Repository logo
 
Publication

Group B Streptococcus Hijacks the Host Plasminogen System to Promote Brain Endothelial Cell Invasion

dc.contributor.authorMagalhães, V.
dc.contributor.authorAndrade, E.
dc.contributor.authorAlves, J.
dc.contributor.authorRibeiro, A:
dc.contributor.authorKim, K.
dc.contributor.authorLima, M.
dc.contributor.authorTrieu-Cuot, P.
dc.contributor.authorFerreira, P.
dc.date.accessioned2014-10-23T10:15:16Z
dc.date.available2014-10-23T10:15:16Z
dc.date.issued2013-05
dc.description.abstractGroup B Streptococcus (GBS) is the leading cause of meningitis in neonates. We have previously shown that plasminogen, once recruited to the GBS cell surface and converted into plasmin by host-derived activators, leads to an enhancement of bacterial virulence. Here, we investigated whether plasmin(ogen) bound at the GBS surface contributes to blood-brain barrier penetration and invasion of the central nervous system. For that purpose, GBS strain NEM316 preincubated with or without plasminogen plus tissue type plasminogen activator was analyzed for the capacity to adhere to, invade and transmigrate the human brain microvascular endothelial cell (hBMEC) monolayer, and to penetrate the central nervous system using a neonatal mouse model. At earlier times of infection, plasmin(ogen)-treated GBS exhibited a significant increase in adherence to and invasion of hBMECs. Later, injury of hBMECs were observed with plasmin(ogen)-treated GBS that displayed a plasmin-like activity. The same results were obtained when hBMECs were incubated with whole human plasma and infected with untreated GBS. To confirm that the observed effects were due to the recruitment and activation of plasminogen on GBS surface, the bacteria were first incubated with epsilon-aminocaproic acid (εACA), an inhibitor of plasminogen binding, and thereafter with plasmin(ogen). A significant decrease in the hBMECs injury that was correlated with a decrease of the GBS surface proteolytic activity was observed. Furthermore, plasmin(ogen)-treated GBS infected more efficiently the brain of neonatal mice than the untreated bacteria, indicating that plasmin(ogen) bound to GBS surface may facilitate the traversal of the blood-brain barrier. A higher survival rate was observed in offspring born from εACA-treated mothers, compared to untreated mice, and no brain infection was detected in these neonates. Our findings suggest that capture of the host plasmin(ogen) by the GBS surface promotes the crossing of the blood-brain barrier and contributes to the establishment of meningitis.por
dc.description.sponsorshipFunding: This work was supported by research funding from Fundação para a Ciência e Tecnologia (FCT), Fundo Europeu de Desenvolvimento Regional (FEDER) and Programa Operacional Fatores de Competitividade (COMPETE) through the grant n° PTDC/SAU-MIC/111387/2009. Elva Bonifacio Andrade and Joana Alves were supported by a PhD FCT fellowship SFRH/BD/38380/2007 and SRFH/BD/77232/2011, respectively. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.por
dc.identifier.citationMagalhães V, Andrade EB, Alves J, Ribeiro A, Kim KS, et al. (2013) Group B Streptococcus Hijacks the Host Plasminogen System to Promote Brain Endothelial Cell Invasion. PLoS ONE 8(5): e63244. doi:10.1371/journal.pone.0063244por
dc.identifier.doi10.1371/journal.pone.0063244
dc.identifier.issn1932-6203
dc.identifier.urihttp://hdl.handle.net/10400.16/1716
dc.language.isoengpor
dc.peerreviewedyespor
dc.publisherPublic Library of Sciencepor
dc.relation.publisherversionhttp://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0063244por
dc.titleGroup B Streptococcus Hijacks the Host Plasminogen System to Promote Brain Endothelial Cell Invasionpor
dc.typejournal article
dspace.entity.typePublication
oaire.citation.conferencePlaceUnited States of Americapor
oaire.citation.titlePLoS Onepor
oaire.citation.volume8(5)por
rcaap.rightsopenAccesspor
rcaap.typearticlepor

Files

Original bundle
Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
Group B Streptococcus Hijacks.pdf
Size:
3.31 MB
Format:
Adobe Portable Document Format
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
1.35 KB
Format:
Item-specific license agreed upon to submission
Description: