A PLASMID CONTROLLING DOWN-REGULATION OF THE CRUCIAL B BURGDORFERI OSPC PROTEIN

控制重要 B 布氏 OSPC 蛋白下调的质粒

• 批准号: 7716318
• 负责人: MONICA E EMBERS
• 金额: $ 2.41万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-21 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7716318
• 关键词: Antibodies; Antigens; Appearance; Borrelia burgdorferi; Computer Retrieval of Information on Scientific Projects Database; Dialysis procedure; Down-Regulation; Event; Failure; Funding; Genes; Grant; Greater sac of peritoneum; Immune; Immune response; Immunity; Implant; Infection; Institution; Lipoproteins; Mediating; Membrane; Messenger RNA; Monoclonal Antibodies; Mus; Order Spirochaetales; Organism; OspC protein; Physical Dialysis; Plasmids; Proteins; Rattus; Research; Research Personnel; Resources; Source; Time; Tissues; United States National Institutes of Health; day; in vivo

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 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.

这个子项目是众多研究子项目之一