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

从鱼群、鸟群到细菌群，集体行为是生命系统的一个共同特征。集体行为可能有助于种群的生存。然而，人们对集体行为究竟是如何编排的仍知之甚少。细菌有助于高等生物的功能和健康，如植物、动物和人类。某些细菌集体移动的能力促进了它们的宿主的定居。这个项目将调查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种群成员用作信号。该项目还将调查这些化学物质是否对寄主殖民很重要。在这些研究中将使用细菌-海绵模型。海绵是最古老的动物之一，是全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。具体地说，科学研讨会将为一个课外项目设计和开展，该项目服务于伊利诺伊大学芝加哥分校附近一个以西语裔和非裔美国人为主的社区的6-8年级学生。这些研讨会的主要目标将是通过展示细菌是地球上生命的重要组成部分，以及化学物质如何被用作允许细菌相互交流以及与高等有机体交流的语言形式，让中学生参与科学研究。关于细菌的运动和宿主的相互作用，还有许多问题需要回答。一个关键的问题是，哪些专门的代谢物调节了这些过程，以及它们是如何做到这一点的。细菌的运动性与一个保守的非核糖体多肽合成酶(NRPS)基因簇家族之间存在联系，该家族编码可能分泌的修饰多肽。NRPS基因簇家族分别保守于假弧菌属和假单胞菌属的α-和γ-变形杆菌中，已知它们与真核宿主如海洋海绵(假弧菌)、植物和昆虫(假单胞菌)建立了有益和拮抗的相互作用。在巴西假弧菌中，这个基因簇的失活会损害群体和游泳运动。据推测，非核糖体肽作为以前未知的信号分子发挥作用，促进运动性，提高存活率和使宿主定植。在该项目的工作期间，将整合突变、转录、结构、成像、相对适合度和宿主定植研究，以假弧菌-海绵相互作用为模型来揭示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。该项目预计将阐明变形杆菌用来协调运动和定植真核宿主的保守机制，最终扩大目前对单细胞生物体集体行为和原核生物-真核生物相互作用的了解。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.