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，文化和经济利益。自20世纪50年代以来，世界已经失去了大约一半的珊瑚礁覆盖面积，这归因于人为气候变化和疾病爆发等威胁。海洋温度的上升与珊瑚发病率和疾病爆发的增加有关。海洋细菌Vibrio coralliilyticus是一种病原体，感染许多种类的珊瑚，并导致漂白和组织损失以及其他疾病。这项研究的重点是了解促进V. coralliilyticus珊瑚定殖的信号线索，并使这种细菌能够超越宿主的保护性微生物组并引发珊瑚疾病。全面了解溶珊瑚弧菌的信号传导和毒力基因调控机制将有助于开发珊瑚病害的实用治疗方法。此外，了解引发疾病暴发的环境因素对于疾病管理和疾病暴发预测至关重要。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，其天然微生物组和微生物病原体。这三个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，促进教学，培训和不同群体的参与：印第安纳州大学的生物学暑期研究所、印第安纳州大学的科学节、特拉维夫大学的阿尔法项目以及科学、访问、信息，和多样性委员会在北卡罗来纳州威尔明顿大学。珊瑚领域有丰富的描述性观察疾病生态学和细菌分离的患病珊瑚。然而，缺乏详细的信息，驱动疾病的启动和珊瑚病原体对这些信号作出反应的分子机制的环境信号。细菌信号传导是致病机制的核心组成部分，弧菌是研究细菌群体感应控制毒力的中心模型。核心假设是群体感应信号和温度变化控制珊瑚的V. coralliilyticus致病所需的毒力基因。初步数据表明，毒力基因包括直接靶向宿主珊瑚细胞的毒素，通过杀死保护性天然微生物组和/或共生菌科内共生体间接影响宿主珊瑚的毒素，以及赋予解珊瑚弧菌对抗菌化合物的抗性的保护性基因。研究人员将测试群体感应，温度和宿主来源的信号如何影响体外和体内的毒力因子。前三个目标将确定和检查由三个主要细菌系统控制的毒力因子，这些系统对环境做出反应：1）V. coralliilyticus群体感应信号系统，2）毒素调节因子ToxR，3）VI型分泌系统。第四个目标将研究这些系统中的每一个如何影响活珊瑚感染模型及其微生物组中的珊瑚定殖和疾病进展。这项合作研究将大大有助于珊瑚发病机理领域，因为它将确定V. coralliilyticus毒力基因，毒力调节剂，和健身的菌株是有缺陷的毒力pathways.This奖项反映了NSF的法定使命，并已被认为是值得的支持，通过评估使用基金会的知识价值和更广泛的影响审查标准。

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.