ArticleProceedings of the National Academy of Sciences of the United States of America2016
ppGpp negatively impacts ribosome assembly affecting growth and antimicrobial tolerance in Gram-positive bacteria.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 141 papers.
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Who cites it
141 citing papers in PubMed, 219 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
- Staphylococcus aureus biofilms: molecular mechanisms, resistance determinants, and emerging therapeutic strategies.Molecular biology reports · 2026Review
- The (p)ppGpp Synthetase RelA Contributes to Virulence, Competition Capability and Antibiotic Resistance of Avian PathogenicMicroorganisms · 2026Article
- Environment-dependent epistasis shapes adaptation to fluctuating resources.bioRxiv : the preprint server for biology · 2026Article
- Sustained ppGpp production underpins months-long survival of a bacterium in growth arrest.mBio · 2026Article
- Targeting the stringent response alters gene expression and extracellular vesicle RNA inMicrobiology spectrum · 2026Article
- Heterogeneity in microbial antibiotic responses: genetic basis and within-host evolution.Trends in genetics : TIG · 2026Review
- Stress-induced ribosome degradation in Bacillus subtilis is mediated by the RNase Y-specificity complex.Nature communications · 2026Article
- Clinical Rel mutations that increase basal (p)ppGpp promote conjugal transfer of staphylococcal resistance plasmids.Microbiology (Reading, England) · 2026Article
- Integrated multiomics reveals starvation-driven keratin degradation and persistence iniScience · 2026Article
- Nanobody-mediated control of long RSH Rel and RelA catalysis by restriction of their conformational landscape.Nature communications · 2026Article
- Emergence of Dalbavancin, Vancomycin, and Daptomycin Cross-resistance in MRSA During Long-term LVAD Suppression With Vancomycin Followed by Dalbavancin: Genomic Insights and Synergy With Cefadroxil.Open forum infectious diseases · 2026Article
- Starvation-independent alarmone production inhibits translation through GTP depletion.bioRxiv : the preprint server for biology · 2026Article
- Molecular Basis of Persister Awakening and Lag-Phase Recovery inInternational journal of molecular sciences · 2026Review
- HflX mediates rifampicin resistance inFrontiers in microbiology · 2026Article
- Proteomic and metabolomic responses of priority bacterial pathogens to subinhibitory concentration of antibiotics.npj antimicrobials and resistance · 2025Article
- Staphylococcus aureus COL: An Atypical Model Strain of MRSA That Exhibits Slow Growth and Antibiotic Tolerance due to a Mutation in PRPP Synthetase.Molecular microbiology · 2025Article
- DNA aptamer AptScientific reports · 2025Article
- A shared alarmone-GTP switch controls persister formation in bacteria.Nature microbiology · 2025Article
81 more citing papers are in PubMed but not listed here.
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4 authors at 2 institutions in 1 country.
Funding
Abstract
The stringent response is a survival mechanism used by bacteria to deal with stress. It is coordinated by the nucleotides guanosine tetraphosphate and pentaphosphate [(p)ppGpp], which interact with target proteins to promote bacterial survival. Although this response has been well characterized in proteobacteria, very little is known about the effectors of this signaling system in Gram-positive species. Here, we report on the identification of seven target proteins for the stringent response nucleotides in the Gram-positive bacterium Staphylococcus aureus We demonstrate that the GTP synthesis enzymes HprT and Gmk bind with a high affinity, leading to an inhibition of GTP production. In addition, we identified five putative GTPases--RsgA, RbgA, Era, HflX, and ObgE--as (p)ppGpp target proteins. We show that RsgA, RbgA, Era, and HflX are functional GTPases and that their activity is promoted in the presence of ribosomes but strongly inhibited by the stringent response nucleotides. By characterizing the function of RsgA in vivo, we ascertain that this protein is involved in ribosome assembly, with an rsgA deletion strain, or a strain inactivated for GTPase activity, displaying decreased growth, a decrease in the amount of mature 70S ribosomes, and an increased level of tolerance to antimicrobials. We additionally demonstrate that the interaction of ppGpp with cellular GTPases is not unique to the staphylococci, as homologs from Bacillus subtilis and Enterococcus faecalis retain this ability. Taken together, this study reveals ribosome inactivation as a previously unidentified mechanism through which the stringent response functions in Gram-positive bacteria.
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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.