Toxins – E. coli heat-stable enterotoxin (ST) The heat-stable enterotoxin (ST) of enterotoxigenic Escherichia coli (ETEC) exerts its secretory effect primarily by activating which host cell enzyme/signaling target?

Introduction / Context:
Enterotoxigenic E. coli (ETEC) causes traveler’s diarrhea and childhood diarrhea via enterotoxins. Distinguishing the molecular targets of heat-labile (LT) and heat-stable (ST) toxins is essential for understanding pathophysiology and for exam preparation.

Given Data / Assumptions:

• ST is a small, heat-stable peptide.
• ETEC toxins drive chloride and water secretion from enterocytes, producing watery diarrhea.
• Different toxins use distinct second messenger systems.

Concept / Approach:
ST binds and activates membrane-bound guanylate cyclase C on intestinal epithelial cells, increasing intracellular cGMP. Elevated cGMP activates protein kinase G and modulates ion channels (e.g., CFTR), enhancing chloride secretion and inhibiting sodium absorption. In contrast, LT ADP-ribosylates Gs to stimulate adenylate cyclase, elevating cAMP.

Step-by-Step Solution:
Identify ST (heat-stable) as a cGMP-linked toxin.Map target to guanylate cyclase C on enterocytes.Select “Guanylate cyclase (cGMP pathway).”

Verification / Alternative check:
Physiology and pharmacology literature (e.g., mechanism of plecanatide/linaclotide as GC-C agonists) mirrors the ST–cGMP secretory pathway.

Why Other Options Are Wrong:

• Adenylate cyclase: target of LT, not ST.
• Both equally: mechanistically inaccurate.
• None/PLC: unrelated to ST’s primary effect.

Common Pitfalls:
Confusing ST with LT; mnemonics: “ST → cGMP,” “LT → cAMP.”

Final Answer:
Guanylate cyclase (cGMP pathway).