What toxins define enterotoxigenic E. coli (ETEC) and how do they contribute to disease?

• A. Heat-labile toxin (LT) and heat-stable toxin (ST); LT increases cAMP, ST increases cGMP; both cause watery diarrhea; colonization factors aid attachment.
• B. Shiga toxin and cholera toxin cause watery diarrhea.
• C. Tetanus toxin raises intracellular calcium and blocks GABA.
• D. Cholera toxin is the only toxin producing watery diarrhea.

Answer: (A)

ETEC causes disease through two distinct enterotoxins and bacterial adherence to the intestine. The heat-labile toxin (LT) and the heat-stable toxin (ST) are the defining virulence factors. LT acts like an AB toxin that ADP-ribosylates the Gs subunit of the stimulatory signaling pathway, keeping adenylate cyclase active and driving a rise in cAMP. This surge in cAMP stimulates chloride secretion through CFTR channels and pulls water into the gut lumen, producing watery diarrhea. ST, on the other hand, directly activates guanylate cyclase on the intestinal mucosa, increasing cGMP and also promoting secretion of chloride and water. The combination of these secretory effects leads to the characteristic watery, nonbloody diarrhea seen with ETEC infection.

Attachment to the intestinal lining is facilitated by colonization factors (adhesins/fimbriae), which help the bacteria adhere long enough to deliver toxins effectively. This adherence is essential for disease, as it localizes the toxins to the epithelium where they can disrupt ion transport and fluid balance.

In contrast, other toxins mentioned come from different organisms or cause different patterns of disease (for example, Shiga toxin–producing E. coli can cause invasive illness with bloody diarrhea; cholera toxin is produced by Vibrio cholerae). The combination of LT and ST with colonization factors is what specifically defines enterotoxigenic E. coli and its diarrheal illness.