Fighting microbial infections: A lesson from amphibian skin-derived esculentin-1 peptides

Fighting microbial infections: A lesson from amphibian skin-derived esculentin-1 peptides
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DOI:
10.1016/j.peptides.2015.04.018
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发表时间:
2015-09-01
期刊:
影响因子:
3
通讯作者:
McDermott, Alison M.
McDermott, Alison M.
中科院分区:
医学3区
文献类型:
--
作者:
Mangoni, Maria Luisa;Luca, Vincenzo;McDermott, Alison M.

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由于几乎所有临床微生物病原体对市售抗生素/抗真菌剂的耐药性日益增加,因此非常需要发现替代的抗感染剂。基因编码的抗菌肽(AMP)有望成为新型疗法。特别是,两栖动物的皮肤是 AMP 最丰富的仓库之一,尤其是林蛙属,其中 esculentins-1 是迄今为止在自然界中发现的最长(46 个氨基酸)的 AMP 之一。在这里,我们报告了最近发现的 esculentin-1a 和 -1b 肽 N 端部分的两种衍生物的体外和体内活性和作用机制,主要针对两种相关的机会性微生物,在全球范围内引起大量危及生命的感染;即革兰氏阴性细菌铜绿假单胞菌和酵母白色念珠菌。由于与几种哺乳动物 AMP 相比具有明显的优势,两种选定的青蛙皮 AMP 衍生物代表了开发具有扩展特性的新型抗菌化合物的有吸引力的候选者,适用于人类和兽药。 (C) 2015 Elsevier Inc. 保留所有权利。
Due to the growing emergence of resistance to commercially available antibiotics/antimycotics in virtually all clinical microbial pathogens, the discovery of alternative anti-infective agents, is greatly needed. Gene-encoded antimicrobial peptides (AMPs) hold promise as novel therapeutics. In particular, amphibian skin is one of the richest storehouses of AMPs, especially that of the genus Rana, with esculentins-1 being among the longest (46 amino acids) AMPs found in nature to date. Here, we report on the recently discovered in vitro and in vivo activities and mechanism of action of two derivatives of the N-terminal part of esculentin-1a and -1b peptides, primarily against two relevant opportunistic microorganisms causing a large number of life-threatening infections worldwide; i.e. the Gram-negative bacterium Pseudomonas aeruginosa and the yeast Candida albicans. Because of distinct advantages compared to several mammalian AMPs, the two selected frog skin AMP-derivatives represent attractive candidates for the development of new antimicrobial compounds with expanded properties, for both human and veterinary medicine. (C) 2015 Elsevier Inc. All rights reserved.