含脂多糖和荚膜多糖的细菌外膜建模与仿真,Journal of Chemical Information and Modeling

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含脂多糖和荚膜多糖的细菌外膜建模与仿真
Journal of Chemical Information and Modeling ( IF 5.6 ) Pub Date : 2023-02-20 , DOI: 10.1021/acs.jcim.3c00072
Ya Gao _{1,

2} , Göran Widmalm ₃ , Wonpil Im ₂

Affiliation

荚膜是革兰氏阴性细菌中保护病原体免受宿主防御的常见毒力因子之一，由固定在外膜 (OM) 中的长链荚膜多糖 (CPS) 组成。阐明 CPS 的结构特性对于理解其生物学功能和 OM 特性很重要。然而，由于 CPS 的复杂性和多样性，当前模拟研究中 OM 的外部传单仅由 LPS 表示。在这项工作中，代表性的大肠杆菌CPS、K _LPS（脂质 A 连锁形式）和 K _PG（一种磷脂酰甘油连接的形式），被建模并掺入各种对称双层中，并以不同的比例共存 LPS。已经对这些系统进行了全原子分子动力学模拟，以表征各种双层特性。K _LPS的掺入使 LPS 的酰基链更加刚性和有序，而 K _PG的掺入使它们的有序性和柔性降低。这些结果与 LPS 的每脂质计算面积 (APL) 一致，其中当掺入K _LPS时，LPS 的 APL 变小，而当加入 K _{PG时，它变大}已经包括了。扭转分析表明，CPS 的存在对 LPS 糖苷键构象分布的影响很小，并且在 CPS 的内部和外部区域也检测到微小差异。结合先前以混合双层形式建模的肠杆菌共同抗原 (ECA)，这项工作提供了更真实的 OM 模型以及表征 OM 和 OM 蛋白之间相互作用的基础。

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Modeling and Simulation of Bacterial Outer Membranes with Lipopolysaccharides and Capsular Polysaccharides

Capsule is one of the common virulence factors in Gram-negative bacteria protecting pathogens from host defenses and consists of long-chain capsular polysaccharides (CPS) anchored in the outer membrane (OM). Elucidating structural properties of CPS is important to understand its biological functions as well as the OM properties. However, the outer leaflet of the OM in current simulation studies is represented exclusively by LPS due to the complexity and diversity of CPS. In this work, representative Escherichia coli CPS, K_LPS (a lipid A-linked form) and K_PG (a phosphatidylglycerol-linked form), are modeled and incorporated into various symmetric bilayers with co-existing LPS in different ratios. All-atom molecular dynamics simulations of these systems have been conducted to characterize various bilayer properties. Incorporation of K_LPS makes the acyl chains of LPS more rigid and ordered, while incorporation of K_PG makes them less ordered and flexible. These results are consistent with the calculated area per lipid (APL) of LPS, in which the APL of LPS becomes smaller when K_LPS is incorporated, whereas it gets larger when K_PG is included. Torsional analysis reveals that the influence of the CPS presence on the conformational distributions of the glycosidic linkages of LPS is small, and minor differences are also detected for the inner and outer regions of the CPS. Combined with previously modeled enterobacterial common antigens (ECAs) in the form of mixed bilayers, this work provides more realistic OM models as well as the basis for characterization of interactions between the OM and OM proteins.

更新日期：2023-02-20

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