The antibiotic activity of cationic linear amphipathic peptides:: lessons from the action of leucine/lysine copolymers on bacteria of the class Mollicutes
The antibiotic activity of cationic linear amphipathic peptides:: lessons from the action of leucine/lysine copolymers on bacteria of the class Mollicutes
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DOI：
10.1046/j.1432-1033.2003.03587.x
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发表时间：
2003-05-01
期刊：
影响因子：
--
通讯作者：
Wróblewski, H
中科院分区：
文献类型：
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作者：
Béven, L;Castano, S;Wróblewski, H
使用柔膜菌纲的无细胞壁细菌（无鞭毛体、支原体和螺原体）作为靶标，比较具有不同组成和序列的由亮氨酰和赖氨酰残基组成的肽（“LK肽”）的抗菌活性。两亲性α-螺旋肽的抗菌活性随其大小而变化，15个残基是最佳长度，与膜疏水核心厚度和胆固醇的量无关。具有+5正净电荷的15个残基的理想两亲性α螺旋（KLLKLLLKLLLKLLK）具有最强的抗菌活性，与蜂毒肽的抗菌活性相似。相比之下，缺乏两亲性的乱序肽和疏水性较低的β-折叠肽[（LK）（n）K]，即使是那些15个残基长的肽，也远不如螺旋肽有效。此外，肽的生长抑制活性与其消除膜电位的能力相关。这些数据与LK肽在脂质/水界面上的主要平坦取向完全一致，并强烈支持这些肽和可能的线性聚阳离子两亲防御肽根据“地毯”模型以四个主要步骤作用于细菌膜：（a）界面分配，单体在靶膜上积累（限制步骤）;（B）肽结构变化与脂双层相互作用诱导的（构象、聚集和取向）（c）通过去污剂样作用的质膜透化/去极化;和（d）如果去极化的程度维持在临界阈值以上，则细菌细胞快速死亡。
Peptides composed of leucyl and lysyl residues ('LK peptides') with different compositions and sequences were compared for their antibacterial activities using cell wall-less bacteria of the class Mollicutes (acholeplasmas, mycoplasmas and spiroplasmas) as targets. The antibacterial activity of the amphipathic alpha-helical peptides varied with their size, 15 residues being the optimal length, independent of the membrane hydrophobic core thickness and the amount of cholesterol. The 15-residue ideally amphipathic alpha helix with a +5 positive net charge (KLLKLLLKLLLKLLK) had the strongest antibacterial activity, similar to that of melittin. In contrast, scrambled peptides devoid of amphipathy and the less hydrophobic beta-sheeted peptides [(LK) (n) K], even those 15-residue long, were far less potent than the helical ones. Furthermore, the growth inhibitory activity of the peptides was correlated with their ability to abolish membrane potential. These data are fully consistent with a predominantly flat orientation of LK peptides at the lipid/water interface and strongly supports that these peptides and probably the linear polycationic amphipathic defence peptides act on bacterial membranes in four main steps according to the 'carpet' model: (a) interfacial partitioning with accumulation of monomers on the target membrane (limiting step); (b) peptide structural changes (conformation, aggregation, and orientation) induced by interactions with the lipid bilayer (as already shown with liposomes and erythrocytes); (c) plasma membrane permeabilization/depolarization via a detergent-like effect; and (d) rapid bacterial cell death if the extent of depolarization is maintained above a critical threshold.