Which pathogen is correctly matched with the pathophysiologic mechanism responsible for diarrhea: Clostridium difficile (C. difficile) with toxin-mediated, Enterotoxigenic Escherichia coli (E. coli) with preformed toxin production, Salmonella with invasive mechanism causing inflammation, or Vibrio cholerae with invasion causing mucosal inflammation?

Correct Answer: A - Clostridium difficile is toxin-mediated

The correct answer is A: Clostridium difficile causes diarrhea through a toxin-mediated mechanism, not through invasion of the intestinal mucosa. 1

Pathophysiologic Mechanisms by Pathogen

Clostridium difficile - Toxin-Mediated (CORRECT)

• C. difficile is not invasive and toxin production is the key to pathogenesis - non-toxigenic strains do not cause diarrhea 1
• The organism produces toxins A and B that bind to epithelial cells, causing internalization and subsequent cellular damage 1, 2
• These toxins function as glucosyltransferases that disrupt the cytoskeleton of colonocytes through glucosylation of Rho family GTPases, leading to cell death and colitis 1, 3, 2
• The toxins disrupt epithelial integrity via microtubules and cell-cell tight junctions, resulting in cytokine release (such as IL-8), promoting inflammatory infiltrate in the colonic mucosa, fluid shifts leading to diarrhea, and epithelial necrosis 1

Enterotoxigenic E. coli - NOT Preformed Toxin (INCORRECT)

• Option B is incorrect because ETEC produces toxins in vivo, not preformed toxins 1
• Preformed toxin producers include organisms like Staphylococcus aureus and Clostridium perfringens that cause foodborne outbreaks through toxins produced in contaminated food before ingestion 1
• ETEC causes secretory diarrhea through heat-labile and heat-stable enterotoxins produced after colonization of the small intestine

Salmonella - Invasive with Variable Inflammation (CORRECT mechanism but wrong answer choice)

• Salmonella is correctly described as an invasive enteropathogen causing variable inflammation 1, 4
• It penetrates intestinal epithelial cells and can cause systemic bacteremia 4
• Clinical presentation includes fever (58-100% of cases), bloody diarrhea (25-51% of cases), and prominent inflammatory signs 4

Vibrio cholerae - NOT Invasive (INCORRECT)

• Option D is incorrect because V. cholerae causes diarrhea through enterotoxin production, not mucosal invasion
• V. cholerae is the classical example of secretory diarrhea mediated by cholera toxin 5
• The organism remains in the intestinal lumen and does not invade the mucosa

Clinical Implications

The distinction between toxin-mediated and invasive mechanisms has important diagnostic and therapeutic implications:

• Toxin-mediated pathogens (C. difficile, V. cholerae, ETEC) cause watery diarrhea without significant mucosal inflammation 1, 5
• Invasive pathogens (Salmonella, Shigella, invasive E. coli) cause dysentery-like illness with fever, abdominal cramps, and bloody diarrhea 1, 4
• Testing strategies differ: C. difficile requires toxin assays, while invasive pathogens require stool cultures 1