A 6-year-old, previously healthy girl is brought to the office due to diarrhea and abdominal pain. The patient started having watery diarrhea after a barbeque she attended 4 days ago; her stools became grossly bloody 2 days later. Her mother also had similar symptoms. Temperature is 37 C (98.6 F). The abdomen is soft with mild, generalized tenderness. Stool culture performed on sorbitol-MacConkey agar shows sorbitol-negative colonies with biochemical properties of Escherichia coli. Enzyme immunoassay detects an exotoxin capable of inhibiting protein synthesis in human cells. Which of the following bacteria produces a toxin that is most similar to the one detected in this patient?
Shiga toxin | |
Microbiology |
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Mechanism |
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Clinical |
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*Also referred to as high-risk Shiga-toxin–producing or enterohemorrhagic E coli. | |
This patient has bloody diarrhea due to Escherichia coli, with enzyme immunoassay detecting a substance capable of inhibiting protein synthesis in human cells. These findings are characteristic of Shiga toxin produced by Shiga toxin–producing E coli, or enterohemorrhagic E coli.
E coli and Shigella species are closely related genetically, and Shiga toxin is also produced by Shigella dysenteriae. Shiga toxin is an AB cytotoxin with an active (A) subunit and 5 binding (B) subunits:
The B subunits, which form pentamers with a central pore, recognize specific receptors on target cells and induce receptor-mediated endocytosis and toxin internalization.
The enzymatically active A subunit is then released and catalyzes the removal of a specific adenine residue in the 60S ribosomal subunit, thereby preventing transfer RNA from binding to the ribosome complex and inhibiting protein synthesis.
This leads to intestinal mucosal cell death (bloody diarrhea) and, with hematogenous spread, toxicity to renal epithelial cells (hemolytic uremic syndrome).
(Choice A) Clostridioides difficile produces toxin A (enterotoxin) and toxin B (cytotoxin). In contrast to Shiga toxin, toxin A primarily initiates an inflammatory response, whereas toxin B depolymerizes actin filaments, causing gastrointestinal mucosal cell death.
(Choice B) Pseudomonas aeruginosa produces exotoxin A, which is similar in function to diphtheria toxin in that it halts human cellular protein synthesis by inhibiting elongation factor 2. Although Shiga toxin also disrupts protein synthesis, it does so via a different mechanism (inhibition of the 60S ribosomal subunit).
(Choice C) Salmonella typhi causes typhoid fever, which is characterized by fever, abdominal pain, diarrhea and/or constipation, and faintly erythematous macules on the abdomen (rose spots). The bacterium penetrates the intestinal mucosa and releases typhoid toxin (not Shiga toxin), which damages cellular DNA.
(Choice E) Staphylococcus aureus typically causes a vomiting-predominant foodborne illness with or without watery diarrhea due to a preformed toxin. Unlike Shiga toxin, this enterotoxin is not cytotoxic.
(Choice F) Vibrio cholerae, the causative agent of cholera, produces choleragen, which acts similarly to the heat-labile toxin of enterotoxigenic Escherichia coli. It increases intracellular cyclic AMP in intestinal mucosal cells, leading to decreased absorption and increased secretion of sodium, chloride, and water.
Educational objective:
Shiga toxin is produced by enterohemorrhagic Escherichia coli and Shigella dysenteriae. It inhibits the 60S ribosomal subunit in human cells, blocking protein synthesis and causing cell death.