Group B Streptococcus Interactions with Human Meningeal Cells and Astrocytes In Vitro

BackgroundStreptococcus agalactiae (Group B Streptococcus, GBS) is a leading cause of life-threatening neonatal meningitis and survivors often suffer permanent neurological damage. How this organism interacts with the meninges and subsequently with astrocytes that constitute the underlying cortical glia limitans superficialis is not known. Methodology/Principal FindingsIn this paper, we demonstrate dose-dependent adherence of GBS over time to human meningioma cells and fetal astrocytes in vitro, which was not influenced by expression of either β-haemolysin/cytolysin (β-h/c) toxin, different capsule serotypes or by absence of capsule (p>0.05). Internalization of GBS by both cell types was, however, a slow and an infrequent event (only 0.02–0.4% of associated bacteria were internalised by 9 h). Expression of β-h/c toxin did not play a role in invasion (p>0.05), whereas capsule expression lead to a reduction (pi.e. from weakly, to normo- to hyper-haemolytic. However, cytotoxicity was significantly greater (p+) and mutant (ΔcylE β-h/c−) strains and β-h/c toxin extracts and by using the surfactant dipalmitoylphosphatidylcholine in cytotoxicity inhibition experiments, β-h/c toxin was demonstrated as principally responsible for cell death. Conclusions/SignificanceThis study has described key events in the interactions of GBS with meningeal cells and astrocytes in vitro and a major virulence role for β-h/c toxin. Understanding the mechanisms involved will help to identify potential therapies for improving patient survival and for reducing the incidence and severity of neurological sequelae.