Discretely calibrated regulatory loops controlled by ppGpp partition gene induction across the 'feast to famine' gradient in Escherichia coli

Mol Microbiol. 2011 Feb;79(4):830-45. doi: 10.1111/j.1365-2958.2010.07498.x. Epub 2010 Dec 30.


Bacteria comprehensively reorganize their global gene expression when faced with starvation. The alarmone ppGpp facilitates this massive response by co-ordinating the downregulation of genes of the translation apparatus, and the induction of biosynthetic genes and the general stress response. Such a large reorientation requires the activities of multiple regulators, yet the regulatory network downstream of ppGpp remains poorly defined. Transcription profiling during isoleucine depletion, which leads to gradual starvation (over > 100 min), allowed us to identify genes that required ppGpp, Lrp and RpoS for their induction and to deduce the regulon response times. Although the Lrp and RpoS regulons required ppGpp for their activation, they were not induced simultaneously. The data suggest that metabolic genes, i.e. those of the Lrp regulon, require only a low level of ppGpp for their induction. In contrast, the RpoS regulon was induced only when high levels of ppGpp accumulated. We tested several predictions of a model that explains how bacteria allocate transcriptional resources between metabolism and stress response by discretely tuning two regulatory circuits to different levels of ppGpp. The emergent regulatory structure insures that stress survival circuits are only triggered if homeostatic metabolic networks fail to compensate for environmental deficiencies.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Bacterial Proteins / metabolism
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Escherichia coli / physiology*
  • Escherichia coli Proteins / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation, Bacterial*
  • Guanosine Tetraphosphate / biosynthesis*
  • Guanosine Tetraphosphate / genetics
  • Guanosine Tetraphosphate / metabolism
  • Isoleucine / metabolism
  • Leucine-Responsive Regulatory Protein / metabolism
  • Metabolic Networks and Pathways
  • Oligonucleotide Array Sequence Analysis
  • Promoter Regions, Genetic
  • Regulon
  • Sigma Factor / metabolism
  • Stress, Physiological


  • Bacterial Proteins
  • Escherichia coli Proteins
  • Lrp protein, E coli
  • Sigma Factor
  • sigma factor KatF protein, Bacteria
  • Isoleucine
  • Leucine-Responsive Regulatory Protein
  • Guanosine Tetraphosphate