Borrelia burgdorferi basic membrane proteins A and B participate in the genesis of Lyme arthritis.
Lyme arthritis results from colonization of joints by Borrelia burgdorferi and the ensuing host response. Using gene array-based differential analysis of B. burgdorferi gene expression and quantitative reverse trancription-polymerase chain reaction, we identified two paralogous spirochete genes, bmpA and bmpB, that are preferentially up-regulated in mouse joints compared with other organs. Transfer of affinity-purified antibodies against either BmpA or BmpB into B. burgdorferi-infected mice selectively reduced spirochete numbers and inflammation in the joints. B. burgdorferi lacking bmpA/B were therefore generated to further explore the role of these proteins in the pathogenesis of Lyme disease. B. burgdorferi lacking bmpA/B were infectious in mice, but unable to persist in the joints, and they failed to induce severe arthritis. Complementation of the mutant spirochetes with a wild-type copy of the bmpA and bmpB genes partially restored the original phenotype. These data delineate a role for differentially produced B. burgdorferi antigens in spirochete colonization of mouse joints, and suggest new strategies for the treatment of Lyme arthritis.
Pal
Utpal
U
Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
Wang
Penghua
P
Bao
Fukai
F
Yang
Xiuli
X
Samanta
Swapna
S
Schoen
Robert
R
Wormser
Gary P
GP
Schwartz
Ira
I
Fikrig
Erol
E
D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology*; D025065:Borrelia burgdorferi / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D005816:Genetic Complementation Test; D007249:Inflammation; D008193:Lyme Disease / Q000382:microbiology*; D051379:Mice; D008809:Mice, Inbred C3H; D016366:Open Reading Frames; D010641:Phenotype; D016133:Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013144:Spirochaetales / Q000378:metabolism; D013987:Ticks
D001426:Bacterial Proteins; C501736:BmpB protein, Borrelia burgdorferi; C088728:P39 antigen, Borrelia burgdorferi