Shiga Toxin: Biochemistry, Genetics, Mode of Action, and Role in Pathogenesis

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Dysentery was well known and clearly described in many ancient texts and histories. The first step towards the description of the genus Shigella, however, was the identification of Entamoeba histolytica by Losch in 1875 and the separation of amebic from all other forms of dysentery (Losch, 1875). With this discovery, attention could be focused on the etiology of epidemic dysentery, and a partial description of the prototype Shigella sp., Shigella dysenteriae type 1, was published by Chantemesse and Widal in 1888. The definitive description of this organism was provided by Kiyoshi Shiga following an extensive dysentery epidemic in Japan in 1896 (Shiga 1898). It did not take long to determine that there was a potent toxic activity in this organism, and in 1900 Flexner reported that either living or killed cultures of Shiga’s bacillus injected into the peritoneal cavity of animals caused fever and diarrhea. Flexner concluded that shigellosis was due to a “toxic agent rather than to an infection per se”; however, the Observed effects were Probably due to endotoxin. The presence of a lethal toxin in extracts of heat-killed bacteria was shown independently by Neisser and Shiga (1903) and by Conradi (1903). Conradi (1903) also described the limb paralysis following parenteral inoculation of Shigella extracts in rabbits, characteristic of the so-called Shiga neurotoxin.