ArticlemBio2022
Adenosine Awakens Metabolism to Enhance Growth-Independent Killing of Tolerant and Persister Bacteria across Multiple Classes of Antibiotics.
Article in mBio, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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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.
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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.
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Who cites it
30 citing papers in PubMed, 44 citations in OpenAlex.
- Biofilm-mediated antibiotic tolerance in bacterial pathogens: Integrated molecular networks and novel therapeutic avenues.Virulence · 2026Review
- Synthesis, antibacterial, and antibiofilm activities of an adenosine-benzoic acid conjugate against Streptococcus mutans and Escherichia coli: insights from molecular docking.Folia microbiologica · 2026Article
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- Drug-resistant Escherichia coli metabolomics via pseudo-targeted SWATH/IDA-MRM: Bridging high coverage and precision.Journal of advanced research · 2026Article
- DksA inhibitors against intracellular and persistentScience advances · 2026Article
- Colistin Resistance: From Laboratory Research to Modern Clinical Management.Antibiotics (Basel, Switzerland) · 2026Review
- Article
- Sequential eradication of bacterial persisters: integrating phytochemical pharmacology with microenvironment-responsive delivery strategies.Frontiers in microbiology · 2026Review
- Alternative nucleic acid structures in microbial biology: regulatory functions and antimicrobial opportunities.Frontiers in cellular and infection microbiology · 2026Review
- Omadacycline Pharmacokinetics: Characteristics, Contributing Factors, and Clinical Significance.Drugs in R&D · 2025Review
- Article
- The impact of bacterial purine metabolism on antibiotic efficacy.npj antimicrobials and resistance · 2025Review
- The role of bacterial metabolism in antimicrobial resistance.Nature reviews. Microbiology · 2025Review
- Exogenous NADH promotes the bactericidal effect of aminoglycoside antibiotics againstVirulence · 2024Article
- Adenosine Monophosphate as a Metabolic Adjuvant Enhances Antibiotic Efficacy against Drug-Resistant Bacterial Pathogens.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Deciphering the Antibacterial Mechanisms of 5-Fluorouracil inAntibiotics (Basel, Switzerland) · 2024Article
- Purine and pyrimidine synthesis differently affect the strength of the inoculum effect for aminoglycoside and β-lactam antibiotics.bioRxiv : the preprint server for biology · 2024Article
- A Methylazanediyl Bisacetamide Derivative Sensitizes Staphylococcus aureus Persisters to a Combination of Gentamicin And Daptomycin.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Metabolic and growth arrest are primary drivers of antibiotic tolerance and persistence in clinically diverse bacterial pathogens. We recently showed that adenosine (ADO) suppresses bacterial growth under nutrient-limiting conditions. In the current study, we show that despite the growth-suppressive effect of ADO, extracellular ADO enhances antibiotic killing in both Gram-negative and Gram-positive bacteria by up to 5 orders of magnitude. The ADO-potentiated antibiotic activity is dependent on purine salvage and is paralleled with a suppression of guanosine tetraphosphate synthesis and the massive accumulation of ATP and GTP. These changes in nucleoside phosphates coincide with transient increases in rRNA transcription and proton motive force. The potentiation of antibiotic killing by ADO is manifested against bacteria grown under both aerobic and anaerobic conditions, and it is exhibited even in the absence of alternative electron acceptors such as nitrate. ADO potentiates antibiotic killing by generating proton motive force and can occur independently of an ATP synthase. Bacteria treated with an uncoupler of oxidative phosphorylation and NADH dehydrogenase-deficient bacteria are refractory to the ADO-potentiated killing, suggesting that the metabolic awakening induced by this nucleoside is intrinsically dependent on an energized membrane. In conclusion, ADO represents a novel example of metabolite-driven but growth-independent means to reverse antibiotic tolerance. Our investigations identify the purine salvage pathway as a potential target for the development of therapeutics that may improve infection clearance while reducing the emergence of antibiotic resistance.
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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.