A 24-year-old man who recently emigrated from a region with low vaccination coverage presents to the emergency department with a 3-day history of severe sore throat, low-grade fever, and neck swelling. Physical examination reveals a tightly adherent, grayish-white pseudomembrane over the tonsils and posterior pharynx that bleeds slightly when manipulated. He also exhibits prominent bilateral cervical lymphadenopathy. A diagnosis of respiratory diphtheria is suspected, and appropriate therapy is initiated. Arrange the following steps in chronological order to describe the cellular mechanism of action for the primary virulence factor responsible for this patient's condition.
- 1Binding of the exotoxin B subunit to the heparin-binding epidermal growth factor receptor on the host cell
- 2Internalization of the toxin-receptor complex into a host endosome via receptor-mediated endocytosis
- 3Acidification of the endosomal lumen triggering a conformational change and membrane insertion of the B subunit
- 4Translocation of the catalytically active A subunit across the endosomal membrane into the cytoplasm
- 5Catalytic inactivation of host elongation factor-2 via ADP-ribosylation, ceasing protein synthesis
Cevap
The correct sequence for the mechanism of action of the diphtheria toxin begins with receptor binding, followed by endocytosis, endosomal acidification, A subunit translocation, and finally ADP-ribosylation of elongation factor-2.
The correct sequence accurately reflects the biological cascade of the diphtheria A-B exotoxin. First, the B subunit binds to the host cell's HB-EGF receptor. This triggers receptor-mediated endocytosis. The acidic environment of the resulting endosome then causes a conformational change, allowing the B subunit to form a pore in the endosomal membrane. The A subunit is translocated through this pore into the cytoplasm, where it catalyzes the ADP-ribosylation of EF-2, definitively halting cellular protein synthesis and causing cell death.
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Anahtar Kavram
Diphtheria toxin is an A-B exotoxin that enters host cells via receptor-mediated endocytosis and causes cell death by ADP-ribosylating elongation factor-2 (EF-2), thereby inhibiting protein synthesis.