Salmonella species are among the most common foodborne pathogens. As an intracellular pathogen, Salmonella employs multiple virulence factors to interfere with critical host cell pathways to achieve successful colonization of the host. Past studies have provided many molecular insights into Salmonella-host cell interactions. However, many aspects of Salmonella pathogenesis are still not well understood. Furthermore, emerging antibiotic-resistant Salmonella strains represent a significant clinical threat, and it is crucial to develop novel anti-Salmonella therapeutics.
Previous studies have established that IFNγ plays a pivotal role driving the clearance of Salmonella from infected hosts. Although several elegant examples of IFNγ-triggered host defense mechanisms have been elucidated, the activities of many IFNγ-regulated genes remain elusive. In this project, we aimed to uncover novel aspects of IFNγ-regulated, Salmonella-host cell interactions via conducting a macrophage-based drug screen. A drug library of 3,088 compounds, mainly comprised of FDA approved drugs, were used to treat RAW264.7 cells before cells were stimulated with IFNγ and subsequently infected with Salmonella. The infection was examined by confocal microscopy and analyzed through the CellProfiler data analysis pipeline. From the primary screen, we identified 86 drugs that inhibited Salmonella intracellular replication with IFNγ treatment when compared to untreated samples, while 121 drugs appeared to enhance Salmonella intracellular replication. Our preliminary data suggests that IFNγ stimulation alters Salmonella host cell infection outcomes from various drug treatments.