Pathogenesis of shigellosis: from molecular and cellular biology of epithelial cell invasion to tissue inflammation and vaccine development.

INTRODUCTION Shigellosis, or bacillary dysentery, is a bloody diarrhea caused by the invasion of the human colonic and rectal mucosa by Shigella, a gramnegative microorganism belonging to the family enterobacteriaceae. In the developing world, children are the major victims with 600,000 deaths every year. The symptoms are characterized by early watery diarrhea rapidly followed by fever, intestinal cramps, and emission of mucopurulent and bloody stools. Immediate complications may occur, such as hypoglykemia, seizure, toxic megacolon, and the hemolytic uremic syndrome (HUS). A chronic enteropathy may also be observed with delayed thriving of affected children. There are four species of Shigella (Shigella sonnei, Shigella flexneri, Shigella dysenteriae and Shigella boydii). The worldwide endemic form of the disease is caused by S. sonnei and S. flexneri. The epidemic form, which accounts for deadly outbreaks in developing areas, is caused by S. dysenteriae 1. The latter, which was discovered in 1898 by the Japanese microbiologist Shiga, is still often referred to as the Shiga bacillus. It is characterized by the production of Shiga toxin, a potent cytotoxin accounting for the particular severity of the cases the Shiga bacillus usually causes. Shigella is a highly contagious microorganism which is transmitted directly from person to person by hand contact, or indirectly by contaminated food or water. High infectious capacity and rapid occurrence of multiple resistance to antibiotics make prevention and treatment of shigellosis a difficult task. No vaccine is yet available.