Metabolic Interactions between Salmonella and E. coli Nissle 1917

沙门氏菌和大肠杆菌 Nissle 之间的代谢相互作用 1917

基本信息

批准号：
10663378
负责人：
Sebastian E Winter
金额：
$ 20万
依托单位：
UNIVERSITY OF CALIFORNIA AT DAVIS
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-07-11 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10663378
关键词：
Acute Bacteria Colorectal Cancer Curiosities Data Development Diarrhea Disease Ecosystem Enterobacteriaceae Enterobactin Environment Escherichia coli Exhibits Family member Gastroenteritis Genetic Goals Growth Immunocompetent In Vitro Infection Inflammation Inflammatory Inflammatory Bowel Diseases Inflammatory Response Intervention Intestines Invaded Iron LCN2 gene Laboratories Mediating Medical Care Costs Metabolic Metabolism Microbe Modeling Molecular Mus Nitrate Reductases Nitrates Nutrient Oxidants Pathogenicity Patients Probiotics Process Production Productivity Property Proteins Reactive Nitrogen Species Resources Respiration Salmonella Salmonella enterica Salmonella infections Salmonella typhimurium Serotyping Siderophores Sulfur Symptoms System Testing United States Virulence Factors Work aerobactin antagonist bacterial metabolism colonization resistance commensal microbes cost diarrheal disease enteric pathogen gut colonization gut inflammation gut microbiota member metabolic abnormality assessment microbial microbial community microbiota mouse model non-typhoidal Salmonella novel pathogen pathogenic bacteria prevent respiratory transmission process uptake yersiniabactin

项目摘要

PROJECT SUMMARY Infection with Salmonella enterica serovar Typhimurium (S. Tm) is a common cause of inflammatory diarrhea. As part of the infection process, S. Tm colonizes the intestinal tract and competes with the microbiota for nutrients. Gut-associated microbial communities antagonize invasion of the ecosystem by enteric pathogens (colonization resistance). The molecular mechanisms of how colonization resistance is achieved remain incompletely understood. Our preliminary data suggest that E. coli Nissle 1917, an E. coli strain with presumed probiotic properties, prevents S. Tm gut colonization and intestinal inflammation by competing efficiently for the respiratory electron acceptor nitrate, a limiting nutrient. We hypothesize that EcN uses one or more siderophore systems to acquire sufficient iron for the iron-sulfur cluster-containing nitrate reductases and to produce high levels of nitrate reductase activity. We will test key aspects of our hypothesis in mouse models of infection and in vitro using a strategic combination of bacterial and host genetics. We will pursue the following specific aims: 1. Investigate how EcN and S. Tm compete for nitrate in the mouse intestine, and 2. Determine whether siderophore-mediated uptake of iron is required for nitrate reductase activity. This work will advance our understanding of how intestinal pathogens, such as S. Tm, and commensal microbes compete for limiting resources in the intestinal tract. These studies are also expected to reveal a molecular property of a probiotic strain, which may help devise novel intervention strategies for Salmonella gastroenteritis.

项目概要肠沙门氏菌鼠伤寒血清型 (S.Tm) 感染是引起以下疾病的常见原因炎症性腹泻。作为感染过程的一部分，S.Tm 定植于肠道并与微生物群竞争营养。肠道相关微生物群落对抗肠道病原体对生态系统的入侵（定植抗性）。这如何实现定植抗性的分子机制仍然不完全明白了。我们的初步数据表明，大肠杆菌 Nissle 1917 是一种具有以下特征的大肠杆菌菌株：假定的益生菌特性，可预防 S. Tm 肠道定植和肠道炎症通过有效竞争呼吸电子受体硝酸盐（一种限制性营养素）。我们假设 EcN 使用一个或多个铁载体系统来获取足够的铁含有铁硫簇的硝酸还原酶并产生高水平的硝酸盐还原酶活性。我们将在小鼠感染模型中测试我们假设的关键方面并在体外使用细菌和宿主遗传学的策略组合。我们将追求具体目标如下： 1. 研究 EcN 和 S.Tm 如何在环境中竞争硝酸盐小鼠肠道，以及 2. 确定铁载体介导的铁吸收是否是硝酸还原酶活性所需的。这项工作将加深我们对如何肠道病原体（例如 S. Tm）和共生微生物竞争限制肠道内的资源。这些研究也有望揭示分子益生菌菌株的特性，这可能有助于设计新的干预策略沙门氏菌胃肠炎。