Review Question - QID 106293

The boy has a Corynebacterium diphtheriae infection, which produces a toxin that inactivates elongation factor 2 (EF-2).

C. diphtheriae is a gram-positive, non-spore forming bacillus that is transmitted via respiratory droplets. Infections are rare within the U.S. and are usually seen in immigrants from eastern Europe and Asia due to the low prevalence of DTaP vaccination in those areas. C. diphtheriae produces an exotoxin, diphtheria toxin, that inactivates the EF-2 by inhibiting protein synthesis via ADP ribosylation and leading to cell death. Acute treatment for the infection is the administration of the antitoxin, along with antibiotics (erythromycin, penicillin, and aminoglycosides).

Murphy describes in further detail the pathogenesis of C. diphtheriae infection, in which disease is caused by growth of the bacteria and the release of the diphtheria toxin in either the nasopharynx or the skin. The toxin is composed of two subunits (fragment A and B): fragment B is responsible for binding to the cell surface and assisting in the delivery of fragment A into the cell. Fragment A is the catalytic domain that catalyzes the "NAD+ dependent ADP-ribosylation of EF-2," which inhibits protein synthesis and results in cell death.

Murphy describes the clinical manifestations of a C. diphtheriae infection that affects either the nasopharynx or skin. Symptoms include a fever (>103 deg F), sore throat, severe lymphadenopathy ("bull neck") or swelling in the affected area, and, sometimes, difficulty breathing. The area with diphtheritic lesions typically is covered in a grayish-white pseudomembrane composed of C. diphtheriae, inflammatory cells, and fibrin. If the toxin is distributed throughout the body, systemic complications can occurs, such as paralysis and congestive heart failure.

Figure A demonstrates the severe lymphadenopathy of C. diphtheriae resulting in the characteristic swollen neck referred to as a "bull neck". Figure B demonstrates the pseudomembranous pharyngitis that develops in this infection. Figure C shows the characteristic "Chinese-letter" arrangement of the bacteria along with the metachromatic granules due to the presence of inorganic phosphate inclusions.

Incorrect Answers:
Answer 1: Pertussis toxin inhibits the G-protein Gi alpha subunit (via ADP ribosylation) which leads to increased cAMP concentrations which subsequently activates protein kinases and other intracellular messengers.
Answer 2: Enterotoxigenic E. coli (ETEC) produces a heat-stable toxin that overactivates guanylate cyclase.
Answer 3: Shigella produces Shiga toxin that inactivates the 60S ribosomal subunit inhibiting protein synthesis.
Answer 5: Clostridium botulinum and tetani produce toxins (botulinum and tetanospasmin) that cleaves the SNARE proteins which are necessary for neurotransmitter exocytosis.