Quorum Sensing in Sinorhizobium meliloti

苜蓿中华根瘤菌的群体感应

• 批准号: 7247178
• 负责人: Juan E E GONZALEZ
• 金额: $ 35.31万
• 依托单位: UNIVERSITY OF TEXAS DALLAS
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7247178
• 关键词: Active Biological Transport; Affect; Alfalfa; Animals; Antibiotics; Bacteria; Biological; Biological Assay; Biological Models; Complex; Cytotoxic agent; Detection; Dissection; Fabaceae; Foundations; Gene Expression Regulation; Genes; Goals; Laboratories; Link; Medicago; Melilotus; Membrane; Microarray Analysis; Molecular Profiling; Multi-Drug Resistance; Nitrogen; Nitrogen Fixation; Nodule; Numbers; Organism; Pathogenesis; Plants; Plasmids; Play; Population Density; Process; Production; Prokaryotic Cells; Publishing; Pump; Regulation; Regulon; Research; Resistance; Rest; Role; Role playing therapy; Saliva; Series; Signal Transduction; Signaling Molecule; Sinorhizobium meliloti; Sodium; Specific qualifier value; Symbiosis; System; Time; Upper arm; Work; acylated homoserine lactone; base; density; design; efflux pump; exoenzyme; fighting; inhibitor/antagonist; insight; mutant; novel; quorum sensing; research study; surfactant; tool

DESCRIPTION (provided by applicant): The symbiotic relationship between the nitrogen-fixing Sinorhizobium meliloti and its legume host (Medicago sativa) is the result of an intricate signaling network between the host and the symbiont. We have shown that quorum sensing, a process that involves the population density-dependent regulation of gene expression, plays an integral part of this complex association. This process involves the release and detection of small extra-cellular signal molecules termed autoinducers. The best characterized of these autoinducers are acylated homoserine lactones (AHLs), mostly found in gram-negative organisms. The overall goal of this research is to determine the role that quorum-sensing plays in the well-characterized relationship between S. meliloti and its host. As a result of our recent work, this symbiotic association is rapidly becoming a paradigm for the study of quorum sensing. S. meliloti possesses a complex series of linked quorum-sensing systems. We have characterized three of those systems (Mel, Sin and Tra) and established that they play a part in nodulation, exopolysaccharide production, nitrogen fixation and conjugal plasmid transfer. The Sin system produces the longest AHLs detected to date. Our work has determined that one of these long-chain AHLs plays a key role in regulating the production of the syrnbiotically important exopolysaccharide II. In addition, the Sin quorum-sensing system affects the timing and number of nodules it induces on its plant host. The first aim of this proposal is to determine how the multiple quorum-sensing systems of S. meliloti are regulated and coordinated. This will provide insights into a regulatory aspect of quorum sensing that is impossible to study in the presently employed model systems. Second, we will investigate how the highly hydrophobic AHLs produced by the Sin system are transported across biological membranes. This could help elucidate the mechanisms used by the transmembrane pumps that confer resistance to cytotoxic drugs and potentially arm us in the struggle to fight multidrug resistance by enabling the rational design of inhibitors of these pumps. Third, this project seeks to identify, through microarray analysis, the genes controlled by the Sin and Mel quorum sensing systems and determine their function in the S. meliloti/alfalfa symbiosis. This study will provide a better understanding of the symbiotic/pathogenic relationships between prokaryotes and their eukaryotic hosts and might provide tools for the control and manipulation of such relationships.

描述（申请人提供）：固氮苜蓿中华根瘤菌与其豆科植物宿主（苜蓿）之间的共生关系是宿主与共生体之间复杂的信号网络的结果。我们已经证明，群体感应是一个涉及群体密度依赖性基因表达调节的过程，在这种复杂的关联中发挥着不可或缺的作用。该过程涉及称为自诱导剂的小细胞外信号分子的释放和检测。这些自诱导剂中最具特征的是酰化高丝氨酸内酯（AHL），主要存在于革兰氏阴性生物体中。这项研究的总体目标是确定群体感应在苜蓿中华根瘤菌与其宿主之间的明确关系中所发挥的作用。作为我们最近工作的结果，这种共生关联正在迅速成为群体感应研究的范例。苜蓿中华根瘤菌拥有一系列复杂的相互连接的群体感应系统。我们对其中三个系统（Mel、Sin 和 Tra）进行了表征，并确定它们在结瘤、胞外多糖产生、固氮和接合质粒转移中发挥作用。 Sin 系统产生迄今为止检测到的最长的 AHL。我们的工作已经确定，这些长链 AHL 之一在调节共生重要的胞外多糖 II 的产生中发挥着关键作用。此外，Sin群体感应系统会影响它在植物宿主上诱导根瘤的时间和数量。该提案的首要目标是确定苜蓿中华根瘤菌的多个群体感应系统是如何调控和协调的。这将为群体感应的监管方面提供见解，而这在目前使用的模型系统中是不可能研究的。其次，我们将研究 Sin 系统产生的高度疏水性 AHL 如何跨生物膜运输。这可能有助于阐明跨膜泵所使用的机制，这些机制赋予细胞毒性药物耐药性，并可能通过合理设计这些泵的抑制剂来武装我们对抗多药耐药性。第三，该项目旨在通过微阵列分析来识别由 Sin 和 Mel 群体传感系统控制的基因，并确定它们在苜蓿/苜蓿共生中的功能。 这项研究将更好地理解原核生物与其真核宿主之间的共生/致病关系，并可能为控制和操纵这种关系提供工具。