YagZ Pilus Adhesin of Attaching and Effacing E. coli

YagZ 菌毛粘附素对大肠杆菌的附着和消除作用

• 批准号: 7106096
• 负责人: JORGE A GIRON
• 金额: $ 33.42万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7106096
• 关键词: adhesin; clinical research; pilus; role; virulence

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

描述（由申请人提供）：肠病原性（EPEC）和肠出血性大肠杆菌（EHEC）被认为是全世界肠道疾病的重要病原学病原体。它们被统称为“附着和消灭大肠杆菌（AEEC）”，因为它们会引起严重的肠道损伤，从而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多种粘附素的参与。而粘附素则介导EPEC 的附着显然是已知的（intimin、形成束的菌毛、鞭毛和 EspA 纤维），intimin 是 EHEC 中唯一识别的粘附素。对大肠杆菌 K-12 和 EHEC EDL933 的基因组序列的分析揭示了几个假定的菌毛基因的存在，但它们在 AEEC 毒力方案中的作用很大程度上未知，这表明必须存在其他尚未表征的粘附素。 我们发现 AEEC 菌株在 37oC 时产生宿主细胞诱导型 YagZ 菌毛，该菌毛由 22 kDa 蛋白质组成，由大肠杆菌 K-12 和 EHEC EDL933 中发现的 yagZ 基因编码。有明确的迹象表明，AEEC 中 YagZ 菌毛的表达与严格的调控有关，并且可能与毒力基因调控有关，而上皮细胞的存在可以克服毒力基因调控。我们假设 YagZ 菌毛是有助于 AEEC 粘合性能的辅助粘附因子。该提案的中心重点在于功能调节生物发生研究，该研究将解决有关 YagZ 菌毛在粘附上皮细胞中的作用、YagR 与已知毒力和全局调节因子之间复杂的调节相互作用的问题。该项目的长期目标是提供分子基础，以增进对 AEEC 粘附和发病机制的了解，并为有关这些重要病原体引起的动物和人类感染的免疫预防的有趣策略奠定基础。 具体目标 1：确定 YagZ 菌毛在 AEEC 粘附中的作用 具体目标 2. 确定 AEEC 中 YagZ 菌毛调节如何发生 具体目标 3. 确定 AEEC 中 YagZ 菌毛生物发生如何发生