The Mechanism of Ethionine Toxicity to Escherichia coli 1

Abstract

Summary

Toxic effects of ethionine on Escherichia coli in a glucose salts medium are manifested by growth inhibition and loss of viability. ¹⁴C-valine incorporation studies and β-galactosidase studies indicate that ethionine rapidly inhibits protein synthesis. The methionine precursors, homocysteine and cystathionine, as well as methionine itself, reverse all ethionine effects while O-succinylhomoserine and homoserine do not. Homoserine O-transsuccinylase, the first enzyme unique for methionine biosynthesis, is inhibited by ethionine while the analog does not inhibit cystathionine synthetase or methionine tRNA synthetase. The available data indicate that the initial effect of ethionine on E. coli is to act as an inhibitor of homoserine O-transuccinylase resulting in a severe depletion of methionine available for protein and other cellular synthesis.