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.
Highlights
This article is an open access articleStreptococcus suis (S. suis) can cause many symptoms, such as septicemia, meningitis, arthritis, and endocarditis in both humans and pigs and is associated with high mortality [1,2,3]
We demonstrated that auranofin can bind to TrxB protein active centers to inhibit their function, with the resulting increase in reactive oxygen species (ROS) levels being the primary cause of S. suis cell death
To assess the antimicrobial activity of auranofin, we evaluated the effect on auranofin against 18 multidrug-resistant Staphylococcal and Streptococcal strains (Table 1)
Summary
This article is an open access articleStreptococcus suis (S. suis) can cause many symptoms, such as septicemia, meningitis, arthritis, and endocarditis in both humans and pigs and is associated with high mortality [1,2,3]. During July and August of 2005, a sudden outbreak of 215 human cases S. suis infection was described in Sichuan province, where Streptococcal toxic shock-like syndrome (STSLS) caused by this bacterium was reported to cause severe symptoms, such as acute high fever, hypotension, shock, blood spots, and dysfunction of multiple organs. This outbreak was associated with acute death and a mortality rate higher than 80%, even after adequate treatment [9]
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