Role of hopanoid microbial lipids in a legume:microbe nitrogen-fixing symbiosis

藿香类微生物脂质在豆科植物中的作用：微生物固氮共生

• 批准号: 10221864
• 负责人: Brittany Jo Belin
• 金额: $ 24.9万
• 依托单位: CARNEGIE INSTITUTION OF WASHINGTON, D.C.
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10221864
• 关键词: Actins; Affect; Antibiotic Resistance; Antibiotics; Award; Bacillus cereus; Bacteria; Bacterial Infections; Biological Process; Biophysics; Biosensor; Bradyrhizobium; Cell Wall; Cell division; Cell surface; Cells; Chemicals; Complex; Cytoskeleton; Defect; Development; Doctor of Philosophy; Environment; Eukaryota; Exposure to; Fabaceae; Genetic Determinism; Goals; Growth; High temperature of physical object; Hydrocarbons; Immune; Infection; Institution; Laboratories; Lead; Lipids; Lipopolysaccharides; Measures; Mechanics; Mediating; Mediator of activation protein; Membrane; Microbe; Microbial Physiology; Microelectrodes; Mitosis; Modeling; Modification; Molecular Profiling; Nitrogen; Nodule; Nuclear; Organ; Organism; Organogenesis; Penetration; Peptidoglycan; Plant Roots; Plants; Process; Quantitative Microscopy; Recording of previous events; Research; Resistance; Role; S-Phase Fraction; Signal Transduction; Signaling Molecule; Steroids; Sterols; Stress; Surface; Survival Rate; Symbiosis; System; Tail; Testing; Time; Tissues; Training; Training Support; Work; antimicrobial; bacterial resistance; beneficial microorganism; career; chronic infection; environmental stressor; extracellular; gene product; human pathogen; human tissue; microbial; mutant; pathogen; pathogenic bacteria; pathogenic microbe; physical property; pressure; research study; response; skills; stressor; symbiont; tissue culture

Project Abstract It is well known that components of the bacterial cell wall are crucial to successful host interactions for both pathogenic and beneficial microbes. While detailed mechanistic information is available on the roles of a subset of cell wall components (i.e. lipopolysaccharides (LPS) and peptidoglycan) in these associations, few other bacterial cell surface molecules have been as rigorously investigated. Bacterial hopanoids are emerging as new determinants of the efficiency of the interactions between a subset of bacteria and their eukaryotic hosts. Hopanoids are sterol-like lipids produced by diverse eukaryote-associated bacteria, including the human pathogens in the Burkolderia cepacia complex and Bacillus cereus spp. In addition to rigidifying bacterial membranes, similarly to eukaryotic sterols, hopanoids are known to confer broad stress resistance to bacteria in culture. In native infection contexts, the significance of the increase stress resistance provided by hopanoids, and whether hopanoids confer other advantages, has not been mechanistically clarified. Recent work in the Newman lab has demonstrated that a specific class of hopanoids, extended hopanoids containing an extracellular hydrocarbon tail, regulates the efficiency of the symbiotic interaction between the nitrogen-fixing bacterium Bradyrhizobium diazoefficiens with the legume host Aeschynomene afraspera. I have determined that extended hopanoids affect the progression of the symbiosis at all stages, including the initial bacterial infection of plant roots and subsequent proliferation of bacterial symbionts within host cells. I hypothesize that the role of extended hopanoids during these stages is to enhance bacterial growth under abiotic stressors, specifically the mechanical and chemical pressures provided by the host niche. In my Research Plan, I propose to characterize further the role of extended hopanoids in the B. diazoefficiens-A. afraspera symbiosis and to use this system as a model for how hopanoids facilitate persistent infections of eukaryotic hosts more generally. In my PhD I studied the nuclear actin cytoskeleton in human tissue culture models, using approaches in quantitative microscopy and biophysics, and completing my Research Plan will require me to significantly expand my skill set. I am applying for a K99 award to support the training I need to develop both the research and non-research skills necessary to achieve my long-term career goal of establishing a successful independent laboratory at an R1 institution. I hope to synthesize approaches in biophysics, quantitative microscopy, plant cultivation and microbial physiology to study microbial responses to the chemical and mechanical environments of their hosts. I believe that my training history makes me uniquely suited to occupy this under-studied research niche, which I expect to yield key principles of microbial adaptation to hosts that will be broadly applicable to many host:microbe systems.

项目摘要 众所周知，细菌细胞壁的成分对于成功的宿主至关重要 病原和有益微生物的相互作用。而详细的机械信息是 可在细胞壁成分子集（即脂多糖（LPS）和 肽聚糖）在这些关联中，很少其他细菌细胞表面分子严格如此 调查。细菌霍甘酸正在作为相互作用效率的新决定因素出现 在细菌的子集及其真核宿主之间。霍甘酸是由固醇样脂质产生的 多种真核生物相关的细菌，包括伯科尔德氏菌中的人类病原体 复杂和蜡状芽孢杆菌属。除了刚化细菌膜外，与真核类似 已知固醇，霍甘酸会赋予对培养细菌的巨大抗压力。在天然感染中 环境，霍甘酸酯提供的增加压力抗性的意义，以及hopanoids是否 赋予其他优势，尚未在机械上澄清。 Newman Lab的最新工作表明，特定类别的霍托甘油类似 含有细胞外碳氢化合物尾巴的霍生类，调节共生的效率 固氮细菌Bradyrhizobium Zoefficiens与豆科植物宿主之间的相互作用 Aeschynomene Afraspera。我已经确定刺激的霍生物会影响 在各个阶段的共生，包括植物根的初始细菌感染和随后的增殖 宿主细胞中的细菌共生体。我假设在这些过程中延伸的霍托素的作用 阶段是在非生物压力源下增强细菌生长，特别是机械和化学 主机利基提供的压力。在我的研究计划中，我建议进一步表征 芽孢杆菌中的hopanoids扩展。 Afraspera共生，并将该系统用作模型 Hopanoids如何更普遍地促进真核宿主的持续感染。 在我的博士学位上，我研究了人类组织培养模型中的核肌动蛋白细胞骨架 定量显微镜和生物物理学的方法，完成我的研究计划将需要我 大大扩大我的技能。我正在申请K99奖励，以支持我需要的培训 发展我的长期职业目标所必需的研究和非研究技能 在R1机构建立成功的独立实验室。我希望在 生物物理学，定量显微镜，植物培养和微生物生理学研究微生物 对宿主的化学和机械环境的反应。我相信我的训练历史 让我独特地适合占据这一研究不足的研究利基市场，我希望这能产生关键 微生物适应对宿主的原理将广泛适用于许多主机：微生物系统。