A 47-year-old woman presents to a local medical shelter while on a mission trip with her church to help rebuild homes after a hurricane. She has been experiencing severe nausea, vomiting, and diarrhea for the last 2 days and was feeling too fatigued to walk this morning. On presentation, her temperature is 99.2°F (37.3°C), blood pressure is 95/62 mmHg, pulse is 121/min, and respirations are 17/min. Physical exam reveals decreased skin turgor, and a stool sample reveals off-white watery stools. Gram stain reveals a gram-negative, comma-shaped organism that produces a toxin. Which of the following is consistent with the action of the toxin most likely involved in the development of this patient's symptoms?

Increased adenylyl cyclase activity

Increased membrane permeability

Cleavage of junctional proteins

Activation of receptor tyrosine kinase

A 62-year-old woman presents to the emergency department for evaluation of a spreading skin infection that began from an ulcer on her foot. The patient has type 2 diabetes mellitus that is poorly controlled. On examination, there is redness and erythema to the lower limb with skin breakdown along an extensive portion of the leg. The patient’s tissues separate readily from the fascial plane, prompting a diagnosis of necrotizing fasciitis. What is the exotoxin most likely associated with this patient’s presentation?

Streptococcal pyogenic exotoxin B

Streptococcal pyogenic exotoxin A

A 27-year-old man presents to the emergency department with unrelenting muscle spasms for the past several hours. The patient’s girlfriend states that he started having jaw spasms and soreness last night but now his neck, back, and arms are spasming. She also states that he stepped on a nail about 1 week ago. Past medical history is noncontributory. The patient's vaccination status is unknown at this time. Today, the vital signs include temperature 39.1°C (102.4°F), heart rate 115/min, blood pressure 145/110 mm Hg, and respiratory rate 10/min. On exam, the patient is in obvious discomfort, with a clenched jaw and extended neck. Labs are drawn and a basic metabolic panel comes back normal and the white blood cell (WBC) count is moderately elevated. Which of the following is the most likely etiology of this patient’s symptoms?

An exotoxin that cleaves SNARE proteins

An exotoxin that causes ADP-ribosylation of EF-2

An edema factor that functions as adenylate cyclase

A heat-labile toxin that inhibits ACh release at the NMJ

A toxin that disables the G-protein coupled receptor

A 48-year-old woman comes to the physician for a follow-up examination. Six months ago, she was diagnosed with overactive bladder syndrome and began treatment with oxybutynin. She continues to have involuntary loss of urine with sudden episodes of significant bladder discomfort that is only relieved by voiding. A substance is injected into the detrusor muscle to treat her symptoms. The physician informs the patient that she will have transitory relief for several months before symptoms return and will require repeated treatment. The injected substance is most likely produced by an organism with which of the following microbiological properties?

Gram-positive, spore-forming rod

Gram-negative, encapsulated diplococcus

Gram-negative, comma-shaped rod

Gram-negative, aerobic coccobacillus

A 6-year-old boy presents with fever, sore throat, hoarseness, and neck enlargement. The symptoms started 3 days ago and progressed gradually with an elevated temperature and swollen lymph nodes. His family immigrated recently from Honduras. He was born via spontaneous vaginal delivery at 39 weeks after an uneventful gestational period and he is now on a catch-up vaccination schedule. He lives with several family members, including his parents, in a small apartment. No one in the apartment smokes tobacco. On presentation, the patient’s blood pressure is 110/75 mm Hg, heart rate is 103/min, respiratory rate is 20/min, and temperature is 39.4°C (102.9°F). On physical examination, the child is acrocyanotic and somnolent. There is widespread cervical edema and enlargement of the cervical lymph nodes. The tonsils are covered with a gray, thick membrane which spreads beyond the tonsillar bed and reveals bleeding, erythematous mucosa with gentle scraping. The lungs are clear to auscultation. Which of the following is the target of the virulence factor produced by the pathologic organism infecting this child?

Eukaryotic elongation factor-2 (eEF-2)

A 16-year-old male is brought to the clinic by his mother for the complaints of fever, nonproductive cough, fatigue, lack of appetite, and sore throat for the past 2 months. Several other students at his high school have had similar symptoms. Physical exam shows a whitish membrane in his oropharynx, bilateral enlarged cervical lymphadenopathy, and mild splenomegaly. Which of the following tests is most likely to diagnose his condition?

Enzyme-linked immunosorbent assay

Corynebacterium species — USMLE Lesson

Corynebacterium - The Club-Shaped Invaders

Gram-positive, non-motile, club-shaped (coryneform) rods arranged in V/Y shapes or palisades.
Contain metachromatic (Babes-Ernst) granules.
Pathogenesis (C. diphtheriae): Diphtheria toxin, an A-B exotoxin, inhibits protein synthesis by ADP-ribosylating Elongation Factor 2 (EF-2).
- Clinical Triad: Pharyngitis with thick, gray pseudomembrane, "bull neck" (cervical lymphadenopathy), and low-grade fever.
- Systemic: Myocarditis, arrhythmias, and neuropathies.
Diagnosis: Culture on Tellurite agar (black colonies) or Loeffler medium. Toxin detection via Elek test or PCR.
Treatment: Antitoxin (most critical) + Erythromycin or Penicillin.
Prevention: DTaP/Tdap toxoid vaccine.

⭐ The gene encoding the diphtheria toxin (tox) is introduced into C. diphtheriae by a lysogenic bacteriophage (β-prophage).

Pharyngeal pseudomembrane in diphtheria

Diphtheria Toxin - The Protein Assassin

An A-B polypeptide exotoxin that irreversibly inhibits protein synthesis.

Source: The tox gene is acquired via lysogenic conversion from a temperate β-prophage.
Mechanism of Action:
- B (Binding) subunit attaches to the Heparin-Binding EGF-like growth factor (HB-EGF) receptor, which is abundant on cardiac and nerve cells.
- A (Active) subunit enters the cell cytoplasm.
- It catalyzes the ADP-ribosylation of Elongation Factor 2 (EF-2).
- This inactivation of EF-2 halts polypeptide chain elongation, leading to cell death.

Diphtheria toxin mechanism of action

⭐ The systemic effects (e.g., myocarditis, arrhythmias, neuropathies) are the direct result of toxin dissemination and its action on cells expressing the HB-EGF receptor. This is distinct from the local tissue necrosis that forms the pharyngeal pseudomembrane.

Diphtheria Clinical - From Grey Neck to Failing Heart

Respiratory Diphtheria (Local Toxin)
- Presents 2-5 days post-exposure with sore throat, malaise, and low-grade fever.
- Hallmark: A dense, grey, adherent pseudomembrane forms over the tonsils and pharynx; bleeds if dislodged.
- Severe cases develop a "bull neck" from massive cervical adenopathy and edema, which can compromise the airway.

Diphtheria: Bull Neck and Pharyngeal Pseudomembrane

Systemic Toxin Complications
- Myocarditis (1-2 wks): The most common cause of mortality. Can cause arrhythmias, heart block, and acute heart failure.
- Neuropathy (wks-mos): A progressive, symmetric polyneuropathy. Often starts with paralysis of the soft palate and diaphragm.

⭐ The diphtheria exotoxin irreversibly inactivates Elongation Factor-2 (EF-2) via ADP-ribosylation, which halts protein synthesis and causes cell death, especially in the heart and nerves.

Lab & Treatment - Tinsdale, Toxoids & Triage

Lab Diagnosis
- Culture on Tinsdale agar → black colonies with brown halos.
- Loeffler's medium → metachromatic (blue/red) granules.
- Elek test → detects toxin production (in vitro precipitation line).
Treatment & Prevention
- Triage Priority: Administer diphtheria antitoxin immediately on suspicion.
- Antibiotics: Penicillin G or erythromycin.
- Prevention: DTaP vaccine (diphtheria toxoid).

⭐ Crucial step: Antitoxin administration should NOT be delayed for lab confirmation. It neutralizes circulating toxin only.

Corynebacterium diphtheriae on Tinsdale agar

High‑Yield Points - ⚡ Biggest Takeaways

Gram-positive, club-shaped rods arranged in V or Y shapes ("Chinese letters").

C. diphtheriae causes diphtheria via an exotoxin that inhibits protein synthesis by ADP-ribosylating EF-2.

Presents with a grayish-white pseudomembrane in the pharynx and a "bull neck" due to lymphadenopathy.

Systemic complications include myocarditis and neuropathy.

Grows on tellurite agar (black colonies) and Loeffler's medium.

The toxoid vaccine (in DTaP) is key for prevention.

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