Influences of Vibrio cholerae Lipid A Types on LPS Bilayer Properties
Influences of Vibrio cholerae Lipid A Types on LPS Bilayer Properties
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DOI：
10.1021/acs.jpcb.0c09144
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发表时间：
2021-02-18
影响因子：
3.3
通讯作者：
Im, Wonpil
中科院分区：
文献类型：
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作者：
Luna, Emanuel;Kim, Seonghoon;Im, Wonpil
存在于革兰氏阴性细菌外膜的外小叶中的脂多糖（LPS）保护细菌免受外部威胁并影响抗生素渗透性以及免疫系统识别。脂A是脂多糖分子外膜的锚，其结构直接影响膜的性质。特别地，在霍乱弧菌（一种引起霍乱的革兰氏阴性细菌，一种严重的霍乱疾病）中，脂质A结构的修饰赋予抗生素抗性，并且是导致当前霍乱大流行的主要因素。然而，这种修饰引起的结构性质的差异尚未得到充分探讨。在这项工作中，五个对称的双层系统由不同的脂质A结构的霍乱弧菌LPS与O 1 O-抗原进行建模和模拟，以探讨不同的脂质A类型对膜性能的影响。全原子分子动力学模拟表明，膜的性质，如疏水厚度，酰基链序参数，和面积每脂质在很大程度上受到脂质A的修改，由于在组合物和酰基链扭曲的差异。修饰的脂质A也带较少的负电荷，这可能揭示了对阳离子抗微生物肽逃避的抗性机制。这些发现为霍乱弧菌的免疫系统逃避特性提供了一种可能的解释，并建立了脂质A类型之间的差异，这对革兰氏阴性菌的任何未来研究都是有用的。
Lipopolysaccharides (LPS) present in the outer leaflet of Gram-negative bacterial outer membranes protect the bacteria from external threats and influence antibiotic permeability as well as immune system recognition. The structure of lipid A, the anchor of an LPS molecule to the outer membrane, can make direct influences on membrane properties. Particularly, in Vibrio cholerae, a Gram-negative bacterium responsible for cholera, a severe diarrheal disease, modifications of lipid A structures grant antibiotic resistance and are a primary factor that led to the current cholera pandemic. However, the difference in structural properties incurred by such modifications has not been fully explored. In this work, five symmetric bilayer systems comprised of distinct lipid A structures of Vibrio cholerae LPS with O1 O-antigen were modeled and simulated to explore influences of different lipid A types on membrane properties. All-atom molecular dynamics simulations reveal that membrane properties such as hydrophobic thickness, acyl chain order parameter, and area per lipid are largely impacted by lipid A modifications due to differences in composition and acyl chain distortions. The modified lipid A is also less negatively charged, which possibly reveals a resistance mechanism to cationic antimicrobial peptide evasion. These findings present a possible explanation for Vibrio cholerae's immune system evasion properties and establish the differences between the lipid A types, which should be of use for any future study of the Gram-negative bacteria.