Antivirulence activity of auranofin against vancomycin-resistant enterococci: in vitro and in vivo studies.

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  • Author(s): Abutaleb NS;Abutaleb NS; Seleem MN; Seleem MN; Seleem MN
  • Source:
    International journal of antimicrobial agents [Int J Antimicrob Agents] 2020 Mar; Vol. 55 (3), pp. 105828. Date of Electronic Publication: 2019 Oct 26.
  • Publication Type:
    Journal Article
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Elsevier Science Publishers Country of Publication: Netherlands NLM ID: 9111860 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-7913 (Electronic) Linking ISSN: 09248579 NLM ISO Abbreviation: Int J Antimicrob Agents Subsets: MEDLINE
    • Publication Information:
      Original Publication: Amsterdam : Elsevier Science Publishers, c1991-
    • Subject Terms:
      Anti-Bacterial Agents/*pharmacology ; Auranofin/*pharmacology ; Vancomycin-Resistant Enterococci/*drug effects; Animals ; Antirheumatic Agents/pharmacology ; Gram-Positive Bacterial Infections/drug therapy ; Gram-Positive Bacterial Infections/microbiology ; Linezolid/pharmacology ; Mice ; Microbial Sensitivity Tests ; Vancomycin-Resistant Enterococci/pathogenicity
    • Abstract:
      Introduction: Vancomycin-resistant enterococci (VRE) are a leading cause of nosocomial infections because of the limited number of effective therapeutic options. In an effort to repurpose FDA-approved drugs against antibiotic-resistant bacteria, auranofin has been identified as a potent drug against VRE.
      Methods and Results: The present study determined that auranofin's antibacterial activity was not affected when evaluated against a higher inoculum size of VRE (~10 7 CFU/mL), and auranofin successfully reduced the burden of stationary phase VRE cells via a time-kill assay. In addition, auranofin reduced VRE production of key virulence factors, including proteases, lipase and haemagglutinin. The promising features of auranofin prompted evaluation of its in vivo efficacy in a lethal mouse model of VRE septicaemia. All mice receiving auranofin at 0.125 mg/kg orally, 0.125 mg/kg subcutaneously (SC) or 0.0625 mg/kg (SC) survived the lethal VRE challenge. Additionally, auranofin was superior to linezolid, the current drug of choice, in reducing VRE burden in the liver, kidneys and spleen of mice. Remarkably, auranofin successfully reduced VRE below the limit of detection in murine internal organs after 4 days of oral or subcutaneous treatment.
      Conclusion: These results indicate that auranofin warrants further investigation as a new treatment for systemic VRE infections.
      (Copyright © 2020 Elsevier Ltd. All rights reserved.)
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    • Grant Information:
      R01 AI130186 United States AI NIAID NIH HHS
    • Contributed Indexing:
      Keywords: Antivirulence; Auranofin; Lipase; Protease; Septicaemia
    • Accession Number:
      0 (Anti-Bacterial Agents)
      0 (Antirheumatic Agents)
      3H04W2810V (Auranofin)
      ISQ9I6J12J (Linezolid)
    • Publication Date:
      Date Created: 20191101 Date Completed: 20200325 Latest Revision: 20210302
    • Publication Date:
      20221213
    • Accession Number:
      PMC7073294
    • Accession Number:
      10.1016/j.ijantimicag.2019.10.009
    • Accession Number:
      31669742