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

合作研究：NSF-BSF：细菌间和环境信号对珊瑚弧菌发病机制的影响

• 批准号: 2207168
• 负责人: Julia van Kessel
• 金额: $ 52.04万
• 依托单位: Indiana University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-15 至 2026-06-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2207168&HistoricalAwards=false
• 关键词: Collaborative; Research; NSF; BSF; Interbacterial

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.

珊瑚礁为 25% 的海洋鱼类和无脊椎动物提供了栖息地和营养物质，珊瑚礁不仅是一个重要的生态系统，而且还为当地提供了大量的生态、文化和经济效益。自 20 世纪 50 年代以来，珊瑚礁总覆盖率不断下降，这是由于人为气候变化和疾病爆发等威胁造成的。海洋温度升高与珊瑚疾病发病率和爆发有关。 Coralliilyticus 是一种感染多种珊瑚并导致珊瑚白化、组织损失和其他疾病的病原体，这项研究的重点是了解促进 Coralliilyticus 珊瑚定植的信号线索，并使这种细菌能够超越宿主的保护性微生物组并启动。对珊瑚弧菌信号传导和毒力基因调节机制的综合了解将有助于开发珊瑚疾病的应用治疗方法。爆发对于疾病管理和爆发预测至关重要。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：印第安纳大学生物学暑期学院、印第安纳大学科学节、特拉维夫大学阿尔法计划以及科学、获取、包容和多样性北卡罗来纳大学威尔明顿分校委员会。珊瑚领域对疾病生态学和从患病珊瑚中分离出的细菌进行了丰富的描述性观察，但是，缺乏详细说明驱动疾病发生的环境信号以及疾病产生的分子机制的信息。细菌信号传导是发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，其中心假设是群体感应信号传导和温度变化控制毒力基因。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、通过杀死保护性天然微生物组和/或共生体内共生体间接影响宿主珊瑚的毒素，以及赋予抗性的保护性基因。研究人员将在体外测试群体感应、温度和宿主来源信号毒力因子的影响。前三个目标将识别和检查由对环境做出反应的三个主要细菌系统控制的毒力因子：1）解珊瑚弧菌群体感应信号系统，2）毒素调节剂ToxR，以及3）类型。第四个目标将研究这些系统如何影响活珊瑚感染模型及其微生物组中的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，因为它将识别 V. Coralliilyticus 毒力基因、毒力调节剂以及毒力途径有缺陷的菌株的适应性。该奖项是 NSF 的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。