title: 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.
mesh_terms: D049933:Aminocoumarins; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000096:biosynthesis; D003090:Coliphages / Q000378:metabolism; D003374:Coumarins / Q000494:pharmacology*; D004261:DNA Replication / Q000187:drug effects*; D004269:DNA, Bacterial / Q000096:biosynthesis; D004352:Drug Resistance, Microbial; D004926:Escherichia coli / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D007930:Leucine / Q000378:metabolism; D008970:Molecular Weight; D009154:Mutation; D009675:Novobiocin; D012329:RNA, Bacterial / Q000096:biosynthesis; D013698:Templates, Genetic; D013936:Thymidine / Q000378:metabolism; D014466:Ultraviolet Rays; D014498:Uracil / Q000378:metabolism
chemical_list: D049933:Aminocoumarins; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D003374:Coumarins; D004269:DNA, Bacterial; D012329:RNA, Bacterial; D009675:Novobiocin; D014498:Uracil; D007930:Leucine; C004628:coumermycin; D013936:Thymidine