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.

中文翻译：

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金刚霉素在重症猪链球菌感染的治疗中比一线药物更具优势

当个体感染猪链球菌（S. suis）流行株时，可能会发生链球菌中毒性休克样综合征（STSLS），其特征是细胞因子风暴，多器官功能障碍综合征（MODS）和尽管有足够的死亡率也有很高的发病率治疗。许多抗生素在体内表现出优异的杀菌作用，例如氟喹诺酮类，氨基糖苷类（庆大霉素）和β-内酰胺类（青霉素G，头孢噻呋或阿莫西林），但对STSLS的治疗效果较差。因此，迫切需要寻找可以减少由STSLS引起的损害的新化合物。在本研究中，我们确定了口服生物可利用的FDA批准的抗风湿药金诺芬（Auranofin）作为治疗重症的候选药物。猪链球菌感染。我们的结果表明金诺芬可以与细菌硫氧还蛋白还原酶的功能域结合，从而降低靶细菌的还原性氧化还原反应能力，并可以杀死猪链球菌。我们还观察到金诺芬对其他革兰氏阳性细菌（例如耐多药肺炎链球菌（MDRSP），无乳链球菌和耐万古霉素的金黄色葡萄球菌）具有抗菌活性。另外，金诺芬能够消除感染的巨噬细胞内部存在的细胞内猪链球菌。小鼠模型实验结果表明金诺芬可以有效降低猪链球菌感染小鼠的死亡率。与氨苄西林治疗组相比，金诺芬治疗组小鼠在重度感染模型小鼠中的存活率显着提高。这些结果表明金诺芬具有用作抗猪链球菌的有效抗生素的潜力。