ArticlePloS one2019
The Ps and Qs of alarmone synthesis in Staphylococcus aureus.
Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- Starvation-independent alarmone production inhibits translation through GTP depletion.bioRxiv : the preprint server for biology · 2026Article
- Antibiotic tolerance among clinical isolates: mechanisms, detection, prevalence, and significance.Clinical microbiology reviews · 2024Review
- C-terminal deletion of RelA protein is suggested as a possible cause of infective endocarditis recurrence withAntimicrobial agents and chemotherapy · 2024Article
- Functional Characterization of Small Alarmone Synthetase and Small Alarmone Hydrolase Proteins from Treponema denticola.Microbiology spectrum · 2023Article
- Sound the (Smaller) Alarm: The Triphosphate Magic Spot Nucleotide pGpp.Infection and immunity · 2023Review
- Role of (p)ppGpp in antibiotic resistance, tolerance, persistence and survival in Firmicutes.microLife · 2023Review
- Molecular Characterization of Clinical Rel Mutations and Consequences for Resistance Expression and Fitness in Staphylococcus aureus.Antimicrobial agents and chemotherapy · 2022Article
- Crosstalk between guanosine nucleotides regulates cellular heterogeneity in protein synthesis during nutrient limitation.PLoS genetics · 2022Article
- Unique Features of Alarmone Metabolism in Clostridioides difficile.Journal of bacteriology · 2022Article
- InJournal of bacteriology · 2022Article
- Article
- The extended (p)ppGpp family: New dimensions in Stress response.Current research in microbial sciences · 2021Review
- The stringent response and physiological roles of (pp)pGpp in bacteria.Nature reviews. Microbiology · 2021Review
- Inducible expression of (pp)pGpp synthetases in Staphylococcus aureus is associated with activation of stress response genes.PLoS genetics · 2020Article
- Survival of the Fittest: The Relationship of (p)ppGpp With Bacterial Virulence.Frontiers in microbiology · 2020Review
- Manganese Depletion Leads to Multisystem Changes in the Transcriptome of the Opportunistic PathogenFrontiers in microbiology · 2020Article
- Possible Roles for Basal Levels of (p)ppGpp: Growth Efficiency Vs. Surviving Stress.Frontiers in microbiology · 2020Review
- Pleiotropic Effects of Bacterial Small Alarmone Synthetases: Underscoring the Dual-Domain Small Alarmone Synthetases inFrontiers in microbiology · 2020Review
- The C-Terminal RRM/ACT Domain Is Crucial for Fine-Tuning the Activation of 'Long' RelA-SpoT Homolog Enzymes by Ribosomal Complexes.Frontiers in microbiology · 2020Article
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
During the stringent response, bacteria synthesize guanosine-3',5'-bis(diphosphate) (ppGpp) and guanosine-5'-triphosphate 3'-diphosphate (pppGpp), which act as secondary messengers to promote cellular survival and adaptation. (p)ppGpp 'alarmones' are synthesized and/or hydrolyzed by proteins belonging to the RelA/SpoT Homologue (RSH) family. Many bacteria also encode 'small alarmone synthetase' (SAS) proteins (e.g. RelP, RelQ) which may also be capable of synthesizing a third alarmone: guanosine-5'-phosphate 3'-diphosphate (pGpp). Here, we report the biochemical properties of the Rel (RSH), RelP and RelQ proteins from Staphylococcus aureus (Sa-Rel, Sa-RelP, Sa-RelQ, respectively). Sa-Rel synthesized pppGpp more efficiently than ppGpp, but lacked the ability to produce pGpp. Sa-Rel efficiently hydrolyzed all three alarmones in a Mn(II) ion-dependent manner. The removal of the C-terminal regulatory domain of Sa-Rel increased its rate of (p)ppGpp synthesis ca. 10-fold, but had negligible effects on its rate of (pp)pGpp hydrolysis. Sa-RelP and Sa-RelQ efficiently synthesized pGpp in addition to pppGpp and ppGpp. The alarmone-synthesizing abilities of Sa-RelQ, but not Sa-RelP, were allosterically-stimulated by the addition of pppGpp, ppGpp or pGpp. The respective (pp)pGpp-synthesizing activities of Sa-RelP/Sa-RelQ were compared and contrasted with SAS homologues from Enterococcus faecalis (Ef-RelQ) and Streptococcus mutans (Sm-RelQ, Sm-RelP). Results indicated that EF-RelQ, Sm-RelQ and Sa-RelQ were functionally equivalent; but exhibited considerable variations in their respective biochemical properties, and the degrees to which alarmones and single-stranded RNA molecules allosterically modulated their respective alarmone-synthesizing activities. The respective (pp)pGpp-synthesizing capabilities of Sa-RelP and Sm-RelP proteins were inhibited by pGpp, ppGpp and pppGpp. Our results support the premise that RelP and RelQ proteins may synthesize pGpp in addition to (p)ppGpp within S. aureus and other Gram-positive bacterial species.
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