Vibrio fischeri as a model of Bacterial Colonization

费氏弧菌作为细菌定植的模型

• 批准号: 8668878
• 负责人: MARGARET J MC FALL-NGAI
• 金额: $ 43.33万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-12-01 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8668878
• 关键词: Address; Affect; Animals; Apical; Bacteria; Bacterial Model; Binding; Biochemical; Biochemistry; Biological Models; Cell Culture Techniques; Cells; Cellular biology; Chemicals; Complement; Complex; Data; Developmental Cell Biology; Disease; Environment; Epithelial; Epithelium; Event; Fostering; Gene Expression; Generations; Genetic; Germ-Free; Goals; Gram-Negative Bacteria; Health; Hour; Human; Human body; Image; Immune response; Individual; Investigation; Language; Learning; Life; Maintenance; Membrane; Microbe; Microbial Genetics; Modeling; Molecular; Mucous Membrane; Mucous body substance; Outcome; Pathogenesis; Pattern; Pattern recognition receptor; Pharmacology; Pilum; Play; Process; Production; Receptor Signaling; Recording of previous events; Research; Resolution; Scientist; Shapes; Signal Transduction; Site; Specificity; Squid; Structure; Surface; Symbiosis; System; Time; Tissues; Ursidae Family; Vertebrates; Vesicle; Vibrio; Vibrio fischeri; Virulence; Work; antimicrobial; bacterial genetics; cell motility; critical period; human tissue; insight; microbial; microbial community; molecular/cellular imaging; pathogen; public health relevance; research study; response

DESCRIPTION (provided by applicant): The long-term objectives of the proposed research are to understand the complex dialogue that occurs between humans and their microbiota during the initial minutes to hours of their interaction. These relationships, whether pathogenic or beneficial, typically begin at mucosal surfaces, sites that are often inaccessible to experimental study. In addition, they usual support a complex consortium consisting of hundreds of microbial species. At these sites, the interplay between the surface features of bacteria and the corresponding mechanisms of host recognition controls the initiation and persistence of both beneficial and pathogenic associations. How is this same cellular and molecular 'language' used differently to produce the two opposite outcomes of health or disease? To answer this question in the face of the daunting microbial complexity in the human body, simpler model systems are used that are more amenable to experimental manipulation. Biologists use such systems to discover fundamental principles that reveal how an individual bacterial species associates successfully with its host. One such model is the binary symbiosis between the bioluminescent Gram-negative bacterium, Vibrio fischeri, and its squid host, Euprymna scolopes. As in humans, the squid's relationship with this bacterium begins a new each generation, with the microbe transitioning from the environment into a functional beneficial relationship. In both cases, a 'winnowing' occurs that promotes an association with only that small subset of environmental bacteria that are recognized through complex molecular interactions. In the squid-vibrio system, this process occurs over minutes to hours, and can be directly imaged in its entirety. As such, the system offers the rare opportunity to decipher, with high temporal and spatial resolution, the reciprocal molecular and biochemical dialogue that is essential for a natural association to develop normally. This project brings together a team of scientists with expertise in cell and developmental biology, biochemistry, and genetics, to address the following specific aims: 1) to examine how interactions between host cells and the specific symbiont shape the microenvironment to promote partner recognition and specificity; 2) to characterize the genetic factors of the symbiont that are essential to the selection process; and, 3) to define how bacterial motility and outer membrane vesicles, well known virulence and colonization determinants, play a key role in the dialogue between host and symbiont.

描述（由申请人提供）：拟议的研究的长期目标是了解在相互作用的最初几分钟到几小时的人类与其微生物群之间发生的复杂对话。这些关系，无论是致病性的还是有益的，通常从粘膜表面开始，通常无法无法获得实验研究。此外，它们通常支持一个由数百种微生物物种组成的复杂财团。在这些地点，细菌表面特征与宿主识别的相应机制之间的相互作用控制有益和致病性关联的起始和持久性。这种相同的细胞和分子“语言”如何不同地产生健康或疾病的两个相反结果？为了面对人体中艰巨的微生物复杂性的回答，使用了更简单的模型系统，这些模型系统更适合实验性操纵。生物学家使用此类系统来发现基本原理，这些原理揭示了单个细菌物种如何成功与宿主联系。这样的模型是生物发光革兰氏阴性细菌，颤音fischeri及其鱿鱼宿主Euprymna scolopes之间的二元共生。与人类一样，鱿鱼与该细菌的关系开始了新一代，微生物从环境转变为功能有益关系。在这两种情况下，都会发生“奖励”，这仅促进与通过复杂分子相互作用识别的一小部分环境细菌的关联。在Squid-Vibrio系统中，此过程发生在数分钟到几个小时的时间内，并且可以直接成像。因此，该系统提供了一种难得的机会，可以通过较高的时间和空间分辨率解密，这是自然关联正常发展至关重要的相互分子和生化对话。该项目汇集了一个具有细胞和发育生物学，生物化学和遗传学专业知识的科学家团队，以解决以下特定目的：1）研究宿主细胞与特定共生体之间的相互作用如何塑造微环境以促进伴侣的认可和特异性； 2）表征共生体对于选择过程至关重要的遗传因素； 3）为了定义细菌运动和外膜外囊泡，众所周知的毒力和定殖决定因素如何在宿主和共生体之间的对话中起关键作用。