Identifying Parameters Of Host Cell Vulnerability During Salmonella Infection By Quantitative Image Analysis And Modeling

Salmonella target and enter epithelial cells at permissive entry sites: some cells are more likely to be infected than others. However the parameters that lead to host cell heterogeneity are not known. Here, we quantitatively characterized host cell \"vulnerability\" towards Salmonella infection based on imaged parameters. We performed successive infections of the same host cell population followed by automated high-throuput microscopy and observed that infected cells have higher probability of being re-infected. Establishing a predictive model we identified two combined origins of host cell vulnerability: the pathogen-induced cellular vulnerability emerging from Salmonella uptake and persisting at later stage of the infection, and the host cell-inherent vulnerability. We linked the host cell inherent vulnerability with its morphological attributes such as the local cell crowding, and with host cell cholesterol content. This showed that the probability of Salmonella infection success can be forecast from morphological or molecular host cell parameters.