Rsd balances (p)ppGpp level by stimulating the hydrolase activity of SpoT during carbon source downshift in Escherichia coli

Abstract

SignificanceMost bacteria accumulate the molecular alarmone (p)ppGpp to divert resources away from growth and division toward biosynthesis under various nutrient limitations. Despite its crucial role, uncontrolled accumulation of this alarmone causes severe growth inhibition and cell death. Thus, fine-tuning the cellular (p)ppGpp level is required to ensure survival and adaptation under harsh nutritional conditions. Here, we identify Rsd as a stimulator of the (p)ppGpp-degrading activity of SpoT during carbon source downshift in Escherichia coli, and this regulation is controlled by the phosphorylation state of HPr, a general component of the PEP-dependent sugar transport system. This study establishes a direct link between sugar signaling and the bacterial stringent response.

The expanded specificity and physiological role of a widespread N-degron recognin

“…The latter results are in agreement with previous studies showing that changes in SpoT amounts were not always reflective of its enzymatic output in vivo (38). Thus, ClpS might control the abundance of factors, such as Rsd or CgtA (54)(55)(56), that control SpoT output but not its stability.…”

Acclimation of bacterial cell state for high-throughput enzyme engineering using a DmpR-dependent transcriptional activation system

“…SpoT also plays a role in the response to various types of environmental stresses, such as carbon, iron or fatty acid depletions [37][38][39][40] . Although the detailed molecular mechanism of regulation by SpoT is yet unclear, holo-acyl carrier protein (ACP, carrying 4′-PP) and regulator of sigma D (Rsd) can bind to SpoT to inhibit (p)ppGpp hydrolysis while promoting (p)ppGpp synthesis 38,39 . Further, the binding of SpoT with ACP and Rsd was induced by amino acid deficiency or unfavourable carbon sources 38,39 .…”

“…Although the detailed molecular mechanism of regulation by SpoT is yet unclear, holo-acyl carrier protein (ACP, carrying 4′-PP) and regulator of sigma D (Rsd) can bind to SpoT to inhibit (p)ppGpp hydrolysis while promoting (p)ppGpp synthesis 38,39 . Further, the binding of SpoT with ACP and Rsd was induced by amino acid deficiency or unfavourable carbon sources 38,39 . Therefore, the different fluorescent signals observed in minimal media with different carbon sources in the relA-null host may be due to the different levels of SpoT activity.…”

Linking glucose metabolism to the stringent response through the PTS

“…Thus, Rsd facilitates transcription from promoters recognized by alternative RNAP holoenzymes instead of promoters recognized by the major RNAP holoenzyme, Eσ 70 . However, Lee et al (1) show that Rsd's regulatory role in ppGpp metabolism is unlinked to its role as an antisigma.…”

“…However, SpoT's primary activity is ppGpp hydrolysis to prevent uncontrolled ppGpp production, which is lethal. In PNAS, Lee et al (1) report a link between SpoT activity and the function of the phosphoenolpyruvate-dependent sugar transferase system (PTS), thereby connecting sugar metabolism with the stringent response.…”