A new paper reports that Salmonella enterica usurps a mechanism for homeostatic turnover of gastrointestinal epithelial cells to ensure host cell exit.

Intracellular bacterial pathogens such as S. enterica not only need to establish a replicative niche within host cells, but must also have an effective exit strategy to ensure dissemination and transmission. S. enterica replicates within a membrane-bound Salmonella-containing vacuole (SCV) in the polarized epithelial cells that line the gastrointestinal tract. Although we have a detailed understanding of the intracellular lifestyle of S. enterica, little is known about how this pathogen escapes from its intracellular niche and spreads within the host.

Analysis of the replication of S. enterica within a human colonic epithelial cell monolayer revealed the presence of a subpopulation of 'hyper-replicating' bacteria that had a doubling time of ∼20 minutes and were not contained in an SCV but were free in the cytoplasm. A transcriptional fusion assay showed that in these bacteria the expression of type III secretion system 1 (T3SS1) and flagella, which are required for invasion, was upregulated late in infection, suggesting that this bacterial subpopulation is 'primed' for invasion.

Using scanning electron and fluorescence microscopy, the authors followed the fate of the cytoplasmic bacteria during the infection cycle. In vitro, cytoplasmic bacteria-filled cells were shown to be extruded from the apical side of a colonic epithelial cell monolayer, and in vivo, in a mouse model of gallbladder infection, T3SS1-induced, flagellated bacteria were found free in the gallbladder lumen and in sloughed cells. The authors noted that the cellular reorganization that occurred during the extrusion of infected cells was reminiscent of that required for the homeostatic turnover of epithelial cells. However, in contrast to homeostatic extrusion, infected extruded cells underwent caspase 1-dependent inflammatory cell death.

Increased turnover of epithelial cells can be an effective mechanism to protect against infection. In this instance, Knodler et al. propose that S. enterica hijacks the mechanisms involved in homeostatic turnover to exit host epithelial cells, completing the infection cycle.