ArticleCell chemical biology2017
Carbon Sources Tune Antibiotic Susceptibility in Pseudomonas aeruginosa via Tricarboxylic Acid Cycle Control.
Article in Cell chemical biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 236 papers.
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Who cites it
236 citing papers in PubMed, 370 citations in OpenAlex.
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- Xylose-induced tricarboxylic acid cycle activation resensitizes gentamicin-resistantApplied and environmental microbiology · 2026Article
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- An integrated computational-experimental approach identifies Malate Synthase G as therapeutic target to disrupt carbon metabolism in chronic Pseudomonas aeruginosa infection.Functional & integrative genomics · 2026Article
- Redefining Antimicrobial Resistance inInternational journal of molecular sciences · 2026Review
- In vitro exposure to non-antipseudomonal antibiotics (NAPA) induces Pseudomonas aeruginosa resistance to antipseudomonal antibiotics (APA).The Journal of antimicrobial chemotherapy · 2026Article
- Drug-resistant Escherichia coli metabolomics via pseudo-targeted SWATH/IDA-MRM: Bridging high coverage and precision.Journal of advanced research · 2026Article
- Iron-manganese superoxide dismutases are primarily responsible for antioxidative responses, antibiotic tolerance, and virulence of Salmonella Pullorum.Poultry science · 2026Article
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- Beyond antibiotics: Multidimensional interventions and coordinated governance against ESKAPE resistance.Biosafety and health · 2026Article
- Glnk Mediates Carbapenem Resistance Through the NtrB/NtrC-OprD Regulatory Pathway inPathogens (Basel, Switzerland) · 2026Article
176 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
Abstract
Metabolically dormant bacteria present a critical challenge to effective antimicrobial therapy because these bacteria are genetically susceptible to antibiotic treatment but phenotypically tolerant. Such tolerance has been attributed to impaired drug uptake, which can be reversed by metabolic stimulation. Here, we evaluate the effects of central carbon metabolite stimulations on aminoglycoside sensitivity in the pathogen Pseudomonas aeruginosa. We identify fumarate as a tobramycin potentiator that activates cellular respiration and generates a proton motive force by stimulating the tricarboxylic acid (TCA) cycle. In contrast, we find that glyoxylate induces phenotypic tolerance by inhibiting cellular respiration with acetyl-coenzyme A diversion through the glyoxylate shunt, despite drug import. Collectively, this work demonstrates that TCA cycle activity is important for both aminoglycoside uptake and downstream lethality and identifies a potential strategy for potentiating aminoglycoside treatment of P. aeruginosa infections.
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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.