Streptococcus suis serotype 2 enolase interaction with host brain microvascular endothelial cells and RPSA-induced apoptosis lead to loss of BBB integrity.
Streptococcus suis serotype 2 enolase interaction with host brain microvascular endothelial cells and RPSA-induced apoptosis lead to loss of BBB integrity.
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DOI：
10.1186/s13567-020-00887-6
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发表时间：
2021-02-22
影响因子：
4.4
通讯作者：
Lei L
中科院分区：
文献类型：
--
作者：
Liu H;Lei S;Jia L;Xia X;Sun Y;Jiang H;Zhu R;Li S;Qu G;Gu J;Sun C;Feng X;Han W;Langford PR;Lei L
与病原体相互作用的宿主蛋白作为潜在的治疗靶点在分子医学中受到越来越多的关注。猪链球菌2型（SS 2）是引起人和猪脑膜炎的重要病原。SS 2烯醇化酶（Eno）以前被鉴定为毒力因子，具有改变血脑屏障（BBB）完整性的作用，但Eno的宿主细胞膜受体及其所涉及的机制尚不清楚。该研究确定SS 2 Eno与猪脑微血管内皮细胞表面上的40 S核糖体蛋白SA（RPSA）结合，导致细胞内p38/ERK-eIF 4 E信号传导的激活，其促进HSPD 1（热休克蛋白家族D成员1）的细胞内表达，并启动宿主细胞凋亡，以及促进细菌入侵的BBB通透性增加。这项研究揭示了宿主间质分子RPSA和HSPD 1在BBB完整性中的新功能，并为脑膜炎的新治疗策略提供了见解。
Host proteins interacting with pathogens are receiving more attention as potential therapeutic targets in molecular medicine. Streptococcus suis serotype 2 (SS2) is an important cause of meningitis in both humans and pigs worldwide. SS2 Enolase (Eno) has previously been identified as a virulence factor with a role in altering blood brain barrier (BBB) integrity, but the host cell membrane receptor of Eno and The mechanism(s) involved are unclear. This study identified that SS2 Eno binds to 40S ribosomal protein SA (RPSA) on the surface of porcine brain microvascular endothelial cells leading to activation of intracellular p38/ERK-eIF4E signalling, which promotes intracellular expression of HSPD1 (heat-shock protein family D member 1), and initiation of host-cell apoptosis, and increased BBB permeability facilitating bacterial invasion. This study reveals novel functions for the host-interactional molecules RPSA and HSPD1 in BBB integrity, and provides insight for new therapeutic strategies in meningitis.
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影响因子：
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