A 28-year-old male suddenly develops severe abdominal cramping and bloody diarrhea. The patient reports consuming undercooked ground beef four days prior to the onset of the symptoms. Which of the following best describes the toxin-mediated mechanism of this disease process?
1.Depolymerization of action filements in gastreontestinal mucosal cells leadiffing to mocosal cell dath
2.Increased pH of gastointestional lumen resulting in reduced mucosal absorption
3.Increased intracellular cAMP in gastrointestinal mucosal cells resulting in decreased absorption and increased secretion in the degestive tract
4.Inhibition of elongation factor-2 EF-2 resulting in decreased protein synthesis in gastrointestinal mucosal cells
5.Inhibiiton of the 60S ribosomal subunit,relsulting in decreased protein synthesis in gastrointerstinal mucosal cells
sol:
This patient’s presentation is consistent with an Enterohemorrhagic E. coli infection (EHEC), which leads to colitis through inhibition of the 60S ribosomal subunit and decreased protein synthesis in gastrointestinal mucosal cells.
EHEC produces a shiga-like toxin. Shiga-like toxin prevents tRNA binding to the 60S ribosomal subunit, thereby inhibiting protein synthesis and leading to subsequent death of gastrointestinal mucosal cells. Shiga-like toxin not only yields bloody diarrhea through damage to intestinal mucosal cells but can also result in hemolytic uremic syndrome (HUS) through damage to renal endothelial cells. O157:H7 is the most common EHEC strain.
Razzaq reviews HUS in the context of shiga toxin-producing E. coli infection, stating that ingestion of contaminated ground beef is the most common source of infection with EHEC in the US. The classic presentation of HUS in children includes gastroenteritis (abdominal pain, nausea, vomiting, fever); however, affected adults may be asymptomatic.
Illustration A depicts the mechanisms of bacterial toxin secretion and processing as can be seen in EHEC. The right hand panel depicts the AB structure of the shiga-like toxin. The B subunit binds to the cell surface while the A subunit cleaves the 28S component of the 60S ribosomal subunit, thereby inhibiting protein synthesis within the cell.