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Title: Ingested Shiga Toxin 2 (Stx2) Causes Histopathological Changes in Kidney, Spleen and Thymus Tissues and Mortality in Mice

item Rasooly, Reuven
item Do, Paula
item GRIFFEY, STEPHEN - University Of California
item VILCHES-MOURE, JOSE - University Of California
item Friedman, Mendel

Submitted to: Journal of Agricultural and Food Chemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/19/2010
Publication Date: 7/27/2010
Citation: Rasooly, R., Do, P.M., Griffey, S.M., Vilches-Moure, J.G., Friedman, M. 2010. Ingested Shiga Toxin 2 (Stx2) Causes Histopathological Changes in Kidney, Spleen and Thymus Tissues and Mortality in Mice. Journal of Agricultural and Food Chemistry. (58):9821-9286

Interpretive Summary: E. coli serotype O157:H7 produces a family of two major related toxins: Shiga toxin 1 (Stx1) and Shiga toxin 2. Human exposure to these toxins is generally through the consumption of bacterially contaminated red meats, milk and their products. The main objective of this study was to find out whether orally ingested Stx2 can survive the gastrointestinal tract environments of mice, and whether it can be absorbed into the blood circulation, reach and damage the kidney and other tissues, and cause lethality. The results of this study suggest that this may be the case. Our study also implies that there is a need to prevent early contamination of food, as it may be impractical to eliminate the heat-stable toxin from the food by thermal treatment once it has formed.

Technical Abstract: The Shiga toxin (Stxs) producing bacterial strain, Escherichia coli O157:H7, colonizes the distal small intestine and the colon, initiating a very broad spectrum of illnesses such as hemolytic-uremic syndrome (HUS) characterized by microangiopathic hemolytic anemia, thrombocytopenia and acute renal failure. It has not been conclusively established as to whether ingestion of Stxs alone without the bacterium poses a potential health risk. To help answer this question, in this study, we fed Shiga toxin 2 (Stx2) directly into the stomachs of mice via gavage. Our data show that in mice, ingestion of Stx2 at a concentration of 50 ug/mouse induces weight loss and kills the mice during 3 to 5 days post-gavage. Additional studies revealed that the toxin retains activity at low pH and that about 1% of the fed toxin is absorbed into the blood circulation, thus lethality by intraperitoneal (IP) injection of Stx2 occurred at much lower doses than by ingestion. Although after 3 days the toxin in blood was not active in a Vero cell assay, detailed histopathological evaluation of stained tissues by light microscopy revealed severe histopathological changes in kidneys, spleen, and thymus, but apparently not in the pancreas, lymph nodes, heart, lungs, trachea, thymus, esophagus, stomach, duodenum, jejunum, ileum, cecum, and colon. The pathological changes in the kidney appeared similar to those seen in humans with HUS. The cited data suggest that (a) most, but not all, of the toxin is inactivated in the digestive tract; (b) part of the oral ingested toxin is absorbed from digestive tract into the circulation; (c), enough active toxin reached susceptible organs to induce lethality; (d) lethality by IP injection of Stx2 occurred at much lower doses than by ingestion; and (e) Stx2 in the absence of toxin-producing bacteria can be harmful to mice. The results may be clinically relevant for food safety because we also found that heat treatments (pasteurization) that destroy bacteria did not inactivate the heat resistant toxin produced and secreted by the bacteria. The possible harmful role of Shiga toxin in the human diet is discussed.