Journal: International journal of antimicrobial agents

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

doi: 10.1016/j.ijantimicag.2019.10.009

Figure Lengend Snippet: Minimum inhibitory concentration (MIC, µg/mL) of auranofin and linezolid against clinical isolates of vancomycin-resistant E. faecium and E. faecalis at standard and high inocula.

Article Snippet: Auranofin, linezolid (Chem-Impex International, Wood Dale, IL, USA) and vancomycin hydrochloride (Gold Biotechnology, St. Louis, MO, USA) were purchased from commercial vendors.

Techniques: Concentration Assay

Journal: International journal of antimicrobial agents

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

doi: 10.1016/j.ijantimicag.2019.10.009

Figure Lengend Snippet: Time-kill kinetics assay of auranofin and linezolid against stationary phase vancomycin-resistant Enterococcus faecium NR-31909. Bacteria were incubated with test agents, and samples were collected at 0,12- and 24-h incubation period. The error bars represent standard deviation values obtained from triplicate samples used for each agent studied. (*) represents significant difference from 0 time. # represents significant difference from linezolid (*, # P < 0.05). Data were analyzed with two way ANOVA with post hoc Dunnet’s test.

Article Snippet: Auranofin, linezolid (Chem-Impex International, Wood Dale, IL, USA) and vancomycin hydrochloride (Gold Biotechnology, St. Louis, MO, USA) were purchased from commercial vendors.

Techniques: Incubation, Standard Deviation

Journal: International journal of antimicrobial agents

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

doi: 10.1016/j.ijantimicag.2019.10.009

Figure Lengend Snippet: Total protease inhibition activity of auranofin and linezolid against vancomycin-resistant E. faecium NR-31909. Data are presented as percent protease production of each drug (tested in sexruplicate). TSB with skim milk served as a negative control. Data were analyzed via unpaired Student t test (p<0.05). Auranofin was compared to untreated (*) and to linezolid (#).

Article Snippet: Auranofin, linezolid (Chem-Impex International, Wood Dale, IL, USA) and vancomycin hydrochloride (Gold Biotechnology, St. Louis, MO, USA) were purchased from commercial vendors.

Techniques: Inhibition, Activity Assay, Negative Control

Journal: International journal of antimicrobial agents

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

doi: 10.1016/j.ijantimicag.2019.10.009

Figure Lengend Snippet: Lipase inhibition activity of auranofin and linezolid against vancomycin-resistant E. faecium NR-31909. Data are presented as percent lipase production in presence of each drug (tested in sexruplicate). TSB with egg yolk emulsion served as a negative control. Data were analyzed via unpaired Student t test (p<0.05). Auranofin was compared to untreated (*) and to linezolid (#).

Article Snippet: Auranofin, linezolid (Chem-Impex International, Wood Dale, IL, USA) and vancomycin hydrochloride (Gold Biotechnology, St. Louis, MO, USA) were purchased from commercial vendors.

Techniques: Inhibition, Activity Assay, Negative Control

Journal: International journal of antimicrobial agents

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

doi: 10.1016/j.ijantimicag.2019.10.009

Figure Lengend Snippet: Hemagglutination inhibitory activities of auranofin and linezolid against E. faecalis NR-31909. Sub-inhibitory concentrations (starting from 0.5 µg/mL to 0.015 µg/mL) of the drugs were added with bacterial supernatant and RBCs, and then incubated for 1 hour at 37 °C. Positive hemagglutination inhibition results appear as dots in the center of round-bottomed plates. Negative hemagglutination inhibition results appear as a uniform reddish color across the well.

Article Snippet: Auranofin, linezolid (Chem-Impex International, Wood Dale, IL, USA) and vancomycin hydrochloride (Gold Biotechnology, St. Louis, MO, USA) were purchased from commercial vendors.

Techniques: Incubation, HI Assay

Journal: International journal of antimicrobial agents

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

doi: 10.1016/j.ijantimicag.2019.10.009

Figure Lengend Snippet: In vivo antibacterial activity of auranofin against E. faecium NR-31909 in the murine septicemia model when administered (A) Orally at 0.125 mg/kg, 0.25 mg/kg and 0.5 mg/kg; and (B) Subcutaneously (S.C.) at 0.0625 mg/kg, 0.125 mg/kg and 0.25 mg/kg compared to the vehicle control and the standard antibiotic linezolid given orally at 20 mg/kg. Mice survival was monitored for 5 days. Results were analyzed for statistical difference utilizing graphpad prism. (*) Denotes significant difference between each treated group and the untreated group (P < 0.05).

Article Snippet: Auranofin, linezolid (Chem-Impex International, Wood Dale, IL, USA) and vancomycin hydrochloride (Gold Biotechnology, St. Louis, MO, USA) were purchased from commercial vendors.

Techniques: In Vivo, Activity Assay

Journal: International journal of antimicrobial agents

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

doi: 10.1016/j.ijantimicag.2019.10.009

Figure Lengend Snippet: VRE counts in (A) liver, (B) kidney, and (C) spleen of the infected mice (5/group) orally treated with auranofin, and (D) liver, (E) kidney, and (F) spleen of the infected mice (5/group) treated S.C. after 4 days. Auranofin was compared to untreated (*) and to linezolid (#). (P < 0.05).

Article Snippet: Auranofin, linezolid (Chem-Impex International, Wood Dale, IL, USA) and vancomycin hydrochloride (Gold Biotechnology, St. Louis, MO, USA) were purchased from commercial vendors.

Techniques: Infection

Journal: PLoS ONE

Article Title: The Cellular Thioredoxin-1/Thioredoxin Reductase-1 Driven Oxidoreduction Represents a Chemotherapeutic Target for HIV-1 Entry Inhibition

doi: 10.1371/journal.pone.0147773

Figure Lengend Snippet: An ELISA was performed with two set-ups for each compound, the reference compound (auranofin), a vehicle control (DMSO) and DTT. In the first set-up (TrxR1 + Trx1) preincub ., TrxR1 was shortly (15 min) pre-incubated with Trx1 before adding the compounds. In the second set-up (TrxR1 + compounds) preincub , TrxR1 was shortly (15 min) pre-incubated with the compounds before adding Trx1. The final reaction mixture contained 1 μM Trx1 + 100 nM TrxR1 + 240 μM NADPH + 100 μM compound or auranofin. DTT was used as a reduction control. ELISA plates were coated with recombinant human gp120. The reaction mixtures were added to the wells to allow reduction of the coated gp120, incubated for 15 min at room temperature and exposed to streptavidine-ALP and p-nitrophenyl phosphate. The value for the DTT was set to 100% in each individual experiment and all other values were normalised against this reference value. The data are means of three independent experiments; the error bars represent the SEM. P-values were calculated for each reaction in relation to its control and are indicated if significant (*: p < 0.05; **: p < 0.01; ***: p < 0.001).

Article Snippet: Auranofin was obtained from Alexis Biochemicals (Lausen, Switzerland), AMD3100 from AnorMed (Langley, British Colombia, Canada) and MagicMark XP Western Protein Standard from Novex (Ghent, Belgium).

Techniques: Enzyme-linked Immunosorbent Assay, Incubation, Recombinant

Journal: Antibiotics

Article Title: Auranofin Has Advantages over First-Line Drugs in the Treatment of Severe Streptococcus suis Infections

doi: 10.3390/antibiotics10010026

Figure Lengend Snippet: Strain used in the study.

Article Snippet: Auranofin was purchased from Topscience, and a 0.22-µm syringe filter (Millipore, Burlington, MA, USA) was used to filter auranofin dissolved in dimethyl sulfoxide (Sigma-Aldrich, Burlington, MA, USA) to make stock solutions of various concentrations.

Techniques:

Journal: Antibiotics

Article Title: Auranofin Has Advantages over First-Line Drugs in the Treatment of Severe Streptococcus suis Infections

doi: 10.3390/antibiotics10010026

Figure Lengend Snippet: CFU of SC19 treated with DMSO or auranofin at a concentration of 4× MIC (MIC value: auranofin 0.125 mg/L).

Article Snippet: Auranofin was purchased from Topscience, and a 0.22-µm syringe filter (Millipore, Burlington, MA, USA) was used to filter auranofin dissolved in dimethyl sulfoxide (Sigma-Aldrich, Burlington, MA, USA) to make stock solutions of various concentrations.

Techniques: Concentration Assay

Journal: Antibiotics

Article Title: Auranofin Has Advantages over First-Line Drugs in the Treatment of Severe Streptococcus suis Infections

doi: 10.3390/antibiotics10010026

Figure Lengend Snippet: ( A ) Vero or RAW264.7 cell viability was measured after treatment with serially dilutions of auranofin (0.25–32 mg/L). ( B ) Body weight changes of BALB/c mice treated with auranofin or PBS. The average weight change of mice was calculated daily. The error bars represent the standard deviations of at least three independent experiments.

Article Snippet: Auranofin was purchased from Topscience, and a 0.22-µm syringe filter (Millipore, Burlington, MA, USA) was used to filter auranofin dissolved in dimethyl sulfoxide (Sigma-Aldrich, Burlington, MA, USA) to make stock solutions of various concentrations.

Techniques:

Journal: Antibiotics

Article Title: Auranofin Has Advantages over First-Line Drugs in the Treatment of Severe Streptococcus suis Infections

doi: 10.3390/antibiotics10010026

Figure Lengend Snippet: Liver and kidney functions in the blood of mice in the control and treated groups.

Article Snippet: Auranofin was purchased from Topscience, and a 0.22-µm syringe filter (Millipore, Burlington, MA, USA) was used to filter auranofin dissolved in dimethyl sulfoxide (Sigma-Aldrich, Burlington, MA, USA) to make stock solutions of various concentrations.

Techniques:

Journal: Antibiotics

Article Title: Auranofin Has Advantages over First-Line Drugs in the Treatment of Severe Streptococcus suis Infections

doi: 10.3390/antibiotics10010026

Figure Lengend Snippet: Auranofin can disrupt thiol−redox homeostasis by directly binding to TrxB. ( A ) Auranofin was docked into the binding site of TrxB (overall view). ( B ) The auranofin and TxrB binding site (detailed view). The representative binding residues within 4.0 Å of this substrate are shown in lines; auranofin is represented with red sticks; the hydrogen bond is shown as a yellow dotted line. ( C ) ITC analysis of the interaction between auranofin and TxrB, where 0.2 mmol/L of auranofin (50 μL) was added to 0.02 mmol/L of TrxB (300 μL) at 25 °C. Thermodynamic parameters were calculated the equilibrium dissociation constant (KD = 2.136 × 10 −6 mol/L).

Article Snippet: Auranofin was purchased from Topscience, and a 0.22-µm syringe filter (Millipore, Burlington, MA, USA) was used to filter auranofin dissolved in dimethyl sulfoxide (Sigma-Aldrich, Burlington, MA, USA) to make stock solutions of various concentrations.

Techniques: Binding Assay

Journal: Antibiotics

Article Title: Auranofin Has Advantages over First-Line Drugs in the Treatment of Severe Streptococcus suis Infections

doi: 10.3390/antibiotics10010026

Figure Lengend Snippet: Auranofin protects RAW264.7 cells from SC19-mediated cell damage. ( A ) SC19-infected cells, Scale bar, 10 µm. ( B ) untreated cells + auranofin, Scale bar, 10 µm. ( C ) SC19-infected cells treated with 0.25 mg/L of auranofin. Scale bar, 10 µm ( D ) SC19-infected RAW264.7A.1 cells were treated with auranofin or ampicillin for 24 h, and the percent bacterial reduction was calculated compared to the uninfected control groups. The results are presented as the means ± SD ( n = 3), **** p < 0.0001.

Article Snippet: Auranofin was purchased from Topscience, and a 0.22-µm syringe filter (Millipore, Burlington, MA, USA) was used to filter auranofin dissolved in dimethyl sulfoxide (Sigma-Aldrich, Burlington, MA, USA) to make stock solutions of various concentrations.

Techniques: Infection

Journal: Antibiotics

Article Title: Auranofin Has Advantages over First-Line Drugs in the Treatment of Severe Streptococcus suis Infections

doi: 10.3390/antibiotics10010026

Figure Lengend Snippet: Auranofin depletes intracellular thiols and sensitizes S. suis to oxidizing agents and oxidative stress. ( A ) The free thiol concentration in Streptococcus suis cells was significantly decreased after auranofin treatment compared to that observed in the control group. ( B ) PSET2−TrxB/SC19 cultures treated with auranofin only show a slight dose−dependent depletion of thiols. ( C ) The ROS content in SC19 or pSET2−TrxB/SC19 cells treated with 2.5 mg/L auranofin. ( D ) PSET2−TrxB/SC19 showed notably increased resistance to auranofin compared to the SC19 strain. ( E ) The combination treatment of S. suis with auranofin and paraquat exhibited synergistic antimicrobial activity. S. suis cultures were treated for 4 h with the indicated concentrations of paraquat and 0.25 mg/L auranofin, separately or combination. * p < 0.05; ** p < 0.01; *** p < 0.001; **** p < 0.0001.

Article Snippet: Auranofin was purchased from Topscience, and a 0.22-µm syringe filter (Millipore, Burlington, MA, USA) was used to filter auranofin dissolved in dimethyl sulfoxide (Sigma-Aldrich, Burlington, MA, USA) to make stock solutions of various concentrations.

Techniques: Concentration Assay, Activity Assay

Journal: Antibiotics

Article Title: Auranofin Has Advantages over First-Line Drugs in the Treatment of Severe Streptococcus suis Infections

doi: 10.3390/antibiotics10010026

Figure Lengend Snippet: ( A ) The survival rates of severely infected mouse models treated with auranofin or ampicillin. The number of SC19 cells in the presence or absence of auranofin. Mice were intraperitoneally injected with 5 × 10 8 CFU of SC19. The number of bacteria in the lung ( B ), spleen ( C ), brain ( D ) and liver ( E ) was determined at 8 h post infection (two-tailed, unpaired t-tests, n = 5). *** p < 0.001.

Article Snippet: Auranofin was purchased from Topscience, and a 0.22-µm syringe filter (Millipore, Burlington, MA, USA) was used to filter auranofin dissolved in dimethyl sulfoxide (Sigma-Aldrich, Burlington, MA, USA) to make stock solutions of various concentrations.

Techniques: Infection, Injection, Two Tailed Test

Journal: Antibiotics

Article Title: Auranofin Has Advantages over First-Line Drugs in the Treatment of Severe Streptococcus suis Infections

doi: 10.3390/antibiotics10010026

Figure Lengend Snippet: ( A ) Comparison of the anti-inflammatory activity of auranofin and ampicillin in SC19-infected mice. Serum levels of TNF-α, IL-6, IL-1β and INF-γ (two-tailed, unpaired t-tests, n = 5). ( B ) Comparison of the protective effect of auranofin and ampicillin on lung damage in infected mice. The H&E images (40×) of lung lesions after infection. ( C ) Blood levels of AST, ALT, and CK at 8 h treatment (two-tailed, unpaired t-tests, n = 5). * p < 0.05; ** p < 0.01; *** p < 0.001.

Article Snippet: Auranofin was purchased from Topscience, and a 0.22-µm syringe filter (Millipore, Burlington, MA, USA) was used to filter auranofin dissolved in dimethyl sulfoxide (Sigma-Aldrich, Burlington, MA, USA) to make stock solutions of various concentrations.

Techniques: Activity Assay, Infection, Two Tailed Test