Abstract Generalist and human-restricted Salmonella enterica serovars cause diseases ranging from gastroenteritis to typhoid fever. Using live-imaging with controlled-polarity human intestinal epithelial cell (IEC) organoids, we identify epithelial cell sensing as a pre-invasion stage of infection. The generalist serovar Typhimurium migrates toward apical but away from basolateral IEC surfaces, whereas the human-restricted serovar Typhi exhibits the opposite behavior.
