Independent Bottlenecks Characterize Colonization of Systemic Compartments and Gut Lymphoid Tissue by <i>Salmonella</i>

<div><p>Vaccination represents an important instrument to control typhoid fever in humans and protects mice from lethal infection with mouse pathogenic serovars of <i>Salmonella</i> species. Mixed infections with tagged <i>Salmonella</i> can be used in combination with probabilistic models to describe the dynamics of the infection process. Here we used mixed oral infections with tagged <i>Salmonella</i> strains to identify bottlenecks in the infection process in naïve and vaccinated mice. We established a next generation sequencing based method to characterize the composition of tagged <i>Salmonella</i> strains which offers a fast and reliable method to characterise the composition of genome-tagged <i>Salmonella</i> strains. We show that initial colonization of <i>Salmonella</i> was distinguished by a non-Darwinian selection of few bacteria setting up the infection independently in gut associated lymphoid tissue and systemic compartments. Colonization of Peyer's patches fuels the sustained spread of bacteria into mesenteric lymph nodes via dendritic cells. In contrast, infection of liver and spleen originated from an independent pool of bacteria. Vaccination only moderately reduced invasion of Peyer's patches but potently uncoupled bacterial populations present in different systemic compartments. Our data indicate that vaccination differentially skews the capacity of <i>Salmonella</i> to colonize systemic and gut immune compartments and provide a framework for the further dissection of infection dynamics.</p>