title: Nitrogen stress response and stringent response are coupled in Escherichia coli.
abstract: Assimilation of nitrogen is an essential process in bacteria. The nitrogen regulation stress response is an adaptive mechanism used by nitrogen-starved Escherichia coli to scavenge for alternative nitrogen sources and requires the global transcriptional regulator NtrC. In addition, nitrogen-starved E. coli cells synthesize a signal molecule, guanosine tetraphosphate (ppGpp), which serves as an effector molecule of many processes including transcription to initiate global physiological changes, collectively termed the stringent response. The regulatory mechanisms leading to elevated ppGpp levels during nutritional stresses remain elusive. Here, we show that transcription of relA, a key gene responsible for the synthesis of ppGpp, is activated by NtrC during nitrogen starvation. The results reveal that NtrC couples these two major bacterial stress responses to manage conditions of nitrogen limitation, and provide novel mechanistic insights into how a specific nutritional stress leads to elevating ppGpp levels in bacteria.
authors.affiliation: MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London SW7 2AZ, UK.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Brown
authors.affiliation: Centre for Systems Biology and Bioinformatics, Division of Biosciences, Imperial College London, London SW7 2AZ, UK.
authors.forename: Geraint
authors.initials: G
authors.lastname: Barton
authors.affiliation: MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London SW7 2AZ, UK.
authors.forename: Zhensheng
authors.initials: Z
authors.lastname: Pan
authors.affiliation: Department of Life Sciences, Imperial College London, London SW7 2AZ, UK.
authors.forename: Martin
authors.initials: M
authors.lastname: Buck
authors.affiliation: MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London SW7 2AZ, UK.
authors.forename: Sivaramesh
authors.initials: S
authors.lastname: Wigneshweraraj
mesh_terms: D001665:Binding Sites / Q000235:genetics; D047369:Chromatin Immunoprecipitation; D024202:Electrophoretic Mobility Shift Assay; D004926:Escherichia coli / Q000502:physiology*; D029968:Escherichia coli Proteins / Q000378:metabolism*; D006159:Guanosine Tetraphosphate / Q000378:metabolism*; D059014:High-Throughput Nucleotide Sequencing; D008025:Ligases / Q000378:metabolism*; D009584:Nitrogen / Q000172:deficiency* / Q000378:metabolism; D051922:PII Nitrogen Regulatory Proteins / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D013312:Stress, Physiological / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D029968:Escherichia coli Proteins; D051922:PII Nitrogen Regulatory Proteins; D014157:Transcription Factors; C497876:glnG protein, E coli; D006159:Guanosine Tetraphosphate; D008025:Ligases; C028812:guanosine 3',5'-polyphosphate synthetases; D009584:Nitrogen