Host HSPD1 translocation from mitochondria to the cytoplasm induced by streptococcus suis Serovar 2 enolase mediates apoptosis and loss of blood–brain barrier integrity
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Streptococcus suis serovar 2 (S. suis serovar 2) is a zoonotic pathogen that causes meningitis in pigs and humans, and is a serious threat to the swine industry and public health. Understanding the mechanism(s) by which S. suis serovar 2 penetrates the blood–brain barrier (BBB) is crucial to elucidating the pathogenesis of meningitis. In a previous study, we found that expression of the virulence factor enolase (Eno) by S. suis serovar 2 promotes the expression of host heat shock protein family D member 1 (HSPD1) in brain tissue, which leads to the apoptosis of porcine brain microvascular endothelial cells (PBMECs) and increased BBB permeability, which in turn promotes bacterial translocation across the BBB. However, the mechanism by which HSPD1 mediates Eno-induced apoptosis remains unclear. In this study, we demonstrate that Eno promotes the translocation of HSPD1 from mitochondria to the cytoplasm, where HSPD1 binds to β-actin (ACTB), the translocated HSPD1, and its interaction with ACTB led to adverse changes in cell morphology and promoted the expression of apoptosis-related proteins, second mitochondria-derived activator of caspases (Smac), and cleaved caspase-3; inhibited the expression of X-linked inhibitor of apoptosis protein (XIAP); and finally promoted cell apoptosis. These results further elucidate the role of HSPD1 in the process of Eno-induced apoptosis and increased BBB permeability, increasing our understanding of the pathogenic mechanisms of meningitis, and providing a framework for novel therapeutic strategies.
Date Issued
2022-06-29
Date Acceptance
2022-06-26
Citation
Cells, 2022, 11 (13), pp.1-16
ISSN
2073-4409
Publisher
MDPI AG
Start Page
1
End Page
16
Journal / Book Title
Cells
Volume
11
Issue
13
Copyright Statement
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
This article is an open access article
distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
This article is an open access article
distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
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Sponsor
Biotechnology and Biological Sciences Research Council (BBSRC)
Identifier
https://www.mdpi.com/2073-4409/11/13/2071
Grant Number
BB/S019901/1
Publication Status
Published
Date Publish Online
2022-06-29