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

Abstract

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.

• Authors: Nina M van Sorge, Darin Quach, Michael A Gurney, Paul M Sullam, Victor Nizet, Kelly S Doran
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 199 Issue 10 Pg. 1479-87 (May 15 2009) ISSN: 0022-1899 [Print] United States
• PMID: 19392623 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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