ArticleNature microbiology2025
A shared alarmone-GTP switch controls persister formation in bacteria.
Article in Nature microbiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- Translation factors that keep the ribosome Pro-active.Microbiology and molecular biology reviews : MMBR · 2026Review
- Bacterial growth rate in populations and single cells.Nature microbiology · 2026Review
- The alarmone pGpp inhibits translation through GTP depletion.Nucleic acids research · 2026Article
- Contributions of persisters and the Eagle effect to survival ofMicrobiology spectrum · 2026Article
- Association ofPathogens (Basel, Switzerland) · 2026Article
- Sustained ppGpp production underpins months-long survival of a bacterium in growth arrest.mBio · 2026Article
- Antibiotic exposure and recovery of persister states influence virulence phenotypes in Pseudomonas aeruginosa.Archives of microbiology · 2026Article
- Article
- Review
- Controlled Delivery and Light-Induced Release of Magic Spot Nucleotides in Escherichia coli.Angewandte Chemie (International ed. in English) · 2026Article
- Antibiotic Persistence Emerges from Cell-State-Driven Transcriptional Reprogramming.bioRxiv : the preprint server for biology · 2026Article
- Global response to antibiotic exposure reveals a critical role for nucleotide metabolism in high-level β-lactam tolerance.npj antimicrobials and resistance · 2026Article
- Survival of ampicillin-treated uropathogenic Escherichia coli is independent of single-cell growth rates.npj antimicrobials and resistance · 2026Article
- Enzymatic activity of PBP1B is required for growth rate-independent ppGpp-mediated resistance to PBP2 inhibitors inJournal of bacteriology · 2026Article
- Starvation-independent alarmone production inhibits translation through GTP depletion.bioRxiv : the preprint server for biology · 2026Article
- An integrative multi-omics approach points to membrane composition as a key factor in E. coli persistence.PloS one · 2026Article
- Article
- Global response to antibiotic exposure uncovers a critical role for nucleotide metabolism in high-level β-lactam tolerance.Research square · 2025Article
- Flipping the magic switch to persistence via GTP depletion.Nature microbiology · 2025Article
- Targeting the bacterial stringent response to combat human pathogens.Frontiers in immunology · 2025Review
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10 authors.
Funding
Abstract
Persisters are phenotypically switched bacteria that survive antibiotic exposure despite being genetically susceptible. Three pathways to persistence-triggered, spontaneous and antibiotic-induced-have been described, but the underlying molecular mechanisms are poorly understood. Here, we used antibiotic time-kill assays as well as single-cell approaches to show that all of the pathways depend on a common switch involving the alarmone guanosine tetra/penta-phosphate ((p)ppGpp) in Bacillus subtilis, each stemming from different alarmone synthetase(s). The accumulation of (p)ppGpp promotes persistence through depletion of intracellular GTP. We developed a fluorescent GTP reporter to visualize rare events of persister formation in wild-type bacteria, revealing a rapid switch from growth to dormancy in single cells as their GTP levels drop beneath a threshold. While a decrease in GTP in the bulk population slows growth and promotes antibiotic tolerance, (p)ppGpp drives persistence by driving rapid, switch-like decreases in GTP levels beneath the persister threshold in single cells. Persistence through alarmone-GTP antagonism is probably a widespread mechanism to survive antibiotics in B. subtilis and potentially beyond.
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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.