Group B Streptococcal Colonization, Molecular Characteristics, and Epidemiology

Abstract

Streptococcus agalactiae or group B streptococcus (GBS) is a leading cause of serious neonatal infections. GBS is an opportunistic commensal constituting a part of the intestinal and vaginal physiologic flora and maternal colonization is the principal route of GBS transmission. GBS is a pathobiont that converts from the asymptomatic mucosal carriage state to a major bacterial pathogen causing severe invasive infections. At present, as many as 10 serotypes (Ia, Ib, and II-IX) are recognized. The aim of the current review is to shed new light on the latest epidemiological data and clonal distribution of GBS in addition to discussing the most important colonization determinants at a molecular level. The distribution and predominance of certain serotypes is susceptible to variations and can change over time. With the availability of multilocus sequence typing scheme (MLST) data, it became clear that GBS strains of certain clonal complexes possess a higher potential to cause invasive disease, while other harbor mainly colonizing strains. Colonization and persistence in different host niches is dependent on the adherence capacity of GBS to host cells and tissues. Bacterial biofilms represent well-known virulence factors with a vital role in persistence and chronic infections. In addition, GBS colonization, persistence, translocation, and invasion of host barriers are largely dependent on their adherence abilities to host cells and extracellular matrix proteins (ECM). Major adhesins mediating GBS interaction with host cells include the fibrinogen-binding proteins (Fbs), the laminin-binding protein (Lmb), the group B streptococcal C5a peptidase (ScpB), the streptococcal fibronectin binding protein A (SfbA), the GBS immunogenic bacterial adhesin (BibA), and the hypervirulent adhesin (HvgA). These adhesins facilitate persistent and intimate contacts between the bacterial cell and the host, while global virulence regulators play a major role in the transition to invasive infections. This review combines for first time epidemiological data with data on adherence and colonization for GBS. Investigating the epidemiology along with understanding the determinants of mucosal colonization and the development of invasive disease at a molecular level is therefore important for the development of strategies to prevent invasive GBS disease worldwide.

Keywords: Streptococcus agalactiae; colonization; epidemiology; molecular characteristics; serotype.

FIGURE 1

Major adhesins mediating Streptococcus agalactiae (GBS) interaction with host cells. GBS colonization, persistence, translocation, and invasion of host barriers are largely dependent on their ability to adhere to host cells and extracellular matrix proteins (ECM), an important step in breaching cellular barriers. The best characterized surface proteins mediating GBS adherence are the fibrinogen-binding proteins Fbs (including FbsA, FbsB, FbsC, or BsaB, the serine-rich repeat glycoproteins Srr1 and Srr2), the laminin-binding protein (Lmb), the Streptococcal C5a peptidase from group B (ScpB), the streptococcal fibronectin-binding protein A (SfbA), and the GBS immunogenic bacterial adhesin BibA. In addition, surface-protruding structures like pili are considered as essential adhesins in promoting GBS colonization, persistence, biofilm production, and central nervous system invasion. Associated virulence traits are illustrated for each adhesin as follows. FbsA was mainly shown to promote adherence whereas FbsB was shown to be required for invading human cells. Srr1 and Srr2 were reported to mediate invasion of microvascular endothelial cells. Additionally, Srr1 was demonstrated to promote vaginal colonization and persistence. FbsC was recently characterized to promote invasion of epithelial and endothelial barriers and biofilm formation. The Lmb adhesin appears to have a pronounced role in bacterial tropism of the central nervous system (CNS). ScpB interrupts complement activation through cleaving the neutrophil chemoattractant C5a. It is also involved in invasion of human epithelial cells. The SfbA adhesin is involved in human brain microvascular endothelial cells invasion. Furthermore, SfbA contributes to GBS invasion of vaginal and cervical epithelial cells and hence may take part in GBS colonization and niche establishment in the vagina. BibA was reported to aid GBS survival in human blood through interfering with the classic complement pathway by binding the C4-binding protein and by conferring anti-phagocytic activity against opsonophagocytic killing by human neutrophils. HvgA is specific for the hypervirulent clone ST-17. It was suggested to promote meningeal tropism in neonates. Pili in GBS have been shown to be primarily involved in epithelial cell colonization, biofilm formation, translocation, and invasion. PI-1 pili were also found to play an important role in evasion of innate immunity mechanism. The PI-2b protein, however, was demonstrated to increase the intracellular survival in macrophage. Pilus 2b was further identified as important for infection and penetration of the blood brain barrier.