A Tale about : Evolution, Plasmid, and Virulence.

spp. cause hundreds of millions of intestinal infections each year. They target the mucosa of the human colon and are an important model of intracellular bacterial pathogenesis. is a pathovar of that is characterized by the presence of a large invasion plasmid, pINV, which encodes the characteristic type III secretion system and used for cytosol invasion and cell-to-cell spread, respectively. First, we review recent advances in the genetic aspects of , shedding light on its evolutionary history within the lineage and its relationship to the acquisition of pINV. We then discuss recent insights into the processes that allow for the maintenance of pINV. Finally, we describe the role of the transcription activators VirF, VirB, and MxiE in the major virulence gene regulatory cascades that control the expression of the type III secretion system and . This provides an opportunity to examine the interplay between these pINV-encoded transcriptional activators and numerous chromosome-encoded factors that modulate their activity. Finally, we discuss novel chromosomal genes , , and that are regulated by MxiE. This review emphasizes the notion that and have walked the fine line between commensalism and pathogenesis for much of their history.