Dataset Information

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

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 (~10⁷ 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.

SUBMITTER: Abutaleb NS

PROVIDER: S-EPMC7073294 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Publications

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

Abutaleb Nader S NS Seleem Mohamed N MN

International journal of antimicrobial agents 20191026 3

<h4>Introduction</h4>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.<h4>Methods and results</h4>The present study determined that auranofin's antibacterial activity was not affected when evaluated against a higher inoculum size of VRE (~10<sup>7</sup> CFU/ ...[more]

PMID: 31669742

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Project description:Enterococci can cause various infectious diseases, including urinary tract infection, wound infection, and life-threatening endocarditis and meningitis. The emergence and transmission of vancomycin-resistant enterococci (VRE) have presented a challenge to clinical treatment. There is an urgent need to develop new strategies to fight against this pathogen. This study investigated the antibacterial and anti-biofilm activity of celastrol (CEL), a natural product originating from Tripterygium wilfordii Hook F, against enterococci, and its adjuvant capacity of restoring the susceptibility of VRE to vancomycin in vitro and in vivo. CEL inhibited all enterococcus strains tested, with MICs ranging from 0.5 to 4 μg/mL. More than 50% of biofilm was eliminated by CEL at 16 μg/mL after 24 h of exposure. The combination of CEL and vancomycin showed a synergistic effect against all 23 strains tested in checkerboard assays. The combination of sub-MIC levels of CEL and vancomycin showed a synergistic effect in a time-kill assay and exhibited significant protective efficacy in Galleria mellonella larval infection model compared with either drug used alone. The underlying mechanisms of CEL were explored by conducting biomolecular binding interactions and an enzyme inhibition assay of CEL on bacterial cell-division protein FtsZ. CEL presented strong binding and suppression ability to FtsZ, with Kd and IC50 values of 2.454 μM and 1.04 ± 0.17 μg/mL, respectively. CEL exhibits a significant antibacterial and synergic activity against VRE in vitro and in vivo and has the potential to be a new antibacterial agent or adjuvant to vancomycin as a therapeutic option in combating VRE. IMPORTANCE The emergence and transmission of VRE pose a significant medical and public health challenge. CEL, well-known for a wide range of biological activities, has not previously been investigated for its synergistic effect with vancomycin against VRE. In the present study, CEL exhibited antibacterial activity against enterococci, including VRE strains, and restored the activity of vancomycin against VRE in vitro and in vivo. Hence, CEL has the potential to be a new antibacterial adjuvant to vancomycin and could provide a promising therapeutic option in combating VRE.

Dataset Information

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

Introduction

Methods and results

Conclusion

Publications

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

Similar Datasets

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