Lysylated phospholipids stabilize models of bacterial lipid bilayers and protect against antimicrobial peptides.
Lysylated phospholipids stabilize models of bacterial lipid bilayers and protect against antimicrobial peptides.
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DOI：
10.1016/j.bbamem.2014.04.018
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发表时间：
2014-09
期刊：
影响因子：
--
通讯作者：
Pokorny A
中科院分区：
文献类型：
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作者：
Cox E;Michalak A;Pagentine S;Seaton P;Pokorny A
氨酰化磷脂酰甘油是细菌细胞质膜中常见的脂质。它们在金黄色葡萄球菌中的存在与对多种抗菌剂（包括抗菌肽）的抗性增加有关。最常见的是，磷脂酰甘油头部基团与赖氨酸发生酯化反应，这将阴离子型磷脂酰甘油转化为头部基团尺寸大幅增加的阳离子脂质。在本研究中，我们研究了两种经过充分研究的抗菌肽——天蚕素A和蜂毒肽X与由1 - 棕榈酰 - 2 - 油酰 - 磷脂酰胆碱（POPC）和1 - 棕榈酰 - 2 - 油酰 - 磷脂酰甘油（POPG）组成的脂质囊泡的相互作用，这些囊泡含有不同比例的氨酰化磷脂酰乙醇胺，它是相应磷脂酰甘油衍生物的一种稳定类似物。为了区分头部基团大小和电荷对肽 - 脂质相互作用的影响，我们合成了两种不同的衍生物。在一种衍生物中，头部基团通过添加赖氨酸进行修饰，在另一种中则通过谷氨酰胺修饰。谷氨酰胺修饰产生的磷脂头部基团大小与赖氨酸化版本相当。然而，赖氨酰磷脂酰乙醇胺（Lys - PE）是阳离子型的，而谷氨酰胺基磷脂酰乙醇胺（Gln - PE）是两性离子型的。我们发现，如果氨酰化磷脂酰乙醇胺的含量不超过20摩尔%（这是在细菌膜中发现的浓度），蜂毒肽X和天蚕素A的结合没有显著改变。然而，20摩尔%的赖氨酰磷脂酰乙醇胺含量会显著抑制脂质囊泡的染料释放，其程度取决于肽的种类。对于蜂毒肽X，在20摩尔%赖氨酰磷脂酰乙醇胺时染料释放基本被消除，而天蚕素A对赖氨酰磷脂酰乙醇胺的存在不太敏感。这些观察结果可以通过肽结合和膜稳定之间作为氨酰化脂质含量函数的复杂相互作用来理解。
Aminoacylated phosphatidylglycerols are common lipids in bacterial cytoplasmic membranes. Their presence in S. aureus has been linked to increased resistance to a number of antibacterial agents, including antimicrobial peptides. Most commonly, the phosphatidylglycerol headgroup is esterified to lysine, which converts anionic phosphatidylglycerol into a cationic lipid with a considerably increased headgroup size. In the present work, we investigated the interactions of two well-studied antimicrobial peptides, cecropin A and mastoparan X, with lipid vesicles composed of 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC) and 1-palmitoyl-2-oleoyl-phosphatidylglycerol (POPG), containing varying fractions of an aminoacylated phosphatidylethanolamine, a stable analog of the corresponding phosphatidylglycerol-derivative. To differentiate between the effects of headgroup size and charge on peptide-lipid interactions, we synthesized two different derivatives. In one, the headgroup was modified by the addition of lysine, and in the other, by glutamine. The modification by glutamine results in a phospholipid with a headgroup size comparable to that of the lysylated version. However, whereas lysylphosphatidylethanolamine (Lys-PE) is cationic, glutaminylphosphatidylethanolamine (Gln-PE) is zwitterionic. We found that binding of mastoparan X and cecropin A was not significantly altered if the content of aminoacylated phosphatidylethanolamines did not exceed 20 mol%, which is the concentration found in bacterial membranes. However, a lysylphosphatidylethanolamine content of 20 mol% significantly inhibits dye release from lipid vesicles, to a degree that depends on the peptide. In the case of mastoparan X, dye release is essentially abolished at 20 mol% lysylphosphatidylethanolamine, whereas cecropin A is less sensitive to the presence of lysylphosphatidylethanolamine. These observations are understood through the complex interplay between peptide binding and membrane stabilization as a function of the aminoacylated lipid content.