Exploring Salmonella-host cell interactions from inside out
In a recent PLOS Biology article, the Vorholt group (IMB) together with the Hardt (IMB) and Sellin (Uppsala University) labs report the direct placement of the bacterial pathogen Salmonella into the cytosol of enteroid cells, enabling spatiotemporal analysis of host-pathogen interactions.
The cells that line the lumen of the intestine, the intestinal epithelial cells, are crucial for protecting the underlying tissues from gut microbes. However, pathogens such as Salmonella are able to invade these cells and use them as a replicative niche. Researchers from the Vorholt group, in collaboration with the Hardt and Sellin labs, apply the single cell injection technology FluidFM to study this intricate process using an organoid model.
They place the pathogen directly into the cytosol of intestinal epithelial cells and study niche-specific host-pathogen interactions uncoupled from otherwise preceding pathogen docking, invasion and vacuolar escape. Using a fluorescence reporter, the authors observe inflammasome formation in single cells, followed by cell expulsion in real-time. Disarmed bacteria lacking proteins normally required for cell invasion remain unrecognized by this innate immune system of the host cells. Strikingly, despite their inability to invade, these bacterial mutants are still able to use the cytosol as growth environment upon FluidFM-mediated injection. These findings indicate that these specific bacterial structures, that is flagella and type III secretion systems, are not required for replication in the cytosol of host cells.
Link to the paper in external page"PLOS Biology"