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肺炎链球菌肺炎球菌溶血素的 4 结构域是一个多功能结构域,有助于 TLR4 的激活和溶血活性。

Domain 4 of pneumolysin from Streptococcus pneumoniae is a multifunctional domain contributing TLR4 activating and hemolytic activity.

机构信息

National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan Town, Miaoli, Taiwan, ROC.

National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan Town, Miaoli, Taiwan, ROC; Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan, ROC; Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC.

出版信息

Biochem Biophys Res Commun. 2019 Oct 1;517(4):596-602. doi: 10.1016/j.bbrc.2019.07.063. Epub 2019 Aug 5.

Abstract

The pneumolysin (Ply) protein of Streptococcus pneumoniae is composed of four domains and possesses several different but related activities. In this study, recombinant Ply and two truncated forms, Ply domain 1-3 and Ply domain 4 (rPly4), were expressed and characterized regarding their participation in apoptosis, the stimulation of cytokine production, hemolytic activity and virulence. rPly4 activated murine bone marrow-derived dendritic cells in a Toll-like receptor (TLR) 4-dependent manner. The rPly4 alone was able to produce hemolytic activity at high concertation and penetrate the lipid bilayer. We further demonstrated that domain 4 of Ply involved in the virulence of the bacteria in mouse model. In the absence of apoptotic activity, the virulence level caused by rPly4 was similar to that of full length Ply. Our data suggested that domain 4 of Ply alone with TLR4 agonist and hemolytic activity may play roles in virulence of Streptococcus pneumoniae.

摘要

肺炎链球菌的肺炎球菌溶血素(Ply)蛋白由四个结构域组成,具有几种不同但相关的活性。在这项研究中,表达并表征了重组 Ply 及其两种截断形式,Ply 结构域 1-3 和 Ply 结构域 4(rPly4),以研究它们在凋亡、细胞因子产生刺激、溶血活性和毒力方面的作用。rPly4 以 Toll 样受体(TLR)4 依赖性方式激活小鼠骨髓来源的树突状细胞。rPly4 单独在高浓度下即可产生溶血活性并穿透脂质双层。我们进一步证明 Ply 的结构域 4 参与了细菌在小鼠模型中的毒力。在没有凋亡活性的情况下,rPly4 引起的毒力水平与全长 Ply 相似。我们的数据表明,单独的 Ply 结构域 4 与 TLR4 激动剂和溶血活性可能在肺炎链球菌的毒力中发挥作用。

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