ArticleJournal of cellular and molecular medicine2019
Theaflavin-3,3´-digallate increases the antibacterial activity of β-lactam antibiotics by inhibiting metallo-β-lactamase activity.
Article in Journal of cellular and molecular medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 31 citations in OpenAlex.
- Biophysical and Computational Insights into Alpha-1 Antitrypsin Aggregation and Its Inhibition by Natural Polyphenols.Biomedicines · 2026Article
- Herbal extracts as antibiotic adjuvants against ESKAPE pathogens: mechanisms and therapeutic potential.Engineering microbiology · 2026Review
- Advances regarding physiological functions and mechanisms of theaflavin‑3,3'‑digallate (Review).Molecular medicine reports · 2026Review
- Natural Products as Potentiators of β-Lactam Antibiotics: A Review of Mechanisms, Advances, and Future Directions.Antioxidants (Basel, Switzerland) · 2026Review
- A Comprehensive Review of Theaflavins: Physiological Activities, Synthesis Techniques, and Future Challenges.Food science & nutrition · 2025Review
- Metabolic Master Switch: Pyruvate Carboxylase Fuels Antimicrobial Resistance and Virulence in FoodborneFoods (Basel, Switzerland) · 2025Article
- Nature's Arsenal: Uncovering Antibacterial Agents Against Antimicrobial Resistance.Antibiotics (Basel, Switzerland) · 2025Review
- Kaempferol restores the susceptibility of ESBLsFrontiers in microbiology · 2024Article
- Antibacterial and Sporicidal Activity Evaluation of Theaflavin-3,3'-digallate.International journal of molecular sciences · 2022Article
- Molecular docking and proteomics reveals the synergistic antibacterial mechanism of theaflavin with β-lactam antibiotics against MRSA.Frontiers in microbiology · 2022Article
- Article
- Specific NDM-1 Inhibitor of Isoliquiritin Enhances the Activity of Meropenem against NDM-1-positiveInternational journal of environmental research and public health · 2020Article
- Isoalantolactone Enhances the Antimicrobial Activity of Penicillin G againstPathogens (Basel, Switzerland) · 2020Article
- Palmatine Is a Plasmid-Mediated Quinolone Resistance (PMQR) Inhibitor That Restores the Activity of Ciprofloxacin Against QnrS and AAC(6')-Ib-cr-ProducingInfection and drug resistance · 2020Article
- Discovery of a Novel Natural Allosteric Inhibitor That Targets NDM-1 AgainstFrontiers in pharmacology · 2020Article
- Theaflavin-3,3´-digallate increases the antibacterial activity of β-lactam antibiotics by inhibiting metallo-β-lactamase activity.Journal of cellular and molecular medicine · 2019Article
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8 authors at 2 institutions in 1 country.
Funding
Abstract
Metallo-β-lactamases (MBLs) are some of the best known β-lactamases produced by common Gram-positive and Gram-negative pathogens and are crucial factors in the rise of bacterial resistance against β-lactam antibiotics. Although many types of β-lactamase inhibitors have been successfully developed and used in clinical settings, no MBL inhibitors have been identified to date. Nitrocefin, checkerboard and time-kill assays were used to examine the enzyme behaviour in vitro. Molecular docking calculation, molecular dynamics simulation, calculation of the binding free energy and ligand-residue interaction decomposition were used for mechanistic research. The behaviour of the enzymes in vivo was investigated by a mouse infection experiment. We showed that theaflavin-3,3´-digallate (TFDG), a natural compound lacking antibacterial activities, can inhibit the hydrolysis of MBLs. In the checkerboard and time-kill assays, we observed a synergistic effect of TFDG with β-lactam antibiotics against methicillin-resistant Staphylococcus aureus BAA1717. Molecular dynamics simulations were used to identify the mechanism of the inhibition of MBLs by TFDG, and we observed that the hydrolysis activity of the MBLs was restricted by the binding of TFDG to Gln242 and Ser369. Furthermore, the combination of TFDG with β-lactam antibiotics showed effective protection in a mouse Staphylococcus aureus pneumonia model. These findings suggest that TFDG can effectively inhibit the hydrolysis activity of MBLs and enhance the antibacterial activity of β-lactam antibiotics against pathogens in vitro and in vivo.
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