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pIgR and PECAM-1 bind to pneumococcal adhesins RrgA and PspC mediating bacterial brain invasion
Streptococcus pneumoniae is the main cause of bacterial meningitis, a life-threating disease with a high case fatality rate despite treatment with antibiotics. Pneumococci cause meningitis by invading the blood and penetrating the blood–brain barrier (BBB). Using stimulated emission depletion (STED)...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5461002/ https://www.ncbi.nlm.nih.gov/pubmed/28515075 http://dx.doi.org/10.1084/jem.20161668 |
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author | Iovino, Federico Engelen-Lee, Joo-Yeon Brouwer, Matthijs van de Beek, Diederik van der Ende, Arie Valls Seron, Merche Mellroth, Peter Muschiol, Sandra Bergstrand, Jan Widengren, Jerker Henriques-Normark, Birgitta |
author_facet | Iovino, Federico Engelen-Lee, Joo-Yeon Brouwer, Matthijs van de Beek, Diederik van der Ende, Arie Valls Seron, Merche Mellroth, Peter Muschiol, Sandra Bergstrand, Jan Widengren, Jerker Henriques-Normark, Birgitta |
author_sort | Iovino, Federico |
collection | PubMed |
description | Streptococcus pneumoniae is the main cause of bacterial meningitis, a life-threating disease with a high case fatality rate despite treatment with antibiotics. Pneumococci cause meningitis by invading the blood and penetrating the blood–brain barrier (BBB). Using stimulated emission depletion (STED) super-resolution microscopy of brain biopsies from patients who died of pneumococcal meningitis, we observe that pneumococci colocalize with the two BBB endothelial receptors: polymeric immunoglobulin receptor (pIgR) and platelet endothelial cell adhesion molecule (PECAM-1). We show that the major adhesin of the pneumococcal pilus-1, RrgA, binds both receptors, whereas the choline binding protein PspC binds, but to a lower extent, only pIgR. Using a bacteremia-derived meningitis model and mutant mice, as well as antibodies against the two receptors, we prevent pneumococcal entry into the brain and meningitis development. By adding antibodies to antibiotic (ceftriaxone)-treated mice, we further reduce the bacterial burden in the brain. Our data suggest that inhibition of pIgR and PECAM-1 has the potential to prevent pneumococcal meningitis. |
format | Online Article Text |
id | pubmed-5461002 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-54610022017-06-07 pIgR and PECAM-1 bind to pneumococcal adhesins RrgA and PspC mediating bacterial brain invasion Iovino, Federico Engelen-Lee, Joo-Yeon Brouwer, Matthijs van de Beek, Diederik van der Ende, Arie Valls Seron, Merche Mellroth, Peter Muschiol, Sandra Bergstrand, Jan Widengren, Jerker Henriques-Normark, Birgitta J Exp Med Research Articles Streptococcus pneumoniae is the main cause of bacterial meningitis, a life-threating disease with a high case fatality rate despite treatment with antibiotics. Pneumococci cause meningitis by invading the blood and penetrating the blood–brain barrier (BBB). Using stimulated emission depletion (STED) super-resolution microscopy of brain biopsies from patients who died of pneumococcal meningitis, we observe that pneumococci colocalize with the two BBB endothelial receptors: polymeric immunoglobulin receptor (pIgR) and platelet endothelial cell adhesion molecule (PECAM-1). We show that the major adhesin of the pneumococcal pilus-1, RrgA, binds both receptors, whereas the choline binding protein PspC binds, but to a lower extent, only pIgR. Using a bacteremia-derived meningitis model and mutant mice, as well as antibodies against the two receptors, we prevent pneumococcal entry into the brain and meningitis development. By adding antibodies to antibiotic (ceftriaxone)-treated mice, we further reduce the bacterial burden in the brain. Our data suggest that inhibition of pIgR and PECAM-1 has the potential to prevent pneumococcal meningitis. The Rockefeller University Press 2017-06-05 /pmc/articles/PMC5461002/ /pubmed/28515075 http://dx.doi.org/10.1084/jem.20161668 Text en © 2017 Iovino et al. https://creativecommons.org/licenses/by/4.0/This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Research Articles Iovino, Federico Engelen-Lee, Joo-Yeon Brouwer, Matthijs van de Beek, Diederik van der Ende, Arie Valls Seron, Merche Mellroth, Peter Muschiol, Sandra Bergstrand, Jan Widengren, Jerker Henriques-Normark, Birgitta pIgR and PECAM-1 bind to pneumococcal adhesins RrgA and PspC mediating bacterial brain invasion |
title | pIgR and PECAM-1 bind to pneumococcal adhesins RrgA and PspC mediating bacterial brain invasion |
title_full | pIgR and PECAM-1 bind to pneumococcal adhesins RrgA and PspC mediating bacterial brain invasion |
title_fullStr | pIgR and PECAM-1 bind to pneumococcal adhesins RrgA and PspC mediating bacterial brain invasion |
title_full_unstemmed | pIgR and PECAM-1 bind to pneumococcal adhesins RrgA and PspC mediating bacterial brain invasion |
title_short | pIgR and PECAM-1 bind to pneumococcal adhesins RrgA and PspC mediating bacterial brain invasion |
title_sort | pigr and pecam-1 bind to pneumococcal adhesins rrga and pspc mediating bacterial brain invasion |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5461002/ https://www.ncbi.nlm.nih.gov/pubmed/28515075 http://dx.doi.org/10.1084/jem.20161668 |
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