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聚焦2015 - 2019年期间发现的精选新型抗菌天然免疫肽。

Spotlight on the Selected New Antimicrobial Innate Immune Peptides Discovered During 2015-2019.

作者信息

Dang Xiangli, Wang Guangshun

机构信息

Department of Pathology and Microbiology, College of Medicine, University of Nebraska Medical Center, 985900 Nebraska Medical Center, Omaha, NE 68198-5900, United States.

出版信息

Curr Top Med Chem. 2020;20(32):2984-2998. doi: 10.2174/1568026620666201022143625.

Abstract

BACKGROUND

Antibiotic resistance is a global issue and new anti-microbials are required.

INTRODUCTION

Anti-microbial peptides are important players of host innate immune systems that prevent infections. Due to their ability to eliminate drug-resistant pathogens, AMPs are promising candidates for developing the next generation of anti-microbials.

METHODS

The anti-microbial peptide database provides a useful tool for searching, predicting, and designing new AMPs. In the period from 2015-2019, ~500 new natural peptides have been registered.

RESULTS

This article highlights a selected set of new AMP members with interesting properties. Teixobactin is a cell wall inhibiting peptide antibiotic, while darobactin inhibits a chaperone and translocator for outer membrane proteins. Remarkably, cOB1, a sex pheromone from commensal enterococci, restricts the growth of multidrug-resistant Enterococcus faecalis in the gut at a picomolar concentration. A novel proline-rich AMP has been found in the plant Brassica napus. A shrimp peptide MjPen- II comprises three different sequence domains: serine-rich, proline-rich, and cysteine-rich regions. Surprisingly, an amphibian peptide urumin specifically inhibits H1 hemagglutinin-bearing influenza A virus. Defensins are abundant and typically consist of three pairs of intramolecular disulfide bonds. However, rat rattusin dimerizes via forming five pairs of intermolecular disulfide bonds. While human LL-37 can be induced by vitamin D, vitamin A induces the expression of resistin-like molecule alpha (RELMα) in mice. The isolation and characterization of an alternative human cathelicidin peptide, TLN-58, substantiates the concept of one gene multiple peptides. The involvement of a fly AMP nemuri in sleep induction may promote the research on the relationship between sleep and infection control.

CONCLUSION

The functional roles of AMPs continue to grow and the general term "innate immune peptides" becomes useful. These discoveries widen our view on the anti-microbial peptides and may open new opportunities for developing novel peptide therapeutics for different applications.

摘要

背景

抗生素耐药性是一个全球性问题,需要新的抗菌药物。

引言

抗菌肽是宿主先天免疫系统预防感染的重要组成部分。由于其能够清除耐药病原体,抗菌肽是开发下一代抗菌药物的有希望的候选者。

方法

抗菌肽数据库为搜索、预测和设计新的抗菌肽提供了一个有用的工具。在2015年至2019年期间,已登记了约500种新的天然肽。

结果

本文重点介绍了一组具有有趣特性的新抗菌肽成员。Teixobactin是一种抑制细胞壁的肽类抗生素,而darobactin抑制外膜蛋白的伴侣蛋白和转运体。值得注意的是,共生肠球菌的性信息素cOB1在皮摩尔浓度下可限制肠道中耐多药粪肠球菌的生长。在植物甘蓝型油菜中发现了一种新型富含脯氨酸的抗菌肽。虾肽MjPen-II由三个不同的序列结构域组成:富含丝氨酸、富含脯氨酸和富含半胱氨酸的区域。令人惊讶的是,一种两栖类肽urumin特异性抑制携带H1血凝素的甲型流感病毒。防御素丰富,通常由三对分子内二硫键组成。然而,大鼠的rattusin通过形成五对分子间二硫键而二聚化。虽然人LL-37可由维生素D诱导,但维生素A可诱导小鼠中抵抗素样分子α(RELMα)的表达。另一种人cathelicidin肽TLN-58的分离和表征证实了一个基因多种肽的概念。果蝇抗菌肽nemuri参与睡眠诱导可能会促进对睡眠与感染控制之间关系的研究。

结论

抗菌肽的功能作用不断增加,“先天免疫肽”这一通用术语变得很有用。这些发现拓宽了我们对抗菌肽的认识,并可能为开发用于不同应用的新型肽类疗法带来新的机会。

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本文引用的文献

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Two distinct amphipathic peptide antibiotics with systemic efficacy.两种具有全身疗效的两亲性肽抗生素。
Proc Natl Acad Sci U S A. 2020 Aug 11;117(32):19446-19454. doi: 10.1073/pnas.2005540117. Epub 2020 Jul 28.
4
Antibacterial mechanism of peptide Cec4 against .肽Cec4对……的抗菌机制
Infect Drug Resist. 2019 Aug 5;12:2417-2428. doi: 10.2147/IDR.S214057. eCollection 2019.

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