Shiga toxin 2 (Stx2) is a potent poison produced by specific strains of bacteria, primarily Shiga toxin-producing E. coli (STEC). The toxin leaves the gastrointestinal tract and enters the bloodstream, where it targets and damages the lining of blood vessels throughout the body. This cascade of cellular damage ultimately leads to life-threatening complications, most notably kidney failure.
Bacterial Origin and Transmission Routes
The source of Shiga toxin 2 (Stx2) is Shiga toxin-producing E. coli (STEC), most notably the serotype E. coli O157:H7. These bacteria naturally reside in the intestines of healthy cattle and other ruminants, serving as the main reservoir. Contamination of meat, particularly ground beef, occurs during slaughter, making the consumption of undercooked meat a frequent route of human infection.
Transmission also occurs through the ingestion of contaminated food or water, including unpasteurized products like milk, juice, or cider, and produce exposed to animal feces. Because the bacteria are highly infectious, secondary transmission, such as person-to-person spread, is common in households or daycare settings with poor hand hygiene. Preventing infection relies on robust food safety practices, including thoroughly cooking meat and avoiding unpasteurized dairy and juices.
Molecular Mechanism of Cellular Attack
Shiga toxin 2 (Stx2) is classified as an AB5 toxin, composed of one catalytically active A subunit and a ring of five identical B subunits. The B pentamer binds to a specific glycolipid receptor called globotriaosylceramide (Gb3) found on the surface of human cells.
The Gb3 receptor is particularly abundant on the endothelial cells lining the small blood vessels, especially those in the kidneys. Once bound, the toxin is internalized and trafficked toward the endoplasmic reticulum. Inside the cell, the A subunit is cleaved and released. This active component acts as an N-glycosidase, removing a specific adenine base from the 28S ribosomal RNA of the 60S ribosomal subunit. This molecular action halts the cell’s ability to synthesize proteins, leading to rapid cellular dysfunction and programmed cell death (apoptosis).
Pathological Consequences: Hemorrhagic Colitis and HUS
The initial phase of infection presents as gastroenteritis, often called hemorrhagic colitis. Symptoms begin with severe abdominal cramps and watery diarrhea, progressing to bloody diarrhea within a few days. This intestinal inflammation results from Stx2 damaging the lining of the digestive tract. While most people recover, a small percentage, particularly young children, develop the most severe complication.
The systemic spread of Stx2 through the bloodstream triggers Hemolytic Uremic Syndrome (HUS), typically developing about one week after the first signs of diarrhea. HUS is a type of thrombotic microangiopathy characterized by a triad of specific conditions. These include hemolytic anemia, which results from the mechanical destruction of red blood cells as they pass through damaged and narrowed small blood vessels. Thrombocytopenia, or a low platelet count, occurs because platelets are consumed to form microclots within the injured vessels. The third component is acute kidney injury (AKI).
AKI occurs because Stx2-damaged endothelial cells in the kidney’s small blood vessels become activated, leading to inflammation and the formation of numerous tiny blood clots. These microclots obstruct blood flow, particularly within the glomeruli (the kidney’s filtering structures). The resulting lack of blood flow causes damage to the nephron, leading to a sudden decline in kidney function and potential renal failure. The toxin can also target endothelial cells in other organs, causing neurological complications like seizures or coma in up to 25% of pediatric cases.
Clinical Management and Supportive Care
Management of illness caused by Shiga toxin 2 and HUS focuses on supportive care, as no specific antitoxin is currently available. Maintaining adequate hydration and preventing electrolyte imbalances is essential, often requiring aggressive intravenous fluid replacement with isotonic solutions. This volume expansion helps mitigate tubular injury and may reduce microvascular clot formation.
Patients who develop acute kidney injury frequently require renal replacement therapy, often needing temporary dialysis to perform the filtering function of the failing kidneys. Blood transfusions address severe hemolytic anemia and thrombocytopenia. A significant concern is the use of antibiotics, which are generally avoided in early STEC infection. Evidence suggests some antibiotics may trigger the bacteria to release more Shiga toxin, increasing the risk and severity of HUS.