Shiga Toxin Research Paper

The Shiga toxin comprises a family of related protein toxins produced by bacteria Shigella dysenteriae. The bacteria S. dysenteriae was discovered by Japanese bacteriologist Kiyoshi Shiga in 1898. Shiga studied 36 patients at the Institute for Infectious Diseases (Tokyo, Japan) and isolated a bacterium from the intestinal tissue of dysentery patient. Bacterial isolates were cultured and fed to dogs; that resulted in dysenteric disease (Shiga, 1898). Shigella belongs to enterobacteriaceae bacterial family and occur into four species: S. dysenteriae (group A), S. flexneri (group B), S. boydii (group C), and S. sonnei (group D). They are Gram negative, non-motile rods that do not ferment lactose (except for group D). All four species produce similar
The bacteria then invade epithelial cells and have the capacity to reprogram these cells to produce pro-inflammation mediators, such as interleukin 8, which plays a major role in the strong inflammatory response facilitating further bacterial invasion. Most of the virulence determinates responsible for invasion of epithelial cells are encoded on a 213 kb plasmid that is unique to virulent Shigella. The bacterial replication time is approximately 40 minutes and the incubation period for disease onset is only 1-7 days with an average of 3 days. Shigella has no animal reservoir, so infection always results from contamination with human’s feces. Transmission occurs through contaminated food and water or through person to person contact. Shigella infection is also common among travelers and military troops deployed in camp situations with less than optimal hygiene conditions (Nataro, 2004). Transmission by houseflies has also been reported (Levine et al., 1999). A current review of the literature concluded that the annual number of cases of Shigella diarrhea worldwide was approximately 90 million, 99% of which occurred in developing countries. Approximately 1.1 million deaths are estimated due to Shigella infection each year and 60% of them being children under 5 year age (Niyogi,
Shiga toxin is one of the most potent toxin known to human that is why Centers for Disease Control and Prevention (CDC), USA has listed it as a potential bio terrorist agent in category ‘B’ list. It has been used as biological warfare agent at the time of World War II. Shigella produce various toxins, however S. dysenteriae type 1 is known to produce Shiga toxin which is the most studied toxin among various toxins. It is also reported to synthesize comparatively in large quantities (O’Brien et al., 1992). Active Shiga toxin (holotoxin) is a bipartite molecule composed of five B subunits of 7 kDa each, and one A subunit of 32 kDa. The B subunit binds to the disaccharide Galα1-4Galβ, found in glycolipids such as globotriaosylceramide (Gb3). The A subunit is a toxic component of Shiga toxin, which becomes enzymatically active upon proteolytic cleavage. After cleavage, two fragments are produced; the large amino-terminal A1-fragment is of ~27 kDa, which is the toxic moiety, and the small carboxy-terminal A2-fragment of ~4 kDa (O’Brien et al., 1992). The A1-fragmet exerts its toxic effect by inhibiting protein synthesis. It is an N-glycosidase, which cleaves off adenine from a specific adenosine of 28S component of the 60S ribosomal subunit, thus irreversibly hindering ribosomal function (Endo et