Genetic and molecular basis of epithelial cell invasion by Shigella species

Abstract

Bacteria that belong to the four species of the genus Shigella cause a dysenteric syndrome by means of their unique capacity to invade the human colonic mucosa. The various steps of invasion of epithelial cells are controlled by a 220-kilobase plasmid. Plasmid genes that encode for entry into cells through bacterium-directed phagocytosis have been identified. Among these, ipa genes encode four highly immunogenic polypeptides. The ability of intracellular bacteria to multiply subsequently in an efficient manner is attributable to their capacity to lyse phagocytic membrane with a plasmid-encoded contact hemolysin that also determines bacterial entry capacity. In a further step, bacteria that lie free within the cytosol spread intracellularly and infect adjacent cells by inducing rapid polymerization of actin or accumulation of actin. Another plasmid gene, icsA (virG), that encodes a 120-kDa outer-membrane protein accounts for this phenotype. Finally, intracellular shigellae kill host cells rapidly by means of an unknown mechanism that does not seem to involve production of Shiga toxin or Shiga-like toxin. The invasion genes are controlled by both positive and negative regulatory systems.