title: Independent bottlenecks characterize colonization of systemic compartments and gut lymphoid tissue by salmonella.
abstract: Vaccination represents an important instrument to control typhoid fever in humans and protects mice from lethal infection with mouse pathogenic serovars of Salmonella species. Mixed infections with tagged Salmonella can be used in combination with probabilistic models to describe the dynamics of the infection process. Here we used mixed oral infections with tagged Salmonella 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 Salmonella strains which offers a fast and reliable method to characterise the composition of genome-tagged Salmonella strains. We show that initial colonization of Salmonella 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 Salmonella to colonize systemic and gut immune compartments and provide a framework for the further dissection of infection dynamics.
authors: Institute of Immunology, Hannover Medical School, Hannover, Germany.
authors: Chee Han
authors: CH
authors: Lim
authors: Institute of Immunology, Hannover Medical School, Hannover, Germany.
authors: Sabrina
authors: S
authors: Voedisch
authors: Institute of Immunology, Hannover Medical School, Hannover, Germany.
authors: Benjamin
authors: B
authors: Wahl
authors: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
authors: Syed Fazle
authors: SF
authors: Rouf
authors: Department of Genome Analytics, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors: Robert
authors: R
authors: Geffers
authors: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
authors: Mikael
authors: M
authors: Rhen
authors: Institute of Immunology, Hannover Medical School, Hannover, Germany; Institute of Molecular Medicine, RWTH Aachen University, Aachen, Germany.
authors: Oliver
authors: O
authors: Pabst
mesh_terms: D000284:Administration, Oral; D000818:Animals; D004269:DNA, Bacterial / Q000235:genetics; D041981:Gastrointestinal Tract / Q000276:immunology / Q000382:microbiology*; D059014:High-Throughput Nucleotide Sequencing; D007413:Intestinal Mucosa / Q000382:microbiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010581:Peyer's Patches / Q000276:immunology / Q000382:microbiology*; D012481:Salmonella Infections, Animal / Q000276:immunology / Q000382:microbiology* / Q000517:prevention & control; D012486:Salmonella typhimurium / Q000235:genetics / Q000472:pathogenicity*; D013154:Spleen / Q000382:microbiology*; D014611:Vaccination
chemical_list: D004269:DNA, Bacterial