Mechanism of growth inhibition by 2'-amino-2'-deoxyguanosine in Escherichia coli.

Abstract

The mechanism of inhibition of E. coli by the new nucleoside antibiotic, 2''-amino-2''-deoxyguanosine (2AG), is described. Upon the addition of 2AG, the syntheses of macromolecules continued for 15 min. After this lag time, protein synthesis sharply decreased and RNA synthesis slightly decreased, but DNA synthesis was not affected. Tritiated 2AG was readily incorporated into the acid-soluble fraction of cells in the form of the mono-, di- and triphosphates. In the acid-soluble fraction, radioactivity was found only in the RNA fraction. The major part of the radioactivity apparently was guanylate; only 25% existed as the nucleotide of 2AG. In resistant strains of E. coli, there was a lower degree of phosphorylating activity and less incorporation of 2AG into RNA per unit of cell mass increase. 2AG apparently inhibits growth by its incorporation into RNA and the subsequent disturbance of RNA function causing a block in protein synthesis.