Microbiota outgrowth by Salmonella

摘要 我们的肠道是一个复杂的微生物群落的宿主，肠道微生物群， 属于梭菌纲和拟杆菌纲的专性厌氧细菌。这 社区通过营养、免疫教育和生态位为宿主提供利益 防止肠道病原体（定植抗性）。然而，肠道沙门氏菌 血清型（S.）鼠伤寒可以利用其毒力因子，克服殖民抵抗力， 引发肠道炎症宿主的炎症反应重塑了肠道 环境，这助长了病原体的生长，但也导致了微生物群的不平衡 （生态失调）。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学和病原体扩张， 一个高影响力的主题，将在此应用程序中解决。本申请的目的是 来研究病原体获得优势的机制 肠道炎症期间的肠道菌群。我们的中心假设是S.鼠伤寒 毒力因子触发宿主反应，重塑肠道环境， 这些资源既能促进病原体的生长，同时又能使其在竞争中脱颖而出， 肠球菌目为了检验这一假设，我们将在具体目标1中确定S。 鼠伤寒受益于肠道炎症，因为这种宿主反应增加了 多元醇的供应情况。在具体目标2中，我们将确定S是否。鼠伤寒沙门氏菌消耗a 神经递质与肠球菌竞争铁。最后，我们的第三个具体目标是 确定S.鼠伤寒在比赛中提供了一个好处 与内源性肠球菌感染我们期望， 拟议的实验将在理解这一问题上带来重要的概念性进展， 病原菌在S. Typhimurium引起的胃肠炎。

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.