Repurposing ebselen for treatment of multidrug-resistant staphylococcal infections.
Repurposing ebselen for treatment of multidrug-resistant staphylococcal infections.
复制标题
重新利用Ebselen治疗多药抗性葡萄球菌感染。
DOI：
10.1038/srep11596
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发表时间：
2015-06-26
影响因子：
4.6
通讯作者：
Seleem MN
中科院分区：
文献类型：
--
作者：
Thangamani S;Younis W;Seleem MN
迫切需要新型抗菌药物和开发它们的新方法。重新利用具有充分表征的毒理学和药理学的已批准药物是减少与抗生素创新相关的时间、成本和风险的新方法。依布硒啉 (Ebselen) 是一种有机硒化合物，已知临床安全且具有众所周知的药理学特征。它对多重耐药金黄色葡萄球菌临床分离株（包括耐甲氧西林和万古霉素金黄色葡萄球菌（MRSA 和 VRSA））表现出强大的杀菌活性。我们证明依布硒啉通过抑制蛋白质合成发挥作用，并随后抑制 MRSA 中毒素的产生。此外，依布硒啉具有显着的活性并显着减少已形成的葡萄球菌生物膜。在葡萄球菌皮肤感染小鼠模型中评估了依布硒啉的治疗效果。 Ebselen 1% 和 2% 显着降低 MRSA USA300 皮损中的细菌负荷和促炎细胞因子肿瘤坏死因子-α (TNF-α)、白介素-6 (IL-6)、白细胞介素-1 β (IL-1β) 和单核细胞趋化蛋白-1 (MCP-1) 的水平。此外，它与传统抗菌剂具有协同作用。本研究提供了证据表明依布硒啉在局部治疗MRSA皮肤感染方面具有巨大潜力，并为进一步分析和开发依布硒啉作为多重耐药葡萄球菌感染的潜在治疗方法奠定了基础。
Novel antimicrobials and new approaches to developing them are urgently needed. Repurposing already-approved drugs with well-characterized toxicology and pharmacology is a novel way to reduce the time, cost, and risk associated with antibiotic innovation. Ebselen, an organoselenium compound, is known to be clinically safe and has a well-known pharmacology profile. It has shown potent bactericidal activity against multidrug-resistant clinical isolates of staphylococcus aureus, including methicillin- and vancomycin-resistant S. aureus (MRSA and VRSA). We demonstrated that ebselen acts through inhibition of protein synthesis and subsequently inhibited toxin production in MRSA. Additionally, ebselen was remarkably active and significantly reduced established staphylococcal biofilms. The therapeutic efficacy of ebselen was evaluated in a mouse model of staphylococcal skin infections. Ebselen 1% and 2% significantly reduced the bacterial load and the levels of the pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1 beta (IL-1β), and monocyte chemo attractant protein-1 (MCP-1) in MRSA USA300 skin lesions. Furthermore, it acts synergistically with traditional antimicrobials. This study provides evidence that ebselen has great potential for topical treatment of MRSA skin infections and lays the foundation for further analysis and development of ebselen as a potential treatment for multidrug-resistant staphylococcal infections.
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DOI：
10.1126/science.1176667
发表时间：
2009-08-28
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Fischbach MA;Walsh CT
通讯作者：
Walsh CT
影响因子：
--
作者：
Handa, Y;Kaneko, M;Kubota, T
通讯作者：
Kubota, T
影响因子：
11.8
作者：
Farrell, David J.;Castanheira, Mariana;Chopra, Ian
通讯作者：
Chopra, Ian
影响因子：
4.8
作者：
Lu, Jun;Vlamis-Gardikas, Alexios;Holmgren, Arne
通讯作者：
Holmgren, Arne
影响因子：
2.9
作者：
Cowin, Allison J.;Hatzirodos, Nicholas;Belford, David A.
通讯作者：
Belford, David A.