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

大肠杆菌素是由肠杆菌科细菌（即E.大肠杆菌、沙门氏菌）。大肠杆菌素作为生产者群体的共同利益，但仅由一部分生产者群体合成，因为单个细菌在大肠杆菌素释放后死亡。因此，劳动分工可以增加生产者群体在与大肠杆菌素敏感的肠细菌植物群竞争中的整体适应性。在这里，我们将测试的假设，即异质性大肠杆菌素的表达增加了健身的菌株对竞争对手。我们将使用大肠杆菌素Ib表达的模型，由肠道病原体，沙门氏菌肠道血清型鼠伤寒沙门氏菌（S。Tm）。在这个项目中，我们将产生适当的报告工具，并调查环境线索和细菌调节因子导致随机表达以及大肠杆菌素表达个体的生存后果。此外，我们将工程师S。大肠杆菌素Ib表达率升高和降低的Tm菌株。在一系列感染实验中，使用不含固有肠杆菌科的无菌小鼠模型，我们将确定在存在或不存在竞争者的情况下大肠杆菌素Ib表达的适应性益处以及潜在成本（Escherosal E. coli）。这些实验数据将使我们能够建立一个数学模型来解释大肠杆菌素Ib在S.在竞争性的自然栖息地--肠道中获得种群和适合度的好处。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。

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.