Inhibition of Replication of T2 Bacteriophage in Escherichia coli by 6-diazo-5-oxo-L-norleucine (DON)

Abstract

The antibiotic known as 6-diazo-5-oxo-L-norleucine, DON, inhibits the growth of several types of Gram positive and Gram negative bacteria. It has also been demonstrated that DON inhibits the replication of poliovirus, respiratory syncytial virus, mumps and herpes simplex virus in cultured eukaryotic cells. At a concentration of 0.03 mM DON, the replication of Escherichia coli cells was inhibited by 11.0% after 2 h of growth. In cultures of E. coli, cells infected with T2 bacteriophage and treated with 0.03 mM DON, the yield of T2 bacteriophage decreased by 88.0%. In E. coli, cells infected with T2 bacteriophage and treated with 0.03 mM DON, the addition of 45 mM glutamine completely reversed the DON inhibition of T2 bacteriophage replication. Likewise, adding a 15 mM concentration each of adenosine, cytidine, guanosine, and thymidine reversed the DON inhibition of T2 bacteriophage replication by 65%. Conversely, the addition of as much as 15 mM glucosamine had no effect on the DON inhibition of T2 bacteriophage replication in treated E. coli cells. These results suggest that DON inhibits the replication of T2 bacteriophage in E. coli cells by inhibiting the metabolism of glutamine and/or nucleosides during viral replication but not glycoprotein synthesis.