Collaborative Research: NSF-BSF: Interbacterial and environmental signaling impacts on Vibrio coralliilyticus pathogenesis of coral

造礁珊瑚为25%的海洋鱼类和无脊椎动物提供栖息地和营养。珊瑚礁不仅是一个重要的生态系统，而且还为当地提供了许多生态、文化和经济效益。自20世纪50年代以来，由于人为气候变化和疾病爆发等威胁，世界上已经失去了大约一半的珊瑚礁覆盖面积。海洋温度的升高与珊瑚疾病发病率和爆发的增加有关。海洋细菌珊瑚弧菌是一种病原体，可以感染许多种类的珊瑚，导致珊瑚白化、组织丧失和其他疾病。本研究的重点是了解促进V. coralliilyticus珊瑚定植的信号信号，并使这种细菌能够超越宿主的保护性微生物群并在珊瑚中引发疾病。综合了解珊瑚弧菌的信号和调控毒力基因的机制将有助于开发珊瑚病的应用治疗方法。此外，了解引发疫情的环境因素对于疾病管理和疫情预测至关重要。这里提出的工作还旨在向社区展示全球变暖如何影响珊瑚，它们的天然微生物群和微生物病原体。这三家研究机构将共同参与四个项目/委员会，以扩大科学发现的传播，促进不同群体的教学、培训和参与：印第安纳大学的生物暑期研究所、印第安纳大学的科学节、特拉维夫大学的阿尔法项目，以及北卡罗来纳大学威尔明顿分校的科学、准入、包容和多样性委员会。珊瑚领域对疾病生态学和从患病珊瑚中分离出来的细菌有丰富的描述性观察。然而，目前还缺乏详细的信息，说明驱动疾病启动的环境信号和珊瑚病原体对这些信号作出反应的分子机制。细菌信号是致病机制的核心组成部分，而弧菌是研究群体感应控制毒力的核心模型。核心假设是群体感应信号和温度变化控制珊瑚弧菌致病所需的毒力基因。初步数据表明，毒力基因包括直接针对宿主珊瑚细胞的毒素，通过杀死具有保护作用的天然微生物组和/或共生科内共生体间接影响宿主珊瑚的毒素，以及赋予珊瑚弧菌对抗菌化合物的抗性的保护基因。研究人员将测试群体感应、温度和宿主来源的信号如何在体外和体内影响毒力因子。前三个目标将确定和检查由三种主要细菌系统控制的毒力因子，这些系统对环境作出反应：1)珊瑚弧菌群体感应信号系统，2)毒素调节剂ToxR，以及3)VI型分泌系统。第四个目标将研究这些系统如何在活珊瑚感染模型及其微生物组中影响珊瑚定植和疾病进展。这项合作研究将对珊瑚发病机制领域做出重大贡献，因为它将确定珊瑚弧菌的毒力基因、毒力调节因子以及在毒力途径中有缺陷的菌株的适应性。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。

Reef-building corals provide habitats and nutrients for 25% of marine fish and invertebrates. Not only are coral reefs a critical ecosystem, but they also provide local areas with numerous ecological, cultural, and economic benefits. The world has lost about half of its total coral reef cover since the 1950s, which is attributed to threats like anthropogenic climate change and disease outbreaks. Increasing ocean temperatures correlates with increased disease incidence and outbreaks in coral. The marine bacterium Vibrio coralliilyticus is a pathogen that infects numerous species of coral and causes bleaching and tissue loss and other diseases. The focus of this research is to understand the signaling cues that promote V. coralliilyticus coral colonization and enable this bacterium to overtake the host’s protective microbiome and initiate disease in coral. An integrated understanding of V. coralliilyticus signaling and mechanisms of regulating virulence genes will contribute to the development of applied treatments for coral disease. Further, understanding the environmental cues that trigger outbreaks will be critical for disease management and prediction of outbreaks. The work proposed here also aims to demonstrate to the community how global warming affects coral, their natural microbiomes, and microbial pathogens. The three research institutions will collectively participate in four programs/committees to broaden dissemination of scientific discoveries and promote teaching, training, and participation of diverse groups: the Biology Summer Institute at Indiana University, Science Fest at Indiana University, The Alpha Program at Tel Aviv University, and the Science, Access, iNclusion, and Diversity committee at University of North Carolina Wilmington.The coral field has a wealth of descriptive observations of disease ecology and the bacteria isolated from diseased coral. However, there is a dearth of information detailing the environmental signals that drive disease initiation and the molecular mechanisms employed by coral pathogens to respond to these signals. Bacterial signaling is a core component of pathogenesis, and Vibrio bacteria are central models for studying quorum sensing control of virulence. The central hypothesis is that quorum sensing signaling and temperature variations control virulence genes required for V. coralliilyticus pathogenesis of coral. Preliminary data suggest that virulence genes include toxins that directly target host coral cells, toxins that indirectly affect the host coral by killing the protective natural microbiome and/or the Symbiodiniaceae endosymbionts, and protective genes that confer resistance to V. coralliilyticus against antibacterial compounds. The researchers will test how quorum sensing, temperature, and host-derived signals affect virulence factors in vitro and in vivo. The first three objectives will identify and examine the virulence factors controlled by three primary bacterial systems that respond to the environment: 1) the V. coralliilyticus quorum sensing signaling system, 2) the toxin regulator ToxR, and 3) the type VI secretion system. The fourth objective will examine how each of these systems influence coral colonization and disease progression in a live coral infection model and its microbiome. This collaborative research will significantly contribute to the coral pathogenesis field because it will identify V. coralliilyticus virulence genes, virulence regulators, and the fitness of strains that are defective in virulence pathways.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.