Microbiota outgrowth by Salmonella

沙门氏菌引起的微生物群生长

• 批准号: 10448362
• 负责人: Andreas J Baumler
• 金额: $ 46.24万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10448362
• 关键词: Address; Affect; Anaerobic Bacteria; Bacteria; Bile Acids; Cause of Death; Cell Respiration; Clinical; Colon; Colorectal; Communities; Complex; Disease; Disease Outbreaks; Ecosystem; Education; Enterobactin; Environment; Epithelial; Equilibrium; Gastroenteritis; Goals; Growth; Health; Human; Immune; Immune response; Infection; Inflammation; Inflammatory; Inflammatory Response; Intestines; Iron; Knowledge; LCN2 gene; Link; Mediating; Medical Care Costs; Modification; Molecular; Neurotransmitters; Nutrient; Parasites; Pathogenesis; Phase; Physiology; Production; Productivity; Research; Research Personnel; Resources; Salmonella; Salmonella enterica; Serotyping; Sulfides; Sulfur Metabolism Pathway; Testing; Time; United States; Virulence Factors; Virus; Work; colonization resistance; diarrheal disease; dysbiosis; enteric pathogen; expectation; experimental study; foodborne illness; gut inflammation; gut microbiota; host-associated microbial communities; innovation; insight; interest; microbial; microbial community; microbiota; non-typhoidal Salmonella; nutrition; pathogen; polyol; preempt; public health relevance; shift work

ABSTRACT Our intestine is host to a complex microbial community, the gut microbiota, which is dominated by obligate anaerobic bacteria belonging to the classes Clostridia and Bacteroidia. This community provides benefit to the host by contributing to nutrition, immune education and niche protection against enteric pathogens (colonization resistance). However, Salmonella enterica serovar (S.) Typhimurium can use its virulence factors to overcome colonization resistance by triggering intestinal inflammation. The host inflammatory response remodels the intestinal environment, which fuels growth of the pathogen, but also causes an imbalance in the microbiota (dysbiosis). The question of how intestinal inflammation drives changes in the microbiota composition and how these changes affect host physiology and pathogen expansion represents a high-impact topic that will be addressed in this application. The objectives of this application are to study the mechanisms that enable the pathogen to gain an edge over competing Enterobacterales during intestinal inflammation. Our central hypothesis is that S. Typhimurium virulence factors trigger host responses that remodel the intestinal environment to generate resources that fuel pathogen growth while at the same time enabling it to edge out competing Enterobacterales. To test this hypothesis, we will determine in Specific Aim 1 whether S. Typhimurium benefits from intestinal inflammation because this host response increases the availability of polyols. In Specific Aim 2 we will determine whether S. Typhimurium depletes a neurotransmitter to compete with Enterobacterales for iron. Finally, our third specific aim will determine whether sulfide production by S. Typhimurium provides a benefit during competition with endogenous Enterobacterales. It is our expectation that successful completion of the proposed experiments will usher in important conceptual advances in understanding the mechanisms underlying pathogen expansion during S. Typhimurium-induced gastroenteritis.

抽象的 我们的肠道是一个复杂的微生物群落，肠道微生物群，这是主导的 通过属于梭状芽胞杆菌和拟杆菌类的厌氧菌细菌。这 社区通过贡献营养，免疫教育和利基市场为主人提供好处 防止肠道病原体（定殖抗性）。但是，沙门氏菌肠 血清（S.）鼠伤寒可以使用其毒力因子克服定殖抗性 触发肠炎。宿主炎症反应重塑了肠道 环境，它为病原体的生长增长，但也会导致微生物群失衡 （营养不良）。肠道炎症如何驱动微生物群变化的问题 组成以及这些变化如何影响宿主生理和病原体的扩展代表 该应用程序将在此应用程序中解决的一个高影响主题。此应用程序的目标是 研究使病原体能够获得竞争优势的机制 肠炎期间的肠杆菌。我们的中心假设是鼠伤寒链球菌 毒力因子触发宿主反应，以重塑肠道环境以产生 促进病原体增长的资源，同时使其能够竞争竞争 肠杆菌。为了检验这一假设，我们将在特定的目标1中确定是否S。 鼠伤寒会受益于肠道炎症，因为这种宿主反应增加了 多元元的可用性。在特定的目标2中，我们将确定孢子链球菌是否耗尽A 神经递质与肠杆菌竞争铁。最后，我们的第三个特定目标 确定在竞争期间通过鼠伤寒沙门氏菌生产硫化物是否提供了好处 内源性肠杆菌。我们期望成功完成 拟议的实验将带来重要的概念进步 鼠伤寒链球菌诱导的胃肠炎期间病原体扩张的机制。