YagZ Pilus Adhesin of Attaching and Effacing E. coli

描述（由申请人提供）：肠致病性（EPEC）和肠出血性大肠杆菌（EHEC）被认为是世界范围内肠道疾病的重要病原体。它们被统称为“附消性大肠杆菌”（AEEC），因为它们会引起严重的肠道病变，导致肠道上皮细胞的破坏。细菌与宿主上皮细胞的相互作用需要几种粘附素的参与。虽然介导肠出血性大肠杆菌黏附的黏附素是已知的（内膜素、束形成毛、鞭毛和肠出血性大肠杆菌纤维），但内膜素是唯一在肠出血性大肠杆菌中被识别的黏附素。大肠杆菌K-12和肠出血性大肠杆菌EDL933的基因组序列分析揭示了几个假定的菌毛基因的存在，它们在AEEC毒力机制中的作用在很大程度上是未知的。这表明一定存在其他尚未表征的粘附素。

DESCRIPTION (provided by applicant): Enteropathogenic (EPEC) and enterohemorrhagic E. coli (EHEC) are recognized as important ethiologic agents of intestinal disease world-wide. They are collctively called "attaching and effacing E. coli (AEEC) because they cause dramatic intestinal lesions that lead to destruction of the gut epithelium. The interaction of the bacteria with host epithelial cells entails the participation of several adhesins. While the adhesins the mediate attachment of EPEC are apparently known (intimin, bundle-forming pilus, flagella and the EspA fiber), intimin is the only adhesin recognized in EHEC. The analysis of the genome sequence of E. coli K-12 and EHEC EDL933 reveals the presence of several putative fimbrial genes, for which their role in the virulence scheme of AEEC is largely unknown. This suggests that other yet uncharacterized adhesins must exist. We have discovered that AEEC strains produce host-cell inducible YagZ pili at 37oC, which are composed of 22 kDa-proteins encoded by the yagZ gene found in E. coli K-12 and EHEC EDL933. There is a clear indication that the expression of YagZ pili in AEEC is linked to a strict regulatory control, and perhaps to virulence gene regulation, which is overcome by the presence of epithelial cells. We hypothesize that YagZ pili are accessory adherence factors that contribute to the adhesive properties of AEEC. The central focus of this proposal lies in function-regulation-biogenesis studies that will address questions concerning the role of YagZ pili in adherence to epithelial cells, the complex regulatory interplay between YagR and the known virulence and global rergulators. The long-term objective of this project is provide the molecular bases to advance knowledge of AEEC mechanisms of adherence and pathogenesis, and to establish a ground for interesting strategies regarding immunoprophylaxis of animal and human infections caused by these important pathogens. Specific Aim 1: To define the role of YagZ pili in AEEC adhesion Specific Aim 2. To determine how YagZ pilus regulation occurs in AEEC Specific Aim 3. To determine how YagZ pili biogenesis occurs in AEEC