REGULATION OF EXPRESSION OF ADHERENCE FACTORS

描述(改编自申请人的摘要)：产肠毒素 大肠埃希氏菌(ETEC)是导致婴儿和婴儿腹泻的主要原因 儿童和前往发展中国家的旅行者，包括军人 人事部。建立感染的第一步是附着 病原体感染宿主组织，据信是由菌毛(和/或 更薄、更灵活的纤维结构)。它的主要长期目标是 工作是理解菌毛合成的机制和 调节它们合成的机制。有限数量的血清学 从人类疾病中分离的ETEC菌株中流行的不同菌毛包括 由同源基因编码的一组，CS1是其原型。 研究人员发现，编码CS1的基因受到 RNS，与AraC同源。调查人员发现， RNS的自动激活涉及DNA区域的上游和下游 虽然这是史无前例的，但调查人员发现 许多与RNS相关的全球肠道毒力决定因素调控因子 病原体可以替代RNS，因此其作用类似。调查人员 希望进一步研究RNS和CS1菌毛的表达调控。 目的一是针对RNS的监管。在其他系统中，由 RNS相关蛋白，通常控制一个以上的毒力操纵子。 初步工作表明，ETEC似乎也是如此。 AIM II提议继续这项工作，希望找到其他 ETEC的毒力因素和更好地理解ETEC的病理 由ETEC引起的感染。研究人员发现，需要的基因 人ETEC菌毛的合成与其他菌毛的合成完全无关 和CS1菌毛似乎是简单得多的结构，所以似乎有可能一个 对它们的形态发生的详细了解是触手可及的。目标III和目标IV 这项提案的目的就是接近这一点。调查人员希望 这项工作将为人类抗ETEC的开发提供新的途径 疫苗和疗法，以及提供对蛋白质的更多了解 细菌中多蛋白质结构的相互作用和组装。

DESCRIPTION (Adapted from the Applicant's Abstract): Enterotoxigenic Escherichia coli (ETEC) are a major cause of diarrheal disease in infants and small children and in travelers to developing countries, including military personnel. 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 prevalent among ETEC strains isolated from human disease include a group encoded by homologous genes, for which CS1 serves as the prototype. The investigators found that the genes encoding CS1 are positively regulated by Rns, which shows homology to AraC. The investigators have found that autoactivation by Rns involves DNA regions both upstream and downstream of the regulated promoter.Although this is unprecedented, the investigators found that many Rns-related global regulators of virulence determinants of enteric pathogens can substitute for Rns and therefore act similarly. The investigators wish to study regulation of expression of Rns and of CS1 pili further. Aim I addresses the regulation of Rns. In other systems activated by a Rns-related protein, more than one virulence operon is usually controlled. Preliminary work indicates that this appears to be the case in ETEC as well. Aim II proposes to continue this work with the hope of identifying other virulence factors of ETEC and better understanding the pathology of the infections ETEC cause. The investigators have found that the genes needed for synthesis of human ETEC pili are completely unrelated to those of other pili and CS1 pili appear to be much simpler structures, so it seems possible that a detailed understanding of their morphogenesis is within reach. Aims III and IV of this proposal are directed at approaching this.The investigators hope that this work will suggest new approaches to development of human anti-ETEC vaccines and therapies, as well as providing a greater understanding of protein interaction and assembly of multi-protein structures in bacteria.