Shigella 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. Shigella is a pathovar of Escherichia coli that is characterized by the presence of a large invasion plasmid, pINV, which encodes the characteristic type III secretion system and icsA used for cytosol invasion and cell-to-cell spread, respectively. First, we review recent advances in the genetic aspects of Shigella, shedding light on its evolutionary history within the E. coli 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 icsA. 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 icaR, icaT, and yccE that are regulated by MxiE. This review emphasizes the notion that Shigella and E. coli have walked the fine line between commensalism and pathogenesis for much of their history.
Keywords: Escherichia coli; MxiE; Shigella; VirB; VirF; cell-to-cell spread; pathogenesis; plasmid; regulation of virulence genes; type III secretion system.