Computer simulation of Salmonella typhimurium accumulation within tumors

Abstract

Salmonella typhimurium exhibit the ability to specifically chemotax and proliferate in heterogeneous tumor tissue in vitro. Based on this observation, we present a computer simulation to describe how S. typhimurium strains respond to chemotaxis signals that are secreted by different type of tumor cells. To test the effect of each chemoattractant on the chemotaxis of S. typhimurium toward different tumor regions, a range of simulations have been carried out by quantifying the accumulation of chemotaxis machinery knockouts, including generalized strains lacking individual cell surface chemoreceptors. To measure the bacterial accumulation affected by tumor size and structures, we compared the average bacterial density in small tumors (diameter < 500 ηm without quiescent region) with large tumors (diameter > 500 ηm contains quiescent and necrotic regions). Our work demonstrates the value of combining computer simulation with experiments to uncover potential mechanisms that are involved in bacterial chemotaxis tumor targeting and accumulation. In addition, it also demonstrates the utility of the Glazier-Graner-Hogeweg methodology (GGH) for modeling the links between cellular dynamics and environment signaling as well as predicting unanticipated results.