Metabolic Interactions between Salmonella and E. coli Nissle 1917

项目摘要 鼠伤寒沙门氏菌感染。Tm）是一种常见的 炎症性腹泻作为感染过程的一部分，S. Tm在肠道中定植 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）。的 如何实现定殖抗性的分子机制仍然不完全 明白我们的初步数据表明，E. coliNissle 1917，E.大肠杆菌菌株 假定的益生菌特性，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，限制营养素。我们 假设EcN使用一种或多种铁载体系统来获得足够的铁， 含铁硫簇的硝酸盐还原酶，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。我们将奉行 具体目标如下：1.研究EcN和S.它们竞争硝酸盐， 小鼠肠，和2.确定铁载体介导的铁摄取是否 需要硝酸还原酶活性。这项工作将促进我们了解如何 肠道病原体，如S. Tm，和肠道微生物竞争限制 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， 沙门氏菌胃肠炎。

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.