Streptococcus suis serotype 2 enolase interaction with host brain microvascular endothelial cells and RPSA-induced apoptosis lead to loss of BBB integrity.

Hongtao Liu, Siyu Lei, Li Jia, Xiaojing Xia, Yingying Sun, Hexiang Jiang, Rining Zhu, Shuguang Li, Guanggang Qu, Jingmin Gu, Changjiang Sun, Xin Feng, Wenyu Han, Paul R Langford, Liancheng Lei

Veterinary research 2021 Feb 22

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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.

Citation

Hongtao Liu, Siyu Lei, Li Jia, Xiaojing Xia, Yingying Sun, Hexiang Jiang, Rining Zhu, Shuguang Li, Guanggang Qu, Jingmin Gu, Changjiang Sun, Xin Feng, Wenyu Han, Paul R Langford, Liancheng Lei. Streptococcus suis serotype 2 enolase interaction with host brain microvascular endothelial cells and RPSA-induced apoptosis lead to loss of BBB integrity. Veterinary research. 2021 Feb 22;52(1):30