title: Identification of a group B streptococcal fibronectin binding protein, SfbA, that contributes to invasion of brain endothelium and development of meningitis.
abstract: Group B Streptococcus (GBS) is currently the leading cause of neonatal meningitis. This is due to its ability to survive and multiply in the bloodstream and interact with specialized human brain microvascular endothelial cells (hBMEC), which constitute the blood-brain barrier (BBB). The exact mechanism(s) of GBS-BBB penetration is still largely unknown. We and others have shown that GBS interacts with components of the extracellular matrix. In this study, we demonstrate that GBS of representative serotypes binds immobilized and cell surface fibronectin and identify a putative fibronectin binding protein, streptococcal fibronectin binding protein A (SfbA). Allelic replacement of sfbA in the GBS chromosome resulted in a significant decrease in ability to bind fibronection and invade hBMEC compared with the wild-type (WT) parental strain. Expression of SfbA in the noninvasive strain Lactococcus lactis was sufficient to promote fibronectin binding and hBMEC invasion. Furthermore, the addition of an antifibronectin antibody or an RGD peptide that blocks fibronectin binding to integrins significantly reduced invasion of the WT but not the sfbA-deficient mutant strain, demonstrating the importance of an SfbA-fibronectin-integrin interaction for GBS cellular invasion. Using a murine model of GBS meningitis, we also observed that WT GBS penetrated the brain and established meningitis more frequently than did the ΔsfbA mutant strain. Our data suggest that GBS SfbA plays an important role in bacterial interaction with BBB endothelium and the pathogenesis of streptococcal meningitis.
authors.affiliation: Department of Biology, San Diego State University, San Diego, California, USA.
authors.forename: Rong
authors.initials: R
authors.lastname: Mu
authors.forename: Brandon J
authors.initials: BJ
authors.lastname: Kim
authors.forename: Czarinah
authors.initials: C
authors.lastname: Paco
authors.forename: Yvette
authors.initials: Y
authors.lastname: Del Rosario
authors.forename: Harry S
authors.initials: HS
authors.lastname: Courtney
authors.forename: Kelly S
authors.initials: KS
authors.lastname: Doran
mesh_terms: D018829:Adhesins, Bacterial / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D001422:Bacterial Adhesion / Q000502:physiology; D001921:Brain / Q000382:microbiology*; D002460:Cell Line; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000382:microbiology; D004730:Endothelium, Vascular / Q000382:microbiology*; D015964:Gene Expression Regulation, Bacterial; D016023:Integrins / Q000502:physiology; D016920:Meningitis, Bacterial / Q000209:etiology / Q000503:physiopathology*; D051379:Mice; D009154:Mutation; D013290:Streptococcal Infections / Q000503:physiopathology*; D013292:Streptococcus agalactiae / Q000472:pathogenicity / Q000502:physiology*
chemical_list: D018829:Adhesins, Bacterial; D016023:Integrins; C078635:fibronectin-binding proteins, bacterial