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

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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.