Interaction of cationic antimicrobial peptides with phospholipid vesicles and their antibacterial activity
Interaction of cationic antimicrobial peptides with phospholipid vesicles and their antibacterial activity
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DOI：
10.1016/j.peptides.2010.06.021
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发表时间：
2010-10-01
期刊：
影响因子：
3
通讯作者：
Chen, Wei-Jung
中科院分区：
文献类型：
--
作者：
Chou, Hung-Ta;Wen, Hsiao-Wei;Chen, Wei-Jung
我们设计并合成了一系列阳离子α-螺旋抗菌肽，它们对广谱G（+）和G（-）细菌具有更好的抗菌活性和选择性。在目前的研究中，我们打算进一步了解AMP和细胞膜之间的作用机制，使用模型脂质体的各种磷脂组合物。圆二色谱分析表明，在带负电荷的囊泡（DOPC/DOPG = 1：3）存在下，AMP分子呈两亲性α-螺旋构象，而在中性囊泡（DOPC）存在下，AMP分子基本上呈非结构化构象。通过钙黄绿素渗漏实验进一步分析AMP与磷脂囊泡的相互作用。AMP对DOPC（中性）囊泡表现出弱的染料渗漏活性，而当与DOPC/DOPG-截留囊泡相互作用时，它们有效地诱导钙黄绿素渗漏。这些结果表明，我们新设计的阳离子AMP确实显示出对细菌模拟阴离子膜的偏好。所有这些都通过选择性结合并插入靶膜后折叠成两亲性螺旋来发挥其细胞溶解活性，导致膜结构破裂，从而引起细胞内容物泄漏，最终导致细胞死亡。阐明AMP的膜溶解活性的机制可能有助于开发更有效的抗菌剂。(C)2010年爱思唯尔公司All rights reserved.
We have designed and synthesized a series of cationic a-helical AMPs with improved antibacterial activity and selectivity against a broad spectrum of G(+) and G(-) bacteria. In the current study, we intended to gain further insight into the mechanisms of action between AMPs and cellular membranes using model liposomes of various phospholipid compositions. Circular dichroism measurements showed that AMPs adopted amphipathic a-helical conformation in the presence of negatively charged vesicles (DOPC/DOPG = 1:3), while they were largely unstructured when incubated with neutral vesicles (DOPC). The interaction of AMPs with phospholipid vesicles were further analyzed by calcein leakage experiments. AMPs exhibited weak dye-leakage activity for DOPC (neutral) vesicles, while they effectively induced calcein leakage when interacted with DOPC/DOPG-entrapped vesicles. These results indicated that our newly designed cationic AMPs did show preferences for bacteria-mimicking anionic membranes. All of them exert their cytolytic activity by folding into an amphipathic helix upon selectively binding and insertion into the target membrane, leading to breakdown of the membrane structure, thus causing leakage of cell contents, resulting finally in cell death. Elucidating the mechanism of the membranolytic activity of AMPs may facilitate the development of more effective antimicrobial agents. (C) 2010 Elsevier Inc. All rights reserved.