Perinatal Group B Streptococcal Infections: Virulence Factors, Immunity, and Prevention Strategies

Abstract

Group B streptococcus (GBS) or Streptococcus agalactiae is a β-hemolytic, Gram-positive bacterium that is a leading cause of neonatal infections. GBS commonly colonizes the lower gastrointestinal and genital tracts and, during pregnancy, neonates are at risk of infection. Although intrapartum antibiotic prophylaxis during labor and delivery has decreased the incidence of early-onset neonatal infection, these measures do not prevent ascending infection that can occur earlier in pregnancy leading to preterm births, stillbirths, or late-onset neonatal infections. Prevention of GBS infection in pregnancy is complex and is likely influenced by multiple factors, including pathogenicity, host factors, vaginal microbiome, false-negative screening, and/or changes in antibiotic resistance. A deeper understanding of the mechanisms of GBS infections during pregnancy will facilitate the development of novel therapeutics and vaccines. Here, we summarize and discuss important advancements in our understanding of GBS vaginal colonization, ascending infection, and preterm birth.

Keywords: Group B streptococcus; ascending infection; perinatal; preterm birth; vaginal colonization infection.

Figure 1. Ascending GBS infection

GBS vaginal colonization increases the risk of ascending infection during pregnancy. Ascending GBS infection during pregnancy involves bacterial trafficking from the vagina ultimately leading to bacterial invasion of placental membranes (chorion and amnion), the amniotic cavity and fetus. GBS express a number of virulence factors that promote vaginal colonization, adhesion and invasion of host cells, activation of inflammatory responses or conversely for suppression of inflammatory responses (see Table 1 and Figure 2). These factors increase the risk of ascending infection, fetal injury or preterm birth.

Figure 2. GBS Interaction with Innate Immune Cells During Genital Infection

Upon primary vaginal colonization, vaginal-resident mast cells are activated and de-granulated through the hemolytic activity of the GBS pigment. De-granulation leads to the release of inflammatory mediators, including IL-6, IL-8, TNFα, and histamine, which in turn recruits other immune cells, such as neutrophils and macrophages, to aid in bacterial clearance [69]. Neutrophils clear GBS through phagocytosis and extrusion of NETs [67]. Additionally, GBS activates the NLRP3 inflammasome in neutrophils, leading to secretion of IL-1β, as well as other inflammatory cytokines. GBS are able to use the pigment to prevent phagocytic death through sequestration of reactive oxygen species [66], and to avoid being killed by NETs [39]. Macrophages also aid in GBS clearance through phagocytosis. GBS, in turn, activate the NLRP3 inflammasome in macrophages through membrane permeabilization by pigment, leading to pyroptosis and fetal damage during pregnancy [46].