MECHANISM AND FUNCTION OF UNIPOLARITY OF SHIGELLA ICSA

志贺氏菌ICSA单极性的机制和作用

• 批准号: 6687733
• 负责人: Marcia B Goldberg
• 金额: $ 36.08万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-08-01 至 2004-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6687733
• 关键词: Shigella; actins; bacterial proteins; pathologic process; protein localization; protein protein interaction; protein structure function

DESCRIPTION (Adapted from the Applicant's Abstract): Shigella spp. continue to be a leading cause of dysentery and diarrhea annually worldwide. Shigella is unique among Gram-negative enteric pathogens in that it accesses the cytoplasm of host cells and assembles actin into long tails, which propel bacterial spread through tissues. The investigators have previously shown that the Shigella outer membrane protein IcsA is sufficient for actin assembly and that IcsA is localized to a single pole of the bacillus. The molecular mechanisms involved in the unipolar localization of IcsA are unknown. Their data demonstrate that IcsA is directly targeted to the bacterial pole. In conjunction with this, they have developed constructs that provide the tools necessary to directly address the molecular mechanisms of unipolar targeting of IcsA, a major goal of this proposal. In contrast, IcsA that is uniformly distributed over the surface of certain E. coli strains is able to mediate actin tail assembly without capping of the IcsA. This proposal also specifically addresses the function of unipolar localization of IcsA in Shigella pathogenesis, which they are now in a position to test critically. The Specific Aims of this proposal are: (1) the identification and characterization of residues and domains of IcsA required for its unipolar localization; (2) the identification of Shigella proteins that directly interact with IcsA and analysis of their potential role in IcsA unipolar localization; and (3) an assessment of the role of IcsA unipolarity in Shigella pathogenesis. This application proposes to obtain information that will provide insight into the molecular mechanisms of unipolar targeting of the S. flexneri virulence factor IcsA. Further, their studies will elucidate the role of IcsA unipolarity in the pathogenesis and virulence of Shigella. Finally, their studies will likely provide insight into the fundamental mechanisms that mediate three-dimensional targeting of proteins in bacteria and the molecular characteristics of the bacterial old pole that distinguish it from the new pole and the sides of the bacillus.

描述（改编自申请人摘要）：志贺氏菌属继续 是每年全球痢疾和腹泻的主要原因。志贺氏菌属 在革兰氏阴性肠道病原体中的独特之处在于它进入细胞质 并将肌动蛋白组装成长长的尾巴， 通过组织传播调查人员此前曾表示， 志贺氏菌外膜蛋白IcsA足以进行肌动蛋白组装， ICSA定位于芽孢杆菌的单极。的分子机制 参与IcsA单极定位的基因尚不清楚。他们的数据 证明IcsA直接靶向细菌极。在 与此同时，他们开发了提供工具的结构， 有必要直接解决单极靶向的分子机制， ICSA是该提案的一个主要目标。与此相反，IcsA是一致的， 分布在某些E.大肠杆菌菌株能够介导 肌动蛋白尾装配而不加帽的IcsA。该提案还 明确阐述了ICSA的单极定位在 志贺氏菌的致病机理，他们现在可以进行严格的测试。 该提案的具体目标是：（1）识别和 IcsA的单极所需的残基和结构域的表征 （2）志贺菌蛋白的鉴定， 与ICSA相互作用及其在ICSA单极化中潜在作用分析 定位;（3）评估IcsA单极在志贺氏菌中的作用 发病机制本申请旨在获取信息， 深入了解S.福氏 毒力因子IcsA。此外，他们的研究将阐明ICSA的作用， 志贺菌的致病性和毒力呈单极性。最后，他们 研究可能会提供对基本机制的深入了解， 介导细菌中蛋白质的三维靶向， 细菌旧极与新极的区别特征 和芽孢杆菌的侧面。