Interaction of variable bacterial outer membrane lipoproteins with brain endothelium

Gaurav Gandhi, Diana Londoño, Christine R. Whetstine, Nilay Sethi, Kwang Sik Kim, Wolfram R. Zückert, Diego Cadavid

Research output: Contribution to journalArticle

Abstract

Background: Previously we reported that the variable outer membrane lipoprotein Vsp1 from the relapsing fever spirochete Borrelia turicatae disseminates from blood to brain better than the closely related Vsp2 [1]. Here we studied the interaction between Vsp1 and Vsp2 with brain endothelium in more detail.Methodology/Principal Findings: We compared Vsp1 to Vsp2 using human brain microvascular endothelial cell (HBMEC) association assays with aminoacid radiolabeled Vsp-expressing clones of recombinant Borrelia burgdorferi and lanthanidelabeled purified lipidated Vsp1 (LVsp1) and Vsp2 (LVsp2) and inoculations of the lanthanide-labeled proteins into mice. The results showed that heterologous expression of LVsp1 or LVsp2 in B. burgdorferi increased its association with HBMEC to a similar degree. Purified lanthanide-labeled lipidated Vsp1 (LVsp1) and LVsp2 by themselves were capable of associating with HBMEC. The association of LVsp1 with brain endothelium was time-dependent, saturable, and required the lipidation. The association of Vsp1 with HBMEC was inhibited by incubation at lower temperature or with excess unlabeled LVsp1 or LVsp2 but not with excess rVsp1 or mouse albumin or an anti Vsp1 monoclonal antibody. The association of LVsp2 with HBMEC and its movement from blood to brain parenchyma significantly increased in the presence of LVsp1.Conclusions/Significance: Variable bacterial outer membrane lipoproteins interact with brain endothelium differently; the lipidation and variable features at the protein dome region are key modulators of this interaction.

Original languageEnglish (US)
Article numbere13257
JournalPLoS One
Volume5
Issue number10
DOIs
StatePublished - 2010

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Bacterial Outer Membrane Proteins
endothelium
lipoproteins
Endothelium
Brain
brain
Endothelial cells
endothelial cells
Endothelial Cells
Association reactions
Lanthanoid Series Elements
rare earth elements
Borrelia burgdorferi
Borrelia turicatae
Blood
Relapsing Fever
Borrelia
Spirochaetales
blood
mice

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Gandhi, G., Londoño, D., Whetstine, C. R., Sethi, N., Kim, K. S., Zückert, W. R., & Cadavid, D. (2010). Interaction of variable bacterial outer membrane lipoproteins with brain endothelium. PLoS One, 5(10), [e13257]. https://doi.org/10.1371/journal.pone.0013257

Interaction of variable bacterial outer membrane lipoproteins with brain endothelium. / Gandhi, Gaurav; Londoño, Diana; Whetstine, Christine R.; Sethi, Nilay; Kim, Kwang Sik; Zückert, Wolfram R.; Cadavid, Diego.

In: PLoS One, Vol. 5, No. 10, e13257, 2010.

Research output: Contribution to journalArticle

Gandhi, G, Londoño, D, Whetstine, CR, Sethi, N, Kim, KS, Zückert, WR & Cadavid, D 2010, 'Interaction of variable bacterial outer membrane lipoproteins with brain endothelium', PLoS One, vol. 5, no. 10, e13257. https://doi.org/10.1371/journal.pone.0013257
Gandhi, Gaurav ; Londoño, Diana ; Whetstine, Christine R. ; Sethi, Nilay ; Kim, Kwang Sik ; Zückert, Wolfram R. ; Cadavid, Diego. / Interaction of variable bacterial outer membrane lipoproteins with brain endothelium. In: PLoS One. 2010 ; Vol. 5, No. 10.
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