ArticleJournal of bacteriology2014
GTP dysregulation in Bacillus subtilis cells lacking (p)ppGpp results in phenotypic amino acid auxotrophy and failure to adapt to nutrient downshift and regulate biosynthesis genes.
Article in Journal of bacteriology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 107 citations in OpenAlex.
- The alarmone pGpp inhibits translation through GTP depletion.Nucleic acids research · 2026Article
- Mfd interacts with RNA polymerase to modulate flagellum-dependent motility, chemotaxis, and population heterogeneity in the stationary phase ofJournal of bacteriology · 2026Article
- Starvation-independent alarmone production inhibits translation through GTP depletion.bioRxiv : the preprint server for biology · 2026Article
- The stringent response does not influence ribosome pausing in Bacillus subtilis.Nucleic acids research · 2025Article
- Unveiling the probiotic potential of the genus Geobacillus through comparative genomics and in silico analysis.Scientific reports · 2025Article
- 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
- Distantly related bacteria share a rigid proteome allocation strategy with flexible enzyme kinetics.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- MOB rules: Antibiotic Exposure Reprograms Metabolism to MobilizebioRxiv : the preprint server for biology · 2024Article
- Tale of Twin Bifunctional Second Messenger (p)ppGpp Synthetases and Their Function in Mycobacteria.ACS omega · 2023Review
- Sound the (Smaller) Alarm: The Triphosphate Magic Spot Nucleotide pGpp.Infection and immunity · 2023Review
- Review
- Protein-Ligand Interactions in Scarcity: The Stringent Response from Bacteria to Metazoa, and the Unanswered Questions.International journal of molecular sciences · 2023Review
- Termination factor Rho mediates transcriptional reprogramming of Bacillus subtilis stationary phase.PLoS genetics · 2023Article
- Role of (p)ppGpp in antibiotic resistance, tolerance, persistence and survival in Firmicutes.microLife · 2023Review
- Recent functional insights into the magic role of (p)ppGpp in growth control.Computational and structural biotechnology journal · 2023Review
- Methionine addition improves the acid tolerance of Lactiplantibacillus plantarum by altering cellular metabolic flux, energy distribution, lipids composition.Stress biology · 2022Article
- Multiple mechanisms for overcoming lethal over-initiation of DNA replication.Molecular microbiology · 2022Article
- Structural variations between small alarmone hydrolase dimers support different modes of regulation of the stringent response.The Journal of biological chemistry · 2022Article
- Article
3 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
The nucleotide (p)ppGpp inhibits GTP biosynthesis in the Gram-positive bacterium Bacillus subtilis. Here we examined how this regulation allows cells to grow in the absence of amino acids. We showed that B. subtilis cells lacking (p)ppGpp, due to either deletions or point mutations in all three (p)ppGpp synthetase genes, yjbM, ywaC, and relA, strongly require supplementation of leucine, isoleucine, valine, methionine, and threonine and modestly require three additional amino acids. This polyauxotrophy is rescued by reducing GTP levels. Reduction of GTP levels activates transcription of genes responsible for the biosynthesis of the five strongly required amino acids by inactivating the transcription factor CodY, which represses the ybgE, ilvD, ilvBHC-leuABCD, ilvA, ywaA, and hom-thrCB operons, and by a CodY-independent activation of transcription of the ilvA, ywaA, hom-thrCB, and metE operons. Interestingly, providing the eight required amino acids does not allow for colony formation of (p)ppGpp(0) cells when transitioning from amino acid-replete medium to amino acid-limiting medium, and we found that this is due to an additional role that (p)ppGpp plays in protecting cells during nutrient downshifts. We conclude that (p)ppGpp allows adaptation to amino acid limitation by a combined effect of preventing death during metabolic transitions and sustaining growth by activating amino acid biosynthesis. This ability of (p)ppGpp to integrate a general stress response with a targeted reprogramming of gene regulation allows appropriate adaptation and is likely conserved among diverse bacteria.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.