ArticleNature communications2021
A trimethoprim derivative impedes antibiotic resistance evolution.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 91 citations in OpenAlex.
- Evolutionary Convergence on a Dihydrofolate Reductase Mutation Drives Trimethoprim-Sulfamethoxazole Resistance in Burkholderia thailandensis.ACS infectious diseases · 2026Article
- Conserved protein sequence-structure signatures identify antibiotic resistance genes from the human microbiome.Microbiome · 2026Article
- Chaperonin recognition of protein dynamics drives drug resistance.bioRxiv : the preprint server for biology · 2026Article
- FLEXTAG: a small and self-renewable protein labeling system for anti-fading multi-color super-resolution imaging.Nature communications · 2026Article
- Site-resolved energetic information from HX-MS experiments.Nature chemical biology · 2026Article
- Synthesis, Characterization, Antimicrobial Activity, Docking, and In Silico ADMET Analysis of Some New 2,3-Dihydrobenzo[b][1,4]thiazepine Derivatives.BioMed research international · 2026Article
- Antibiotic: a boon to mankind and doom to the environment - an insight on biological and non-biological degradation processes.Frontiers in microbiology · 2026Review
- Disclosing New Insights on Pyrazolo[3,4-Journal of microbiology and biotechnology · 2025Article
- Continuous targeted hypermutation with a tunable mutation window.Nature communications · 2025Article
- Notoginsenoside Ft1 enhances the effectiveness of gentamicin against Escherichia coli by interfering with intrinsic antibacterial mechanisms.BMC microbiology · 2025Article
- Antibiotic resistance ofOpen veterinary journal · 2025Article
- Recent Progress in the Synthesis, Functionalization, and Biological Outlook of Pyrimidines.ACS omega · 2025Review
- Time-Resolved Analysis of Protein-Protein Ensembles Using a Destabilizing Domain to Map Dynamic Interactions of SARS-CoV-2 nsp15.ACS chemical biology · 2025Article
- Exploring antibiotic resistance in diverse homologs of the dihydrofolate reductase protein family through broad mutational scanning.Science advances · 2025Article
- Enhancing the Solubility and Oral Bioavailability of Trimethoprim Through PEG-PLGA Nanoparticles: A Comprehensive Evaluation of In Vitro and In Vivo Performance.Pharmaceutics · 2025Article
- The role of bacterial metabolism in antimicrobial resistance.Nature reviews. Microbiology · 2025Review
- Cross-talk between Pseudomonas aeruginosa and urinary tract infections.World journal of urology · 2025Review
- A Thermodynamic Cycle to Predict the Competitive Inhibition Outcomes of an Evolving Enzyme.Journal of chemical theory and computation · 2025Article
- Targeting efflux pumps prevents the multi-step evolution of high-level resistance to fluoroquinolone inMicrobiology spectrum · 2025Article
- High throughput screening identifies potential inhibitors targeting trimethoprim resistant DfrA1 protein in Klebsiella pneumoniae and Escherichia coli.Scientific reports · 2025Article
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 2 countries.
Funding
Abstract
The antibiotic trimethoprim (TMP) is used to treat a variety of Escherichia coli infections, but its efficacy is limited by the rapid emergence of TMP-resistant bacteria. Previous laboratory evolution experiments have identified resistance-conferring mutations in the gene encoding the TMP target, bacterial dihydrofolate reductase (DHFR), in particular mutation L28R. Here, we show that 4'-desmethyltrimethoprim (4'-DTMP) inhibits both DHFR and its L28R variant, and selects against the emergence of TMP-resistant bacteria that carry the L28R mutation in laboratory experiments. Furthermore, antibiotic-sensitive E. coli populations acquire antibiotic resistance at a substantially slower rate when grown in the presence of 4'-DTMP than in the presence of TMP. We find that 4'-DTMP impedes evolution of resistance by selecting against resistant genotypes with the L28R mutation and diverting genetic trajectories to other resistance-conferring DHFR mutations with catalytic deficiencies. Our results demonstrate how a detailed characterization of resistance-conferring mutations in a target enzyme can help identify potential drugs against antibiotic-resistant bacteria, which may ultimately increase long-term efficacy of antimicrobial therapies by modulating evolutionary trajectories that lead to 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.