RNA helicases in bacterial pathogenesis

RNA解旋酶在细菌发病机制中的作用

基本信息

批准号：
10360660
负责人：
Melissa Kendall
金额：
$ 19.7万
依托单位：
UNIVERSITY OF VIRGINIA
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：
2021-03-01 至 2024-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10360660
关键词：
Alternative Therapies Anaerobic Bacteria Antibiotics Bacteria Bacteria sigma factor KatF protein Cells Colon Complication Cues Data Development Disease Disease Outbreaks Dose Enterocytes Environment Epithelial Epithelial Cells Escherichia coli EHEC Escherichia coli O157:H7 Gastrointestinal tract structure Gene Expression Genes Growth Hemolytic-Uremic Syndrome Hemorrhagic colitis Human Infection Ingestion Lead Lesion Life Maps Modeling Molecular Morbidity - disease rate Nutrient Oxygen Pathogenesis Physiological Play Post-Transcriptional Regulation RNA Degradation RNA Helicase RNA metabolism Regulation Regulon Risk Role Shiga Toxin Supportive care System Transcript Translations Travel Viral Genome Virulence Virulence Factors Work design enteric pathogen helicase improved in vivo microbiota mortality negative affect pathogen pathogenic bacteria response spatiotemporal trait transcriptome virtual

项目摘要

PROJECT SUMMARY The ability of bacteria to rapidly sense and respond to changes in the environment is fundamental to colonization and survival. 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 encodes several important virulence factors, including the potent Shiga toxin that causes HUS and a type three secretion system (T3SS) and effectors necessary for attaching and effacing (AE) lesion formation on enterocytes. EHEC has a very low infectious dose, suggesting that EHEC has evolved mechanisms to spatiotemporally control virulence gene expression to occur within appropriate host niches. RNA helicases are ubiquitous in all kingdoms of life, as well as within viral genomes, and are involved in virtually all aspects of RNA metabolism, including RNA degradation or protection and translation. Our studies underlie the importance of RNA helicases to EHEC niche adaptation and coordination of virulence gene expression. The proposed work will investigate the importance of RNA helicases to niche recognition and host-pathogen interactions using a physiologically relevant infection model. We will also utilize unbiased approaches to comprehensively map the regulon of an EHEC helicase and identify targets of regulation.

项目概要细菌快速感知和响应环境变化的能力至关重要殖民和生存。转录后调控正在成为一种重要的策略促进对细菌毒力的有效和精确控制，从而在发病。肠出血性大肠杆菌 O157:H7 (EHEC) 是一种细菌病原体，定植于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），这可能是致命的。 EHEC 编码多种重要的毒力因子，包括强效毒力因子引起 HUS 的志贺毒素和三型分泌系统 (T3SS) 以及肠上皮细胞上附着和消除（AE）损伤的形成。 EHEC 的感染剂量非常低，表明肠出血性大肠杆菌已经进化出时空控制毒力基因的机制表达发生在适当的宿主生态位内。 RNA解旋酶在所有领域中普遍存在生命体以及病毒基因组内，并且几乎参与RNA代谢的所有方面，包括 RNA 降解或保护和翻译。我们的研究强调了 RNA 的重要性解旋酶对肠出血性大肠杆菌生态位的适应和毒力基因表达的协调。拟议的这项工作将调查 RNA 解旋酶对生态位识别和宿主病原体的重要性使用生理相关感染模型进行相互作用。我们还将采用公正的方法全面绘制肠出血性大肠杆菌解旋酶的调控图谱并确定调控目标。