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1
Question:

A 30-year-old primigravid woman at 35 weeks gestation comes to the emergency department due to fever, nausea, vomiting, watery diarrhea, and myalgias that began one day ago.  She has no contractions, vaginal bleeding, or leakage of fluid.  Temperature is 39.3 C (102.7 F), blood pressure is 90/60 mm Hg, and pulse is 126/min.  The abdomen is soft, and the uterus is nontender.  Fetal heart rate is 180/min on Doppler ultrasound.  The remainder of the physical examination is normal.  Blood cultures grow gram-positive rods.  Which of the following is the major virulence factor of the organism responsible for this patient's clinical presentation?

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Explanation:

Gram-positive rods in blood cultures

  • Corynebacterium species (diphtheroid)
  • Clostridium species
  • Nocardia species or the anaerobic Actinomyces species
  • Listeria species

This pregnant woman has febrile gastroenteritis (eg, fever, vomiting, diarrhea) and gram-positive rods in her bloodstream, raising strong suspicion for Listeria monocytogenes infection.  L monocytogenes is a motile, facultatively intracellular organism with several unique adaptations that allow it to evade the host immune response, including the following:

  • Listeriolysin O:  This major virulence factor generates pores in phagosome membranes, which allows phagocytosed L monocytogenes to escape into the cytoplasm of monocytes and avoid lysosomal destruction.

  • Actin-based transcellular spread:  The organism hijacks the actin-based cellular motility mechanism of host cells, which allows it to spread to adjacent cells without reentering the extracellular space.  This significantly reduces exposure of L monocytogenes to antibodies and phagocytic cells.

Because of these adaptations, antibody- and phagocyte-mediated destruction of the pathogen is impaired; therefore, infections are controlled primarily by the cytotoxic T-cell response.

Most L monocytogenes infections occur in pregnant women in the third trimester.  Although antibiotics are curative, L monocytogenes quickly invades the placenta and may cause fetal death, premature birth, and neonatal infection.

(Choice B)  Bacterial lipopolysaccharide (endotoxin) is the major component of the cell wall in gram-negative, not gram-positive, bacteria (some sources erroneously report that L monocytogenes contains lipopolysaccharide).  Endotoxin activates complement, coagulation, and fibrinolysis, which can lead to septic shock and disseminated intravascular coagulation.

(Choice C)  Clostridium botulinum, an anaerobic gram-positive rod, produces an exotoxin (botulinum toxin) that inhibits the synaptic transmission of motor neurons.  Patients typically develop descending, symmetric motor deficits; minimal sensory changes; and no fever.

(Choice D)  Pathogenic strains of Corynebacterium diphtheriae produce an exotoxin that inhibits elongation factor in host cells, which causes pseudomembranous pharyngitis and myocarditis.  Although C diphtheriae is a gram-positive rod, it does not cause febrile gastroenteritis.

Educational objective:
Listeria monocytogenes is a facultative intracellular, gram-positive rod that most often causes febrile gastroenteritis.  Pathogenesis is mediated largely by listeriolysin O, an enzyme that creates pores in phagosomes, which allows the bacteria to escape lysosomal destruction.  Pregnant women in the third trimester are at greatest risk; infection increases the risk of fetal demise, early labor, and neonatal infection.