Microbiology – Toxin Similarity: Which bacterial toxin most closely resembles cholera toxin in structure and mechanism of action?

Introduction:
Cholera toxin is a classical AB5 enterotoxin that activates adenylate cyclase via Gs alpha ADP-ribosylation, driving persistent elevation of intracellular cAMP and secretory diarrhea. This question tests recognition of which other bacterial toxin shares the closest structural class and mechanism with cholera toxin.

Given Data / Assumptions:

• Cholera toxin: AB5 architecture, enzymatic A subunit with ADP-ribosyltransferase activity.
• Primary effect: sustained rise in cAMP in enterocytes leading to chloride and water secretion.
• Need to identify a toxin with similar structure–function features.

Concept / Approach:
The key discriminator is whether the candidate toxin is an AB5 enterotoxin that ADP-ribosylates Gs alpha to increase cAMP. Toxins using different targets (e.g., EF-2, synaptic proteins) or second messengers (cGMP) do not truly “resemble” cholera toxin mechanistically.

Step-by-Step Solution:
Step 1: Recall cholera toxin mechanism: ADP-ribosylates Gs alpha.Step 2: Identify E. coli LT: It is also an AB5 enterotoxin with the same catalytic activity on Gs alpha.Step 3: Compare alternatives: ST increases cGMP via guanylate cyclase; diphtheria toxin inactivates EF-2; tetanus toxin blocks inhibitory neurotransmitter release; Shiga toxin inactivates 60S ribosomal subunit by depurination.Step 4: Conclude that the closest resemblance is E. coli LT.

Verification / Alternative check:
Both cholera toxin and E. coli LT elevate cAMP and produce watery “secretory” diarrhea. Both are plasmid/phage-encoded AB5 proteins with GM1 ganglioside binding by the B pentamer and A1 enzymatic subfragments with ADP-ribosyltransferase activity.

Why Other Options Are Wrong:

• Heat-stable (ST) enterotoxin: stimulates guanylate cyclase; raises cGMP, not cAMP.
• Diphtheria toxin: halts protein synthesis by ADP-ribosylating EF-2; not an enterotoxin.
• Tetanus neurotoxin: zinc endopeptidase blocking neurotransmitter release; neural, not intestinal.
• Shiga toxin: N-glycosidase that inactivates 28S rRNA; causes dysentery, HUS.

Common Pitfalls:
Confusing “heat-labile” (LT) with “heat-stable” (ST) due to naming; assuming all E. coli toxins mirror cholera toxin; overlooking the cAMP vs cGMP distinction.

Final Answer:
Heat-labile (LT) enterotoxin of Escherichia coli.