ArticleJournal of bacteriology2009
The molecular alarmone (p)ppGpp mediates stress responses, vancomycin tolerance, and virulence in Enterococcus faecalis.
Article in Journal of bacteriology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 124 papers.
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Who cites it
124 citing papers in PubMed, 188 citations in OpenAlex.
- Pheromone cCF10 Enhances Persister Formation inMicroorganisms · 2026Article
- Prolonged exposure to teixobactin generates cross-tolerance to other cell wall-targeting antimicrobials inAntimicrobial agents and chemotherapy · 2025Article
- Functional interplay between (p)ppGpp and RNAP in Acinetobacter baumannii.PLoS pathogens · 2025Article
- (p)ppGpp and DksA play a crucial role in reducing the efficacy of β-lactam antibiotics by modulating bacterial membrane permeability.Microbiology spectrum · 2025Article
- Insights into ecology, pathogenesis, and biofilm formation ofMicrobiology and molecular biology reviews : MMBR · 2025Review
- Genetic adaptation to amoxicillin in Escherichia coli: The limited role of dinB and katE.PloS one · 2025Article
- RelQ-mediated alarmone signalling regulates growth, stress-induced biofilm formation and spore accumulation inMicrobiology (Reading, England) · 2024Article
- RelQ-mediated alarmone signaling regulates growth, sporulation, and stress-induced biofilm formation inbioRxiv : the preprint server for biology · 2024Article
- ClinicalmSphere · 2023Article
- Functional Characterization of Small Alarmone Synthetase and Small Alarmone Hydrolase Proteins from Treponema denticola.Microbiology spectrum · 2023Article
- Dual stable isotopes enhance lipidomic studies in bacterial model organism Enterococcus faecalis.Analytical and bioanalytical chemistry · 2023Article
- Chronicity of high and low level mupirocin resistance in Staphylococcus aureus from 30 Indian hospitals.Scientific reports · 2023Article
- Sound the (Smaller) Alarm: The Triphosphate Magic Spot Nucleotide pGpp.Infection and immunity · 2023Review
- Proof-of-concept for incorporating mechanistic insights from multi-omics analyses of polymyxin B in combination with chloramphenicol against Klebsiella pneumoniae.CPT: pharmacometrics & systems pharmacology · 2023Article
- Genetically Encoded RNA-Based Bioluminescence Resonance Energy Transfer (BRET) Sensors.ACS sensors · 2023Article
- Antibiotics: Precious Goods in Changing Times.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Role of (p)ppGpp in antibiotic resistance, tolerance, persistence and survival in Firmicutes.microLife · 2023Review
- Library Screening for Synergistic Combinations of FDA-Approved Drugs and Metabolites with Vancomycin against VanA-Type Vancomycin-Resistant Enterococcus faecium.Microbiology spectrum · 2022Article
- Heme cross-feeding can augment Staphylococcus aureus and Enterococcus faecalis dual species biofilms.The ISME journal · 2022Article
- Structural variations between small alarmone hydrolase dimers support different modes of regulation of the stringent response.The Journal of biological chemistry · 2022Article
64 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The stringent response is a global bacterial response to stress that is mediated by accumulation of the alarmone (p)ppGpp. In this study, treatment with mupirocin was shown to induce high levels of (p)ppGpp production in Enterococcus faecalis, indicating that this nosocomial pathogen can mount a classic stringent response. In addition, (p)ppGpp was found to accumulate in cells subjected to heat shock, alkaline shock, and inhibitory concentrations of vancomycin. Sequence analysis of the E. faecalis genome indicated that (p)ppGpp synthesis is catalyzed by the bifunctional synthetase/hydrolase RelA and the RelQ small synthase. The (p)ppGpp profiles of DeltarelA, DeltarelQ, and DeltarelAQ strains revealed that RelA is the major enzyme responsible for the accumulation of (p)ppGpp during antibiotic or physical stresses, while RelQ appears to be responsible for maintaining basal levels of alarmone during homeostatic growth. Compared to its parent, the DeltarelA strain was more susceptible to several stress conditions, whereas complete elimination of (p)ppGpp in a DeltarelAQ double mutant restored many of the stress-sensitive phenotypes of DeltarelA. Interestingly, growth curves and time-kill studies indicated that tolerance to vancomycin is enhanced in the DeltarelA strain but diminished in the DeltarelQ and DeltarelAQ strains. Finally, virulence of the DeltarelAQ strain but not of the DeltarelA or DeltarelQ strain was significantly attenuated in the Caenorhabditis elegans model. Taken together, these results indicate that (p)ppGpp pools modulate environmental stress responses, vancomycin tolerance, and virulence in this important nosocomial pathogen.
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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.