly stopped deoxyribonucleic acid (DNA) synthesis with little or no effect on ribonucleic acid (RNA) synthesis or mass increase. The initial imbalance caused by incubation in these drugs was the same for B and B/r as was macromolecular synthesis following a return to normal growth conditions. DNA degradation caused by nalidixic acid was measured and found to be the same for B and B/r. Hydroxyurea caused no DNA degradation in these two strains. Survival curves as determined under various conditions by colony formation suggested that the property of filament formation was responsible for the extrasensitivity offil⁺andlon⁻strains to either nalidixic acid or hydroxyurea.E. coliB was more sensitive to either drug than was B/r or B_s-1. Pantoyl lactone or liquid holding treatment aided division and colony formation of nalidixic acid-treated B but had no effect on B/r. Likewise, the filament-former AB1899NM was more sensitive to nalidixic acid than was the non-filament-former AB1157. The sensitivity of B/r and B_s-1to nalidixic acid was nearly the same except at longer times in nalidixic acid, when B_s-1appeared more resistant. Even though nalidixic acid, hydroxyurea, and ultraviolet light may produce quite different molecular alterations inE. coli, they all cause a metabolic imbalance resulting in a lowered ratio of DNA to RNA and protein. We propose that it is this imbalance per se rather than any specific primary chemical or photochemical alterations which leads to filament formation by some genetically susceptible bacterial strains such aslon⁻andfil⁺.