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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

基本信息

批准号：
10470373
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
项目类别：
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/10470373
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

项目摘要

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，细菌细胞壁的组成对于成功的宿主是至关重要的致病微生物和有益微生物的相互作用。虽然详细的机械信息是可用的作用的一个子集的细胞壁组分（即脂多糖（LPS）和肽聚糖）在这些协会，很少有其他细菌细胞表面分子已作为严格研究了细菌hopanoids正在成为相互作用效率的新决定因素细菌和真核宿主之间的联系Hopanoids是一种甾醇类脂质，多种真核生物相关细菌，包括洋葱伯克霍尔德菌中的人类病原体复合体和蜡状芽孢杆菌属（Bacillus cereus spp.）除了硬化细菌膜，与真核生物类似，已知甾醇类、Hopanoids赋予培养物中细菌广泛的应激抗性。在自然感染中背景下，增加由hopanoids提供的抗应激性的意义，以及hopanoids是否赋予其他优点，还没有被机械地阐明。纽曼实验室最近的工作表明，一类特殊的类Hopanoids， hopanoids含有细胞外碳氢化合物尾巴，调节共生的效率，固氮菌固氮慢生根瘤菌与豆科植物的相互作用细叶合木我已经确定，扩展的hopanoids影响的进展，在所有阶段的共生，包括植物根部的初始细菌感染和随后的增殖宿主细胞内细菌的共生体。我推测，在这些过程中，阶段是为了增强细菌在非生物胁迫下的生长，特别是机械和化学胁迫。由宿主生态位提供的压力。在我的研究计划中，我建议进一步描述在B区有扩展的类Hopanoid。重氮增效剂A. afraspera共生，并使用该系统作为一个模型， hopanoids如何更普遍地促进真核宿主的持续感染。在我的博士学位期间，我研究了人类组织培养模型中的核肌动蛋白细胞骨架，在定量显微镜和生物物理学的方法，并完成我的研究计划将需要我来大大扩展我的技能我正在申请K99奖，以支持我需要的培训，发展必要的研究和非研究技能，以实现我的长期职业目标在R1机构建立成功的独立实验室。我希望综合各种方法，生物物理学，定量显微镜，植物栽培和微生物生理学，以研究微生物对宿主的化学和机械环境的反应。我相信我的训练经历使我特别适合占据这个研究不足的研究利基，我希望产生关键微生物对宿主的适应原理将广泛适用于许多宿主：微生物系统。