Bacterial exotoxins — What is the specific action of the A (active) subunit of diphtheria toxin on host cells?

Introduction / Context:
Diphtheria toxin, produced by toxigenic Corynebacterium diphtheriae, is a prototypical A-B exotoxin. The B subunit binds to cell surface receptors and facilitates entry, while the A subunit carries catalytic activity that disrupts host processes. Understanding its molecular target explains the profound cytotoxicity and tissue necrosis seen in diphtheria.

Given Data / Assumptions:

• A-B toxins have a binding (B) moiety and an enzymatic (A) moiety.
• The clinical effect of diphtheria involves inhibition of host cell protein synthesis.
• We distinguish this action from toxins that raise cAMP or trigger cytokine storms.

Concept / Approach:
The A subunit catalyzes ADP ribosylation of elongation factor 2 (EF-2), a critical component of the translation machinery. This modification inactivates EF-2 and halts protein synthesis, causing cell death. Other toxins, such as cholera toxin and heat-labile enterotoxin of E. coli, instead alter cAMP through G protein or adenylate cyclase interactions, while superantigens provoke cytokine release without this enzymatic mechanism.

Step-by-Step Solution:

Verification / Alternative check:
Cell culture studies show that expression of the A subunit alone is sufficient to block protein synthesis and kill cells, confirming EF-2 modification as the lethal event.

Why Other Options Are Wrong:

• Binds host cell receptors on heart cells: binding is mediated by the B subunit and is not restricted to heart tissue.
• Forms cAMP: describes toxins like cholera or pertussis, not diphtheria.
• Causes macrophage lysis and cytokine release: more aligned with pore-forming toxins or superantigen mechanisms.

Common Pitfalls:
Confusing ADP ribosylation targets across toxins; the specific target for diphtheria toxin is EF-2, not adenylate cyclase or G proteins.

Final Answer:
cause ADP ribosylation of a factor involved in protein synthesis