A negative feedback loop is critical for recovery of RpoS after stress in Escherichia coli

PLoS Genet. 2024 Mar 11;20(3):e1011059. doi: 10.1371/journal.pgen.1011059. eCollection 2024 Mar.

Abstract

RpoS is an alternative sigma factor needed for the induction of the general stress response in many gammaproteobacteria. Tight regulation of RpoS levels and activity is required for bacterial growth and survival under stress. In Escherichia coli, various stresses lead to higher levels of RpoS due to increased translation and decreased degradation. During non-stress conditions, RpoS is unstable, because the adaptor protein RssB delivers RpoS to the ClpXP protease. RpoS degradation is prevented during stress by the sequestration of RssB by anti-adaptors, each of which is induced in response to specific stresses. Here, we examined how the stabilization of RpoS is reversed during recovery of the cell from stress. We found that RpoS degradation quickly resumes after recovery from phosphate starvation, carbon starvation, and when transitioning from stationary phase back to exponential phase. This process is in part mediated by the anti-adaptor IraP, known to promote RpoS stabilization during phosphate starvation via the sequestration of adaptor RssB. The rapid recovery from phosphate starvation is dependent upon a feedback loop in which RpoS transcription of rssB, encoding the adaptor protein, plays a critical role. Crl, an activator of RpoS that specifically binds to and stabilizes the complex between the RNA polymerase and RpoS, is also required for the feedback loop to function efficiently, highlighting a critical role for Crl in restoring RpoS basal levels.

MeSH terms

  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Escherichia coli Proteins* / genetics
  • Escherichia coli Proteins* / metabolism
  • Escherichia coli* / metabolism
  • Feedback
  • Gene Expression Regulation, Bacterial
  • Phosphates / metabolism
  • Sigma Factor / genetics
  • Sigma Factor / metabolism

Substances

  • Escherichia coli Proteins
  • Bacterial Proteins
  • Sigma Factor
  • Phosphates

Grants and funding

This work and all authors (SB, IH, NM, AT and SG) were supported by the intramural research program of the Center for Cancer Research, NCI, NIH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.