ArticleJournal of bacteriology2014
Two small (p)ppGpp synthases in Staphylococcus aureus mediate tolerance against cell envelope stress conditions.
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 116 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
116 citing papers in PubMed, 187 citations in OpenAlex.
- Reactive oxygen detoxification contributes toeLife · 2026Article
- Targeting the stringent response alters gene expression and extracellular vesicle RNA inMicrobiology spectrum · 2026Article
- Clinical Rel mutations that increase basal (p)ppGpp promote conjugal transfer of staphylococcal resistance plasmids.Microbiology (Reading, England) · 2026Article
- Pentaphosphorylated magic spot nucleotides: chemoenzymatic synthesis and disassembly-based sensing.Organic & biomolecular chemistry · 2026Article
- Baloxavir Exhibits Antibacterial Activity AgainstInternational journal of molecular sciences · 2026Article
- Global response to antibiotic exposure reveals a critical role for nucleotide metabolism in high-level β-lactam tolerance.npj antimicrobials and resistance · 2026Article
- Determining the Importance of the Stringent Response for Methicillin-Resistant Staphylococcus aureus Virulence In Vivo.The Journal of infectious diseases · 2025Article
- The toxin-antitoxin system SavRS contributes to vancomycin resistance in vancomycin-intermediate Staphylococcus aureus by mediating cell wall thickening.The Journal of antimicrobial chemotherapy · 2025Article
- Global response to antibiotic exposure uncovers a critical role for nucleotide metabolism in high-level β-lactam tolerance.Research square · 2025Article
- Reactive Oxygen Detoxification Contributes tobioRxiv : the preprint server for biology · 2025Article
- Inactivation of branched-chain amino acid uptake halts Staphylococcus aureus growth and induces bacterial quiescence within macrophages.PLoS pathogens · 2025Article
- A shared alarmone-GTP switch controls persister formation in bacteria.Nature microbiology · 2025Article
- (p)ppGpp-mediated GTP homeostasis ensures survival and antibiotic tolerance of Staphylococcus aureus.Communications biology · 2025Article
- Mechanisms of neutralization of toxSAS from toxin-antitoxin modules.Nature chemical biology · 2025Article
- Article
- Article
- Restriction of arginine induces antibiotic tolerance in Staphylococcus aureus.Nature communications · 2024Article
- mSphere of Influence: Targeting bacterial signaling and metabolism to overcome antimicrobial resistance.mSphere · 2024Article
- ClinicalmSphere · 2023Article
- Biochemical and X-ray analyses of the players involved in the faRel2/aTfaRel2 toxin-antitoxin operon.Acta crystallographica. Section F, Structural biology communications · 2023Article
56 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The stringent response is a conserved global regulatory mechanism that is related to the synthesis of (p)ppGpp nucleotides. Gram-positive bacteria, such as Staphylococcus aureus, possess three (p)ppGpp synthases: the bifunctional RSH (RelA/SpoT homolog) protein, which consists of a (p)ppGpp synthase and a (p)ppGpp hydrolase domain, and two truncated (p)ppGpp synthases, designated RelP and RelQ. Here, we characterized these two small (p)ppGpp synthases. Biochemical analyses of purified proteins and in vivo studies revealed a stronger synthetic activity for RelP than for RelQ. However, both enzymes prefer GDP over GTP as the pyrophosphate recipient to synthesize ppGpp. Each of the enzymes was shown to be responsible for the essentiality of the (p)ppGpp hydrolase domain of the RSH protein. The staphylococcal RSH-hydrolase is an efficient enzyme that prevents the toxic accumulation of (p)ppGpp. Expression of (p)ppGpp synthases in a hydrolase-negative background leads not only to growth arrest but also to cell death. Transcriptional analyses showed that relP and relQ are strongly induced upon vancomycin and ampicillin treatments. Accordingly, mutants lacking relP and relQ showed a significantly reduced survival rate upon treatments with cell wall-active antibiotics. Thus, RelP and RelQ are active (p)ppGpp synthases in S. aureus that are induced under cell envelope stress to mediate tolerance against these conditions.
Indexed as
Identifiers
What OpenQuestion holds
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.