Cathelicidins from the bullfrog Rana catesbeiana provides novel template for peptide antibiotic design.
Cathelicidins from the bullfrog Rana catesbeiana provides novel template for peptide antibiotic design.
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来自牛蛙 Rana catesbeiana 的 Cathelicidins 为肽抗生素设计提供了新的模板
DOI：
10.1371/journal.pone.0093216
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Wang Y
中科院分区：
文献类型：
--
作者：
Ling G;Gao J;Zhang S;Xie Z;Wei L;Yu H;Wang Y
Cathelicidins是一类脊椎动物先天免疫的基因编码效应分子，是抵御微生物入侵的第一道防线。尽管对哺乳动物、鸟类、爬行动物和鱼类的抗菌素进行了广泛的研究，但对两栖动物的抗菌素知之甚少。本文报道了牛蛙（Rana catesbeiana）中两种抗菌素（cathelicidin-RC1和cathelicidin-RC2）的鉴定和鉴定。从已构建的猪肺cDNA文库中成功克隆出编码这两个肽的cDNA序列（分别为677 bp和700 bp）。推导出的成熟肽分别由28和33个残基组成。结构分析表明，cathelicidin-RC1主要呈两亲α -螺旋构象，而cathelicidin-RC2不能形成稳定的两亲结构。抗菌和抑菌动力学分析表明，合成的cathelicidin-RC1具有强效、广谱、快速的抗菌活性，而cathelicidin-RC2的抗菌活性非常弱。此外，cathelicidin-RC1的抑菌活性与盐无关，具有高度的稳定性。扫描电镜（SEM）分析表明，cathelicidin-RC1通过破坏微生物膜杀死微生物。此外，cathelicidin-RC1对哺乳动物正常或肿瘤细胞系具有较低的细胞毒活性，对人红细胞具有较低的溶血活性。抗菌活性强、广谱、快速，且不依赖盐、高稳定性、低细胞毒和溶血活性，使cathelicidin-RC1成为开发新型肽类抗生素的理想模板。
Cathelicidins, a class of gene-encoded effector molecules of vertebrate innate immunity, provide a first line of defense against microbial invasions. Although cathelicidins from mammals, birds, reptiles and fishes have been extensively studied, little is known about cathelicidins from amphibians. Here we report the identification and characterization of two cathelicidins (cathelicidin-RC1 and cathelicidin-RC2) from the bullfrog Rana catesbeiana. The cDNA sequences (677 and 700 bp, respectively) encoding the two peptides were successfully cloned from the constructed lung cDNA library of R. catesbeiana. And the deduced mature peptides are composed of 28 and 33 residues, respectively. Structural analysis indicated that cathelicidin-RC1 mainly assumes an amphipathic alpha-helical conformation, while cathelicidin-RC2 could not form stable amphipathic structure. Antimicrobial and bacterial killing kinetic analysis indicated that the synthetic cathelicidin-RC1 possesses potent, broad-spectrum and rapid antimicrobial potency, while cathelicidin-RC2 exhibited very weak antimicrobial activity. Besides, the antimicrobial activity of cathelicidin-RC1 is salt-independent and highly stable. Scanning electron microscopy (SEM) analysis indicated that cathelicidin-RC1 kills microorganisms through the disruption of microbial membrane. Moreover, cathelicidin-RC1 exhibited low cytotoxic activity against mammalian normal or tumor cell lines, and low hemolytic activity against human erythrocytes. The potent, broad-spectrum and rapid antimicrobial activity combined with the salt-independence, high stability, low cytotoxic and hemolytic activities make cathelicidin-RC1 an ideal template for the development of novel peptide antibiotics.
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