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

Nina M.Van Sorge, Darin Quach, Michael A. Gurney, Paul M. Sullam, Victor Nizet, Kelly S. Doran

Research output: Contribution to journalArticlepeer-review

109 Scopus citations


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 δsrr1 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.

Original languageEnglish
Pages (from-to)1479-1487
Number of pages9
JournalJournal of Infectious Diseases
Issue number10
StatePublished - May 15 2009


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