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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

基本信息

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
项目类别：
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

项目摘要

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.

项目总结/文摘