ArticleNucleic acids research2022
The nucleotide messenger (p)ppGpp is an anti-inducer of the purine synthesis transcription regulator PurR in Bacillus.
Article in Nucleic acids research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 49 citations in OpenAlex.
- Bacterial growth rate in populations and single cells.Nature microbiology · 2026Review
- The alarmone pGpp inhibits translation through GTP depletion.Nucleic acids research · 2026Article
- De novo or Salvage? Nucleotide Availability as a Driver of Bacterial Adaptation and Virulence.MicrobiologyOpen · 2026Review
- Functional diversity and ecological consequences of endophytic Bacillus-plant interactions.Folia microbiologica · 2026Review
- Bacteriophages hijack 2',3'-cNMPs to enhance transposase-mediated phage DNA integration inScience advances · 2026Article
- Article
- Starvation-independent alarmone production inhibits translation through GTP depletion.bioRxiv : the preprint server for biology · 2026Article
- Article
- The stringent response does not influence ribosome pausing in Bacillus subtilis.Nucleic acids research · 2025Article
- Article
- The impact of bacterial purine metabolism on antibiotic efficacy.npj antimicrobials and resistance · 2025Review
- Analysis of (p)ppGpp metabolism and signaling using a dynamic luminescent reporter.PLoS genetics · 2025Article
- A shared alarmone-GTP switch controls persister formation in bacteria.Nature microbiology · 2025Article
- Pleiotropic functions of CpdB in Bacillus anthracis.World journal of microbiology & biotechnology · 2025Article
- The Emerging Role of (p)ppGpp in DNA Repair and Associated Bacterial Survival against Fluoroquinolones.Gene expression · 2025Article
- (p)ppGpp-mediated GTP homeostasis ensures survival and antibiotic tolerance of Staphylococcus aureus.Communications biology · 2025Article
- Article
- The PurR family transcriptional regulator promotes butenyl-spinosyn production in Saccharopolyspora pogona.Applied microbiology and biotechnology · 2025Article
- ENcyclopedia of TRAnscription Factors in Bacteria and Archaea genomes (ENTRAF) version 2.0.Database : the journal of biological databases and curation · 2025Article
- Integrated genomic and proteomic analysis of the mouse-adaptedCurrent research in microbial sciences · 2025Article
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
The nucleotide messenger (p)ppGpp allows bacteria to adapt to fluctuating environments by reprogramming the transcriptome. Despite its well-recognized role in gene regulation, (p)ppGpp is only known to directly affect transcription in Proteobacteria by binding to the RNA polymerase. Here, we reveal a different mechanism of gene regulation by (p)ppGpp in Firmicutes: (p)ppGpp directly binds to the transcription factor PurR to downregulate purine biosynthesis gene expression upon amino acid starvation. We first identified PurR as a receptor of (p)ppGpp in Bacillus anthracis. A co-structure with Bacillus subtilis PurR reveals that (p)ppGpp binds to a PurR pocket reminiscent of the active site of phosphoribosyltransferase enzymes that has been repurposed to serve a purely regulatory role, where the effectors (p)ppGpp and PRPP compete to allosterically control transcription. PRPP inhibits PurR DNA binding to induce transcription of purine synthesis genes, whereas (p)ppGpp antagonizes PRPP to enhance PurR DNA binding and repress transcription. A (p)ppGpp-refractory purR mutant in B. subtilis fails to downregulate purine synthesis genes upon amino acid starvation. Our work establishes the precedent of (p)ppGpp as an effector of a classical transcription repressor and reveals the key function of (p)ppGpp in regulating nucleotide synthesis through gene regulation, from soil bacteria to pathogens.
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