Discovery of Gambogic acid as an antibacterial adjuvant against vancomycin-resistant enterococci in vitro and in vivo.

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  • Additional Information
    • Source:
      Publisher: Urban & Fischer Verlag Country of Publication: Germany NLM ID: 9438794 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1618-095X (Electronic) Linking ISSN: 09447113 NLM ISO Abbreviation: Phytomedicine Subsets: MEDLINE
    • Publication Information:
      Publication: Stuttgart : Urban & Fischer Verlag
      Original Publication: Stuttgart ; New York : G. Fischer, c1994-
    • Subject Terms:
      Xanthones*/pharmacology ; Microbial Sensitivity Tests* ; Vancomycin-Resistant Enterococci*/drug effects ; Anti-Bacterial Agents*/pharmacology ; Vancomycin*/pharmacology ; Drug Synergism*; Animals ; Mice ; Garcinia/chemistry ; Female ; Gram-Positive Bacterial Infections/drug therapy
    • Abstract:
      Background: The emergence and spread of vancomycin-resistant enterococci (VRE) have posed a significant challenge to clinical treatment, underscoring the need to develop novel strategies. As therapeutic options for VRE are limited, discovering vancomycin enhancer is a feasible way of combating VRE. Gambogic acid (GA) is a natural product derived from the resin of Garcinia hanburyi Hook.f. (Clusiaceae), which possesses antibacterial activity.
      Purpose: This study aimed to investigate the potential of GA as an adjuvant to restore the susceptibility of VRE to vancomycin.
      Methods: In vitro antibacterial and synergistic activities were evaluated against vancomycin-susceptible and resistant strains by the broth microdilution method for the Minimal Inhibitory Concentrations (MICs) determination, and checkerboard assay and time-kill curve analysis for synergy evaluation. In vivo study was conducted on a mouse multi-organ infection model. The underlying antibacterial mechanism of GA was also explored.
      Results: GA showed a potent in vitro activity against all tested strains, with MICs ranging from 2 to 4 μg/ml. The combination of GA and vancomycin exhibited a synergistic effect against 18 out of 23 tested VRE strains, with a median fractional inhibitory concentration index (FICI) of 0.254, and demonstrated a synergistic effect in the time-kill assay. The combination therapy exhibited a significant reduction in tissue bacterial load compared with either compound used alone. GA strongly binds to the ParE subunit of topoisomerase IV, a bacterial type II DNA topoisomerase, and suppresses its activity.
      Conclusions: The study suggests that GA has a significant antibacterial activity against enterococci, and sub-MIC concentrations of GA can restore the activity of vancomycin against VRE in vitro and in vivo. These findings indicate that GA has the potential to be a new antibacterial adjuvant to vancomycin in the treatment of infections caused by VRE.
      Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
      (Copyright © 2024 Elsevier GmbH. All rights reserved.)
    • Contributed Indexing:
      Keywords: Antibacterial activity; Gambogic acid; Synergy; Type II DNA topoisomerases; Vancomycin-resistant enterococci
    • Accession Number:
      0 (Xanthones)
      8N585K83U2 (gambogic acid)
      0 (Anti-Bacterial Agents)
      6Q205EH1VU (Vancomycin)
    • Publication Date:
      Date Created: 20240322 Date Completed: 20240430 Latest Revision: 20240430
    • Publication Date:
      20240501
    • Accession Number:
      10.1016/j.phymed.2024.155400
    • Accession Number:
      38518641