A 2-day-old boy is evaluated in the neonatal intensive care unit for lethargy and respiratory distress. The patient was born at home via spontaneous vaginal delivery at term gestation to a mother who did not receive routine prenatal care. Temperature is 38.9 C (102 F) and pulse is 162/min. Physical examination shows tachypnea and grunting. Blood cultures grow beta-hemolytic, gram-positive cocci in chains that elicit a narrow zone of complete hemolysis on blood agar. Which of the following virulence factors most likely contributed to the development of this patient's current condition?
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This neonate has sepsis (eg, fever, lethargy, respiratory distress) due to group B Streptococcus (GBS), a gram-positive coccus that forms chains and exhibits a narrow zone of complete hemolysis on blood agar (beta-hemolytic).
GBS colonizes the gastrointestinal or genitourinary tract of approximately 50% of pregnant women. These women are treated with intrapartum antibiotic prophylaxis (eg, penicillin) as part of routine prenatal care to prevent vertical transmission during rupture of membranes or vaginal delivery. Women who are colonized and do not receive prophylaxis, like this patient's mother, are more likely to transmit the organism to the neonate, leading to increased risk for sepsis, pneumonia, or meningitis within hours to days after birth (ie, early-onset disease).
The virulence of GBS stems from the presence of a thick polysaccharide capsule composed of galactose with terminal sialic acid (SA) residues. These residues are identical to SA epitopes on glycoproteins/glycolipids of host cells, allowing bacteria to evade host defenses via molecular mimicry. Bacterial SA residues are also recognized as "self" by phagocytes, which limits phagocytosis, oxidative burst generation, and production of neutrophil extracellular traps. In addition, SA residues 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/recombination of surface antigens so that antibody formed during a previous infection is unable to prevent future infection. This is commonly seen with viruses (eg, influenza) and some bacteria (eg, Neisseria meningitidis) but not GBS.
(Choice B) Endotoxin (lipopolysaccharide) is a major virulence factor of gram-negative bacteria (eg, Escherichia coli). Although E coli is a common cause of neonatal sepsis, gram-negative rods would be seen in the bloodstream.
(Choice C) Listeriolysin O, the primary virulence factor of Listeria monocytogenes, is an exotoxin that causes pores in the phagosome membrane. This allows the organisms to escape into the cytoplasm of phagocytic cells prior to phagolysosomal destruction. Although Listeria can cause neonatal infection (less commonly than GBS and E coli), it is a gram-positive rod, not a coccus.
(Choice D) M protein, a virulence factor of group A Streptococcus (GAS), prevents opsonization. Although GAS is a beta-hemolytic, gram-positive coccus in chains, it is not a common cause of neonatal sepsis.
Educational objective:
Group B Streptococcus is a major cause of neonatal sepsis. Its virulence factor is the polysaccharide capsule, which contains sialic acid residues that prevent phagocytosis via molecular mimicry.