This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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[unreadable]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 failure to down-regulate 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. A publication in the journal Infection and Immunity resulted from this work.
NIH ExPorter
NIH ExPorter