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.
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). GBSSrr-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: Aimee E Stephenson; Hui Wu; Jan Novak; Milan Tomana; Keith Mintz; Paula Fives-Taylor Journal: Mol Microbiol Date: 2002-01 Impact factor: 3.501
Authors: Carlos J Sanchez; Pooja Shivshankar; Kim Stol; Samuel Trakhtenbroit; Paul M Sullam; Karin Sauer; Peter W M Hermans; Carlos J Orihuela Journal: PLoS Pathog Date: 2010-08-12 Impact factor: 6.823