Abstract
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.
Highlights
Streptococcus suis (SS) is a newly emerging zoonotic pathogen that can cause meningitis, endangering health in both humans and pigs
Eno destroys blood brain barrier (BBB) integrity and mediates SS serotype 2 (SS2) invasion of the brain The co-culture BBB model was established successfully based on Transendothelial electrical resistance (TEER) measurement (Figure 1A) according to
Cross the BBB (Figure 1F) was stronger than that of BL21-23a (BL21-pET23a). These results confirmed that Eno plays an important role in SS2 adhesion to porcine brain microvascular endothelial cells (PBMECs) and penetration into the BBB
Summary
Streptococcus suis (SS) is a newly emerging zoonotic pathogen that can cause meningitis, endangering health in both humans and pigs. SS serotype 2 (SS2), the most virulent serotype, is the most commonly isolated in human infection cases, accounting for 74.7% (n = 1642) [3, 4]. In the case of BMECs, SS2 interaction induces serine/threonine kinase activity that affects the expression of E3 ubiquitin ligase HECTD1, which subsequently increases the degradation of claudin-5, enabling SS2 to traverse the BBB [6]. Once bacteria enter the brain tissue, meningitis is the most serious clinical manifestation of SS2 infection; which is difficult to treat because of the difficulty of delivery of therapeutic drugs to the brain, and the associated long term sequelse [7]. The SS virulence factor suilysin may have a role in inducing BMEC injury, and passage across the BBB to the central nervous system
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