A 4-week-old girl is brought to the emergency department due to poor feeding and increasing lethargy. The patient was born at term and had been well until 2 days ago, when she started sleeping throughout the day. She has been difficult to arouse for feeds and has had little interest in eating when awake. This morning, the patient had several episodes of emesis after the family attempted to feed her. Temperature is 39.4 C (102.9 F), and she is mildly tachypneic. A lumbar puncture is performed, and the patient is admitted due to concerns for infection. CSF culture grows numerous gray colonies on blood agar, with a narrow area of clearing surrounding each colony. Gram staining shows gram-positive cocci in short chains. Which of the following virulence factors is primarily involved in the pathogenesis of this patient's infection?
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This neonate with lethargy, poor feeding, and fever has meningitis. The most common pathogens in this age group are group B Streptococcus (GBS) and gram-negative bacilli (eg, Escherichia coli). In this patient, cerebrospinal fluid shows gram-positive cocci in chains with a narrow zone of hemolysis indicating GBS infection.
GBS is highly virulent due to the presence of a thick polysaccharide capsule composed of galactose with terminal sialic acid (SA) residues. These bacterial SA moieties are identical to SA epitopes on glycoproteins/glycolipids of host cells (molecular mimicry), allowing the bacteria to evade host defenses. SA residues interact with receptors on phagocytes and are recognized as self, which down-regulates phagocytosis, oxidative burst generation, and production of neutrophil extracellular traps. SA residues also inhibit binding of the opsonin C3b (limits opsonophagocytosis) and the generation of the anaphylatoxin C5a (limits immune cell recruitment).
(Choice A) Antigenic variation involves rapid mutation of surface antigens, which limits the ability of immunoglobulin formed during previous infection to prevent future infections. It is seen primarily with viruses (eg, influenza) and certain bacteria (eg, Neisseria meningitidis); however, GBS is virulent primarily due to SA on its capsule, not antigenic variation.
(Choice B) Catalase-producing organisms (eg, Listeria, Staphylococcus) can break down hydrogen peroxide to oxygen and water, which limits oxidative damage. Listeria monocytogenes can cause neonatal meningitis, but Gram stain would show gram-positive rods, not cocci; Staphylococcus species are an uncommon cause of neonatal meningitis and are gram-positive cocci in clusters, not chains.
(Choice C) Increased uptake of extracellular iron, an essential micronutrient for most bacteria, is not a major virulence factor for Streptococcus species.
(Choice D) Lipopolysaccharide is a major virulence factor of gram-negative bacteria such as E coli. It limits host opsonophagocytic killing. However, GBS does not have lipopolysaccharide because it is a gram-positive organism.
(Choice F) Rapid, flagella-mediated motion is a virulence factor because it assists bacterial invasion (eg, E coli). However, GBS does not have flagella; it has pili, cell wall appendages that aid in bacterial adhesion.
Educational objective:
Group B Streptococcus is a common cause of neonatal meningitis. Its major virulence factor is a polysaccharide capsule with abundant sialic acid, which dramatically reduces the effectiveness of host defense mechanisms due to molecular mimicry.