Quantitative single-cell analysis of colicin Ib expression in Salmonella enterica serovar Typhimurium and its role in competition against commensal E. coli in the gut

鼠伤寒沙门氏菌中大肠杆菌素 Ib 表达的定量单细胞分析及其在与肠道共生大肠杆菌竞争中的作用

• 批准号: 218253822
• 负责人: Professorin Dr. Barbara Stecher
• 金额: --
• 依托单位: Max-von-Pettenkofer-Institut für Hygiene und Medizinische Mikrobiologie
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2012
• 资助国家: 德国
• 起止时间: 2011-12-31 至 2015-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/218253822?language=en
• 关键词: Quantitative; single; cell; analysis; colicin

Colicins are protein toxins produced by and toxic for bacteria of the Enterobacteriaceae family (i.e. E. coli, Salmonella). Colicins serve as a common good for the population of producers but are only syn-thesized by a fraction of the producer population, as individual bacteria die upon colicin release. Thus, division of labor may increase the overall fitness of the producer population in competition with a colicin-sensitive enterobacterial flora. Here, we will test the hypothesis, that heterogenous colicin-expression increases the fitness of a strain against competitors. We will use the model of colicin Ib expression by the enteric pathogen, Salmonella enterica serovar Typhimurium (S. Tm). In this project, we will generate appropriate reporter tools and investigate the environmental cues and bacterial regu-lators leading to stochastic expression as well as the consequences for survival of colicin expressing individuals. Furthermore, we will engineer S. Tm strains with increased and decreased colicin Ib ex-pression rates. In a series of infection experiments using a gnotobiotic mouse model free of intrinsic Enterobacteriaceae, we will determine the fitness benefits as well as the costs underlying colicin Ib expression in the presence or absence of a competitor (commensal E. coli). The collective experi-mental data will allow us establishing a mathematical model explaining the link between heterogeneity of colicin Ib expression in a S. Tm population and fitness benefit gained in its competitive natural habitat, the gut. This project has the potential to provide new fundamental insights into microbial interactions in the gut, and their consequences for the outcome of infections.

大肠杆菌素是由肠杆菌科细菌（即大肠杆菌、沙门氏菌）产生的蛋白质毒素，对它们有毒。大肠杆菌素是生产者群体的共同利益，但仅由一小部分生产者合成，因为单个细菌在大肠杆菌素释放后就会死亡。因此，劳动分工可能会提高生产者群体在与大肠菌素敏感的肠杆菌群竞争中的整体适应性。在这里，我们将检验以下假设：异源大肠菌素表达会增加菌株对抗竞争对手的适应性。我们将使用肠道病原体鼠伤寒沙门氏菌 (S. Tm) 表达大肠杆菌素 Ib 的模型。在这个项目中，我们将生成适当的报告工具，并研究导致随机表达的环境线索和细菌调节剂以及表达大肠杆菌素的个体的生存后果。此外，我们将设计大肠杆菌素 Ib 表达率增加和减少的 S.Tm 菌株。在使用不含内在肠杆菌科细菌的无菌小鼠模型进行的一系列感染实验中，我们将确定在存在或不存在竞争者（共生大肠杆菌）的情况下大肠菌素 Ib 表达的健康益处以及潜在成本。集体实验数据将使我们能够建立一个数学模型，解释 S.Tm 群体中大肠菌素 Ib 表达的异质性与其竞争性自然栖息地肠道中获得的健康益处之间的联系。该项目有可能为肠道微生物相互作用及其对感染结果的影响提供新的基本见解。