A 5-year-old child is brought to the emergency department due to difficulty breathing and a low-grade fever. The patient's family recently moved to the United States from rural Nepal. Temperature is 38.1 C (100.6 F). Physical examination shows a grayish pharyngeal exudate, enlarged cervical lymph nodes, and partial soft palate paralysis. A sample of the pharyngeal exudate is obtained by oropharyngeal swab. Bacteria isolated from the exudate demonstrate exotoxin production in the laboratory. Which of the following best describes the mechanism of action of the exotoxin?

Question

A 5-year-old child is brought to the emergency department due to difficulty breathing and a low-grade fever.  The patient's family recently moved to the United States from rural Nepal.  Temperature is 38.1 C (100.6 F).  Physical examination shows a grayish pharyngeal exudate, enlarged cervical lymph nodes, and partial soft palate paralysis.  A sample of the pharyngeal exudate is obtained by oropharyngeal swab.  Bacteria isolated from the exudate demonstrate exotoxin production in the laboratory.  Which of the following best describes the mechanism of action of the exotoxin?

Quizplus · Accepted Answer

11ec160b_3821_7200_9249_3bc8832ddcb5_MD0001_00 This child has diphtheria, a disease caused by Corynebacterium diphtheriae and now rarely seen in most countries as a result of vaccination. The A (active) subunit of the diphtheria AB exotoxin transfers a ribose residue from NAD to a histidine on elongation factor-2 (EF-2). The EF-2 protein is essential for peptide chain translocation on the ribosome in the process of translation. Ribosylation inactivates EF-2, thereby inhibiting protein synthesis and causing cell death. (Choice A) Group A Streptococcus (GAS) pharyngitis can lead to rheumatic fever via antigenic mimicry. GAS and cardiac myocytes have similar antigenic protein sequences. Therefore, when the immune system mounts a response against GAS, it may also cause myocarditis and valve destruction over time. GAS pharyngitis is not typically due to exotoxins and does not classically cause local neuropathies (eg, soft palate paralysis). (Choice B) Lecithinase (also known as phospholipase C, or Clostridium perfringens alpha-toxin) is the exotoxin released by C perfringens. This enzyme degrades membrane phospholipids (including lecithin), leading to cell membrane destruction and cell death. C perfringens causes gas gangrene. (Choice C) The shiga toxin of Shigella and the shigalike toxin of enterohemorrhagic Escherichia coli (EHEC) cause inactivation of the 60S ribosomal subunit. By contrast, diphtheria toxin inactivates EF-2, not the ribosome itself. Shigella and EHEC cause diarrheal illnesses. (Choice D) Pertussis toxin is an AB exotoxin released by Bordetella pertussis that catalyzes ribosylation of G protein α_i subunits. This results in increased cAMP production, which leads to increased insulin production, lymphocyte and neutrophil dysfunction, and increased sensitivity to histamine. Classic pertussis has a catarrhal stage (mild upper respiratory symptoms), a paroxysmal stage (whooping cough), and a convalescent stage. Educational objective: Diphtheria toxin is an AB exotoxin that ribosylates and inactivates elongation factor-2. This action inhibits protein synthesis and ultimately leads to cell death.

A 5-Year-Old Child Is Brought to the Emergency Department Due