Speaker
Description
The bacterium Coxiella burnetii is the causative agent of Q-Fever. Inhalation of a small number of bacteria in the dormant form is sufficient to cause disease. Following exposure, alveolar macrophages host both the morphological switching to a replicative variant, and bacterial proliferation. Upon host cell death, the intracellular population of C. burnetii is released and can propagate infection. We propose a stochastic birth-and-death process with killing, accounting for the two populations of bacterial variant. To calibrate the model we leverage experimental data using host cells from both Vero and THP-1 cell lines, and use Approximate Bayesian Computation to infer parameter values. We establish the distribution of time until host cell death for infected cells in the presence or absence of interferon-$\gamma$ to represent a potential immune activated response. Using this model, we calculate the rupture size distribution for an infected cell which has engulfed a single bacterium. We predict that the rupture size distribution for an infected cell is likely bimodal, with the most probable outcomes being the release of just a few bacteria, or a number closer to the host cell carrying capacity. Explicitly considering the biphasic developmental cycle of C. burnetii, we show how the distribution of time until cellular death impacts the proportion of the two bacterial phenotypes released, and discuss the implications of this when considering within-host infection dynamics.
