The pH-dependence of lipid-mediated antimicrobial peptide resistance in a model staphylococcal plasma membrane: A two-for-one mechanism of epithelial defence circumvention.
The pH-dependence of lipid-mediated antimicrobial peptide resistance in a model staphylococcal plasma membrane: A two-for-one mechanism of epithelial defence circumvention.
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模型葡萄球菌质膜中脂质介导的抗菌肽耐药性的 pH 依赖性：上皮防御规避的二合一机制。
DOI：
10.1016/j.ejps.2018.11.017
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Rehal R
中科院分区：
文献类型：
--
作者：
Rehal R
利用合成的仿生单、双层模型研究了赖氨酰磷脂酰甘油（LPG）的膜防御机制。金黄色葡萄球菌ST 239 TW，基于其在pH 7.4（28%LPG）和pH 5.5（51%LPG）培养物中的脂质组成。这些模型纳入了一个稳定的合成类似物的液化石油气（3adLPG），以促进长期的生物物理研究，这是以前有限的不稳定性天然液化石油气。两者都增加了3adLPG含量和完整的头基电离在pH 5.5，增加双层秩序和抑制整体电荷，通过与阴离子脂质形成中性离子对。在空气/液体界面脂质单层的离子对形成引起了显着的冷凝效果，这与亚相注入爪蟾抗菌素2 F5 W分区的抑制。在液相脂质囊泡中，将3adLPG的比例从28摩尔%增加到51摩尔%完全抑制了肽的膜活性α螺旋构象的采用，而不需要完全的头基电离。仿生PG/3adLPG流体浮动双层上进行的中子反射率测量，显示了显着的有序效应，温和的酸度对双层含有30摩尔% 3adLPG，而肽结合/分区仅完全抑制在双层与55摩尔% 3adLPG在pH 5.5。这些研究结果进行了讨论方面的作用，液化石油气在抵抗人类上皮防御S。金黄色葡萄球菌和这种机会致病菌毒力的持续进化。
The mechanisms of membrane defence by lysylphosphatidylglycerol (LPG), were investigated using synthetic biomimetic mono- and bilayer models of methicillin resistant S. aureus ST239 TW, based on its lipid composition in both pH 7.4 (28% LPG) and pH 5.5 (51% LPG) cultures. These models incorporated a stable synthetic analogue of LPG (3adLPG) to facilitate long-duration biophysical studies, which were previously limited by the lability native LPG. Both increased 3adLPG content and full headgroup ionization at pH 5.5, increased bilayer order and dampened overall charge, via the formation of neutral ion pairs with anionic lipids. Ion pair formation in air/liquid interface lipid monolayers elicited a significant condensing effect, which correlated with the inhibition of subphase-injected magainin 2 F5W partitioning. In fluid phase lipid vesicles, increasing the proportion of 3adLPG from 28 to 51 mol% completely inhibited the adoption of the membrane-active α‑helical conformation of the peptide, without the need for full headgroup ionization. Neutron reflectivity measurements performed on biomimetic PG/3adLPG fluid floating bilayers, showed a significant ordering effect of mild acidity on a bilayer containing 30 mol% 3adLPG, whilst peptide binding/partitioning was only fully inhibited in a bilayer with 55 mol% 3adLPG at pH 5.5. These findings are discussed with respect to the roles of LPG in resistance to human epithelial defences in S. aureus and the continued evolution of this opportunistic pathogen's virulence.