Interaction of variable bacterial outer membrane lipoproteins with brain endothelium.
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.


RESULTS
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 lanthanide-labeled 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
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.
Department of Neurology and Neuroscience and Center for the Study of Emerging Pathogens, UMDNJ-New Jersey Medical School, Newark, New Jersey, USA.
Gaurav
G
Gandhi
Diana
D
Londoño
Christine R
CR
Whetstine
Nilay
N
Sethi
Kwang S
KS
Kim
Wolfram R
WR
Zückert
Diego
D
Cadavid
D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism*; D001483:Base Sequence; D001812:Blood-Brain Barrier; D025065:Borrelia burgdorferi / Q000378:metabolism; D001921:Brain / Q000098:blood supply / Q000378:metabolism*; D002478:Cells, Cultured; D017931:DNA Primers; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D008074:Lipoproteins / Q000378:metabolism*; D051379:Mice
D001425:Bacterial Outer Membrane Proteins; D017931:DNA Primers; D008074:Lipoproteins