Department of Molecular Biology and Nanobiotechnology, National Institute of Chemistry, Hajdrihova 19, 1000, Ljubljana, Slovenia.
School of Chemistry, Bio21 Institute, The University of Melbourne, VIC, 3010, Australia.
Chemistry. 2018 Sep 20;24(53):14220-14225. doi: 10.1002/chem.201802575. Epub 2018 Aug 28.
Listeriolysin O (LLO) is a pore-forming toxin that enables survival and cell-to-cell spread of foodborne bacterial pathogen Listeria monocytogenes, which is responsible for the life-threatening disease, listeriosis. LLO-membrane interactions are crucial for pathogenicity of Listeria, but remained unexplained in detail at the molecular level. Here we addressed them by means of H, P, C and F solid-state NMR spectroscopy. Different fluid and ordered cholesterol-rich membrane lipid bilayer systems were prepared and checked for the integrity and properties in the presence of LLO. LLO has significantly changed dynamics of phospholipid acyl chains of more fluid cholesterol-rich bilayers, whereas the lipid bilayer organization was not affected. LLO has also affected cholesterol dynamics by increasing the intensity of low frequency motions, indicating direct interactions of LLO with cholesterol. Additionally, the LLO protein was shown to interact differently with lipid membranes, depending on the properties of cholesterol-rich membranes. The presented results, therefore, provide new insights into the interactions of the bacterial toxin LLO with cholesterol-rich membrane systems.
溶血素 O（LLO）是一种形成孔的毒素，能够使食源性病原体单核细胞增生李斯特菌在细胞间存活和传播，而单核细胞增生李斯特菌则会导致威胁生命的李斯特菌病。LLO 与膜的相互作用对李斯特菌的致病性至关重要，但在分子水平上仍未详细阐明。在这里，我们通过 H、P、C 和 F 固态 NMR 光谱来解决这些问题。制备了不同的流体和有序富含胆固醇的膜脂双层系统，并在存在 LLO 的情况下检查其完整性和性质。LLO 显著改变了更具流动性的富含胆固醇的脂双层中磷脂酰基链的动力学，而脂质双层的组织不受影响。LLO 还通过增加低频运动的强度来影响胆固醇的动力学，表明 LLO 与胆固醇的直接相互作用。此外，LLO 蛋白与脂质膜的相互作用方式取决于富含胆固醇的膜的性质。因此，提出的结果为细菌毒素 LLO 与富含胆固醇的膜系统的相互作用提供了新的见解。
