Induction of λ prophage by nalidixic acid

The kinetics of induction of λ prophage have been studied with nalidixic acid (NAL), an apparently specific and reversible inhibitor of DNA synthesis. NAL was found to cause inducing conditions in an exponentially growing culture of Escherichia coli W3350 (λ). Its inhibition of DNA synthesis leads to some inducing event in the cells. The kinetics of induction indicate that: (1) the inducing event occurs in some cells immediately upon exposure to NAL; (2) the number of inducing events in a population of cells is proportional to the length of NAL treatment; (3) this rate is larger, the higher the concentration of NAL; (4) the induction rate is 7-fold greater for lysogens bearing the thermosensitive and UV-induction-sensitive prophage λt1; (5) amino acid starved lysogens are poorly induced; (6) prolonged treatment with NAL causes progressive inactivation of plaque-forming ability of cells potentially induced by shorter treatments of NAL, an effect probably caused by the deleterious effect of NAL on phage DNA synthesis itself; and (7) concomitant protein synthesis is necessary to obtain induction with NAL. The results suggest that a population of cells is not homogeneous in its sensitivity to NAL. We propose that this inhomogeneity is closely related to the cyclical variation in DNA replication among individual cells; and that abnormal termination of chromosome replication by NAL mal-triggers the normal terminal functions, during which event the cell is irreversibly converted to the induced state.