Kinetics, thresholds, and a comparison of mechanisms underlying systemic infection by Listeria monocytogenes

Studies on the system-scale pathogenesis of Listeria monocytogenes infection have classically focused on its ability to colonize in the intestines following an exposure event. However, despite this, many of the most dangerous complications arising from L. monocytogenes infection are observed days, weeks, or months after exposure, resulting indirectly from bacteria escaping this intestinal colonization hub and invading other organs. Over time, findings of various individual phenomena observed during systemic infection have accumulated, including a shift away from the principal route of intestinal dissemination, delays in bacterial colonization of the central nervous system, differing bacterial flux rates across organs, and multi-stability of bacterial population levels. To further our quantitative understanding of foodborne bacterial infection dynamics, a compartmental model of systemic infection that synthesizes these findings is proposed. Under parameterization to infection in BALB/c mice, the model is used to show a substantial decrease in bacterial populations resulting from dissemination through the mesenteric lymph nodes, as compared to the portal vein, when controlling for the number of bacteria passing through each route. Due to the compartmental nature of this model, we anticipate that this result may be paralleled in other microbes which make use of these pathways to escape the intestinal environment. Additionally, we predict thresholds for intestinal dissemination along each of these routes, which must be surpassed to induce systemic infection, and describe how these thresholds change over time. Supplementarily, logistic curves are fitted to synthetic data as a means of robustly quantifying the dose–response relationship beyond the intestinal barrier.