A Computational Model of Bacterial Population Dynamics in Gastrointestinal Yersinia enterocolitica Infections in Mice

SIMPLE SUMMARY: Computational modeling of bacterial infection is an attractive way to simulate infection scenarios. In the long-term, such models could be used to identify factors that make individuals more susceptible to infection, or how interference with bacterial growth influences the course of bacterial infection. This study used different mouse infection models (immunocompetent, lacking a microbiota, and immunodeficient models) to develop a basic mathematical model of a Yersinia enterocolitica gastrointestinal infection. We showed that our model can reflect our findings derived from mouse infections, and we demonstrated how crucial the exact knowledge about parameters influencing the population dynamics is. Still, we think that computational models will be of great value in the future; however, to foster the development of more complex models, we propose the broad implementation of the interdisciplinary training of mathematicians and biologists. ABSTRACT: The complex interplay of a pathogen with its virulence and fitness factors, the host’s immune response, and the endogenous microbiome determine the course and outcome of gastrointestinal infection. The expansion of a pathogen within the gastrointestinal tract implies an increased risk of developing severe systemic infections, especially in dysbiotic or immunocompromised individuals. We developed a mechanistic computational model that calculates and simulates such scenarios, based on an ordinary differential equation system, to explain the bacterial population dynamics during gastrointestinal infection. For implementing the model and estimating its parameters, oral mouse infection experiments with the enteropathogen, Yersinia enterocolitica (Ye), were carried out. Our model accounts for specific pathogen characteristics and is intended to reflect scenarios where colonization resistance, mediated by the endogenous microbiome, is lacking, or where the immune response is partially impaired. Fitting our data from experimental mouse infections, we can justify our model setup and deduce cues for further model improvement. The model is freely available, in SBML format, from the BioModels Database under the accession number MODEL2002070001.