Contribution of SPI-1 bistability to Salmonella enterica cooperative virulence: insights from single cell analysis

Salmonella enterica pathogenicity island 1 (SPI-1) is a gene cluster that encodes a type III secretion system and effectors involved in epithelial cell invasion. SPI-1 undergoes bistable expression, with concomitant formation of SPI-1(ON) and SPI-1(OFF) lineages. This study describes single cell analysis of SP1-1 bistability and epithelial cell invasion, and reports the unsuspected observation that optimal invasion of epithelial cells requires the presence of both SPI-1(ON) and SPI-1(OFF) subpopulations. The contribution of SPI-1(OFF) cells to optimal invasion may rely on their ability to invade epithelial cells if a SPI-1(ON) subpopulation is present. In fact, Salmonella SPI-1 mutants are also able to invade epithelial cells in the presence of SPI-1(ON) Salmonellae, a phenomenon described in the 1990’s by Galán and co-workers. Invasion by SPI-1(OFF) cells does not seem to involve a diffusible factor. A small number of SPI-1(ON) cells is sufficient to endow the bacterial population with invasion capacity, a feature that may permit host colonization regardless of the bottlenecks encountered by Salmonella populations inside animals.