WBR0054

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Author PageAuthor::William J Gibson (Reviewed by Yazan Daaboul)
Exam Type ExamType::USMLE Step 1
Main Category MainCategory::Microbiology
Sub Category SubCategory::Head and Neck
Prompt [[Prompt::A 5-year-old boy is brought to the emergency department by his father for low-grade fever. He has recently immigrated from rural Africa. In the ED, the patient appears sick-looking, leaning forward with his neck extended, and drooling. His blood pressure is 110/70 mmHg, heart rate is 110/min, and temperature is 100.7 ºF (38.2 ºC). Physical exam reveals marked cervical lymphadenopathy, and pseudomembranes in the throat. What is the mechanism of action of the toxin produced responsible for this patient's condition?]]
Answer A AnswerA::Inactivation of 60S ribsosome by cleaving rRNA
Answer A Explanation [[AnswerAExp::The toxins produced by Shigella and EHEC inactivate the 60S ribosome by cleaving rRNA.]]
Answer B AnswerB::Activation of adenylate cyclase by stimulating Gs
Answer B Explanation [[AnswerBExp::The toxin produced by Vibrio cholera activate adenylate cyclase by stimulating Gs. This activation of the cAMP pathway in enterocytes leads to a secretory diarrhea. The hallmark of cholera is the development of "rice-water" stools.]]
Answer C AnswerC::Activation of adenylate cyclase by disabling Gi
Answer C Explanation [[AnswerCExp::The toxin produced by Bordetella pertussis activates adenylate cyclase by disabling Gi. Pertussis infection is a highly contagious bacterial disease that manifests as "whooping cough".]]
Answer D AnswerD::Cleavage of SNARE protein
Answer D Explanation [[AnswerDExp::Both Botulinum and Tetanus toxins cleave SNARE protein at synapses, thereby disabling neurotransmitter release at the synaptic cleft.]]
Answer E AnswerE::Inactivation of elongation factor-2
Answer E Explanation [[AnswerEExp::Diptheria toxin causes disease by inactivating elongation factor 2 (EF-2). Diptheria infection can be diagnosed by the presence of pseudomembranes in the throat.]]
Right Answer RightAnswer::E
Explanation [[Explanation::This patient is most likely infected by Corynebacterium diphtheriae, a gram positive rod that is the causative agent of epiglottitis. C. diphtheriae has mostly been eradicated in the developed world through vaccination. Diptheria causes upper respiratory tract infections via exotoxin encoded by β-prophage. C. diphtheriae exotoxin inhibits protein synthesis by ADP ribsolyation of elongation factor-2 (EF-2).

Manifestations include sore throat, cervical lymphadenopathy, and fever. Patients typically present to the emergency department sick or toxic-looking, leaning forward in a "tripod position" with their necks extended upward in the "sniffing dog" position that helps them breathe through the narrow inflamed airway. The hallmark of this infection is an adherent true membrane on the tonsils referred to as pseudomembranes (greyish-white membranes). Diagnosis is based on culture results that show gram-positive rods with metachromatic granules colored grey and blue. Elek test, an immunochromatographic technique, may be used to detect the presence of toxin. Most significant complications are neurological and cardiac. Treatment includes the administration of diphtheria antitoxin that prevents further complications of the infection and administration of penicillin or erythromycin. DTaP, a toxoid vaccine, that includes diphtheria should be adminstered to all children.
Educational Objective: Diptheria toxin causes disease by inactivating elongation factor 2 (EF-2). Diptheria infection can be diagnosed by the presence of pseudomembranes in the throat.
References: First Aid 2014 page 132 (diptheria) First Aid 2014 page 126 (toxins) First Aid 2012 page 152]]

Approved Approved::Yes
Keyword WBRKeyword::Microbiology, WBRKeyword::Diptheria, WBRKeyword::Toxin, WBRKeyword::Bacteria, WBRKeyword::Mechanism, WBRKeyword::Toxins, WBRKeyword::elongation, WBRKeyword::factor, WBRKeyword::pharyngitis, WBRKeyword::gram, WBRKeyword::positive
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