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水解单宁抑制金黄色葡萄球菌α-溶血素与红细胞膜相互作用的构效关系研究。

Inhibition of interaction between Staphylococcus aureus α-hemolysin and erythrocytes membrane by hydrolysable tannins: structure-related activity study.

机构信息

Department of Microbiology and Biotechnology, Laboratory of Molecular Biophysics, Faculty of Biology, University of Bialystok, Konstanty Ciolkowski Street 1J, 15-245, Białystok, Poland.

Laboratory of Bioanalysis, Faculty of Chemistry, University of Bialystok, Konstanty Ciolkowski Street 1K, 15-245, Białystok, Poland.

出版信息

Sci Rep. 2020 Jul 7;10(1):11168. doi: 10.1038/s41598-020-68030-1.

DOI:10.1038/s41598-020-68030-1
PMID:32636484
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7341856/
Abstract

The objective of the study was a comparative analysis of the antihemolytic activity against two Staphylococcus aureus strains (8325-4 and NCTC 5655) as well as α-hemolysin and of the membrane modifying action of four hydrolysable tannins with different molecular mass and flexibility: 3,6-bis-O-di-O-galloyl-1,2,4-tri-O-galloyl-β-D-glucose (T1), 1,2,3,4,5-penta-O-galloyl-β-D-glucose (T2), 3-O-galloyl-1,2-valoneoyl-β-D-glucose (T3) and 1,2-di-O-galloyl-4,6-valoneoyl-β-D-glucose (T4). We showed that all the compounds studied manifested antihemolytic effects in the range of 5-50 µM concentrations. However, the degree of the reduction of hemolysis by the investigated tannins was not uniform. A valoneoyl group-containing compounds (T3 and T4) were less active. Inhibition of the hemolysis induced by α-hemolysin was also noticed on preincubated with the tannins and subsequently washed erythrocytes. In this case the efficiency again depended on the tannin structure and could be represented by the following order: T1 > T2 > T4 > T3. We also found a relationship between the degree of antihemolytic activity of the tannins studied and their capacity to increase the ordering parameter of the erythrocyte membrane outer layer and to change zeta potential. Overall, our study showed a potential of the T1 and T2 tannins as anti-virulence agents. The results of this study using tannins with different combinations of molecular mass and flexibility shed additional light on the role of tannin structure in activity manifestation.

摘要

本研究的目的是对两种金黄色葡萄球菌(8325-4 和 NCTC 5655)的抗溶血活性以及四种不同分子量和柔性的水解单宁的α-溶血素和膜修饰作用进行比较分析:3,6-双-O-二-O-没食子酰基-1,2,4-三-O-没食子酰基-β-D-葡萄糖(T1)、1,2,3,4,5-五-O-没食子酰基-β-D-葡萄糖(T2)、3-O-没食子酰基-1,2-脱水基-β-D-葡萄糖(T3)和 1,2-二-O-没食子酰基-4,6-脱水基-β-D-葡萄糖(T4)。结果表明,所有研究的化合物在 5-50µM 浓度范围内均表现出抗溶血作用。然而,所研究的单宁降低溶血的程度并不均匀。含有脱水基的化合物(T3 和 T4)活性较低。在预先用单宁孵育并随后用洗涤红细胞处理后,也观察到对α-溶血素诱导的溶血的抑制作用。在这种情况下,效率再次取决于单宁的结构,可以表示为:T1>T2>T4>T3。我们还发现研究的单宁的抗溶血活性程度与其增加红细胞膜外层有序参数和改变 ζ 电位的能力之间存在关系。总的来说,我们的研究表明 T1 和 T2 单宁具有作为抗毒力剂的潜力。本研究使用具有不同分子量和柔性组合的单宁的结果进一步阐明了单宁结构在活性表现中的作用。

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