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

2021 ◽  
Vol 52 (1) ◽  
Author(s):  
Hongtao Liu ◽  
Siyu Lei ◽  
Li Jia ◽  
Xiaojing Xia ◽  
Yingying Sun ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Host Cell ◽  
Streptococcus Suis ◽  
Molecular Medicine ◽  
Microvascular Endothelial Cells ◽  
Bacterial Invasion ◽  
Brain Microvascular Endothelial Cells ◽  
Host Cell Membrane ◽  
Microvascular Endothelial ◽  
Induced Apoptosis

AbstractHost 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.

scholarly journals Streptococcus suis Serotype 2 Interactions with Human Brain Microvascular Endothelial Cells

2000 ◽  
Vol 68 (2) ◽  
pp. 637-643 ◽  
Author(s):  
Nathalie Charland ◽  
Victor Nizet ◽  
Craig E. Rubens ◽  
Kwang Sik Kim ◽  
Sonia Lacouture ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Damage ◽  
Umbilical Vein ◽  
Bacterial Species ◽  
Streptococcus Suis ◽  
Neonatal Meningitis ◽  
Microvascular Endothelial Cells ◽  
Brain Microvascular Endothelial Cells ◽  
Group B Streptococci ◽  
Microvascular Endothelial

ABSTRACT Streptococcus suis serotype 2 is a worldwide causative agent of many forms of swine infection and is also recognized as a zoonotic agent causing human disease, including meningitis. The pathogenesis of S. suis infections is poorly understood. Bacteria circulate in the bloodstream in the nonimmune host until they come in contact with brain microvascular endothelial cells (BMEC) forming the blood-brain barrier. The bacterial polysaccharide capsule confers antiphagocytic properties. It is known that group B streptococci (GBS) invade and damage BMEC, which may be a primary step in the pathogenesis of neonatal meningitis. Interactions betweenS. suis and human endothelial cells were studied to determine if they differ from those between GBS and endothelial cells. Invasion assays performed with BMEC and human umbilical vein endothelial cells demonstrated that unlike GBS, S. suisserotype 2 could not invade either type of cell. Adherence assays showed that S. suis adhered only to BMEC, whereas GBS adhered to both types of cell. These interactions were not affected by the presence of a capsule, since acapsular mutants from both bacterial species adhered similarly compared to the wild-type strains. Lactate dehydrogenase release measurements indicated that some S. suis strains were highly cytotoxic for BMEC, even more than GBS, whereas others were not toxic at all. Cell damage was related to suilysin (S. suis hemolysin) production, since only suilysin-producing strains were cytotoxic and cytotoxicity could be inhibited by cholesterol and antisuilysin antibodies. It is possible that hemolysin-positive S. suis strains use adherence and suilysin-induced BMEC injury, as opposed to direct cellular invasion, to proceed from the circulation to the central nervous system.

scholarly journals Application of Signature-Tagged Mutagenesis for Identification ofEscherichia coli K1 Genes That Contribute to Invasion of Human Brain Microvascular Endothelial Cells

2000 ◽  
Vol 68 (9) ◽  
pp. 5056-5061 ◽  
Author(s):  
Julie L. Badger ◽  
Carol A. Wass ◽  
Scott J. Weissman ◽  
Kwang Sik Kim
Keyword(s):  
Endothelial Cells ◽  
Human Brain ◽  
Neonatal Rat ◽  
Microvascular Endothelial Cells ◽  
Selection Strategy ◽  
Bacterial Invasion ◽  
Brain Microvascular Endothelial Cells ◽  
E Coli ◽  
Microvascular Endothelial

ABSTRACT Escherichia coli K1 is the leading cause of gram-negative bacterial meningitis in neonates. It is principally due to our limited understanding of the pathogenesis of this disease that the morbidity and mortality rates remain unacceptably high. To identify genes required for E. coli K1 penetration of the blood-brain barrier (BBB), we used the negative selection strategy of signature-tagged transposon mutagenesis (STM) to screen mutants for loss or decreased invasion of human brain microvascular endothelial cells (HBMEC) which comprise the BBB. A total of 3,360 insertion mutants of E. coli K1 were screened, and potential HBMEC invasion mutants were subjected to a secondary invasion screen. Those mutants that failed to pass the serial invasion screens were then tested individually. Seven prototrophic mutants were found to exhibit significantly decreased invasive ability in HBMEC. We identifiedtraJ and five previously uncharacterized loci whose gene products are necessary for HBMEC invasion by E. coli K1. In addition, cnf1, a gene previously shown to play a role in bacterial invasion, was identified. More importantly, atraJ mutant was attenuated in penetration of the BBB in the neonatal rat model of experimental hematogenous meningitis. This is the first in vivo demonstration that traJ is involved in the pathogenesis of E. coli K1 meningitis.

scholarly journals Adherence to and Invasion of Human Brain Microvascular Endothelial Cells Are Promoted by Fibrinogen-Binding Protein FbsA of Streptococcus agalactiae

2005 ◽  
Vol 73 (7) ◽  
pp. 4404-4409 ◽  
Author(s):  
Tobias Tenenbaum ◽  
Christiane Bloier ◽  
Rüdiger Adam ◽  
Dieter J. Reinscheid ◽  
Horst Schroten
Keyword(s):  
Endothelial Cells ◽  
Human Brain ◽  
Streptococcus Agalactiae ◽  
Host Cells ◽  
Microvascular Endothelial Cells ◽  
Bacterial Invasion ◽  
Brain Microvascular Endothelial Cells ◽  
Gene Encoding ◽  
Fibrinogen Binding ◽  
Microvascular Endothelial

ABSTRACT Streptococcus agalactiae is a frequent cause of bacterial sepsis and meningitis in neonates. During the course of infection, S. agalactiae colonizes and invades a number of host compartments, thereby interacting with different host tissues. Deletion of the fbsA gene, encoding the fibrinogen protein FbsA, significantly impaired the adherence and invasion of human brain microvascular endothelial cells (HBMEC) by S. agalactiae. The adherence and invasiveness of an fbsA deletion mutant were restored by reintroducing the fbsA gene on an expression vector. Heterologous expression of fbsA in Lactococcus lactis enabled this bacterium to adhere to but not to invade HBMEC, suggesting that FbsA is a streptococcal adhesin. Finally, host cell adherence and invasion were significantly blocked in competition experiments with either purified FbsA fusion protein or a monoclonal antibody directed against the fibrinogen-binding epitope of FbsA. The S. agalactiae fbsA mutant induced a release of the neutrophil chemoattractant interleukin-8 (IL-8) equal to that induced by the wild type. Taken together, our studies demonstrate that FbsA promotes the adherence of S. agalactiae to HBMEC but that FbsA neither mediates the bacterial invasion into host cells nor plays a role in IL-8 release for HBMEC.

Vimentin-mediated signalling is required for IbeA+ E. coli K1 invasion of human brain microvascular endothelial cells

2010 ◽  
Vol 427 (1) ◽  
pp. 79-90 ◽  
Author(s):  
Feng Chi ◽  
Timothy D. Jong ◽  
Lin Wang ◽  
Yannan Ouyang ◽  
Chunhua Wu ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Fluorescent Protein ◽  
Microvascular Endothelial Cells ◽  
Bacterial Invasion ◽  
Brain Microvascular Endothelial Cells ◽  
E Coli ◽  
Primary Receptor ◽  
Head Domain ◽  
Microvascular Endothelial ◽  
Green Fluorescent

IbeA in meningitic Escherichia coli K1 strains has been described previously for its role in invasion of BMECs (brain microvascular endothelial cells). Vimentin was identified as an IbeA-binding protein on the surface of HBMECs (human BMECs). In the present study, we demonstrated that vimentin is a primary receptor required for IbeA+ E. coli K1-induced signalling and invasion of HBMECs, on the basis of the following observations. First, E44 (IbeA+ E. coli K1 strain) invasion was blocked by vimentin inhibitors (withaferin A and acrylamide), a recombinant protein containing the vimentin head domain and an antibody against the head domain respectively. Secondly, overexpression of GFP (green fluorescent protein)–vimentin and GFP–VDM (vimentin head domain deletion mutant) significantly increased and decreased bacterial invasion respectively. Thirdly, bacterial invasion was positively correlated with phosphorylation of vimentin at Ser82 by CaMKII (Ca2+/calmodulin-dependent protein kinase II) and IbeA+ E. coli-induced phosphorylation of ERK (extracellular-signal-regulated kinase). Blockage of CaMKII by KN93 and inhibition of ERK1/2 phosphorylation by PD098059 resulted in reduced IbeA+ E. coli invasion. Fourthly, IbeA+ E. coli and IbeA-coated beads induced the clustering of vimentin that was correlated with increased entry of bacteria and beads. Lastly, IbeA+ E. coli K1 invasion was inhibited by lipid-raft-disrupting agents (filipin and nystatin) and caveolin-1 siRNA (small interfering RNA), suggesting that caveolae/lipid rafts are signalling platforms for inducing IbeA–vimentin-mediated E. coli invasion of HBMECs. Taken together, the present studies suggest that a dynamic and function-related interaction between IbeA and its primary receptor vimentin at HBMEC membrane rafts leads to vimentin phosphorylation and ERK-mediated signalling, which modulate meningitic E. coli K1 invasion.

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