RNA-binding proteins in bacterial virulence and host-pathogen interactions

RNA结合蛋白在细菌毒力和宿主-病原体相互作用中的作用

基本信息

批准号：
10659346
负责人：
Melissa Kendall
金额：
$ 48.57万
依托单位：
UNIVERSITY OF VIRGINIA
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-01-14 至 2027-12-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10659346
关键词：
Ablation Affect Animal Model Attenuated Bacteria Bacteria sigma factor KatF protein Bacterial Genes Biochemical Biological Assay Carbon Cell Culture Techniques Citrobacter rodentium Colon Complement Consumption Cues Defect Diffusion Disease Enterobacteriaceae Environment Enzymes Epithelial Cells Epithelium Escherichia coli Escherichia coli EHEC Escherichia coli O157:H7 Exhibits Gene Expression Gene Expression Regulation Genetic Genetic Epistasis Genetic Transcription Genomics Gnotobiotic Goals Growth Hemolytic-Uremic Syndrome Hemorrhagic colitis Human Hyperplasia Image In Vitro Infection Inflammatory Intestines Invaded Knowledge Laboratories Life Location Metabolic Metabolism Molecular Molecular Target Mucous Membrane Mus Mutation Nitrogen Nutrient Oxidation-Reduction Oxygen Pathogenesis Phagocytes Phenotype Physiology Play Post-Transcriptional Regulation RNA Helicase RNA Stability RNA metabolism RNA-Binding Proteins Regulation Respiration Role Shock Signal Transduction Structure Techniques Temperature Testing Thinking Tissues Transcript Translations Type III Secretion System Pathway Virulence Work bacterial genetics cell motility cold temperature cost design experimental study fitness functional outcomes gut colonization helicase improved in vivo member model organism mouse model mutant novel therapeutics pathogen pathogenic bacteria pharmacologic response spatiotemporal trait transcription termination transcriptomics virulence gene

项目摘要

PROJECT SUMMARY The ability of bacteria to rapidly sense and respond to changes in the environment is fundamental to colonization. Post-transcriptional regulation is emerging as an important strategy that promotes efficient and precise control of bacterial virulence, and thus plays a central role in pathogenesis. Enterohemorrhagic Escherichia coli O157:H7 (EHEC) is a bacterial pathogen that colonizes the human colon and causes severe hemorrhagic colitis and hemolytic uremic syndrome (HUS), which can be fatal. EHEC is able to efficiently acquire nutrients and coordinate expression of traits that promote intestinal colonization, suggesting that EHEC has evolved mechanisms to spatiotemporally control virulence gene expression to occur within appropriate host niches. RNA binding proteins play important roles in bacterial gene expression by modulating transcription termination, RNA stability, and translation; however, the targets and molecular mechanisms of most RNA binding proteins and the corresponding impact on bacterial virulence and host interactions are poorly resolved. The proposed work will elucidate the regulatory mechanisms of RNA binding proteins and importance to fitness within the intestine, as well as examine how these RNA binding proteins are activated within transcriptional networks and in response to host cues.

项目概要细菌快速感知和响应环境变化的能力至关重要到殖民化。转录后调控正在成为促进有效而精确地控制细菌毒力，因此在发病机制中发挥着核心作用。肠出血性大肠杆菌 O157:H7 (EHEC) 是一种定植于肠道的细菌病原体。人类结肠并引起严重的出血性结肠炎和溶血性尿毒症综合征（HUS），可能是致命的。 EHEC 能够有效地获取营养并协调性状的表达，促进肠道定植，表明肠出血性大肠杆菌已经进化出时空机制控制毒力基因的表达发生在适当的宿主生态位内。 RNA结合蛋白发挥作用通过调节转录终止、RNA 稳定性、和翻译；然而，大多数 RNA 结合蛋白的靶点和分子机制对细菌毒力和宿主相互作用的相应影响尚未解决。这拟议的工作将阐明 RNA 结合蛋白的调节机制及其重要性肠道内的适应性，以及检查这些 RNA 结合蛋白如何在肠道内被激活转录网络和对宿主线索的反应。