Endre søk
RefereraExporteraLink to record
Permanent link

Direct link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
pIgR and PEC AM-1 bind to pneumococcal adhesins RrgA and PspC mediating bacterial brain invasion
Vise andre og tillknytning
2017 (engelsk)Inngår i: Journal of Experimental Medicine, ISSN 0022-1007, E-ISSN 1540-9538, Vol. 214, nr 6, s. 1619-1630Artikkel i tidsskrift (Fagfellevurdert) 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.

sted, utgiver, år, opplag, sider
Rockefeller University Press, 2017. Vol. 214, nr 6, s. 1619-1630
HSV kategori
Identifikatorer
URN: urn:nbn:se:kth:diva-210488DOI: 10.1084/jem.20161668ISI: 000402863300007PubMedID: 28515075Scopus ID: 2-s2.0-85021856297OAI: oai:DiVA.org:kth-210488DiVA, id: diva2:1120069
Forskningsfinansiär
Knut and Alice Wallenberg FoundationSwedish Research CouncilSwedish Foundation for Strategic Research Stockholm County Council
Merknad

QC 20170705

Tilgjengelig fra: 2017-07-05 Laget: 2017-07-05 Sist oppdatert: 2019-04-04bibliografisk kontrollert
Inngår i avhandling
1. Super resolution fluorescence imaging: analyses, simulations and applications
Åpne denne publikasjonen i ny fane eller vindu >>Super resolution fluorescence imaging: analyses, simulations and applications
2019 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
Abstract [en]

Fluorescence methods offer extraordinary sensitivity and specificity, and are extensively used in the life sciences. In recent years, super resolution fluorescence imaging techniques have developed strongly, uniquely combining ~10 nm sub diffraction resolution and specific labeling with high efficiency. This thesis explores this potential, with a major focus on Stimulated Emission Depletion, STED, microscopy, applications thereof, image analyses and simulation studies. An additional theme in this thesis is development and use of single molecule fluorescence correlation spectroscopy, FCS, and related techniques, as tools to study dynamic processes at the molecular level. In paper I the proteins cytochrome-bo3 and ATP-synthase are studied with fluorescence cross-correlation spectroscopy, FCCS. These two proteins are a part of the energy conversion process in E. coli, converting ADP into ATP. We found that an increased interaction between these proteins, detected by FCCS, correlates with an increase in the ATP production. In paper II an FCS-based imaging method is developed, capable to determine absolute sizes of objects, smaller than the resolution limit of the microscope used. Combined with STED, this may open for studies of membrane nano-domains, such as those investigated by simulations in paper VII. In paper III and paper IV super resolution STED imaging was applied on Streptococcus Pneumoniae, revealing information about function and distribution of proteins involved in the defense mechanism of the bacteria, as well as their role in bacterial meningitis. In paper V, we used STED imaging to investigate protein distributions in platelets. We then found that the adhesion protein P-selectin changes its distribution pattern in platelets incubated with tumor cells, and with machine learning algorithms and classical image analysis of the STED images it is possible to automatically distinguish such platelets from platelets activated by other means. This could provide a strategy for minimally invasive diagnostics of early cancer development, and deeper understanding of the role of platelets in cancer development. Finally, this thesis presents Monte-Carlo simulations of biological processes and their monitoring by FCS. In paper VI, a combination of FCCS and simulations was applied to resolve the interactions between a transcription factor (p53) and an oncoprotein (MDM2) inside live cells. In paper VII, the feasibility of FCS techniques for studying nano-domains in membranes is investigated purely by simulations, identifying the conditions under which such nano-domains would be possible to detect by FCS. In paper VIII, proton exchange dynamics at biological membranes were simulated in a model, verifying experimental FCS data and identifying fundamental mechanisms by which membranes mediate proton exchange on a local (~10nm) scale.

sted, utgiver, år, opplag, sider
KTH Royal Institute of Technology, 2019. s. 81
Serie
TRITA-SCI-FOU ; 2019:20
HSV kategori
Forskningsprogram
Fysik
Identifikatorer
urn:nbn:se:kth:diva-248297 (URN)978-91-7873-171-8 (ISBN)
Disputas
2019-04-26, FA32, KTH, Roslagstullsbacken 21, Stockholm, 18:22 (engelsk)
Opponent
Veileder
Merknad

QC 20190405

Tilgjengelig fra: 2019-04-05 Laget: 2019-04-04 Sist oppdatert: 2019-04-05bibliografisk kontrollert

Open Access i DiVA

Fulltekst mangler i DiVA

Andre lenker

Forlagets fulltekstPubMedScopus

Søk i DiVA

Av forfatter/redaktør
Bergstrand, JanWidengren, Jerker
Av organisasjonen
I samme tidsskrift
Journal of Experimental Medicine

Søk utenfor DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric

doi
pubmed
urn-nbn
Totalt: 179 treff
RefereraExporteraLink to record
Permanent link

Direct link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf