Hemolytic Uremic Syndrome is characterized by the triad of
90% of HUS cases in the United States are diarrhea associated and Shiga toxin producing E coli O157:H7 is identified in the majority of these.
Recently, a novel Shiga independent mechanism has been proposed for typical HUS involving the virulence factor subtilase cytotoxin (SubAB), which is sometimes present in E coli O157:H7 and other strains of Shiga toxigenic E coli.
SubAB binds to the sialic acid, Neu5Gc which humans are unable to synthesize leading to proteolytic cleavage of an endoplasmic reticulum chaperone triggering a endoplasmic reticulum stress response and eventual cell death.
So where does Neu5Gc in humans comes from? It appears to come from the diet, primarily from red meats and dairy products, the very food types that are sometimes contaminated with Shiga toxigenic E coli.
Once ingested, Neu5Gc is incorporated onto the surface of endothelial, and to a lesser extent intestinal epithelial cells.
In this “two-hit” model those who regularly consume red meat and dairy are potentially priming their intestinal and endothelial surfaces with Neu5Gc while also increasing the likelihood of eating a meal containing a SubAB producing bacteria. This model is nicely summarized in a KI review by Lofling and colleagues.
In a previous post dealing with the Walkerton Ontario HUS outbreak Nate wondered what factors contributed to development of disease in patients with E coli O157:H7 associated diarrhea.
Perhaps, SubAB and previous dietary priming with Neu5Gc are parts of the puzzle.
Graham Abra, MD
- Microangiopathic hemolytic anemia
- Thrombocytopenia
- Renal failure.
- Typical, or diarrhea associated
- Atypical, or diarrhea negative cases.
90% of HUS cases in the United States are diarrhea associated and Shiga toxin producing E coli O157:H7 is identified in the majority of these.
Recently, a novel Shiga independent mechanism has been proposed for typical HUS involving the virulence factor subtilase cytotoxin (SubAB), which is sometimes present in E coli O157:H7 and other strains of Shiga toxigenic E coli.
SubAB binds to the sialic acid, Neu5Gc which humans are unable to synthesize leading to proteolytic cleavage of an endoplasmic reticulum chaperone triggering a endoplasmic reticulum stress response and eventual cell death.
So where does Neu5Gc in humans comes from? It appears to come from the diet, primarily from red meats and dairy products, the very food types that are sometimes contaminated with Shiga toxigenic E coli.
Once ingested, Neu5Gc is incorporated onto the surface of endothelial, and to a lesser extent intestinal epithelial cells.
Graham Abra, MD
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