Pathogenesis of Shigella

· Bacteriology

Shigella is a common cause of bacterial diarrhoea worldwide, especially in developing countries. Humans are the only natural reservoir for disease. Transmission can occur via direct person-to-person spread, as well as via contaminated food and water. Infective dose is very low as 10-100 bacilli can cause disease.

Once ingested, the bacteria survive the gastric environment of the stomach and move on to the large intestine. There, they attach to and penetrate the epithelial cells of the intestinal mucosa. After invasion, they multiply intracellularly and spread to neighboring epithelial cells, resulting in tissue destruction and characteristic pathology of shigellosis.

The pathogenesis of Shigella involves invasion of colonic mucosal cells and induction of an intense inflammatory response, leading to the death of epithelial and immune cells and the formation of colonic mucosal ulcerations and abscesses.

As the bacilli reach the colon, they are phagocytosed by M cells that are associated with micro follicle in the colon. The bacilli are transcytosed through the membrane and reach the sub epithelial space where they are phagocytosed by the resident macrophages.  The macrophage phagosome is subsequently degraded and the intracellular shigella cause release of IL-1 that elicits the infiltration of PMNs (diapedesis).  Eventually, the infected macrophages undergo apoptosis and the bacteria are released onto the basolateral surface of the adjacent colonic enterocytes.

The infiltrating PMNs transmigrate through the tight junction of epithelial cells and into the intestinal lumen that allows the reverse migration of shigella from the lumen to subepithelial spaces.

The bacilli then infect the enterocytes by induced macropinocytosis, at the basolateral surface. The bacilli lyse the macropinocytic vacuole escape into the cytoplasm where it  multiplies. Short filaments of host cell actin then organize into a tight bundle that forms a tail several microns in length behind the bacterial body. The bacilli use this tail for movement through the cytosol and direct passage into adjacent cells by way of finger-like protrusions of the cell membrane.

Following the epithelial cell invasion and penetration of the colonic mucosa, Shigella infection is characterized by degeneration of the epithelium and inflammation of the lamina propria. This results in desquamation and ulceration of the mucosa, and subsequent leakage of blood, inflammatory cells and mucus into the lumen. Patients suffering from Shigella infection will therefore pass frequent, scanty, dysenteric stool mixed with blood and mucus, since, under these conditions, the absorption of water by the colon is inhibited.

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