RUI: Aggregation and Colonization Mediated by Bacterial Surface Factors

RUI：细菌表面因素介导的聚集和定植

• 批准号: 1329248
• 负责人: Robert Fairman
• 金额: $ 53.62万
• 依托单位: Haverford College
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2018-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1329248&HistoricalAwards=false
• 关键词: RUI; Aggregation; Colonization; Mediated; Bacterial

Intellectual MeritBacteria that can colonize multi-cellular organisms live in or on their hosts as part of complex communities. They use specific surface proteins to adhere to one another, and to host cells, to form a stable community of bacteria that are not washed away. In this research, mentored undergraduate students, will identify and characterize protein colonization factors and determine how they interact with one another. Hra1 was previously described as a member of the agglutinin family of outer surface proteins which by self-association mediates adjacent bacterial cells to adhere to one another. Hra1 also mediates in vivo binding of Escherichia coli to eukaryotic cells and specifically promotes colonization of nematode worm intestines in small aggregates. There is preliminary evidence that suggests that a second protein, Aap, prevents Hra1 mediated interactions. The inhibitory activity of Aap provides a mechanism for restricting Hra1 mediated associations as bacteria travel towards their intestinal niche. Once bacteria reach a suitable niche however, Aap must be removed for colonization to ensue. This research, will determine the mechanism for Aap removal and thus how Hra1 and Aap work together to ensure that bacteria can bind and disperse in a manner that optimizes colonization of nematode intestines. The project will also identify new surface factors involved in intestinal colonization and determine how, if at all, they interact with known surface proteins. In addition to identifying proteins involved in binding among identical bacteria, the project will focus on uncovering surface proteins that allow different species of bacteria to interact with one another, as a first step to understanding community organization among the many types of bacteria living within a single multi-cellular organism. Broader Impact Bacteria are the most abundant life-forms on earth and colonize a wide variety of living and non-living niches by mechanisms that are not very well understood. This project will improve current understanding of how communities of bacteria are established and persist within other organisms, as well as add to knowledge on the structure and function of bacterial surface proteins. The research required to address questions relevant to this project will largely be performed by undergraduate students working at Haverford College and overseen by a principal investigator, who teaches there. The project will provide early opportunities for such students with the hope of increasing their interest and retention in science. Four to eight students, including women and other groups underrepresented in the sciences will be engaged in laboratory research projects each year. Several dozen other students will be enriched by course modules and classroom examples in courses that are developed and taught by the principal investigator. This includes 20-40 students who will participate in inquiry-based laboratory research courses each year that will expose them to skills in microbiology, molecular biology and computational science.

智力优势：作为复杂群落的一部分，可以在多细胞生物体内或宿主身上定居的细菌。它们利用特定的表面蛋白质相互粘附，并附着在宿主细胞上，形成一个稳定的细菌群落，不会被冲走。在这项研究中，指导本科生，将识别和表征蛋白质定植因子，并确定它们如何相互作用。Hra1先前被描述为外表面蛋白凝集素家族的成员，通过自结合介导邻近细菌细胞相互粘附。Hra1还介导大肠杆菌与真核细胞的体内结合，并特异性地促进线虫肠道小聚集体的定植。有初步证据表明，第二种蛋白Aap可以阻止Hra1介导的相互作用。Aap的抑制活性提供了一种机制，在细菌向肠道生态位移动时限制Hra1介导的关联。然而，一旦细菌到达一个合适的生态位，Aap必须被移除以进行定植。这项研究将确定Aap去除的机制，从而确定Hra1和Aap如何协同工作，以确保细菌能够以优化线虫肠道定植的方式结合和分散。该项目还将确定参与肠道定植的新表面因子，并确定它们如何（如果有的话）与已知表面蛋白相互作用。除了确定在相同的细菌之间参与结合的蛋白质外，该项目还将重点发现允许不同种类的细菌相互作用的表面蛋白质，作为了解生活在单个多细胞有机体内的多种细菌之间的社区组织的第一步。细菌是地球上最丰富的生命形式，它们以尚不清楚的机制寄居在各种各样的生物和非生物生态位上。该项目将提高目前对细菌群落如何在其他生物体中建立和持续存在的理解，并增加对细菌表面蛋白质结构和功能的了解。解决与本项目相关的问题所需的研究将主要由在哈弗福德学院工作的本科生完成，并由在该学院任教的首席研究员监督。该项目将为这些学生提供早期的机会，希望提高他们对科学的兴趣和记忆力。每年将有四到八名学生，包括妇女和其他在科学领域代表性不足的群体，参与实验室研究项目。其他几十名学生将通过由首席研究员开发和教授的课程模块和课堂实例得到丰富。这包括20-40名学生，他们每年将参加以探究为基础的实验室研究课程，这将使他们接触到微生物学、分子生物学和计算科学的技能。

项目成果

Self-association motifs in the enteroaggregative Escherichia coli heat-resistant agglutinin 1

• DOI: 10.1099/mic.0.000303
• 发表时间: 2016-07-01
• 期刊: MICROBIOLOGY-SGM
• 影响因子: 2.8
• 作者: Glaubman, Jessica;Hofmann, Jennifer;Okeke, Iruka N.
• 通讯作者: Okeke, Iruka N.