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

Abstract

Streptococcal toxic shock-like syndrome (STSLS) likely occurs when an individual is infected with the Streptococcus suis (S. suis) epidemic strain and is characterized by a cytokine storm, multiple organ dysfunction syndrome (MODS) and a high incidence of mortality despite adequate treatment. A number of antibiotics exhibit excellent bactericidal effects in vivo, such as fluoroquinolones, aminoglycosides (gentamicin) and β-lactams (penicillin G, ceftiofur, or amoxicillin), but are less effective for treating STSLS. Therefore, there is an urgent need to identify new compounds that can reduce the damage caused by STSLS. In the present study, we identified auranofin, an orally bioavailable FDA-approved anti-rheumatic drug as a candidate repurposed drug to treat severe S. suis infections. Our results showed that auranofin can bind to the functional domain of bacterial thioredoxin reductase, decreasing the reducing redox-responsive capacity of target bacteria and allowing for the killing of S. suis cells. We also observed that auranofin has antibacterial activity against other gram-positive bacteria, such as multidrug resistant Streptococcus pneumoniae (MDRSP), Streptococcus agalactiae, and vancomycin-resistant strains of Staphylococcus aureus. Additionally, auranofin is capable of eradicating intracellular S.suis present inside infected macrophage cells. Mouse model experimental results showed that auranofin could effectively reduce the mortality of mice infected with S. suis. Compared to the ampicillin treatment group, the survival rate of mice in the auranofin treatment group in severely infected model mice was significantly improved. These results suggest that auranofin has the potential for use as an effective antibiotic against S. suis.

Napyradiomycin A4 and Its Relate Compounds, a New Anti-PRV Agent and Their Antibacterial Activities, from Streptomyces kebangsaanensis WS-68302

“…The minimum inhibitory concentrations of 1–7 were determined against the four bacterial strains ( Staphylococcus aureus ATCC 25923, Erysipelothrix rhusiopathiae WH13013, Streptococcus suis SC19, Escherichia coli ATCC 25922) following the Clinical and Laboratory Standards Institute (CLSI) guidelines [ 34 ]. The microdilution broth method was performed in 96-well plates (Corning Costar ® 3599 Corning, Corning, NY, USA) using MHB (Hopebio, Qingdao, China).…”

Canagliflozin Inhibited the Activity of Hemolysin and Reduced the Inflammatory Response Caused by Streptococcus suis

“…Infection with the prevalent S. suis strain SC19 induces an acute and extremely high inflammatory cytokine response, with SC19 causing much higher levels of inflammation and organ damage than the classical virulent strain P1/7, which can also lead to high mortality [5,6,9]. In previous studies, ampicillin had a good therapeutic effect for S. suis infection after 1 h treatment, but the therapeutic effect was greatly reduced after 6 h of treatment with ampicillin [10]. Inflammatory storms lead to the failure of antibiotic treatment.…”

Theaflavin Ameliorates Streptococcus suis-Induced Infection In Vitro and In Vivo

“…For patients, S. suis infections are usually administrated with penicillin G, accompanied by one or more other antibiotics including ceftriaxone, gentamicin, chloramphenicol, and ampicillin [ 13 ]. For pigs, S. suis infections are often treated with fluoroquinolones, aminoglycosides, and β-lactams in the swine industry [ 17 ]. In recent years, with the abusive use of antibiotics, an increase in multidrug-resistant bacterial strains has led to the poor performance of traditional antibiotic therapies [ 18 , 19 ].…”