STX2

Shiga toxin 2 (STX2) is a potent toxin produced by certain strains of the bacteria Escherichia coli (E. coli), specifically those referred to as Shiga toxin-producing E. coli (STEC). This toxin is one of the primary virulence factors associated with severe forms of foodborne illness, such as hemolytic uremic syndrome (HUS) and bloody diarrhea. STX2 is closely related to Shiga toxin 1 (STX1), but it is generally considered to be more virulent.

Structure and Mechanism

STX2 is a type of AB5 toxin, consisting of one A subunit and five B subunits. The B subunits are responsible for binding to the host cell surface, specifically to the globotriaosylceramide (Gb3) receptor, which is present on the surface of certain human cells, such as renal epithelial cells and endothelial cells. Once bound, the A subunit is internalized by the cell and cleaves a specific adenine residue from the 28S rRNA within the ribosome, thereby inhibiting protein synthesis and leading to cell death.

Clinical Significance

Infection with STEC strains that produce STX2 can lead to severe disease outcomes due to the toxin's ability to cause damage to the endothelial cells lining the blood vessels, particularly in the kidneys and gastrointestinal tract. This damage can result in bloody diarrhea, and in more severe cases, the development of HUS, a life-threatening condition characterized by acute kidney failure, hemolytic anemia, and thrombocytopenia.

Epidemiology

STX2-producing E. coli strains are transmitted to humans primarily through the consumption of contaminated food or water. Outbreaks have been associated with a variety of foods, including undercooked ground beef, raw leafy greens, and unpasteurized milk and juices. Person-to-person transmission can also occur, particularly in settings where hygiene practices are inadequate.

Prevention and Control

Prevention of STX2-associated illness focuses on the proper handling, cooking, and processing of foods to reduce the risk of E. coli contamination. This includes thorough cooking of beef, avoiding the consumption of raw milk and juices, and practicing good hygiene and sanitation. Public health surveillance and prompt investigation of outbreaks are crucial for controlling the spread of STEC infections.

Treatment

There is no specific treatment for STX2-mediated illness. Management of STEC infections primarily involves supportive care, including hydration and, in cases of HUS, dialysis and blood transfusions. The use of antibiotics in STEC infections is controversial, as it may increase the risk of developing HUS.

Research Directions

Research on STX2 is focused on understanding the toxin's mechanism of action, developing methods for detecting and neutralizing the toxin, and creating vaccines to protect against STEC infections. Advances in these areas could significantly reduce the morbidity and mortality associated with STX2-producing E. coli strains.