Apparent Obligatory Dependence of Peptidoglycan Synthesis on Phospholipid Synthesis Studied in Ether-Treated Escherichia coli

Abstract

Amino acid deprivation of Escherichia coli activates ppGpp synthetase I, a ribosome-associated enzyme encoded by the relA gene (reviewed by Cashel and Rudd, 1987). This results in the rapid accumulation of guanosine 5′-diphosphate 3′-diphosphate (ppGpp) in relA + bacteria but not in relA mutants; ppGpp is a putative stress signal compound specifying amino acid deficiency which apparently shuts down a variety of energy-consuming metabolic processes in starved bacteria in what has been termed the stringent response (Cashel and Rudd, 1987). The activities of both the peptidoglycan biosynthetic and the hydrolase systems are among the metabolic processes which are inhibited during the stringent response, and this may account for the well known penicillin tolerance exhibited by amino acid-deprived relA + bacteria (Pisabarro et al., 1991). The fact that amino-acid deprived relA mutant strains lyse when treated with penicillin is consistent with this proposal. Furthermore, lysis of amino acid-deprived relA + cells by inhibitors of peptidoglycan synthesis can be induced by the addition of agents, such as chloramphenicol, which interfere with the stringent response. These stringent response antagonists block the synthesis of ppGpp during amino acid deprivation (Cashel and Rudd, 1987).