Recent advances in understanding the molecular basis of group B Streptococcus virulence

Abstract

Group B Streptococcus commonly colonises healthy adults without symptoms, yet under certain circumstances displays the ability to invade host tissues, evade immune detection and cause serious invasive disease. Consequently, Group B Streptococcus remains a leading cause of neonatal pneumonia, sepsis and meningitis. Here we review recent information on the bacterial factors and mechanisms that direct host-pathogen interactions involved in the pathogenesis of Group B Streptococcus infection. New research on host signalling and inflammatory responses to Group B Streptococcus infection is summarised. An understanding of the complex interplay between Group B Streptococcus and host provides valuable insight into pathogen evolution and highlights molecular targets for therapeutic intervention.

Figure 1. Mechanisms of group B Streptococcus cellular adherence and invasion

Surface-expressed proteins FbsA/B, ScpB, Srr1, pili, BibA, LTA and ACP mediate group B Streptococcus (GBS) binding to host cells and ECM components, such as fibrinogen and fibronectin. Secreted β-haemolysin/cytolysin promotes GBS invasion, possibly by breaking down host barriers to reveal novel receptors on the basement membrane, such as laminin. GBS also use GAPDH to activate host plasminogen and degrade the ECM. Intracellular GBS invasion is enhanced by bacterial-dependent cytoskeletal rearrangements triggered by host PI3K/AKT- and FAK-signalling pathways and the Rho family of GTPases. Alternatively, GBS can also use an unknown mechanism to cross host epithelial barrier by a paracellular route. Several GBS adhesins, including FbsB, ScpB, pili, LTA and ACP, also contribute to cellular invasion. Abbreviations: ACP, alpha C protein; BibA, GBS immunogenic bacterial adhesin; ECM, extracellular matrix; FAK, focal adhesion kinase; FbsA/B, fibrinogen-binding proteins A and B; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; GDP, guanosine diphosphate; GTP, guanosine triphosphate; Lmb, laminin-binding protein, LTA, lipoteichoic acid; PI3K, phosphoinositide 3-kinase; ScpB, C5a peptidase; Srr1, serine-rich repeat domain protein 1.

Figure 2. Mechanisms of group B Streptococcus immune evasion

Group B Streptococcus (GBS) express several surface-expressed or secreted factors to evade host immune defences and promote survival. The Dlt operon is responsible for increasing incorporation of D-alanine residues in cell-wall teichoic acids, thereby reducing electronegativity and affinity for cationic antimicrobial peptides. PBP1a and the pilB subunit of GBS pili also contribute to antimicrobial peptide resistance. ScpB, the sialic acid capsule, BibA, β protein and CspA all inhibit host clearance of GBS by interfering with complement components C5a, C3 and C3bp. SOD properties of the orange carotenoid pigment shield GBS from killing by phagocyte-generated reactive oxygen species. Alternatively, β-haemolysin/cytolysin can boost GBS survival by cytolytic or proapoptotic injury to host phagocytes. Abbreviations: BibA, GBS immunogenic bacterial adhesin; CspA, cell-surface protease A; PBP1a, penicillin-binding protein 1a; ScpB, C5a peptidase; SOD, superoxide dismutase.