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）：拟议研究的长期目标是了解在人类与其微生物群相互作用的最初几分钟到几小时内发生的复杂对话。这些关系，无论是致病的还是有益的，通常始于粘膜表面，这些部位通常无法进行实验研究。此外，它们通常支持由数百种微生物组成的复杂联合体。在这些位点上，细菌表面特征和宿主识别的相应机制之间的相互作用控制着有益和致病关联的开始和持续。同样的细胞和分子“语言”如何被不同地用于产生健康或疾病的两种相反的结果？面对人体中令人生畏的微生物复杂性，为了回答这个问题，我们使用了更简单的模型系统，这些模型系统更易于实验操作。生物学家利用这种系统来发现揭示单个细菌物种如何与宿主成功结合的基本原理。一个这样的模式是生物发光革兰氏阴性菌，费氏弧菌和它的鱿鱼宿主，Euprymna scoloes之间的二元共生。就像人类一样，鱿鱼与这种细菌的关系每一代都开始新的发展，微生物从环境过渡到功能上有益的关系。在这两种情况下，通过复杂的分子相互作用识别的一小部分环境细菌会发生“筛选”，从而促进与这些细菌的关联。在鱿鱼-弧菌系统中，这一过程发生在几分钟到几小时内，并且可以直接对其整体进行成像。因此，该系统提供了难得的机会，以高时间和空间分辨率破译相互的分子和生化对话，这对自然关联的正常发展至关重要。该项目汇集了一组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，以解决以下具体目标：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识别和特异性；2)描述共生体中对选择过程至关重要的遗传因素；3)确定细菌运动和外膜囊泡（众所周知的毒力和定植决定因素）如何在宿主和共生体之间的对话中发挥关键作用。