期刊文献

An anti-infective synthetic peptide with dual antimicrobial and immunomodulatory activities 收藏

具有双重抗菌和免疫调节活性的抗感染合成肽
原文求助 发布源
作者
O. N. Silva[1];C. de la Fuente-Núñez[2];E. F. Haney[3];I. C. M. Fensterseifer[4];S. M. Ribeiro[5];W. F. Porto[6];P. Brown[7];C. Faria-Junior[8];T. M. B. Rezende[4];S. E. Moreno[5];T. K. Lu[2];R. E. W. Hancock[3];O. L. Franco[1]
作者单位
[1]Departamento de Biologia, Instituto de Ciências Biológicas, Programa de pós-graduação em Genética e Biotecnologia, Universidade Federal de Juiz de Fora;[2]Synthetic Biology Group, MIT Synthetic Biology Center, Massachusetts Institute of Technology;[3]Department of Microbiology and Immunology, University of British Columbia;[4]Centro de Análises Proteômicas e Bioquímicas, Programa de Pós-Graduação em Ciências Genômicas e Biotecnologia, Universidade Católica de Brasília;[5]S-Inova Biotech, Pós-graduação em Biotecnologia, Universidade Católica Dom Bosco;[6]Programa de Pós-graduação em Patologia Molecular, Universidade de Brasília;[7]Department of Chemical Engineering, Massachusetts Institute of Technology;[8]Curso de Odontologia, Universidade
发布日期
02 November 2016
DOI
10.1038/srep35465
来源信息
Scientific reports ISSN：2045-2322, 2016年
摘要
Antibiotic-resistant infections are predicted to kill 10 million people per year by 2050, costing the global economy $100 trillion. Therefore, there is an urgent need to develop alternative technologies. We have engineered a synthetic peptide called clavanin-MO, derived from a marine tunicate antimicrobial peptide, which exhibits potent antimicrobial and immunomodulatory properties both in vitro and in vivo. The peptide effectively killed a panel of representative bacterial strains, including multidrug-resistant hospital isolates. Antimicrobial activity of the peptide was demonstrated in animal models, reducing bacterial counts by six orders of magnitude, and contributing to infection clearance. In addition, clavanin-MO was capable of modulating innate immunity by stimulating leukocyte recruitment to the site of infection, and production of immune mediators GM-CSF, IFN-γ and MCP-1, while suppressing an excessive and potentially harmful inflammatory response by increasing synthesis of anti-inflammatory cytokines such as IL-10 and repressing the levels of pro-inflammatory cytokines IL-12 and TNF-α. Finally, treatment with the peptide protected mice against otherwise lethal infections caused by both Gram-negative and -positive drug-resistant strains. The peptide presented here directly kills bacteria and further helps resolve infections through its immune modulatory properties. Peptide anti-infective therapeutics with combined antimicrobial and immunomodulatory properties represent a new approach to treat antibiotic-resistant infections.
摘要译文
预计抗生素耐药性感染到2050年每年将导致1000万人死亡，使全球经济损失100万亿美元。因此，迫切需要开发替代技术。我们设计了一种名为clavanin-MO的合成肽，来源于海洋被囊的抗菌肽，它在体外和体内均显示出有效的抗微生物和免疫调节特性。该肽有效地杀死了一组代表性细菌菌株，包括耐多药的医院分离株。在动物模型中证明了肽的抗微生物活性，将细菌数量减少了六个数量级，并有助于感染清除。此外，clavanin-MO能够通过刺激白细胞募集到感染部位来调节先天免疫，免疫介质GM-CSF，IFN-γ和MCP-1的产生，通过增加抗炎细胞因子如IL-10的合成和抑制促炎细胞因子IL-12和TNF-α的水平，过度和潜在有害的炎症反应。最后，用肽处理保护小鼠免于由革兰氏阴性和阳性耐药菌株引起的其它致死性感染。这里提供的肽直接杀死细菌，并通过其免疫调节特性进一步帮助解决感染。具有组合抗微生物和免疫调节特性的肽抗感染治疗剂代表了治疗抗生素抗性感染的新方法。
O. N. Silva[1];C. de la Fuente-Núñez[2];E. F. Haney[3];I. C. M. Fensterseifer[4];S. M. Ribeiro[5];W. F. Porto[6];P. Brown[7];C. Faria-Junior[8];T. M. B. Rezende[4];S. E. Moreno[5];T. K. Lu[2];R. E. W. Hancock[3];O. L. Franco[1]. An anti-infective synthetic peptide with dual antimicrobial and immunomodulatory activities[J]. Scientific reports, 2016