RESUMO
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.
Assuntos
Trato Gastrointestinal/microbiologia , Mucosa Intestinal/microbiologia , Nódulos Linfáticos Agregados/microbiologia , Salmonelose Animal/microbiologia , Salmonella typhimurium/patogenicidade , Baço/microbiologia , Administração Oral , Animais , DNA Bacteriano/genética , Trato Gastrointestinal/imunologia , Sequenciamento de Nucleotídeos em Larga Escala , Camundongos , Camundongos Endogâmicos C57BL , Nódulos Linfáticos Agregados/imunologia , Salmonelose Animal/imunologia , Salmonelose Animal/prevenção & controle , Salmonella typhimurium/genética , VacinaçãoRESUMO
The article explores the rules and criteria used for the allocation of donor organs in Singapore. Organs are extremely scarce, so hard decisions have to be made about who receives them. Based on an analysis of documents and interviews done with local program directors, both the admission to a waiting list for transplant and the final recipient selection are covered. The observed practices appear remarkably similar to those predominant in several Western countries until recently, when they had to be modified there following public criticism. It remains to be seen whether Singapore can sustain its much stricter standards in the future.