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Infect. Immun. doi:10.1128/IAI.00387-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Immune Evasion Failure by Linear Plasmid 28-1-Deficient Borrelia burgdorferi is Attributable to Persistent Expression of an Outer Surface Protein

Divisions of Bacteriology and Parasitology, Comparative Pathology, and Veterinary Medicine, Tulane National Primate Research Center, Tulane University Health Sciences Center, Covington, LA,

^* To whom correspondence should be addressed. Email: Philipp{at}tpc.tulane.edu.

	Abstract

Infectivity and persistence by Borrelia burgdorferi, the etiologic agent of Lyme disease, relies stringently on regulatory events. Among these is the down-regulation of lipoprotein antigen expression, exemplified by outer surface protein C (OspC), at the advent of specific immunity in the mammalian host. B. burgdorferi spirochetes that lack the linear plasmid (lp) 28-1 succumb to the host's immune response. We thus explored the notion that these two phenomena were related—that lp28-1(-) organisms fail to down-regulate ospC and thus are cleared following the appearance of anti-OspC antibody in the murine host. The lp-28-1(-) isolate and a plasmid-complete wild type (wt) isolate were grown in dialysis membrane chambers that were implanted into rat peritoneal cavities. Analysis of mRNA and protein from these cultures showed that OspC expression levels by lp28-1(-) organisms are abnormally high in vivo. A time-course analysis of ospC expression in tissues following infection indicates also that temporal diminution of the dominant antigen OspC is impaired in lp28-1(-) spirochetes. Finally, passive transfer of monoclonal OspC-specific antibody into severe combined immune-deficient (SCID) mice 8 days post-infection cleared lp28-1 (-) spirochetes, yet the wild type organisms persisted in a majority of animals. These findings indicate that incomplete repression of OspC by lp28-1(-) organisms render them susceptible to immune-mediated clearance. The lp28-1 plasmid must harbor one or more genes involved in OspC down-regulation.