title: Virulence Gene Regulation in Shigella.
abstract: Shigella species are the causative agents of bacillary dysentery in humans, an invasive disease in which the bacteria enter the cells of the epithelial layer of the large intestine, causing extensive tissue damage and inflammation. They rely on a plasmid-encoded type III secretion system (TTSS) to cause disease; this system and its regulation have been investigated intensively at the molecular level for decades. The lessons learned have not only deepened our knowledge of Shigella biology but also informed in important ways our understanding of the mechanisms used by other pathogenic bacteria to cause disease and to control virulence gene expression. In addition, the Shigella story has played a central role in the development of our appreciation of the contribution of horizontal DNA transfer to pathogen evolution.A 30-kilobase-pair "Entry Region" of the 230-kb virulence plasmid lies at the heart of the Shigella pathogenesis system. Here are located the virB and mxiE regulatory genes and most of the structural genes involved in the expression of the TTSS and its effector proteins. Expression of the virulence genes occurs in response to an array of environmental signals, including temperature, osmolarity, and pH.At the top of the regulatory hierarchy and lying on the plasmid outside the Entry Region isvirF, encoding an AraC-like transcription factor.Virulence gene expression is also controlled by chromosomal genes,such as those encoding the nucleoid-associated proteins H-NS, IHF, and Fis, the two-component regulators OmpR/EnvZ and CpxR/CpxA, the anaerobic regulator Fnr, the iron-responsive regulator Fur, and the topoisomerases of the cell that modulate DNA supercoiling. Small regulatory RNAs,the RNA chaperone Hfq,and translational modulation also affect the expression of the virulence phenotypetranscriptionally and/orposttranscriptionally.
authors.affiliation: Department of Microbiology, Moyne Institute of Preventive Medicine, University of Dublin, Trinity College, Dublin 2, Ireland.
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Dorman