Glutarate metabolism in Salmonella

沙门氏菌中的戊二酸代谢

• 批准号: 10640495
• 负责人: Sebastian E Winter
• 金额: $ 12.34万
• 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: 2022-07-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10640495
• 关键词: Glutarate; metabolism; Salmonella

PROJECT SUMMARY Infection with the bacterial pathogen Salmonella enterica serovar Typhimurium (S. Tm) is a common cause of inflammatory diarrhea. Intriguingly, intestinal inflammation drives an expansion of the S. Tm population in the gut lumen. The molecular mechanisms that support S. Tm colonization of the intestinal tract remain incompletely understood. Our central hypothesis is that the inflamed gut constitutes a peculiar nutritional environment that enables S. Tm to outgrow obligate anaerobic commensal bacteria. In this application, we will investigate how inflammatory reactive oxygen and nitrogen species are generating a diverse array of inflammation-associated small metabolites. We hypothesize that reactive oxygen and nitrogen species oxidize sugars to smaller mono- and dicarboxylic acids such as glutarate, which serve as nutrients for S. Tm to support gut colonization. We will test key aspects of our hypothesis in mouse models of infection and in vitro. We will pursue the following specific aims: 1.) Determine whether glutarate and other carboxylic acids are generated as byproducts of RNS metabolism, and 2. Investigate S. Tm glutarate metabolism in the context of infection. This work will advance our understanding of how intestinal pathogens, such as S. Tm, adapt their carbon and energy metabolism to colonize the mammalian intestinal tract. These studies are also expected to advance our understanding of how reactive oxygen and nitrogen species participate in diversity-generating reactions that shape the metabolite landscape during gut inflammation.

项目摘要 细菌病原体沙门氏菌血清鼠伤寒（S. tm）感染 是炎症性腹泻的常见原因。有趣的是，肠炎驱动 肠腔中的S. tm种群的扩展。分子机制 支持S. tm的肠道定植尚未完全理解。我们的 中心假设是发炎的肠道构成一个特殊的营养环境 这使S. tm能够超越厌氧共生细菌的义务。在这个 应用，我们将研究炎性活性氧和氮种如何 正在产生各种炎症相关的小型代谢物。我们 假设活性氧和氮种将糖氧化为较小的单一单体 和二羧酸（例如谷氨酸），它们是S. tm支持的营养素 肠道殖民化。我们将在小鼠感染模型中测试假设的关键方面 并在体外。我们将追求以下特定目的：1。）确定是否谷氨酸 和其他羧酸作为RNS代谢的副产物以及2。 在感染的背景下，研究链球菌的谷氨酸链霉菌代谢。这项工作将进步 我们对肠道病原体（例如S. tm）如何适应其碳和 能量代谢以定居于哺乳动物肠道。这些研究也是 期望提高我们对活性氧和氮种的理解 参加多样性生成的反应，以塑造代谢物景观 肠炎。