ArticleNature communications2018
Mutual potentiation drives synergy between trimethoprim and sulfamethoxazole.
Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
What it found
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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.
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
61 citing papers in PubMed, 120 citations in OpenAlex.
- Fatty Acid Biosynthesis Inhibitors─Fabimycin and Triclosan─Trigger Distinct Resistance Mutations in FabI and Potently Kill Gram-Negative Pathogens.ACS infectious diseases · 2026Article
- Evolutionary Convergence on a Dihydrofolate Reductase Mutation Drives Trimethoprim-Sulfamethoxazole Resistance in Burkholderia thailandensis.ACS infectious diseases · 2026Article
- Off-target anti-leukemic effects of antibiotics: mechanisms and therapeutic insights.Cancer chemotherapy and pharmacology · 2026Review
- Comparative pharmacokinetics of trimethoprim-sulfadiazine and trimethoprim-sulfamethoxazole in dogs.BMC veterinary research · 2026Article
- Host-Pathogen Dual Targeting With Repurposed Drugs Identifies a Synergistic Therapy for Intracellular Staphylococcus aureus.MicrobiologyOpen · 2026Article
- Trimethoprim/Sulfamethoxazole-Induced Systemic Toxic Epidermal Necrolysis Syndrome: A Case Report.Clinical case reports · 2026Article
- Are two really better than one? A retrospective study comparing monotherapy versus combination therapy forMicrobiology spectrum · 2026Article
- Fatty acid biosynthesis inhibitors fabimycin and triclosan trigger distinct resistance mutations in FabI and potently kill Gram-negative pathogens.bioRxiv : the preprint server for biology · 2026Article
- Recent trends in dual-acting hybrid antibiotics and combination therapies against Gram-negative pathogens.Journal of microbiology (Seoul, Korea) · 2026Review
- Ecological partitioning enables phage-antibiotic cooperation in a human Pseudomonas infection.Nature communications · 2026Article
- Molecular Compatibility in Chinese Medicine for Cancer Treatment and Drug Development: From Traditional Wisdom to Innovative Therapeutics.Chinese journal of integrative medicine · 2026Article
- Comparative evaluation of trimethoprim-sulfonamide ratios and synergistic interactions against porcine respiratory pathogens.Frontiers in veterinary science · 2026Article
- Transcription co-inhibition alters drug resistance evolution and enhances Mycobacterium tuberculosis clearance from granulomas.Nature microbiology · 2026Article
- Combining Bile Salt with Gentamicin: A Promising Strategy Against Vibrio Parahaemolyticus and Escherichia Coli.Current microbiology · 2025Article
- Population pharmacokinetic modeling of sulfadimethoxine, sulfadiazine and sulfamethoxazole combined to trimethoprim in pigs.The veterinary quarterly · 2025Article
- Antibiotic-Cyclodextrin Interactions: An Effective Strategy for the Encapsulation of Environmental Contaminants.Molecules (Basel, Switzerland) · 2025Article
- Zinc-metallochaperones ofMicrobiology spectrum · 2025Article
- Silent Dangers in Elderly Pharmacotherapy: The Interplay of Polypharmacy, Multimorbidity, and Drug Interactions.Journal of evaluation in clinical practice · 2025Review
- Evaluation of Adverse Events Associated with the Sulfamethoxazole/Trimethoprim Combination Drug.Journal of clinical medicine · 2025Article
- Genomic insights into the spread of vancomycin- and tigecycline-resistant Enterococcus faecium ST117.Annals of clinical microbiology and antimicrobials · 2025Article
1 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Trimethoprim (TMP)-sulfamethoxazole (SMX) is a widely used synergistic antimicrobial combination to treat a variety of bacterial and certain fungal infections. These drugs act by targeting sequential steps in the biosynthetic pathway for tetrahydrofolate (THF), where SMX inhibits production of the THF precursor dihydropteroate, and TMP inhibits conversion of dihydrofolate (DHF) to THF. Consequently, SMX potentiates TMP by limiting de novo DHF production and this mono-potentiation mechanism is the current explanation for their synergistic action. Here, we demonstrate that this model is insufficient to explain the potent synergy of TMP-SMX. Using genetic and biochemical approaches, we characterize a metabolic feedback loop in which THF is critical for production of the folate precursor dihydropterin pyrophosphate (DHPPP). We reveal that TMP potentiates SMX activity through inhibition of DHPPP synthesis. Our study demonstrates that the TMP-SMX synergy is driven by mutual potentiation of the action of each drug on the other.
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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.