The Genetic Organization and Transcriptional Regulation of Shigella Virulence Genes

Central to bacterial pathogenicity is the precise and coordinated control of virulence gene expression in response to environmental cues encountered in the human host. This chapter focuses on the transcriptional regulation of Shigella virulence genes encoded by the large virulence plasmid, pINV, found in almost all Shigella species. We describe the silencing of pINV-encoded virulence genes by the chromosomally encoded nucleoid structuring protein H-NS, which serves as the backdrop for all other regulatory events on this plasmid. We then describe the four-tiered virulence regulatory cascade emphasizing the environmental stimuli, transcriptional regulators and mechanisms that govern virulence gene expression at each tier. Finally, we review other regulatory inputs that are received from the Shigella chromosome and their role in modulating virulence gene expression. We begin by describing the genetic organization of Shigella, its relationship to Escherichia coli and the different forms of pINV carried by Shigella species to highlight how the regulatory cascades controlling Shigella virulence are, in large part, conserved across species. Overall, this chapter reveals that Shigella is a fascinating model for the study of virulence gene regulation, which promotes our understanding of Shigella pathogenesis and mechanisms of virulence gene regulation in other bacterial pathogens.