An anti-infective synthetic peptide with dual antimicrobial and immunomodulatory activities.
An anti-infective synthetic peptide with dual antimicrobial and immunomodulatory activities.
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DOI：
10.1038/srep35465
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发表时间：
2016-11-02
影响因子：
4.6
通讯作者：
Franco OL
中科院分区：
文献类型：
--
作者：
Silva ON;de la Fuente-Núñez C;Haney EF;Fensterseifer IC;Ribeiro SM;Porto WF;Brown P;Faria-Junior C;Rezende TM;Moreno SE;Lu TK;Hancock RE;Franco OL
预计到2050年，抗生素耐药性感染每年将导致1000万人死亡，给全球经济造成100万亿美元的损失。因此，迫切需要开发替代技术。我们已经设计了一个合成肽称为clavanin-MO，来自海洋被囊动物抗菌肽，它具有强大的抗菌和免疫调节特性，在体外和体内。该肽有效地杀死了一组代表性的细菌菌株，包括多重耐药的医院分离株。在动物模型中证明了肽的抗微生物活性，将细菌计数减少了六个数量级，并有助于感染清除。此外，克拉霉素-MO能够通过刺激白细胞募集至感染部位以及产生免疫介质GM-CSF、IFN-γ和MCP-1来调节先天免疫，同时通过增加抗炎细胞因子如IL-10的合成以及抑制促炎细胞因子IL-12和TNF-α的水平来抑制过度的和潜在有害的炎症反应。最后，用肽治疗保护小鼠免受革兰氏阴性和阳性耐药菌株引起的致命感染。这里介绍的肽直接杀死细菌，并通过其免疫调节特性进一步帮助解决感染。具有抗微生物和免疫调节特性的肽抗感染治疗剂代表了治疗耐药性感染的新方法。
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.
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影响因子：
--
作者：
de la Fuente-Núñez C;Reffuveille F;Mansour SC;Reckseidler-Zenteno SL;Hernández D;Brackman G;Coenye T;Hancock RE
通讯作者：
Hancock RE
影响因子：
5.5
作者：
Hess, Berk;Kutzner, Carsten;Lindahl, Erik
通讯作者：
Lindahl, Erik
影响因子：
3
作者：
Haney EF;Mansour SC;Hilchie AL;de la Fuente-Núñez C;Hancock RE
通讯作者：
Hancock RE
影响因子：
5.6
作者：
HUBER, R;SCHNEIDER, M;KAYSER, H
通讯作者：
KAYSER, H
影响因子：
11.8
作者：
Boucher, Helen W.;Talbot, George H.;Bartlett, John
通讯作者：
Bartlett, John