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

• 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
• 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

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.

项目总结 感染鼠伤寒沙门氏菌(S.TM)是引起 炎症性腹泻。作为感染过程的一部分，S.TM定植于肠道 并与微生物群争夺营养。肠道相关微生物群落 对抗肠道病原体对生态系统的入侵(耐定植)。这个 关于如何获得定殖性抗性的分子机制仍不完全 明白了。我们的初步数据表明，大肠杆菌Nissle 1917是一株具有 推定的益生菌特性，防止S.TM肠道定植和肠道炎症 通过有效地竞争呼吸电子受体硝酸盐，这是一种限制性营养物质。我们 假设ECN使用一个或多个铁载体系统来获得足够的铁 含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战略组合。我们将继续追查 具体目标如下：1.调查ECN和S.TM如何竞争硝酸盐 2.确定铁载体介导的铁摄取是否 硝酸还原酶活性所必需的。这项工作将促进我们对如何 肠道病原体，如S.TM和共生微生物，竞争限制 肠道中的资源。这些研究还有望揭示一种分子 益生菌菌株的特性，这可能有助于设计新的干预策略 沙门氏菌肠胃炎。