Kin recognition and outer membrane exchange regulate social interactions in myxobacteria

亲缘识别和外膜交换调节粘细菌的社会相互作用

• 批准号: 9752591
• 负责人: DANIEL WALL
• 金额: $ 28.97万
• 依托单位: UNIVERSITY OF WYOMING
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-05-01 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9752591
• 关键词: Address; Alleles; Animals; Archaea; Bacteria; Bacterial Adhesins; Behavior; Biochemical; Bioinformatics; Biological; Biological Models; Biology; Cell Cycle; Cell Differentiation process; Cell Surface Receptors; Cell physiology; Cell surface; Cells; Cellular Stress; Chimera organism; Collaborations; Communities; Complex; Cytoplasm; Data; Discrimination; Disease; Elements; Exhibits; Failure; Fruit; Genetic; Genetic Models; Goals; Habitats; Homeostasis; Human; Immunity; Individual; Life; Lipids; Lipoproteins; Malignant Neoplasms; Maps; Mediating; Membrane; Membrane Fusion; Membrane Lipids; Membrane Proteins; Methods; Microscopy; Modeling; Molecular; Mutation Analysis; Myxococcales; Myxococcus xanthus; Nature; Organ; Organism; Outcome; Pathway interactions; Periodicity; Phenotype; Plants; Population; Post-Translational Protein Processing; Process; Prokaryotic Cells; Property; Proteins; Reproduction spores; Research; Resources; Selfish DNA; Site; Social Behavior; Social Interaction; Soil; Sorting - Cell Movement; Specificity; Starvation; Stress; Structure; System; Testing; Tissues; Toxin; Ursidae Family; Variant; Work; base; cell injury; cell type; design; experimental study; fitness; gliding bacteria; insight; member; molecular recognition; mutant; novel; periplasm; receptor; repaired; response; social; time use; tool; trait

Abstract A fundamentally important question in biology is how individual cells within multicellular organisms cooperate to form tissues, organs and a complete organism. One approach to address this complex question is to use simple model systems that exhibit many of the traits found in tissues. Myxococcus xanthus is one such system where, for instance, in response to starvation thousands of cells aggregate, move rhythmically and build fruiting bodies in which vegetative cells differentiate into spores. In M. xanthus we discovered a novel platform that mediates social interactions. This behavior involves kin recognition in which cells identify clonemates and exchange outer membranes (OM) proteins and lipids. Recognition in outer membrane exchange (OME) is mediated by a polymorphic cell surface receptor called TraA and its partner protein TraB. Only cells that bear identical or very similar alleles of traA will recognize one another for OME. Depending of conditions the exchange of OM content leads to beneficial or harmful outcomes. In genetic models we showed that OME can result in cooperative repair of damaged cells. Here, healthy cells replenish mutant cells with missing components that restores their fitness. In other examples, OME leads to antagonisms when polymorphic toxins are transferred and the recipient cells do not contain cognate immunity proteins. Although OME involves the apparent transfer of hundreds of different cellular components with complex social consequences, this system is amendable to powerful approaches that can be applied to bacterial research. This proposal addresses three goals. In Aim 1 we will investigate OM fusion as the mechanism for exchange by using microscopy, genetic and biochemical methods to define the dynamic functions of TraA and TraB. Aim 2 will also use a combination of approaches to define the molecular basis of TraA kin recognition and how it interacts with TraB. Aim 3 will investigate a second pathway that allows toxins delivered by OME to enter the cytoplasm. Our preliminary data suggests that this kin discrimination system impacts strain diversification and population structures found in natural soil habitats. This hypothesis will be tested by genetic and bioinformatic experiments. Last, the ability of OME to repair damage that is inflicted on stressed cells will be tested. These studies will lead to a molecular understanding of the mechanisms of kin recognition and OME, as well as a deeper insights into how a socially sophisticated bacterium transitions from individuals into a cooperative multicellular tissue.

抽象的 生物学中一个根本性的重要问题是多细胞中的单个细胞如何 生物体相互配合，形成组织、器官和完整的有机体。一种解决方法 这个复杂的问题是使用简单的模型系统，该系统表现出许多特征 组织。黄色粘球菌就是这样一种系统，例如，它可以响应饥饿 数以千计的细胞聚集，有节奏地移动并形成子实体，其中营养 细胞分化成孢子。在 M. xanthus 中，我们发现了一个介导社交的新颖平台 互动。这种行为涉及亲属识别，其中细胞识别克隆体并 交换外膜（OM）蛋白质和脂质。外膜交换中的识别 (OME) 由称为 TraA 的多态性细胞表面受体及其伴侣蛋白介导 特拉B.只有具有相同或非常相似的 traA 等位基因的细胞才会相互识别 奥梅。根据条件，OM 内容的交换会带来有益或有害的结果 结果。在遗传模型中，我们表明 OME 可以导致受损细胞的协同修复 细胞。在这里，健康细胞用缺失的成分补充突变细胞，从而恢复它们的功能。 健康。在其他例子中，当多态性毒素转移时，OME 会导致拮抗作用 并且受体细胞不含有同源免疫蛋白。尽管 OME 涉及 数百种不同的细胞成分与复杂的社交的明显转移 结果，该系统可以修改为可应用于细菌的强大方法 研究。该提案涉及三个目标。在目标 1 中，我们将研究 OM 融合 通过使用显微镜、遗传和生化方法来定义交换机制 TraA和TraB的动态函数。目标 2 还将结合使用多种方法来定义 TraA 亲属识别的分子基础及其如何与 TraB 相互作用。目标 3 将进行调查 第二条途径允许 OME 传递的毒素进入细胞质。我们的初步 数据表明，这种亲属歧视制度影响菌株多样化和人口 在自然土壤栖息地中发现的结构。这一假设将通过遗传和 生物信息学实验。最后，OME 修复压力造成的损坏的能力 细胞将被测试。这些研究将导致对机制的分子理解 亲属识别和 OME，以及对社交复杂细菌如何进行更深入的了解 从个体转变为合作的多细胞组织。