Role of a conserved gene cluster family in promoting motility behavior in proteobacteria and in mediating host interactions

保守基因簇家族在促进变形菌运动行为和介导宿主相互作用中的作用

• 批准号: 1917492
• 负责人: Alessandra Eustaquio
• 金额: $ 54.66万
• 依托单位: University of Illinois at Chicago
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-15 至 2024-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1917492&HistoricalAwards=false
• 关键词: Role; conserved; gene; cluster; family

Collective behavior is a common feature of living systems, from schools of fish and flocks of birds to swarms of bacteria. Collective behavior likely contributes to the survival of the population. However, precisely how collective behavior is orchestrated remains poorly understood. Bacteria contribute to the function and health of higher organisms such as plants, animals, and humans. The ability of certain bacteria to move collectively facilitates colonization of their hosts. This project will investigate how certain bacteria coordinate their collective movement by releasing specific chemicals that are likely used as signals by the members of the population. This project will also investigate whether these chemicals are important for host colonization. A bacteria-marine sponge model will be used in these studies. Marine sponges are among the most ancient animals and are a dominant component of oceans worldwide. Work on this project will facilitate training new scientists because it will involve undergraduate and graduate students. This project will also encompass a major outreach effort. Specifically, science workshops will be designed and conducted for an after school program which serves students grades 6-8 in a predominantly Hispanic and African-American neighborhood next to the University of Illinois at Chicago campus. The main objective of the workshops will be to engage middle school students in scientific research by illustrating how bacteria are an essential part of life on Earth and how chemicals are used as a form of language that allows bacteria to communicate with each other and with higher organisms. Many questions remain to be answered regarding bacterial motility and host interaction. One key question is which specialized metabolites mediate these processes and how they do so. A link was identified between bacterial motility and a conserved nonribosomal peptide synthetase (NRPS) gene cluster family which encodes modified peptides that are likely secreted. The NRPS gene cluster family is conserved in alpha- and gamma-Proteobacteria of the Pseudovibrio and Pseudomonas genera, respectively, which are known to establish beneficial and antagonistic interactions with eukaryotic hosts as diverse as marine sponges (Pseudovibrio), plants and insects (Pseudomonas). Inactivation of this gene cluster in Pseudovibrio brasiliensis impairs swarming and swimming motility. It is hypothesized that the nonribosomal peptides function as previously unknown signaling molecules to promote motility, improving survival and enabling host colonization. During work on the project, mutational, transcriptomic, structural, imaging, relative fitness, and host colonization studies will be integrated to unravel the role of the NRPS gene cluster family using the Pseudovibrio-marine sponge interaction as a model. In addition, mutational, structural, and imaging studies will also be performed with representative Pseudomonas spp. This project is expected to shed light on the conserved mechanisms that Proteobacteria employ to coordinate motility and to colonize eukaryotic hosts, ultimately expanding current knowledge of collective behavior of single cell organisms and of prokaryote-eukaryote interactions.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

从鱼群、鸟群到细菌群，集体行为是生命系统的共同特征。集体行为可能有助于种群的生存。然而，集体行为究竟是如何被精心策划的，人们仍然知之甚少。细菌有助于植物、动物和人类等高等生物的功能和健康。某些细菌集体移动的能力有利于其宿主的定植。这个项目将研究某些细菌如何通过释放特定的化学物质来协调它们的集体运动，这些化学物质可能被群体成员用作信号。该项目还将调查这些化学物质对宿主定植是否重要。这些研究将使用细菌-海洋海绵模型。海洋海绵是最古老的动物之一，是世界海洋的主要组成部分。这个项目的工作将有助于培养新的科学家，因为它将涉及本科生和研究生。该项目还将包括一项重大的外联工作。具体来说，科学研讨会将为伊利诺斯大学芝加哥校区附近一个以西班牙裔和非裔美国人为主的社区的6-8年级学生设计和实施课后项目。讲习班的主要目的是通过说明细菌如何成为地球上生命的重要组成部分，以及化学物质如何被用作一种语言形式，使细菌能够相互交流，并与高等生物交流，从而使中学生参与科学研究。关于细菌运动和宿主相互作用的许多问题仍有待回答。一个关键的问题是，哪些专门的代谢物介导了这些过程，以及它们是如何做到的。细菌运动与保守的非核糖体肽合成酶（NRPS）基因簇家族之间存在联系，该基因簇家族编码可能分泌的修饰肽。NRPS基因簇家族分别在α -和γ -变形菌属的假弧菌和假单胞菌属中保守，已知它们与各种真核宿主如海洋海绵（假弧菌）、植物和昆虫（假单胞菌）建立有益和拮抗相互作用。该基因簇在巴西假弧菌中的失活会损害群集和游泳运动。据推测，非核糖体肽作为以前未知的信号分子起着促进运动、改善生存和使宿主定植的作用。在项目工作期间，将整合突变、转录组学、结构、成像、相对适应度和宿主定植研究，以假弧菌-海绵相互作用为模型，揭示NRPS基因簇家族的作用。此外，还将对具有代表性的假单胞菌进行突变、结构和成像研究。该项目有望揭示变形杆菌用于协调运动和定殖真核宿主的保守机制，最终扩展当前对单细胞生物集体行为和原核-真核生物相互作用的了解。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。