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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.

项目摘要细菌快速感知环境变化并做出反应的能力是根本殖民和生存的关键转录后调控正成为一种重要的策略，促进细菌毒力的有效和精确控制，因此在以下方面发挥核心作用：发病机制肠出血性大肠杆菌O 157：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综合征 (HUS)，这可能是致命的。肠出血性大肠杆菌编码几种重要的毒力因子，包括强毒力因子。导致HUS的滋贺毒素和三型分泌系统（T3 SS）以及肠上皮细胞上的附着和消失（AE）损伤形成。肠出血性大肠杆菌的感染剂量非常低，提示肠出血性大肠杆菌已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解旋酶普遍存在于所有生物界中。生命，以及病毒基因组内，并参与RNA代谢的几乎所有方面，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适应和毒力基因表达的协调作用。拟议研究RNA解旋酶在生态位识别和宿主-病原体关系中的重要性使用生理相关的感染模型的相互作用。我们还将利用无偏见的方法全面绘制肠出血性大肠杆菌解旋酶的调节子并确定调节靶点。