ArticleNature microbiology2024
A folate inhibitor exploits metabolic differences in Pseudomonas aeruginosa for narrow-spectrum targeting.
Article in Nature microbiology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
10 citing papers in PubMed, 19 citations in OpenAlex.
- Citrus Flavonoids-Coated Biogenic Nanoparticles for ControllingACS applied bio materials · 2026Article
- The Quantification of Drug Accumulation within Gram-Negative Bacteria.ACS infectious diseases · 2026Article
- Precision antimicrobials: the next paradigm shift after broad-spectrum therapy.Frontiers in microbiology · 2026Article
- Article
- How to spare gut microbiota from antibiotic effects? PK-PD based innovative strategies, target specificity, and molecule-to-medicinal properties.RSC medicinal chemistry · 2025Review
- A novel homoarginine-containing cyclic peptide pioamide with selective antipseudomonal activity isolated from the nematode symbiontApplied and environmental microbiology · 2025Article
- Novel therapeutic strategies targeting infections caused by P. aeruginosa biofilm.Molecular biology reports · 2025Review
- Expanding the Landscape of Dual Action Antifolate Antibacterials through 2,4-Diamino-1,6-dihydro-1,3,5-triazines.ACS infectious diseases · 2025Article
- Dual-function regulator MexL as a target to control phenazines production and pathogenesis of Pseudomonas aeruginosa.Nature communications · 2025Article
- Upregulated Palmitoleate and Oleate Production inMolecules (Basel, Switzerland) · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Pseudomonas aeruginosa is a leading cause of hospital-acquired infections for which the development of antibiotics is urgently needed. Unlike most enteric bacteria, P. aeruginosa lacks enzymes required to scavenge exogenous thymine. An appealing strategy to selectively target P. aeruginosa is to disrupt thymidine synthesis while providing exogenous thymine. However, known antibiotics that perturb thymidine synthesis are largely inactive against P. aeruginosa.Here we characterize fluorofolin, a dihydrofolate reductase (DHFR) inhibitor derived from Irresistin-16, that exhibits significant activity against P. aeruginosa in culture and in a mouse thigh infection model. Fluorofolin is active against a wide range of clinical P. aeruginosa isolates resistant to known antibiotics. Metabolomics and in vitro assays using purified folA confirm that fluorofolin inhibits P. aeruginosa DHFR. Importantly, in the presence of thymine supplementation, fluorofolin activity is selective for P. aeruginosa. Resistance to fluorofolin can emerge through overexpression of the efflux pumps MexCD-OprJ and MexEF-OprN, but these mutants also decrease pathogenesis. Our findings demonstrate how understanding species-specific genetic differences can enable selective targeting of important pathogens while revealing trade-offs between resistance and pathogenesis.
Indexed as
Identifiers
What OpenQuestion holds
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.