SPI1 and infection: Following invasion of 3-D cells, the SPI-1, SPI-2, SPI-1/2 double mutant, and the SPI-1/2 flhDC triple T3SS mutant, all grew to similar levels intracellularly, but to substantially lower levels than wildtype Salmonella. Collectively, we provide evidence that our highly differentiated 3-D models of human colonic epithelium exhibit infection phenotypes that are consistent with an in vivo enteric Salmonella infection.