A 7-year-old unvaccinated boy from rural Maharashtra presents with a 3-day history of sore throat, low-grade fever (38.2°C), and progressive difficulty swallowing. On examination, he has a thick, greyish-white pseudomembrane covering the pharynx and tonsils that bleeds when attempts are made to remove it. Cervical lymphadenopathy is marked, giving a "bull neck" appearance. A throat swab is sent for culture. Which organism is most likely responsible, and what is the pathogenic mechanism of systemic toxicity?

Explanation

## Diagnosis: Corynebacterium diphtheriae **Key Point:** The clinical triad of pseudomembrane (grey-white, adherent, bleeds on removal), bull neck (cervical edema from lymphadenopathy), and systemic toxicity in an unvaccinated child is pathognomonic for diphtheria. ### Pathogenic Mechanism **High-Yield:** Diphtheria toxin is a two-chain exotoxin (A and B subunits) produced by lysogenized strains carrying the tox gene (integrated via β-corynephage). The mechanism unfolds as: 1. **B subunit** binds to heparin-binding EGF-like growth factor (HB-EGF) on host cell surface 2. **Receptor-mediated endocytosis** internalizes the toxin 3. **A subunit** catalyzes ADP-ribosylation of elongation factor 2 (EF-2) 4. **Result:** Inhibition of peptide bond formation → protein synthesis blockade → cell death ### Clinical Manifestations Explained by Toxin | Organ System | Manifestation | Mechanism | |---|---|---| | Heart | Myocarditis, arrhythmia, cardiogenic shock | Toxin-induced myocyte necrosis | | Nervous | Cranial nerve palsies (III, IV, VI, IX, X, XII) | Demyelination of motor nerves | | Kidney | Acute tubular necrosis | Direct toxin effect on renal epithelium | | Airway | Respiratory obstruction | Pseudomembrane extension to larynx | **Clinical Pearl:** Systemic toxicity occurs even before culture confirmation — treatment must begin on clinical suspicion alone. Antitoxin (horse serum-derived) neutralizes unbound circulating toxin but cannot reverse toxin already bound to EF-2. **Mnemonic:** **DIPHTHERIA** = **D**iphtheria toxin **I**nhibits **P**rotein synthesis via **H**igh-affinity **T**oxin binding → **E**longation **F**actor-2 **R**ibosylation → **I**nhibition → **A** (ADP-ribose) addition. ### Culture Characteristics - **Gram stain:** Gram-positive bacilli with metachromatic granules (Loeffler's methylene blue) - **Culture media:** Loeffler's serum slope (selective), tellurite media (grey-black colonies) - **Virulence testing:** Elek immunodiffusion test (toxin production confirmation) **Warning:** Not all C. diphtheriae strains are toxigenic — only those lysogenized with β-corynephage carrying the tox gene produce toxin. Culture alone does not confirm toxigenicity; Elek test is required.