Collaborative Research: Using Transcriptomics to Understand Mechanisms of Stress Response and Toxin Production in Pathogenic and Toxigenic Microbes in Tropical Marine Waters

合作研究：利用转录组学了解热带海水中致病和产毒微生物的应激反应和毒素产生机制

• 批准号: 1129270
• 负责人: Alexandria Boehm
• 金额: $ 28.19万
• 依托单位: Stanford University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-15 至 2016-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1129270&HistoricalAwards=false
• 关键词: Collaborative; Research; Using; Transcriptomics; Understand

In this project an interdisciplinary research team from the University of Hawaii at Manoa, Stanford University, and Rutgers University will study the transcriptomes of Gambierdiscus, Staphylococcus aureus, and Enterococcus in Hawaiian coastal waters - toxin-producing species that pose significant health hazards to humans. Their goal is to elucidate the mechanisms associated with toxin production by Gambierdiscus and inactivation by sunlight of the bacterial pathogen, S. aureus, and the fecal indicator, Enterococcus. Because the transcriptome of an organism reflects the genes that are actively being expressed at any given time, this study, by elucidating levels of messenger RNA expression in the target organisms, should provide valuable insights into the mechanisms responsible for toxin production, responses to stress and/or subsequent bacterial inactivation. The research program will be organized around four working hypotheses: H1: Production of ciguatoxin by Gambierdiscus reflects the physiological condition of the culture as influenced by temperature, irradiance, and growth phase. H2: High throughput transcriptome analysis from toxin (+) and toxin (-) cultures will allow the identification of genes involved in ciguatoxin production and understanding of the light and nutrient conditions that favor this function. H3: Whereas E. faecalis is susceptible to indirect photoinactivation under exposure to sunlight in seawater, S. aureus is not. This is likely due to the presence of carotenoid pigments within the cells, which are able to quench reactive oxygen species. H4: E. faecalis and S. aureus respond to photo-stress in clear seawater by up-regulating genes that encode for proteins to repair cellular damage and mitigate oxidative stress; this "stressome" will change with increasing exposure to photostress, revealing the stress at which repair is no longer possible. Broader Impacts: The information that will be gathered in this study is expected to contribute significantly to advancing the field of risk management with respect to recreational water use and seafood consumption beyond reliance on empirical correlations and towards policies that are based on a mechanistic understanding of the threats these organisms pose to human health.

在这个项目中，来自夏威夷大学马诺阿分校、斯坦福大学和罗格斯大学的一个跨学科研究小组将研究夏威夷沿海水域中的冈比亚圆盘菌、金黄色葡萄球菌和肠球菌的转录本，这些毒素产生的物种对人类的健康构成重大危害。他们的目标是阐明与冈比亚圆盘吸虫产生毒素和阳光对细菌病原体金黄色葡萄球菌和粪便指示剂肠球菌灭活有关的机制。由于生物的转录组反映了在任何给定时间活跃表达的基因，因此本研究通过阐明目标生物中信使RNA的表达水平，应该为解释毒素产生、对压力的反应和/或随后的细菌灭活的机制提供有价值的见解。研究计划将围绕四个工作假设进行组织：H1：冈比亚圆盘藻产生的雪卡毒素反映了温度、光照和生长阶段对培养物生理状况的影响。H2：毒素(+)和毒素(-)培养的高通量转录组分析将使我们能够识别与雪卡毒素产生有关的基因，并了解有利于这一功能的光和营养条件。粪肠球菌在海水中暴露在阳光下容易间接光灭活，而金黄色葡萄球菌则不容易。这可能是由于细胞内存在类胡萝卜素色素，能够熄灭活性氧物种。粪肠球菌和金黄色葡萄球菌在清澈的海水中通过上调编码蛋白质的基因来应对光胁迫，以修复细胞损伤和减轻氧化压力；随着光胁迫暴露的增加，这种“压力”将发生变化，揭示出修复不再可能的压力。更广泛的影响：本研究将收集的信息预计将大大有助于推动娱乐用水和海鲜消费方面的风险管理领域，而不是依赖经验相关性，并有助于制定基于对这些生物对人类健康构成的威胁的机械性理解的政策。