This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Infectivity and persistence by Borrelia burgdorferi 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. 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 relatedthat lp28-1(-) organisms failed to down-regulate OspC and thus succumbed to the appearance of anti-OspC antibody. The lp-28(-) and wild type isolates were grown for either 8 or 14 days 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 implies also that temporal diminution of the dominant antigen OspC is impaired in lp28-1(-) spirochetes. Finally, passive transfer of anti-OspC monoclonal antibodies into scid mice 8 days post-infection cleared lp28-1 spirochetes, yet the wild type organisms persisted. 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 mediating OspC down-regulation.
Showing the most recent 10 out of 352 publications
