公开(公告)号：US20030045702A1

公开(公告)日：2003-03-06

申请号：US10014670

申请日：2001-12-14

申请人： INSTITUT PASTEUR

发明人： Agathe Subtil ,  Claude Parsot ,  Alice Dautry-Varsat

IPC分类号： A61K039/02 ,  C07H021/04 ,  C12N001/21 ,  C12P021/02 ,  C07K014/295

CPC分类号： C07K14/295 ,  A61K39/00

摘要： Chlamydia spp. are strictly intracellular pathogens that grow inside a vacuole, called an inclusion. They possess genes encoding proteins homologous to components of type III secretion machineries which, in other bacterial pathogens, are involved in delivery of bacterial proteins within or through the membrane of eukaryotic host cells. Inc proteins are chlamydial proteins that are associated with the membrane of the inclusion and are characterized by the presence of a large hydrophobic domain in their amino acid sequence. To investigate whether some Chlamydia proteins, especially Inc proteins and other proteins exhibiting a similar hydropathic profile, might be secreted, the inventors used an heterologous secretion system, namely a type III system. Chimeras were constructed by fusing the N-terminal part of these proteins with a reporter, the Cya protein of Bordetella pertussis, and expressed in various strains of Shigella flexneri. The inventors demonstrate that these hybrid proteins are secreted by the type III secretion system of S. flexneri. Moreover, the inventors show that three other proteins from C. pneumoniae, all of which have in common the presence of a large hydrophobic domain, are also secreted by S. flexneri type III secretion machinery.

摘要翻译： 衣原体属 是严格细胞内的病原体，在液泡内生长，称为包涵体。 它们具有编码与III型分泌机制的组分同源的蛋白质的基因，其在其它细菌病原体中涉及在真核宿主细胞的膜内或通过真核宿主细胞的膜中递送细菌蛋白质。 Inc蛋白是与包涵体膜相关的衣原体蛋白，其特征在于在其氨基酸序列中存在大的疏水结构域。 为了研究是否可能分泌某些衣原体蛋白，特别是Inc蛋白质和其他表现出类似亲水性谱的蛋白质，本发明人使用异源分泌系统，即III型系统。 嵌合体通过将这些蛋白质的N末端部分与报告基因（百日咳博德特氏菌的Cya蛋白质）融合并在各种不同的志贺氏菌属菌株中表达来构建。 本发明人证明这些杂交蛋白质是由柔毛氏菌的III型分泌系统分泌的。 此外，本发明人表明，来自肺炎克雷伯杆菌的三种其它蛋白质都具有大的疏水结构域的共同作用，也由S.perflexi III型分泌机制分泌。