Rupture, invasion and inflammatory destruction of the intestinal barrier byShigella, making sense of prokaryote–eukaryote cross-talks

Abstract

Bacillary dysentery is an acute inflammatory bowel disease caused by an infectious agent, the enteroinvasive genus Shigella , hence the name shigellosis. Shigellae have the capacity to invade the colonic and rectal epithelium in humans, thereby causing the acute mucosal inflammation that characterizes the disease. Shigellosis is endemic throughout the world, but 99% of the 150 million annual cases and almost all of the million deaths occur in the developing world, particularly in areas where personal and general hygiene are insufficient. Shigellosis is a disease of impoverished people which in about 70% of the cases affects children between the ages of 1 and 5 years [1]. There are four species of Shigella: S. dysenteriae , among which serotype 1 (shiga bacillus) accounts for brisk and deadly epidemics in the poorest populations, S. flexneri and S. sonnei which account for the endemic form of the disease, the latter being prevalent in the industrialized world, and S. boydii which is only observed in the Indian subcontinent. In view of increasing antibiotic resistance and persistence of the poor hygiene conditions that allow contamination, vaccination appears the most cost-effective approach in spite of tremendous difficulties in developing a new vaccine in this particular situation [2]. Shigella is a highly contagious microorganism since as few as 10–100 bacteria can cause the disease in adult volunteers. After oral contamination, bacteria pass through the stomach and the small intestine before reaching the colon where they invade the mucosa, initiating the acute destructive recto-colitis that causes the dysenteric symptoms: fever, intestinal cramps and emission of mucopurulent and bloody stools. The basis for organ specificity of shigellosis to the rectal and colonic mucosae is not understood. Shigella may express a colon-specific adhesive system, or the colonic and rectal mucosae may be more susceptible to developing acute inflammation …