Group B Streptococcus Hijacks the Host Plasminogen System to Promote Brain Endothelial Cell Invasion
| Autor: | Patrick Trieu-Cuot, Kwang Sik Kim, Margarida Lima, Adília Ribeiro, Paula Ferreira, Joana Alves, Vanessa Magalhães, Elva Bonifácio Andrade |
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| Přispěvatelé: | Faculdade Ciências da Saúde, Universidade Fernando Pessoa, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto = University of Porto, Instituto de Biologia Molecular e Celular (IBMC), Johns Hopkins University (JHU), Hospital de Santo António, Centro Hospitalar do Porto, Biologie des Bactéries pathogènes à Gram-positif, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), 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., European Project: 111387,FCT::,PTDC/2009,PTDC/SAU-MIC/111387/2009(2011), Universidade do Porto, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS) |
| Rok vydání: | 2013 |
| Předmět: |
Male
Mouse Plasmin Bacterial meningitis Cell Plasminogen/metabolism Developmental and Pediatric Neurology medicine.disease_cause Pediatrics Bacterial Adhesion Mice Streptococcus agalactiae/physiology Infectious Diseases of the Nervous System Inbred BALB C Streptococcus agalactiae/metabolism Mice Inbred BALB C 0303 health sciences Multidisciplinary Streptococcus Streptococci Brain Animal Models Endothelial Cells/microbiology Bacterial Pathogens Microvessels/cytology 3. Good health Endothelial stem cell medicine.anatomical_structure Neurology Blood-Brain Barrier Medicine Infectious diseases Female Group B streptococcal infection Blood-Brain Barrier/metabolism Meningitis Research Article medicine.drug Science Bacterial diseases Biology Blood–brain barrier Microbiology Brain/blood supply Streptococcus agalactiae 03 medical and health sciences Model Organisms Blood-Brain Barrier/microbiology medicine Animals Brain/metabolism Humans 030304 developmental biology 030306 microbiology Endothelial Cells Plasminogen medicine.disease [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology Brain/cytology Microvessels Brain/microbiology Neonatology Plasminogen activator |
| Zdroj: | PLoS ONE PLoS ONE, 2013, 8 (5), pp.e63244. ⟨10.1371/journal.pone.0063244⟩ PLoS ONE, Vol 8, Iss 5, p e63244 (2013) PLoS ONE, Public Library of Science, 2013, 8 (5), pp.e63244. ⟨10.1371/journal.pone.0063244⟩ Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) Agência para a Sociedade do Conhecimento (UMIC)-FCT-Sociedade da Informação instacron:RCAAP |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0063244 |
| Popis: | Group 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. Funding: 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. |
| Databáze: | OpenAIRE |
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