ArticleAMB Express2019
Ursolic acid inhibits colistin efflux and curtails colistin resistant Enterobacteriaceae.
Article in AMB Express, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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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.
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Who cites it
12 citing papers in PubMed, 33 citations in OpenAlex.
- Evaluation of the efflux inhibitory potential of gallotannin to restore drug sensitivity in XDRFrontiers in pharmacology · 2026Article
- Advances and mechanisms of traditional Chinese medicine and its active ingredients against antibiotic-resistantJournal of pharmaceutical analysis · 2025Review
- Evaluation of the mechanistic basis for the antibacterial activity of ursolic acid againstFrontiers in microbiology · 2024Article
- Efflux-mediated Multidrug Resistance in Critical Gram-negative Bacteria and Natural Efflux Pump Inhibitors.Current drug research reviews · 2024Review
- Article
- Ursolic acid: biological functions and application in animal husbandry.Frontiers in veterinary science · 2023Review
- Role of efflux pumps, their inhibitors, and regulators in colistin resistance.Frontiers in microbiology · 2023Review
- Does Secondary Plant Metabolite Ursolic Acid Exhibit Antibacterial Activity against UropathogenicPharmaceutics · 2022Article
- Anti-Planktonic and Anti-Biofilm Properties of Pentacyclic Triterpenes-Asiatic Acid and Ursolic Acid as Promising Antibacterial Future Pharmaceuticals.Biomolecules · 2022Review
- Effect of Ursolic and Oleanolic Acids on Lipid Membranes: Studies on MRSA and Models of Membranes.Antibiotics (Basel, Switzerland) · 2021Article
- Article
- Restoring colistin sensitivity in colistin-resistant E. coli: Combinatorial use of MarR inhibitor with efflux pump inhibitor.Scientific reports · 2019Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
Abstract
Colistin resistance in Enterobacteriaceae especially Klebsiella pneumoniae and Escherichia coli is driving the evolution of pan drug resistant strains. Screening a library of 13 plant nutraceuticals led to the identification of acetyl shikonin and ursolic acid, which exhibited synergy with colistin against extremely drug resistant (XDR) clinical strains of E. coli (U3790) and K. pneumoniae (BC936). Ursolic acid caused a significant colistin MIC reversal of 16-fold in U3790 and 4-fold in BC936 strains. Ursolic acid also potentiated the bactericidal effect of colistin against both U3790 and BC936 by causing ~ 4 to 4.5 log fold decline in CFU of both clinical isolates in a time kill assay. At 2× minimum effective concentration, ursolic acid was non-toxic to zebrafish as evidenced by brain and liver enzyme profiles and by histopathology studies. In combination with colistin, ursolic acid reduced bacterial bioburden of U3790/BC936 by 1-1.58 log fold from the infected muscle tissue of zebrafish. Mechanistic explorations via studies on real time efflux, membrane potential and intracellular accumulation of dansyl chloride tagged colistin revealed that colistin efflux is inhibited by ursolic acid. In addition, ursolic acid also enhanced outer membrane permeability which probably facilitates colistin's attack on outer and inner membranes. Our study shows that ursolic acid synergizes with colistin by inhibiting colistin efflux in Enterobacteriaceae that helps to curtail colistin resistant Enterobacteriaceae.
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Registered trials
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