Coumermycin A1: A preferential inhibitor of replicative DNA synthesis in Escherichia coli. I. In vivo characterization

Abstract

Coumermycin A1, an antibiotic related to novobiocin, inhibited nucleic acid synthesis in intact Escherichia coli with replication being slightly more sensitive to this drug than transcription. The ultraviolet-induced repair synthesis of DNA was only partially inhibited under conditions where replication was eliminated by coumermycin A1. Inhibition of protein synthesis was a secondary effect. Coumermycin A1-resistant E. coli were isolated and the mutation was mapped near dnaA. Chromatography of crude protein extracts of sensitive and resistant bacteria on drug affinity columns implicated a soluble protein of approximately 37,000 molecular weight as the target site for coumermycin A1. Depending on the medium used, this antibiotic had either a bacteriocidal or a bacteriostatic effect on E. coli. Results showed that the effect of coumermycin A1 cannot be explained by the degradation of DNA under bacteriocidal growth conditions.