Enterotoxins — Cholera toxin is an A–B toxin. After B subunits bind to the host receptor, what does the A subunit do inside the cell?

Introduction / Context:
Vibrio cholerae causes profuse watery diarrhea via a secreted enterotoxin that hijacks host signaling. Like other A–B toxins, the B subunits mediate binding to specific receptors (GM1 ganglioside), while the A subunit has enzymatic activity that alters intracellular pathways. Knowing the exact target clarifies why cholera leads to massive electrolyte loss without direct mucosal destruction.

Given Data / Assumptions:

• A–B structural organization with receptor binding and enzymatic action.
• Clinical effect is increased chloride and water secretion from enterocytes.
• We distinguish among adenylate cyclase, G proteins, and ribosome-targeting actions.

Concept / Approach:
The A1 fragment of cholera toxin ADP-ribosylates the stimulatory G protein alpha subunit (Gsα), locking it in the GTP-bound active state. This persistent activation continuously stimulates adenylate cyclase, elevating intracellular cAMP. High cAMP drives CFTR chloride channel opening and inhibits sodium absorption, resulting in isotonic fluid loss into the intestinal lumen. The toxin does not ADP-ribosylate adenylate cyclase itself, nor does it target ribosomal RNA, and it acts through cAMP rather than cGMP.

Step-by-Step Solution:

Verification / Alternative check:
Pharmacologic inhibitors that block adenylate cyclase or CFTR reduce secretory responses to cholera toxin in model systems, supporting the cAMP mechanism.

Why Other Options Are Wrong:

• ADP ribosylation of adenylate cyclase: incorrect target.
• rRNA cleavage: describes toxins like Shiga toxin or ricin, not cholera.
• cGMP stimulation: associated with heat-stable E. coli enterotoxin, not cholera.

Common Pitfalls:
Confusing the different second messenger pathways; cholera is cAMP-mediated, whereas some E. coli toxins are cGMP-mediated.

Final Answer:
ADP ribosylation of a G protein that locks it into an active form that stimulates adenylate cyclase to make cAMP