The group B streptococcal serine-rich repeat 1 glycoprotein mediates penetration of the blood-brain barrier.
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.
van Sorge
Nina M
NM
Department of Pediatrics and 2Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, San Diego, CA 92182, USA.
Quach
Darin
D
Gurney
Michael A
MA
Sullam
Paul M
PM
Nizet
Victor
V
Doran
Kelly S
KS
D018829:Adhesins, Bacterial / Q000235:genetics*; D000818:Animals; D001766:Blindness / Q000209:etiology / Q000382:microbiology; D001812:Blood-Brain Barrier; D002547:Cerebral Palsy / Q000209:etiology / Q000382:microbiology; D003072:Cognition Disorders / Q000209:etiology / Q000382:microbiology; D017931:DNA Primers; D003638:Deafness / Q000209:etiology / Q000382:microbiology; D004195:Disease Models, Animal; D006801:Humans; D007231:Infant, Newborn; D016920:Meningitis, Bacterial / Q000235:genetics / Q000473:pathology; D051379:Mice; D016296:Mutagenesis; D016133:Polymerase Chain Reaction; D012640:Seizures / Q000209:etiology / Q000382:microbiology; D012703:Serotyping; D013290:Streptococcal Infections / Q000150:complications / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology*; D013292:Streptococcus agalactiae / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology*; D014774:Virulence
D018829:Adhesins, Bacterial; D017931:DNA Primers; C524542:Srr-1 protein, Streptococcus agalactiae