ArticleACS infectious diseases2016
Crystal Structures of Trimethoprim-Resistant DfrA1 Rationalize Potent Inhibition by Propargyl-Linked Antifolates.
Article in ACS infectious diseases, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 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.
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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
23 citing papers in PubMed, 43 citations in OpenAlex.
- Draft genome sequence ofMicrobiology resource announcements · 2026Article
- Research progress on clinical challenges and prevention strategies of drug-resistantFrontiers in public health · 2026Review
- High throughput screening identifies potential inhibitors targeting trimethoprim resistant DfrA1 protein in Klebsiella pneumoniae and Escherichia coli.Scientific reports · 2025Article
- Deciphering the Role of WWTPs in Cold Environments as Hotspots for the Dissemination of Antibiotic Resistance Genes.Microbial ecology · 2023Article
- Article
- RETRACTED: The Discovery of Novel Antimicrobial Agents through the Application of Isocyanide-Based Multicomponent Reactions.Antibiotics (Basel, Switzerland) · 2023Review
- Molecular epidemiology of enterically colonizingFrontiers in microbiology · 2023Article
- Dual-Wavelength Fluorescence Polarization Immunoassay for Simultaneous Detection of Sulfonamides and Antibacterial Synergists in Milk.Biosensors · 2022Article
- Imaging sensitive and drug-resistant bacterial infection with [11C]-trimethoprim.The Journal of clinical investigation · 2022Article
- Structure-guided functional studies of plasmid-encoded dihydrofolate reductases reveal a common mechanism of trimethoprim resistance in Gram-negative pathogens.Communications biology · 2022Article
- Hypothesis-Driven, Structure-Based Design in Photopharmacology: The Case of eDHFR Inhibitors.Journal of medicinal chemistry · 2022Article
- Deciphering Antifungal Drug Resistance inJournal of chemical information and modeling · 2021Article
- Burden, Antibiotic Resistance, and Clonality ofTropical medicine and infectious disease · 2021Article
- Trimethoprim and other nonclassical antifolates an excellent template for searching modifications of dihydrofolate reductase enzyme inhibitors.The Journal of antibiotics · 2020Review
- Toward Broad Spectrum Dihydrofolate Reductase Inhibitors Targeting Trimethoprim Resistant Enzymes Identified in Clinical Isolates of Methicillin ResistantACS infectious diseases · 2019Article
- Structure-Guided In Vitro to In Vivo Pharmacokinetic Optimization of Propargyl-Linked Antifolates.Drug metabolism and disposition: the biological fate of chemicals · 2019Article
- Multicomponent Reactions Upon the Known Drug Trimethoprim as a Source of Novel Antimicrobial Agents.Frontiers in chemistry · 2019Article
- The Structural and Functional Basis for Recurring Sulfa Drug Resistance Mutations inFrontiers in microbiology · 2018Article
- Characterization of trimethoprim resistantChemical science · 2017Article
- Pharmaceutical analysis of a novel propargyl-linked antifolate antibiotic in the mouse.Journal of chromatography. B, Analytical technologies in the biomedical and life sciences · 2017Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Multidrug-resistant Enterobacteriaceae, notably Escherichia coli and Klebsiella pneumoniae, have become major health concerns worldwide. Resistance to effective therapeutics is often carried by class I and II integrons that can confer insensitivity to carbapenems, extended spectrum β-lactamases, the antifolate trimethoprim, fluoroquinolones, and aminoglycosides. Specifically of interest to the study here, a prevalent gene (dfrA1) coding for an insensitive dihydrofolate reductase (DHFR) confers 190- or 1000-fold resistance to trimethoprim for K. pneumoniae and E. coli, respectively. Attaining inhibition of both the wild-type and resistant forms of the enzyme is critical for new antifolates. For several years, we have been developing the propargyl-linked antifolates (PLAs) as effective inhibitors against trimethoprim-resistant DHFR enzymes. Here, we show that the PLAs are active against both the wild-type and DfrA1 DHFR proteins. We report two high-resolution crystal structures of DfrA1 bound to potent PLAs. The structure-activity relationships and crystal structures will be critical in driving the design of broadly active inhibitors against wild-type and resistant DHFR.
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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.