The group B streptococcal serine-rich repeat 1 glycoprotein mediates penetration of the blood-brain barrier

J Infect Dis. 2009 May 15;199(10):1479-87. doi: 10.1086/598217.


Background: Group B Streptococcus (GBS) is the leading cause of bacterial meningitis in newborn infants. Because GBS is able to invade, survive, and cross the blood-brain barrier, we sought to identify surface-expressed virulence factors that contribute to blood-brain barrier penetration and the pathogenesis of meningitis.

Methods: Targeted deletion and insertional mutants were generated in different GBS clinical isolates. Wild-type and mutant bacteria were analyzed for their capacity to adhere to and invade human brain microvascular endothelial cells (hBMECs) and to penetrate the blood-brain barrier using our model of hematogenous meningitis.

Results: Analysis of a GBS (serotype V) clinical isolate revealed the presence of a surface-anchored serine-rich protein, previously designated serine-rich repeat 1 (Srr-1). GBS Srr-1 is a glycosylated protein with high molecular weight. Deletion of srr1 in NCTC 10/84 resulted in a significant decrease in adherence to and invasion of hBMECs. Additional mutants in other GBS serotypes commonly associated with meningitis showed a similar decrease in hBMEC invasion, compared with parental strains. Finally, in mice, wild-type GBS penetrated the blood-brain barrier and established meningitis more frequently than did the Deltasrr1 mutant strain.

Conclusions: Our data suggest that GBS Srr glycoproteins play an important role in crossing the blood-brain barrier and in the development of streptococcal meningitis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adhesins, Bacterial / genetics*
  • Animals
  • Blindness / etiology
  • Blindness / microbiology
  • Blood-Brain Barrier*
  • Cerebral Palsy / etiology
  • Cerebral Palsy / microbiology
  • Cognition Disorders / etiology
  • Cognition Disorders / microbiology
  • DNA Primers
  • Deafness / etiology
  • Deafness / microbiology
  • Disease Models, Animal
  • Humans
  • Infant, Newborn
  • Meningitis, Bacterial / genetics
  • Meningitis, Bacterial / pathology
  • Mice
  • Mutagenesis
  • Polymerase Chain Reaction
  • Seizures / etiology
  • Seizures / microbiology
  • Serotyping
  • Streptococcal Infections / complications
  • Streptococcal Infections / epidemiology
  • Streptococcal Infections / genetics*
  • Streptococcal Infections / pathology*
  • Streptococcus agalactiae / genetics
  • Streptococcus agalactiae / pathogenicity*
  • Streptococcus agalactiae / physiology*
  • Virulence


  • Adhesins, Bacterial
  • DNA Primers
  • Srr-1 protein, Streptococcus agalactiae