Stringency without ppGpp accumulation

Abstract

Wild-type Escherichia coli deprived of a required amino acid shows a stringent response involving various alterations in the cell's normal physiology, including the arrest of net synthesis of stable (ribosomal and transfer) RNA, lipids, phospholipids and peptidoglycans¹. The stringent response is found in cells of the Rel⁺ (stringent) but not Rel⁻ (relaxed) phenotype. The intracellular concentration of guanosine 5′-diphosphate-3′-diphosphate (ppGpp) and guanosine 5′-triphosphate-3′-diphosphate (pppGpp) increases dramatically in amino acid-deprived Rel⁺ cells due to the enzymatic activity of the relA gene product², which also stimulates ppGpp synthesis in vitro³. The correlation between stringent response and increase in the intracellular concentration of ppGpp has been interpreted as evidence that this nucleotide has a causal role in stringency¹. However, as recent findings show that the correlation does not always hold, ppGpp cannot be considered to act as a unique effector molecule and the idea of a causal role for ppGpp in stringent control has become questionable^4,5. Here we describe experiments that cast further doubt on the proposed biological role of this nucleotide, as they show that stringent control can occur in the absence of ppGpp accumulation.