Bacterial infections are among the top death causes worldwide. Besides the emergence and spread of antibiotic resistance, the transient antibiotics tolerance of so-called bacterial persisters, a bacterial subset linked with the recalcitrance of chronic infections and characterized by a distinct metabolism and growth rate, represents yet another substantial health concern. Accordingly, understanding heterogeneous host-pathogen encounters and the underlying mechanisms determining the disparate outcomes is important for closing tolerant niches in which bacterial pathogens can thrive. Viewing the relevance of finding reliable markers describing heterogeneous host-Salmonella interactions, we will study their interaction for the first time from the integrative proteome perspective of the bacterial pathogen as well as the infected host, making use of phagocytic as well as non-phagocytic hosts. To do this, we will employ state-of-the-art proteomics, effector interactomics and live-cell imaging, overall enabling (host) expression changes to be monitored alongside distinct bacterial inputs to explore the dynamics of the interaction. This way, unique insights gained into the great diversity of host-Salmonella encounters steering disease progression in a differential manner will highlight novel bacterial virulence factors and inform the development of novel antibacterial treatment.