Regulation of the Sinorhizobium meliloti ExoS/ChvI signaling pathway critical for host infection

苜蓿中华根瘤菌 ExoS/ChvI 信号通路的调节对宿主感染至关重要

• 批准号: 10332479
• 负责人: Esther J Chen
• 金额: $ 10.65万
• 依托单位: CALIFORNIA STATE UNIVERSITY FULLERTON
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-20 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10332479
• 关键词: Affect; Alphaproteobacteria; Bacteria; Bartonella; Binding; Biomedical Research; Brucella; Brucella abortus; Candidate Disease Gene; Catalogs; Cations; Cells; Chiroptera; Communicable Diseases; Consensus Sequence; Critical Pathways; Data Set; Defect; Eukaryotic Cell; Exhibits; Gene Expression; Gene Expression Profiling; Genes; Genetic Transcription; Genomic Segment; Human; Infection; Invaded; Knock-out; Lead; Membrane Proteins; Modeling; Molecular; Molecular Genetics; Mutation; Nutrient; Outcome; Pathogenicity; Pathway interactions; Peptides; Phenotype; Phosphorylation; Physiology; Plants; Play; Prevention; Proteins; Quantitative Reverse Transcriptase PCR; Regulation; Regulator Genes; Regulatory Pathway; Regulon; Research; Research Training; Role; Signal Pathway; Signal Transduction; Sinorhizobium; Sinorhizobium meliloti; Small RNA; Students; Symbiosis; Transcriptional Activation; Underrepresented Populations; Underrepresented Students; career; cell envelope; cell motility; cell type; chromatin immunoprecipitation; disorder prevention; genetic approach; genome-wide; genome-wide analysis; host-microbe interactions; human disease; human pathogen; improved; insight; mutant; overexpression; pathogen; plant defensin proteins; response; symbiont; undergraduate student

PROJECT SUMMARY/ABSTRACT Many alpha-proteobacteria invade cells of eukaryotic hosts with pathogenic or beneficial outcomes. Examples of such alpha-proteobacteria are the human pathogens Brucella and Bartonella and the plant symbiont Sinorhizobium. Remarkably, although these alpha-proteobacteria target different cell types in different hosts, they all require a conserved bacterial two-component signaling pathway for successful host interaction: BvrS/BvrR in Brucella, BatS/BatR in Bartonella, and ExoS/ChvI in Sinorhizobium. Mutant bacteria deficient in this pathway fail to invade host cells and exhibit pleiotropic phenotypes such as altered cell envelope function. However, the molecular mechanisms underlying these defects are not well understood. Toward elucidating the crucial roles of this conserved signaling pathway, this project focuses on the ExoS/ChvI signaling pathway of Sinorhizobium meliloti, a model alpha-proteobacterium for studying interactions with eukaryotic hosts. A recent genome-wide study identified 64 protein-encoding genes in the ExoS/ChvI regulon of S. meliloti. This proposal builds from that study and uses molecular genetic approaches to clarify the critical functions of this conserved regulatory pathway. Specific aims of the project are to: (1) Identify small RNA genes directly regulated by ExoS/ChvI, (2) Identify regulatory inputs to ExoS/ChvI, and (3) Characterize transcriptional target genes of ExoS/ChvI. This study will provide insight into the functions controlled by this important signaling pathway during host interaction. In addition, the project will provide valuable biomedical research training to undergraduate and master’s students, including those from groups underrepresented in biomedical research careers.

项目概要/摘要 许多α-变形菌侵入真核宿主细胞，产生致病或有益的结果。 这种α-变形菌包括人类病原体布鲁氏菌和巴尔通体以及植物共生体 值得注意的是，尽管这些α-变形菌针对不同宿主的不同细胞类型， 它们都需要保守的细菌双组分信号通路才能成功地与宿主相互作用： 布鲁氏菌中的 BvrS/BvrR、巴尔通体中的 BatS/BatR 以及中华根瘤菌中缺乏的 ExoS/ChvI。 该途径无法侵入宿主细胞并表现出多效性表型，例如细胞包膜功能。 然而，这些缺陷背后的分子机制尚不清楚。 这一保守信号通路的关键作用，本项目重点关注 ExoS/ChvI 信号通路 苜蓿中华根瘤菌，一种用于研究与真核宿主相互作用的模型α-变形菌。 全基因组研究在苜蓿根瘤菌的 ExoS/ChvI 调节子中鉴定出了 64 个蛋白质编码基因。 以该研究为基础，并使用分子遗传学方法来阐明这一保守的关键功能 该项目的具体目标是：（1）鉴定直接调控的小RNA基因。 ExoS/ChvI，(2) 识别 ExoS/ChvI 的调控输入，以及 (3) 表征 ExoS/ChvI 的转录靶基因 这项研究将深入了解这一重要信号通路控制的功能。 此外，该项目还将为宿主提供有价值的生物医学研究培训。 本科生和硕士生，包括来自生物医学研究中代表性不足的群体的学生 职业生涯。