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Infection and Immunity, March 2000, p. 1222-1230, Vol. 68, No. 3
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Borrelia burgdorferi Gene Expression In
Vivo and Spirochete Pathogenicity
Juan
Anguita,1
Swapna
Samanta,1
Beatriz
Revilla,1
Kyoungho
Suk,1,
Subrata
Das,1
Stephen W.
Barthold,2 and
Erol
Fikrig1,*
Section of Rheumatology, Department of
Internal Medicine, Yale University School of Medicine, New Haven,
Connecticut 06520,1 and Center for
Comparative Medicine, Schools of Medicine and Veterinary Medicine,
University of California at Davis, Davis, California
956162
Received 13 October 1999/Returned for modification 19 November
1999/Accepted 30 November 1999
Borrelia burgdorferi spirochetes that do not cause
arthritis or carditis were developed and used to investigate Lyme
disease pathogenesis. A clonal isolate of B. burgdorferi
N40 (cN40), which induces disease in C3H/HeN (C3H) mice, was repeatedly
passaged in vitro to generate nonpathogenic spirochetes. The passage 75 isolate (N40-75) was infectious for C3H mice but did not cause arthritis or carditis, and spirochetes were at low levels or absent in
the joints or hearts, respectively. N40-75 could, however, cause
disease in severe combined immunodeficient (SCID) mice, suggesting that
the response in immunocompetent mice prevented effective spirochete
dissemination and the subsequent development of arthritis and carditis.
Administration of immune sera at 4 days after spirochete challenge
aborted N40-75, but not cN40, infection in SCID mice. A B. burgdorferi genomic expression library was differentially probed
with sera from cN40- and N40-75-infected mice, to identify genes that
may not be effectively expressed by N40-75 in vivo. N40-75 was
defective in the up-regulation of several genes that are preferentially
expressed during mammalian infection, including dbpAB,
bba64, and genes that map to the cp32 family of plasmids.
These data suggest that adaptation and gene expression may be required
for B. burgdorferi to effectively colonize the host, evade
humoral responses, and cause disease.
*
Corresponding author. Mailing address: 608 Laboratory
of Clinical Investigation, Section of Rheumatology, Department of
Internal Medicine, Yale University School of Medicine, 333 Cedar St.,
New Haven, CT 06520-8031. Phone: (203) 785-2453. Fax: (203) 785-7053. E-mail: ef6{at}emailmed.yale.edu.

Present address: Samsung Biomedical Research Institute, Clinical
Research Center, Seoul, South Korea 135-230.
Infection and Immunity, March 2000, p. 1222-1230, Vol. 68, No. 3
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
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