REGULATION OF LIPOPROTEIN GENE EXPRESSION IN B BURGDORFERI : LYME DISEASE

伯氏疏螺旋体脂蛋白基因表达的调控：莱姆病

• 批准号: 6116194
• 负责人: MARIO TOMAS PHILIPP
• 金额: $ 10.15万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-05-01 至 2000-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6116194
• 关键词: Mammalia; biotechnology; communicable diseases; genome; immunology; inflammation; parasitism; vaccines

Objectives and Background The objective of this research is to increase our understanding of the mechanisms that regulate the expression of B. burgdorferi lipoproteins, a type of molecule that plays a key role in Lyme disease pathogenesis. We have already described the transcriptionally regulated differential levels of expression of two lipoproteins of Borrelia burgdorferi, P35 and P7.5, during growth of the spirochetes in culture from logarithmic phase to stationary phase (K. J. Indest, R. Ramamoorthy, M. Sole 4, R. D. Gilmore, B. J. B. Johnson, and M. T. Philipp, Infect. Immun. 65:1165?1171, 1997). Results We further assessed this phenomenon by investigating whether the expression of other antigens of B. burgdorferi, including some well-characterized ones, are also regulated in a growth-phase-dependent manner in vitro. These studies revealed 13 additional antigens, including OspC, BmpD, and GroEL, that were upregulated 2- to 66-fold and a 28-kDa protein that was downregulated 2- to 10-fold, during the interval between the logarithmic- and stationary-growth phases. Unlike with these in vitro-regulated proteins, the levels of expression of OspA, OspB, P72, flagellin, and BmpA remained unchanged throughout growth of the spirochetes in culture. Furthermore, ospAB, bmpAB, groEL, and fla all exhibited similar mRNA profiles, which is consistent with the constitutive expression of these genes. By contrast, the mRNA and protein profiles of ospC and bmpD indicated regulated expression of these genes. While bmpD exhibited a spike in mRNA expression in early stationary phase, ospC maintained a relatively higher level of mRNA throughout culture. These findings demonstrate that there are additional genes besides P7.5 and P35 whose regulated expression can be investigated in vitro and which may thus serve as models to facilitate the study of regulatory mechanisms in an organism that cycles between an arthropod and a vertebrate host. Future directions To further assess mechanisms of regulation of lipoprotein gene expression. FUNDING Base grant and NIH-NIAID F32 AI09980 PUBLICATIONS Ramamoorthy, R. and Philipp, M.T. 1998. Differential expression of Borrelia burgdorferi proteins during growth in vitro . Infection and Immunity. 66 5119?5124.

目的和背景本研究的目的是 提高我们对调节机制的理解， B的表达。Burgdorferi脂蛋白是一种分子， 在莱姆病发病机制中起关键作用。 我们已经 描述了转录调节的差异水平， 伯氏疏螺旋体的两种脂蛋白P35和P7.5的表达， 在螺旋体在培养物中从对数期到 固定相（K. 因德斯特河Ramamoorthy，M.索莱4河D. 吉尔摩，B。J. B.约翰逊和M. T.菲利普感染 Immun. 65：1165？1171，1997）。 结果我们进一步评估了这一现象， 检测B. burgdorferi，包括一些特征鲜明的，也是 在体外以生长阶段依赖性方式调节。 这些研究 揭示了另外13种抗原，包括OspC、BmpD和GroEL， 上调了2- 66倍，28-kDa的蛋白质， 下调2至10倍，在间隔之间的时间， 对数生长期和稳定生长期。 不像这些在 体外调节蛋白，OspA，OspB，P72， 鞭毛蛋白和BmpA在整个生长过程中保持不变， 培养中的螺旋体 此外，ospAB、bmpAB、groEL和弗拉均 表现出类似的mRNA谱，这与 这些基因的组成型表达。 相反，mRNA和 ospC和bmpD的蛋白质谱表明， 这些基因。 虽然bmpD在早期表达高峰， 稳定期，ospC维持相对较高的mRNA水平 整个文化。 这些发现表明， 除了P7.5和P35之外，其调节表达的其它基因可以 在体外进行研究，因此可以作为模型， 有助于研究生物体中的调节机制， 节肢动物和脊椎动物宿主之间的循环。 未来方向 进一步探讨脂蛋白基因的调控机制 表情 基金基础资助和NIH-NIAID F32 AI 09980出版物 拉马穆尔蒂河Philipp，M.T. 1998. 的差异表达 伯氏疏螺旋体体外生长过程中的蛋白质。 感染和 免疫力 665119？5124.