Group B Streptococcus and Maternal-Neonatal Health

Streptococcus agalactiae

Streptococcus agalactiae, or Group B Streptococcus (GBS), is an opportunistic human pathogen that colonizes the gastrointestinal and genitourinary tracts of healthy individuals and is the most common cause of severe infectious illness in newborn infants, including sepsis, pneumonia, and meningitis. GBS is also an emerging and significant pathogen for pregnant women, the elderly, and adults with medical comorbidities.

Streptococcus agalactiae is a Gram-positive coccus that usually forms chains. On blood agar plates, one of the most important features of S. agalactiae is its beta-hemolytic rings. The cell surface capsular polysaccharide is probably its most important biological trait. This capsule is the principal virulence factor of GBS and it has marked anti-phagocytic properties allowing GBS to resist host clearance. By the antigenicity of its capsular polysaccharide, GBS can be serotyped into at least 10 serotypes. This serotyping is also used for epidemiological surveillance and for the development of vaccines. At the genome level, the Streptococcus agalactiae genome is highly plastic. A multiple genome comparison of S. agalactiae showed that horizontal gene transfer (HGT) has a central role in the evolution of this bacterium. By mobile genetic elements (MGEs) such as phages, plasmids and conjugative elements, GBS can acquire virulence genes and antibiotic resistance genes. Pathogenicity islands in the genome are areas enriched in virulence genes and the presence and variation of these genomic islands may play a role in strain differences in pathogenic potential.

Figure 1. Serotype distribution within each sequence type, using the public MLST database for GBS, for the 12 most represented sequence types within the database, as well as their corresponding clonal complexes
(Source: Furfaro LL, et al. 2018)

GBS is a leading cause of pregnancy-associated infections, preterm birth, and neonatal infections. It was first discovered in bovine mastitis and subsequently isolated from the human vagina and linked to human disease cases. Subsequent research found that vaginal colonization during pregnancy is a risk factor for neonatal GBS disease and preterm birth. Pregnant individuals colonized with GBS in the vagina are at risk of ascending infection during delivery or of transmitting GBS to the newborn. Ascending infection is defined as the passage of vaginal bacteria through the cervix into the uterus and through gestational tissues. When GBS enters the amniotic cavity or the placenta, it can cause chorioamnionitis, a leading cause of preterm birth and stillbirth. The bacterial and host factors that contribute to GBS vaginal colonization, ascending infection, and adverse perinatal outcomes are incompletely understood. Recent studies indicate that increased GBS colonization rates in many low-income countries are associated with rising rates of neonatal infection and preterm birth. In the United States and many other countries, routine screening for GBS colonization via rectovaginal swab culture is performed in the third trimester. If the culture is positive, GBS is detected in the urine, or there is a history of a previous infant with GBS disease, intrapartum antibiotic prophylaxis is administered during delivery to prevent vertical transmission at birth. Neonatal GBS disease is categorized into two types: Early-Onset Disease and Late-Onset Disease. EOD refers to disease that occurs within the first 7 days of life and is typically acquired in utero or during birth through aspiration or contact with GBS contaminated amniotic fluid or birth canal secretions. LOD occurs from 7 days to 3 months of age, and may be acquired from maternal, household environment, or nosocomial sources.

Bacterial Factors

GBS encodes a variety of virulence factors that enable it to persistently colonize the harsh vaginal environment and avoid clearance. Many of these factors are involved in the adhesion to and invasion of host epithelial cells, thereby facilitating persistent colonization. Adhesion and invasion appear to be mediated by GBS interactions with host extracellular matrix components; these interactions may also promote GBS resistance to mechanical clearance, evasion of immune surveillance, and intercellular migration. The GBS outer membrane protein BsaB (also known as FbsC) can bind to host laminin and fibrinogen, enhancing adhesion to cervicovaginal epithelial cells and promoting biofilm formation. The GBS Srr (Serine-rich repeat) glycoprotein family binds to epithelial cells via a unique mechanism and interacts with host fibrinogen. Fibrinogen binding triggers a series of ordered conformational changes in Srr1 and Srr2, thereby strengthening adhesion. Deleting the entire Srr1 glycoprotein or only its latch domain reduces vaginal colonization. GBS pili, which bind to host cell molecules via the PilA adhesin, also mediate colonization and adhesion.

The hemolytic properties of GBS are also important for infection and immune evasion. Some researchers have found that the hemolytic pigment promotes GBS penetration of the human placenta and leads to the loss of barrier function in amniotic epithelial cells. In addition, hyperpigmented GBS strains have been isolated from amniotic fluid or chorioamnion of women who delivered prematurely. In addition to immune cells, pH also influences GBS gene expression that, in turn, influences vaginal colonization. For instance, GBS CovR/S regulatory system is pH-sensitive, and low pH conditions result in increased CovR/S regulation. pH also influences GBS adhesion, survival, and biofilm formation. Expression of GBS hyaluronidase (HylB) has been shown to promote vaginal colonization. HylB is secreted by GBS and specifically targets and degrades host hyaluronic acid. GBS HylB degrades host hyaluronic acid into disaccharide components, which are immunomodulatory and block signaling by binding to TLR2/TLR4 receptors. Deletion of the hylB gene increases the clearance of GBS from the mouse vagina. Similarly, GBS lacking HylB has reduced ability to ascend to the uterus, invade fetal tissues, and induce preterm birth.

S. agalactiae Antibodies

S. agalactiae Antigens