Shiga toxin (Stx) (Stx)

Shiga toxins (Stx) are potent AB5-type bacterial protein exotoxins produced primarily by Shiga toxin-producing Escherichia coli (STEC) and Shigella dysenteriae serotype 1 [1][4]. They are encoded by the stx virulence genes (stx1 and stx2) located on lambdoid bacteriophages integrated into the bacterial genome [1][14]. The toxins consist of an enzymatically active A-subunit and a pentamer of B-subunits that bind to the host cell receptor globotriaosylceramide (Gb3), particularly on endothelial cells in the kidneys and brain [3][8]. Once internalized, the toxin undergoes retrograde transport to the endoplasmic reticulum, where the A-subunit is released into the cytosol to irreversibly inactivate the 60S ribosomal subunit by depurinating 28S rRNA [3][11]. This cessation of protein synthesis leads to cell death and is the primary cause of life-threatening complications such as hemorrhagic colitis and hemolytic uremic syndrome (HUS) [4][15]. Pharmacological management is exceptionally challenging because certain antibiotics can trigger the bacterial lytic cycle, inducing massive toxin release and increasing the risk of HUS, while no direct antitoxins are currently FDA-approved [2][6].

Other names

Shiga-like toxin (SLT)Verotoxin (VT)Verocytotoxinstx1 gene productstx2 gene productShiga-like toxin 1Shiga-like toxin 2

The Shiga toxin complex binds to the host cell glycolipid globotriaosylceramide (Gb3) via its pentameric B-subunit [1][14]. Following receptor-mediated endocytosis, the toxin undergoes retrograde trafficking through the Golgi apparatus to the endoplasmic reticulum [3][5]. Proteolytic cleavage by furin-like proteases releases the active A1 fragment, which is translocated into the cytosol [1][11]. The A1 fragment acts as a highly specific N-glycosidase that cleaves a single adenine residue (A4324) from the 28S ribosomal RNA of the 60S subunit, preventing the binding of aminoacyl-tRNA and permanently halting protein synthesis [3][8][11].