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pIgR and PEC AM-1 bind to pneumococcal adhesins RrgA and PspC mediating bacterial brain invasion
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2017 (English)In: Journal of Experimental Medicine, ISSN 0022-1007, E-ISSN 1540-9538, Vol. 214, no 6, 1619-1630 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Rockefeller University Press, 2017. Vol. 214, no 6, 1619-1630 p.
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Clinical Medicine
Identifiers
URN: urn:nbn:se:kth:diva-210488DOI: 10.1084/jem.20161668ISI: 000402863300007PubMedID: 28515075OAI: oai:DiVA.org:kth-210488DiVA: diva2:1120069
Funder
Knut and Alice Wallenberg FoundationSwedish Research CouncilSwedish Foundation for Strategic Research Stockholm County Council
Note

QC 20170705

Available from: 2017-07-05 Created: 2017-07-05 Last updated: 2017-07-05Bibliographically approved

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Bergstrand, JanWidengren, Jerker

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Experimental Biomolecular Physics
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