Streptococcus suis serotype 2 enolase interaction with host brain microvascular endothelial cells and RPSA-induced apoptosis lead to loss of BBB integrity.
Hongtao LiuSiyu LeiLi JiaXiaojing XiaYingying SunHexiang JiangRining ZhuShuguang LiGuanggang QuJingmin GuChangjiang SunXin FengWenyu HanPaul R LangfordLiancheng LeiPublished in: Veterinary research (2021)
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.
Keyphrases
- blood brain barrier
- endothelial cells
- cerebral ischemia
- heat shock protein
- induced apoptosis
- biofilm formation
- signaling pathway
- escherichia coli
- cell proliferation
- poor prognosis
- endoplasmic reticulum stress
- binding protein
- staphylococcus aureus
- pseudomonas aeruginosa
- white matter
- dengue virus
- resting state
- high glucose
- multiple sclerosis
- working memory
- candida albicans
- cerebrospinal fluid
- klebsiella pneumoniae
- protein protein
- zika virus
- subarachnoid hemorrhage
- vascular endothelial growth factor
- pi k akt
- amino acid