YagZ Pilus Adhesin of Attaching and Effacing E. coli

性状（由申请方提供）：肠致病性（EPEC）和肠出血性大肠杆菌。大肠埃希氏菌（EHEC）是世界公认的重要的肠道疾病病原体。它们统称为“依附与消隐”。大肠杆菌（AEEC），因为它们会引起剧烈的肠道病变，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EPEC粘附的粘附素显然是已知的（紧密素、形成纤毛的鞭毛和EspA纤维），但紧密素是EHEC中唯一识别的粘附素。对E. coli K-12和EHEC EDL 933中发现了几个假定的菌毛基因，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，其他尚未表征的粘附素必须存在。 我们发现AEEC菌株在37 ℃下产生宿主细胞可诱导的YagZ皮利，其由大肠杆菌中发现的yagZ基因编码的22 kDa蛋白组成。coli K-12和EHEC EDL 933。有明确的迹象表明，在AEEC中YagZ皮利的表达与严格的调控有关，并且可能与毒力基因调控有关，这是通过上皮细胞的存在来克服的。我们假设YagZ皮利是辅助粘附因子，有助于AEEC的粘附特性。这项建议的中心焦点在于功能调节生物发生的研究，将解决有关的问题，YagZ皮利粘附上皮细胞的作用，YagR和已知的毒力和全球regulators之间的复杂的监管相互作用。该项目的长期目标是提供分子基础，以促进对AEEC粘附和发病机制的认识，并为这些重要病原体引起的动物和人类感染的免疫预防策略奠定基础。 具体目标1：明确YagZ皮利在AEEC粘附中的作用 具体目标2。确定AEEC中YagZ菌毛调节的发生机制 具体目标3。确定AEEC中YagZ皮利生物发生的方式

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