Corynebacterium diphtheriae is one of those Step bugs that seems “straightforward”… until a vignette starts mixing sore throat, a gray membrane, myocarditis, and incomplete vaccination history. The good news: it’s a highly pattern-recognition–friendly organism if you anchor your thinking around toxin-mediated disease, pseudomembrane, and cardiac/neurologic complications.
Quick ID: What is Corynebacterium diphtheriae?
Definition: A Gram-positive, club-shaped (“coryneform”) rod that causes diphtheria, classically an upper respiratory infection with a pseudomembrane and systemic toxin effects.
High-yield microbiology descriptors
- Gram-positive rods
- Pleomorphic, club-shaped
- Arranged in palisades / “Chinese letters” (V/L shapes)
- Non–spore forming, non-motile
- Catalase-positive
- Has metachromatic granules (polyphosphate)
- Virulence depends on a lysogenic bacteriophage (β-phage) carrying the toxin gene
First Aid cross-reference (by concept): Gram-positive rods; exotoxins; “Chinese letters,” metachromatic granules; diphtheria toxin as an A-B exotoxin that inhibits EF-2.
Where it fits on your Gram-positive map (Step 1 mental sorting)
| Category | Bugs you should immediately think of | One-liner differentiator |
|---|---|---|
| Gram+ cocci | Staph/Strep/Enterococcus | Catalase/hemolysis patterns |
| Gram+ rods (spore-formers) | Bacillus, Clostridium | Spores, severe toxin syndromes |
| Gram+ rods (non–spore formers) | Corynebacterium, Listeria | Coryne = “Chinese letters”; Listeria = tumbling motility |
Transmission & Epidemiology (what the vignette will hint at)
Reservoir: Humans
Spread: Respiratory droplets; close contact; rarely via skin lesions (cutaneous diphtheria)
Risk factors in vignettes
- Unvaccinated or under-immunized (DTaP/Tdap not up to date)
- Recent travel or community outbreak
- Crowded living conditions
Core Step point: Disease severity is tied to toxin production (not just bacterial invasion).
Pathophysiology: The toxin is the star
Step 1 must-know: Diphtheria toxin is an A-B exotoxin
- Encoded by tox gene carried by a lysogenic bacteriophage (β-phage)
- A subunit: enzymatically active
- B subunit: binding/entry
Mechanism (memorize this line)
Diphtheria toxin ADP-ribosylates EF-2 → inhibits protein synthesis → cell death.
- EF-2 is needed for translocation during translation.
- Result: local tissue necrosis + systemic toxic effects (heart + nerves).
Compare/contrast (high-yield association):
- Diphtheria toxin and Pseudomonas exotoxin A share the same mechanism: ADP-ribosylation of EF-2 → ↓ protein synthesis.
Clinical Presentation (Respiratory + Systemic)
Classic respiratory diphtheria
Symptoms
- Sore throat, fever (may be low-grade), malaise
- Cervical LAD → “bull neck”
- Gray/white pseudomembrane on tonsils/pharynx
Pseudomembrane = dead tissue + fibrin + inflammatory cells
- Bleeds when scraped (high-yield)
Airway concern
- Can obstruct airway → stridor, respiratory distress
Systemic toxin effects (the Step 2 trap)
Once toxin disseminates, think:
- Myocarditis → arrhythmias, heart block, heart failure
- Neurologic → cranial neuropathies, peripheral neuropathy (weeks later)
- Possible kidney/liver injury in severe cases
Cutaneous diphtheria
- Chronic non-healing ulcer with a dirty gray membrane
- Less systemic toxicity, but still can transmit
Diagnosis (what you do and what you don’t wait for)
Clinical diagnosis comes first
If the pseudomembrane + vaccine history fits, treat immediately—don’t wait for lab confirmation.
Lab confirmation (board-style)
Specimen: Throat swab from beneath/edge of membrane (careful—bleeding risk)
Culture media:
- Loeffler medium: enhances metachromatic granules
- Tellurite agar: characteristic growth (classically black colonies)
Demonstrating toxin:
- Elek test (immunodiffusion) historically used to detect toxigenic strains
- PCR for tox gene may be used in modern labs, but boards love Elek
Microscopy clues
- Gram-positive, pleomorphic rods in “Chinese letter” arrangement
- Metachromatic granules on special staining
Treatment (Step-ready algorithm)
1) Give antitoxin ASAP
- Diphtheria antitoxin neutralizes circulating (unbound) toxin
- Does not reverse toxin already inside cells → earlier is better
2) Antibiotics to stop toxin production and transmission
Common regimens:
- Erythromycin or Penicillin G
- Also treat/monitor close contacts per public health guidance
3) Airway + isolation
- Airway assessment is critical (pseudomembrane can obstruct)
- Droplet precautions and notify public health
4) Vaccinate after infection
Natural infection does not reliably confer immunity. Patients still need DTaP/Tdap per schedule.
Prevention (this is how Step tests it)
Vaccine basics
- Diphtheria vaccine is a toxoid vaccine (inactivated toxin)
- Given as DTaP (kids) and Tdap/Td boosters (adults)
High-yield immunology tie-in: Toxoids induce neutralizing IgG antibodies that block toxin binding/entry.
High-Yield Associations & “Buzzwords” (rapid review)
If you see this… think diphtheria
- Gray pseudomembrane + bleeds on removal
- Unvaccinated child/adolescent
- Bull neck (cervical LAD/soft tissue swelling)
- Myocarditis after sore throat
- Cranial nerve palsies/peripheral neuropathy after URI symptoms
- A-B exotoxin → ADP-ribosylates EF-2
Rapid Comparison: EF-2 inhibition toxiners (frequently tested)
| Organism | Toxin | Target | Result |
|---|---|---|---|
| C. diphtheriae | Diphtheria toxin (A-B) | EF-2 via ADP-ribosylation | ↓ protein synthesis |
| Pseudomonas aeruginosa | Exotoxin A | EF-2 via ADP-ribosylation | ↓ protein synthesis |
Classic Mini-Vignette (how it’s tested)
A child with incomplete immunizations has sore throat and low-grade fever. Exam shows a gray pharyngeal pseudomembrane that bleeds when scraped, plus cervical LAD (“bull neck”). Two days later, they develop arrhythmia.
Answer anchors
- Organism: Corynebacterium diphtheriae
- Virulence: phage-encoded A-B toxin
- Mechanism: ADP-ribosylation of EF-2
- Immediate management: antitoxin + erythromycin/penicillin + airway precautions
First Aid-Style “What to Memorize”
- Gram+ pleomorphic club-shaped rods in palisades/Chinese letters
- Metachromatic granules
- Pseudomembrane that bleeds on removal
- Toxoid vaccine (DTaP/Tdap)
- A-B exotoxin inhibits protein synthesis via EF-2 ADP-ribosylation
- Complications: myocarditis, neuropathy
- Treatment: antitoxin + erythromycin or penicillin G