scholarly journals Blood-brain barrier invasion by group B Streptococcus depends upon proper cell-surface anchoring of lipoteichoic acid

2005 ◽  
Vol 115 (9) ◽  
pp. 2499-2507 ◽  
Author(s):  
Kelly S. Doran ◽  
Erin J. Engelson ◽  
Arya Khosravi ◽  
Heather C. Maisey ◽  
Iris Fedtke ◽  
...  
Keyword(s):  
Cell Surface ◽  
Blood Brain Barrier ◽  
Group B Streptococcus ◽  
Lipoteichoic Acid ◽  
Brain Barrier ◽  
Surface Anchoring ◽  
Blood Brain ◽  
Group B

scholarly journals Regulation of CovR expression in Group B Streptococcus impacts blood-brain barrier penetration

2010 ◽  
Vol 77 (2) ◽  
pp. 431-443 ◽  
Author(s):  
Annalisa Lembo ◽  
Michael A. Gurney ◽  
Kellie Burnside ◽  
Anirban Banerjee ◽  
Melissa De Los Reyes ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Group B Streptococcus ◽  
Brain Barrier ◽  
Blood Brain ◽  
Barrier Penetration ◽  
Group B

scholarly journals An original model of brain infection identifies the hijacking of host lipoprotein import as a bacterial strategy for blood-brain barrier crossing

2020 ◽  
Author(s):  
Billel Benmimoun ◽  
Florentia Papastefanaki ◽  
Bruno Périchon ◽  
Katerina Segklia ◽  
Nicolas Roby ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Group B Streptococcus ◽  
Ldl Receptor ◽  
Systemic Infection ◽  
Brain Barrier ◽  
Brain Infection ◽  
Blood Brain ◽  
Drosophila Brain ◽  
Group B

AbstractPathogens able to cross the blood-brain barrier (BBB) induce long-term neurological sequelae and death. Understanding how neurotropic pathogens bypass this strong physiological barrier is a prerequisite to devise therapeutic strategies. Here we propose an innovative model of infection in the developing Drosophila brain, combining whole brain explants with in vivo systemic infection. We identified several mammalian pathogens able to cross the Drosophila BBB, including Group B Streptococcus (GBS). Amongst GBS surface components, lipoproteins, and in particular the B leucin-rich Blr, were important for BBB crossing and virulence in Drosophila. Further, we identified (V)LDL receptor LpR2, expressed in the BBB, as a host receptor for Blr, allowing GBS translocation through endocytosis. Finally, we demonstrated that Blr is required for BBB crossing and pathogenicity in a murine model of infection. Our results support the relevance of Drosophila for studying host-pathogen interactions and identify a new mechanism by which pathogens exploit host barriers to generate brain infection.

scholarly journals An original infection model identifies host lipoprotein import as a route for blood-brain barrier crossing

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Billel Benmimoun ◽  
Florentia Papastefanaki ◽  
Bruno Périchon ◽  
Katerina Segklia ◽  
Nicolas Roby ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Ldl Receptor ◽  
Systemic Infection ◽  
Brain Barrier ◽  
Infection Model ◽  
Brain Infection ◽  
Blood Brain ◽  
Group B

AbstractPathogens able to cross the blood-brain barrier (BBB) induce long-term neurological sequelae and death. Understanding how neurotropic pathogens bypass this strong physiological barrier is a prerequisite to devise therapeutic strategies. Here we propose an innovative model of infection in the developing Drosophila brain, combining whole brain explants with in vivo systemic infection. We find that several mammalian pathogens are able to cross the Drosophila BBB, including Group B Streptococcus (GBS). Amongst GBS surface components, lipoproteins, and in particular the B leucine-rich Blr, are important for BBB crossing and virulence in Drosophila. Further, we identify (V)LDL receptor LpR2, expressed in the BBB, as a host receptor for Blr, allowing GBS translocation through endocytosis. Finally, we show that Blr is required for BBB crossing and pathogenicity in a murine model of infection. Our results demonstrate the potential of Drosophila for studying BBB crossing by pathogens and identify a new mechanism by which pathogens exploit the machinery of host barriers to generate brain infection.

scholarly journals Host Cytosolic Phospholipase A2α Contributes to Group B Streptococcus Penetration of the Blood-Brain Barrier

2011 ◽  
Vol 79 (10) ◽  
pp. 4088-4093 ◽  
Author(s):  
Ravi Maruvada ◽  
Longkun Zhu ◽  
Donna Pearce ◽  
Adam Sapirstein ◽  
Kwang Sik Kim
Keyword(s):  
Arachidonic Acid ◽  
Blood Brain Barrier ◽  
Dominant Negative ◽  
Brain Barrier ◽  
Neonatal Meningitis ◽  
Type Iii ◽  
Cytosolic Phospholipase ◽  
Blood Brain ◽  
Group B ◽  
The Brain

ABSTRACTGroup BStreptococcus(GBS) is the most common bacterium causing neonatal meningitis, and neonatal GBS meningitis continues to be an important cause of mortality and morbidity. Here we provide the first direct evidence that host cytosolic phospholipase A2α (cPLA2α) contributes to type III GBS invasion of human brain microvascular endothelial cells (HBMEC), which constitute the blood-brain barrier and penetration into the brain, the key step required for the development of GBS meningitis. This was shown by our demonstration that pharmacological inhibition and gene deletion of cPLA2α significantly decreased GBS invasion of the HBMEC monolayer and penetration into the brain. cPLA2α releases arachidonic acid from membrane phospholipids, and we showed that the contribution of cPLA2α to GBS invasion of HBMEC involved lipoxygenated metabolites of arachidonic acid, cysteinyl leukotrienes (LTs). In addition, type III GBS invasion of the HBMEC monolayer involves protein kinase Cα (PKCα), as shown by time-dependent PKCα activation in response to GBS as well as decreased GBS invasion in HBMEC expressing dominant-negative PKCα. PKCα activation in response to GBS, however, was abolished by inhibition of cPLA2α and cysteinyl LTs, suggesting that cPLA2α and cysteinyl LTs contribute to type III GBS invasion of the HBMEC monolayer via PKCα. These findings demonstrate that specific host factors involving cPLA2α and cysteinyl LTs contribute to type III GBS penetration of the blood-brain barrier and their contribution involves PKCα.

scholarly journals Multidimensional Proteome Profiling of Blood-Brain Barrier Perturbation by Group B Streptococcus

mSystems ◽  
2020 ◽  
Vol 5 (4) ◽  
Author(s):  
Anaamika Campeau ◽  
Robert H. Mills ◽  
Marie Blanchette ◽  
Kaja Bajc ◽  
Mario Malfavon ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Host Protein ◽  
Brain Barrier ◽  
Tissue Type ◽  
Neonatal Meningitis ◽  
Bacterial Invasion ◽  
Blood Brain ◽  
Host Pathogen ◽  
Group B ◽  
The Brain

ABSTRACT Group B Streptococcus (GBS) remains the leading cause of neonatal meningitis, a disease associated with high rates of adverse neurological sequelae. The in vivo relationship between GBS and brain tissues remains poorly characterized, partly because past studies had focused on microbial rather than host processes. Additionally, the field has not capitalized on systems-level technologies to probe the host-pathogen relationship. Here, we use multiplexed quantitative proteomics to investigate the effect of GBS infection in the murine brain at various levels of tissue complexity, beginning with the whole organ and moving to brain vascular substructures. Infected whole brains showed classical signatures associated with the acute-phase response. In isolated brain microvessels, classical blood-brain barrier proteins were unaltered, but interferon signaling and leukocyte recruitment proteins were upregulated. The choroid plexus showed increases in peripheral immune cell proteins. Proteins that increased in abundance in the vasculature during GBS invasion were associated with major histocompatibility complex (MHC) class I antigen processing and endoplasmic reticulum dysfunction, a finding which correlated with altered host protein glycosylation profiles. Globally, there was low concordance between the infection proteome of whole brains and isolated vascular tissues. This report underscores the utility of unbiased, systems-scale analyses of functional tissue substructures for understanding disease. IMPORTANCE Group B Streptococcus (GBS) meningitis remains a major cause of poor health outcomes very early in life. Both the host-pathogen relationship leading to disease and the massive host response to infection contributing to these poor outcomes are orchestrated at the tissue and cell type levels. GBS meningitis is thought to result when bacteria present in the blood circumvent the selectively permeable vascular barriers that feed the brain. Additionally, tissue damage subsequent to bacterial invasion is mediated by inflammation and by immune cells from the periphery crossing the blood-brain barrier. Indeed, the vasculature plays a central role in disease processes occurring during GBS infection of the brain. Here, we employed quantitative proteomic analysis of brain vascular substructures during invasive GBS disease. We used the generated data to map molecular alterations associated with tissue perturbation, finding widespread intracellular dysfunction and punctuating the importance of investigations relegated to tissue type over the whole organ.

scholarly journals Diminished Capsule Exacerbates Virulence, Blood–Brain Barrier Penetration, Intracellular Persistence, and Antibiotic Evasion of Hyperhemolytic Group B Streptococci

2018 ◽  
Vol 217 (7) ◽  
pp. 1128-1138 ◽  
Author(s):  
Claire Gendrin ◽  
Sean Merillat ◽  
Jay Vornhagen ◽  
Michelle Coleman ◽  
Blair Armistead ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Group B Streptococci ◽  
Blood Brain ◽  
Barrier Penetration ◽  
Group B

scholarly journals Penetration of the blood–brain barrier by Staphylococcus aureus: contribution of membrane-anchored lipoteichoic acid

2010 ◽  
Vol 88 (6) ◽  
pp. 633-639 ◽  
Author(s):  
Tamsin R. Sheen ◽  
Celia M. Ebrahimi ◽  
Ida H. Hiemstra ◽  
Steven B. Barlow ◽  
Andreas Peschel ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Blood Brain Barrier ◽  
Lipoteichoic Acid ◽  
Brain Barrier ◽  
Blood Brain
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