Stochastic modeling of the dynamics ofSalmonellainfection of epithelial cells

Abstract

AbstractBacteria of theSalmonellagenus are intracellular pathogens, which cause gastroenteritis and typhoid fever in animals and humans, and are responsible for millions of infections and thousands of deaths across the world every year. Furthermore,Salmonellahas played the role of a model organism for studying host-pathogen interactions. Taking these two aspects into account, enormous efforts in the literature are devoted to study this intracellular pathogen. Within epithelial cells, there are two distinct subpopulations ofSalmonella: (i) a large fraction ofSalmonella, which are enclosed by vacuoles, and (ii) a small fraction of hyper-replicating cytosolicSalmonella. Here, by considering the infection of epithelial cells bySalmonellaas a discrete-state, continuous-time Markov process, we propose a stochastic model of infection, which includes the invasion ofSalmonellainto the epithelial cells by a cooperative strategy, the replication inside theSalmonella-containing vacuole, and the bacterial proliferation in the cytosol. The xenophagic degradation of cytosolic bacteria is considered, too. The stochastic approach provides important insights into stochastic variation and heterogeneity of the vacuolar and cytosolicSalmonellapopulations on a single-cell level over time. Specifically, we predict the percentage of infected human epithelial cells depending on the incubation time and the multiplicity of infection, an d the bacterial load of the infected cells at different post-infection times.