REGULATION OF EXPRESSION OF ADHERENCE FACTORS

描述（改编自申请人的摘要）： 大肠杆菌（ETEC）是婴儿腹泻病的主要原因， 儿童和前往发展中国家的旅行者，包括军人 人员的建立感染的第一步是附着 病原体对宿主组织的作用，这被认为是由皮利介导的（和/或 更薄、更柔韧的纤维状结构）。其主要的长期目标是 我们的工作是了解皮利合成的机制， 调节其合成的机制。有限数量的血清学 从人类疾病中分离的ETEC菌株中流行的不同皮利包括 由同源基因编码的一组基因，以CS 1为原型。 研究人员发现，编码CS 1的基因受到 Rns，其显示与AraC同源。调查人员发现， Rns的自激活涉及DNA区域的上游和下游， 尽管这是前所未有的，但调查人员发现， 许多与Rns相关的肠道病毒毒力决定因子的全球调节因子 病原体可以替代Rns，因此作用类似。调查人员 希望进一步研究Rns和CS 1皮利的表达调控。 目标I涉及RNS的调节。在其他系统中， rns相关蛋白，通常有一个以上的毒力操纵子控制。 初步工作表明，ETEC似乎也是如此。 目标二建议继续开展这项工作，希望确定其他 ETEC的毒力因子，更好地了解 ETEC引起的感染。研究人员发现， 人ETEC皮利合成与其它皮利的合成完全无关 和CS 1皮利似乎是更简单的结构，所以似乎有可能是一个 对它们形态发生的详细了解是可以实现的。目标三和四 这项建议的目的是接近这一点。调查人员希望， 这项工作将为人类抗ETEC的开发提供新的方法 疫苗和治疗，以及提供更好的了解蛋白质 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.