A 25-year-old woman comes to the emergency department due to 2 days of abdominal pain and bloody diarrhea. A few days ago, she attended a church barbeque. She does not know whether anyone else at the party developed similar symptoms. The patient lives alone and has no medical conditions. Temperature is 37.1 C (98.8 F), blood pressure is 119/76 mm Hg, pulse is 92/min, and respirations are 16/min. There is abdominal tenderness with no rebound or guarding. Guaiac-positive bloody stools are detected on rectal examination. Stool cultures reveal an Escherichia coli strain that does not produce glucuronidase and does not ferment sorbitol on sorbitol-containing MacConkey agar, consistent with serotype O157:H7. Which of the following best describes the mechanism of action of the toxin specific to these bacteria?
Escherichia coli virulence factors | ||
Virulence factor | Mechanism | Presentation |
Lipopolysaccharide | Activates macrophages → widespread release of IL-1, IL-6 & TNF-α | Bacteremia & septic shock |
K1 capsular polysaccharide | Prevents phagocytosis & complement-mediated lysis | Neonatal meningitis |
Shiga toxin | Inactivates 60S ribosomal subunit, halting protein synthesis & causing cell death | Gastroenteritis (bloody) |
Heat-stable/heat-labile enterotoxins | Promotes fluid & electrolyte secretion from intestinal epithelium | Gastroenteritis (watery) |
P-fimbriae | Allows adhesion to uroepithelium | Urinary tract infection |
TNF-α = tumor necrosis factor-alpha. | ||
This patient has bloody diarrhea due to Escherichia coli O157:H7, or Shiga toxin–producing E coli (STEC). The transmission of STEC occurs primarily via consumption of contaminated beef products, but isolated cases without a clear source can occur.
After colonization and adherence to intestinal epithelial cells, STEC elaborates Shiga toxin (virtually identical to that produced by Shigella dysenteriae). Enterocytes bind to Shiga toxins, which then inactivate the 60S ribosomal subunit within the host cells by cleaving an adenine nucleobase from the integrated 28S RNA. This leads to inhibition of protein synthesis and apoptosis of intestinal epithelial cells. Clinical manifestations include watery diarrhea that becomes bloody within 1-3 days.
In a minority of cases, Shiga toxin can spread through the damaged intestinal epithelium to the bloodstream and capillary endothelial cells in the kidney, leading to hemolytic uremic syndrome approximately a week after gastrointestinal symptoms. Manifestations include thrombocytopenia, microangiopathic hemolytic anemia, and renal insufficiency.
(Choice A) Clostridioides difficile produces 2 exotoxins, one of which is a cytotoxin (toxin B) that disrupts the cytoskeleton by depolymerizing actin and causing cell death.
(Choice C) Exotoxins produced by Corynebacterium diphtheriae (diphtheria toxin) inactivate elongation factor 2 via ribosylation, which leads to the inhibition of protein synthesis and cell death.
(Choices D and E) Unlike STEC, enterotoxigenic E coli produces heat-labile toxin (LT) and heat-stable toxin (ST). LT increases intracellular cyclic AMP in intestinal mucosal cells, which leads to the decreased absorption and increased secretion of sodium, chloride, and water; ST increases intracellular cyclic guanosine monophosphate (GMP), also contributing to diarrhea and electrolyte loss. Watery, not bloody, diarrhea occurs.
Educational objective:
Shiga toxin–producing Escherichia coli O157:H7 elaborates Shiga toxin, which inactivates 60S ribosomal subunits in colonic mucosal cells, leading to the inhibition of protein synthesis and apoptosis; clinical manifestations include bloody diarrhea. Hematogenous spread of Shiga toxin to renal endothelial cells can also lead to hemolytic uremic syndrome.