REGULATION OF EXPRESSION OF ADHERENCE FACTORS

描述（改编自研究者摘要）：肠毒素 大肠杆菌（ETEC）是婴儿腹泻病的主要原因 小孩子和旅行者。 建立的第一步 感染是病原体附着在宿主组织上， 据信是由皮利（和/或更薄、更柔韧的纤维 结构）。这项工作的主要长期目标是了解 合成皮利的机制和调节 他们的合成。 少数血清学上不同的皮利似乎是流行的 在从人类疾病中分离的ETEC菌株中。 其中包括CS 1和 CS2，在这个项目中研究，以及Cfa/I（这似乎是 相似，基于DNA序列），CS4和CS5。 合成人ETEC皮利所需的基因完全 与研究得较好的E. 大肠杆菌皮利样pap和1型。 CS 1皮利似乎简单得多 结构，所以似乎有可能详细了解他们的 形态发生就在眼前本提案的目标1和2是针对 接近这个。 (aim 1：表征CS 1皮利的形态发生 通过确定每个基因产物在菌毛组装和Aim中的作用， 2：表征菌毛组装和粘附中的蛋白质相互作用。 CS 1和CS2受Rns的正调控，其显示与 AraC，以及许多肠道病毒毒力决定因子的全球调节因子 病原体 一个Rns同系物似乎是必要的表达许多 不同血清学类型的ETEC皮利，以及其他ETEC的皮利 致泻性E.大肠杆菌菌株。目前的信息表明， Rns和Rns的表达调控是不寻常的，涉及DNA区域 调控启动子的上游和下游。 此外还 可能涉及一系列调节因素。 因为它可能 说明了基因控制新原理，而且因为它很可能 对细菌致病、调节CS 1的表达是重要的 对皮利作进一步分析。 (Aim 3：确定 rns和目标4的调节：研究CS 1的其他调节。） 皮利似乎是开发人抗ETEC的良好候选物 疫苗，因为它们有限的血清学变异性，以及 它们的表面定位和免疫原性， 皮利疫苗在预防腹泻病中的应用 动物 这项工作应有助于研制这种疫苗。

DESCRIPTION (adapted from investiators abstract): Enterotoxigenic Escherichia coli (ETEC) are a major cause of diarrheal disease in infants and small children and in travelers. The first step in establishment of infection is attachment of the pathogen to the host tissue, which is believed to be mediated by pili (and/or thinner, more flexible fibrillar structures). The major long-term goals of this work are to understand the mechanisms by which pili are synthesized and the mechanisms that regulate their synthesis. A limited number of serologically different pili appear to be prevelant among ETEC strains isolated from human disease. These include CS1 and CS2, studied in this project, as well as Cfa/I (which appears to be similar, based on DNA sequence), CS4 and CS5. The genes needed for synthesis of human ETEC pili are completely unrelated to those identified for morphogenesis of the better studied E. coli pili like pap and type 1. CS1 pili appear to be much simpler structures, so it seems possible that a detailed understanding of their morphogenesis is within reach. Aims 1 and 2 of this proposal are directed at approaching this. (aim 1: Characterize the morphogenesis of CS1 pili by determining the role of each gene product in pilus assembly and Aim 2: Characterize protein interactions in pilus assembly and adherence.) CS1 and CS2 are positively regulated by Rns, which shows homology to AraC, as do global regulators of virulence determinants of many enteric pathogens. A Rns homolog seems to be necessary for expression of many different serological types of ETEC pili, as well as pili of other diarrheagenic E. coli strains. Current information indicates that regulation of expression of and by Rns is unusual, involving DNA regions both upstream and downstream of the regulated promoter. In addition, it may involve a cascade of regulatory factors. Thus, because it may illustrate new principles of control of gene and because it is likely to be important for bacterial pathogenesis, regulation of expression of CS1 pili will be analyed further. (Aim 3: Determine the mechanism of regulation by rns and Aim 4: Investigate other regulation of CS1.) Pili appear to be good candidates for development of human anti-ETEC vaccines because of their limited serological variability, as well as their surface localiztion and immunogenicity, and because of the success of pili based vaccines in prevention of diarrheal diseases in domestic animals. This work should facilitate the development of such vaccines.