Oral Presentation 20th Lancefield International Symposium on Streptococci and Streptococcal Diseases 2017

Mechanisms of Blood-Brain Barrier Penetration by Group B Streptococcus (#5)

Kelly Doran 1
  1. University of Colorado Denver Medical School, Aurora, CO, United States

Bacterial meningitis is a serious infection of the central nervous system and occurs when blood-borne bacteria cross the blood-brain barrier (BBB). Group B Streptococcus (GBS) is the leading cause of neonatal meningitis, however the molecular mechanisms regulating bacterial BBB disruption and penetration are still being elucidated. We found that infection of human brain microvascular endothelial cells (hBMEC) with GBS and other meningeal pathogens resulted in the induction of Snail1, a host transcriptional repressor of tight junction genes. Transcript and protein levels of tight junction components ZO-1, Claudin-5 and Occludin were decreased in hBMEC following GBS infection, which was dependent on Snail1 induction. Additionally we have conducted mass spectrometry analysis of cell wall extracts of GBS deficient in their ability to activate Snail1. Differential protein expression between these samples has created a candidate list of GBS proteins implicated in activating Snail1. Additional proteomic analysis of GBS has been conducted to investigate the contribution of the Diag mutant to Snail1 activation. Taken together our data suggests a novel mechanism of BBB disruption and penetration by GBS and provide a candidate list of the GBS proteins that should be investigated for their contribution to Snail1 activation and BBB disruption.