Structure-function investigation of vsp serotypes of the spirochete Borrelia hermsii.
BACKGROUND
Relapsing fever (RF) spirochetes are notable for multiphasic antigenic variation of polymorphic outer membrane lipoproteins, a phenomenon responsible for immune evasion. An additional role in tissue localization is suggested by the finding that isogenic serotypes 1 (Bt1) and 2 (Bt2) of the RF spirochete Borrelia turicatae, which differ only in the Vsp they express, exhibit marked differences in clinical disease severity and tissue localization during infection.


RESULTS
Here we used known vsp DNA sequences encoding for B. turicatae and Borrelia hermsii Vsp proteins with variable regions and then studied whether there are differences in disease expression and tissue localization of their corresponding serotypes during mouse infection. For sequence and structural comparisons we focused exclusively on amino acid residues predicted to project away from the spirochetes surface, referred to as the Vsp dome. Disease severity and tissue localization were studied during persistent infection with individual or mixed serotypes in SCID mice. The results showed that all Vsp domes clustered into 3 main trunks, with the domes for B. turicatae Vsp1 (BtVsp1) and BtVsp2 clustering into separate ones. B. hermsii serotypes whose Vsp domes clustered with the BtVsp1 dome were less virulent but localized to the brain more. The BtVsp2 dome was the oddball among all and Bt2 was the only serotype that caused severe arthritis.


CONCLUSIONS
These findings indicate that there is significant variability in Vsp dome structure, disease severity, and tissue localization among serotypes of B. hermsii.
Mehra
Rohit
R
Department of Neurology, Neuroscience and Center for Emerging Pathogens at UMDNJ-New Jersey Medical School, Newark, New Jersey, USA.
Londoño
Diana
D
Sondey
Marie
M
Lawson
Catherine
C
Cadavid
Diego
D
D000818:Animals; D000942:Antigens, Bacterial / Q000737:chemistry* / Q000235:genetics*; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry* / Q000235:genetics*; D001898:Borrelia / Q000378:metabolism*; D016000:Cluster Analysis; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D008968:Molecular Conformation; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D013144:Spirochaetales / Q000235:genetics / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014018:Tissue Distribution
D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D017931:DNA Primers; C121437:Vsp protein, bacterial