YagZ Pilus Adhesin of Attaching and Effacing E. coli

描述(申请人提供)：肠道致病性(EPEC)和肠出血性大肠杆菌(EHEC)是世界范围内公认的肠道疾病的重要伦理病原体。它们被称为“附着和消除大肠杆菌(AEEC)”，因为它们会引起戏剧性的肠道损伤，导致肠道上皮的破坏。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EPEC的中介附着的粘附素是已知的(内膜、束状毛、鞭毛和Espa纤维)，但Intelin是EHEC中唯一被识别的粘附素。对E.ColiK-12和EHEC EDL933的基因组序列分析显示，存在几个假定的菌毛基因，它们在AEEC毒力机制中的作用很大程度上尚不清楚。这表明一定存在其他尚未确定特征的粘附素。 我们发现AEEC菌株在37℃时产生宿主细胞诱导的YagZ菌毛，该菌毛由在E.coliK-12和EHEC EDL933中发现的yagZ基因编码的22 kDa蛋白质组成。有明确的迹象表明，YagZ菌毛在AEEC中的表达与严格的调控有关，也可能与毒力基因调控有关，这种调控被上皮细胞的存在所克服。我们推测YagZ菌毛是影响AEEC黏附性能的辅助黏附因子。这一建议的中心焦点在于功能调节生物发生研究，这些研究将解决YagZ菌毛在黏附上皮细胞中的作用，YagR与已知毒力和全球再调节因子之间的复杂调控相互作用。该项目的长期目标是提供分子基础，促进对AEEC黏附机制和发病机制的了解，并为这些重要病原体引起的动物和人类感染的免疫预防方面的有趣策略奠定基础。 具体目标1：确定YagZ菌毛在AEEC黏附中的作用 具体目标2.确定YagZ菌毛调控在AEEC中是如何发生的 具体目的3.确定AEEC中YagZ菌毛的生物发生

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