dc.contributor.authorIovino, Federico
dc.contributor.authorEngelen-Lee, Joo-Yeon
dc.contributor.authorBrouwer, Matthijs
dc.contributor.authorvan de Beek, Diederik
dc.contributor.authorvan der Ende, Arie
dc.contributor.authorValls Seron, Merche
dc.contributor.authorMellroth, Peter
dc.contributor.authorMuschiol, Sandra
dc.contributor.authorBergstrand, Jan
dc.contributor.authorWidengren, Jerker
dc.contributor.authorHenriques-Normark, Birgitta
dc.identifier.citationIovino, F., Engelen-Lee, J.-Y., Brouwer, M., van de Beek, D., van der Ende, A., Valls Seron, M., et al. (2017). pIgR and PECAM-1 bind to pneumococcal adhesins RrgA and PspC mediating bacterial brain invasion. The Journal of Experimental Medicine, 214(6), 1619-1630.en_US
dc.description.abstractStreptococcus 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.en_US
dc.format.extent12 p.en_US
dc.relation.ispartofseriesThe Journal of Experimental Medicineen_US
dc.rights© 2017 The Author(s) (published by Rockefeller University Press (RUP)). This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).en_US
dc.subjectBacterial meningitisen_US
dc.subjectPneumococcal adhesinsen_US
dc.titlepIgR and PECAM-1 bind to pneumococcal adhesins RrgA and PspC mediating bacterial brain invasionen_US
dc.typeJournal Article
dc.contributor.schoolLee Kong Chian School of Medicine (LKCMedicine)en_US
dc.description.versionPublished versionen_US
dc.contributor.organizationSingapore Centre for Environmental Life Sciences Engineeringen_US

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