title: PbsP, a cell wall-anchored protein that binds plasminogen to promote hematogenous dissemination of group B Streptococcus.
abstract: Streptococcus agalactiae (Group B Streptococcus or GBS) is a leading cause of invasive infections in neonates whose virulence is dependent on its ability to interact with cells and host components. We here characterized a surface protein with a critical function in GBS pathophysiology. This adhesin, designated PbsP, possesses two Streptococcal Surface Repeat domains, a methionine and lysine-rich region, and a LPXTG cell wall-anchoring motif. PbsP mediates plasminogen (Plg) binding both in vitro and in vivo and we showed that cell surface-bound Plg can be activated into plasmin by tissue plasminogen activator to increase the bacterial extracellular proteolytic activity. Absence of PbsP results in a decreased bacterial transmigration across brain endothelial cells and impaired virulence in a murine model of infection. PbsP is conserved among the main GBS lineages and is a major plasminogen adhesin in non-CC17 GBS strains. Importantly, immunization of mice with recombinant PbsP confers protective immunity. Our results indicate that GBS have evolved different strategies to recruit Plg which indicates that the ability to acquire cell surface proteolytic activity is essential for the invasiveness of this bacterium.
authors.affiliation: Metchnikoff Laboratory, Departments of Human Pathology and Medicine, University of Messina, Messina, Italy.|Institut Pasteur, Unité de Biologie des Bactéries Pathogènes à Gram Positif, CNRS ERL3526, 75015, Paris, France.
authors.forename: Marco
authors.initials: M
authors.lastname: Buscetta
authors.affiliation: Institut Pasteur, Unité de Biologie des Bactéries Pathogènes à Gram Positif, CNRS ERL3526, 75015, Paris, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Firon
authors.affiliation: Department of Molecular Medicine, Unit of Biochemistry, University of Pavia, Pavia, Italy.
authors.forename: Giampiero
authors.initials: G
authors.lastname: Pietrocola
authors.affiliation: Metchnikoff Laboratory, Departments of Human Pathology and Medicine, University of Messina, Messina, Italy.
authors.forename: Carmelo
authors.initials: C
authors.lastname: Biondo
authors.affiliation: Metchnikoff Laboratory, Departments of Human Pathology and Medicine, University of Messina, Messina, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Mancuso
authors.affiliation: Metchnikoff Laboratory, Departments of Human Pathology and Medicine, University of Messina, Messina, Italy.
authors.forename: Angelina
authors.initials: A
authors.lastname: Midiri
authors.affiliation: Metchnikoff Laboratory, Departments of Human Pathology and Medicine, University of Messina, Messina, Italy.
authors.forename: Letizia
authors.initials: L
authors.lastname: Romeo
authors.affiliation: Metchnikoff Laboratory, Departments of Human Pathology and Medicine, University of Messina, Messina, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Galbo
authors.affiliation: Metchnikoff Laboratory, Departments of Human Pathology and Medicine, University of Messina, Messina, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Venza
authors.affiliation: Metchnikoff Laboratory, Departments of Human Pathology and Medicine, University of Messina, Messina, Italy.
authors.forename: Isabella
authors.initials: I
authors.lastname: Venza
authors.affiliation: Institut Pasteur, Unité de Biologie des Bactéries Pathogènes à Gram Positif, CNRS ERL3526, 75015, Paris, France.
authors.forename: Pierre-Alexandre
authors.initials: PA
authors.lastname: Kaminski
authors.affiliation: Institut Pasteur, Unité de Biologie des Bactéries Pathogènes à Gram Positif, CNRS ERL3526, 75015, Paris, France.
authors.forename: Myriam
authors.initials: M
authors.lastname: Gominet
authors.affiliation: Metchnikoff Laboratory, Departments of Human Pathology and Medicine, University of Messina, Messina, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Teti
authors.affiliation: Department of Molecular Medicine, Unit of Biochemistry, University of Pavia, Pavia, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Speziale
authors.affiliation: Institut Pasteur, Unité de Biologie des Bactéries Pathogènes à Gram Positif, CNRS ERL3526, 75015, Paris, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Trieu-Cuot
authors.affiliation: Metchnikoff Laboratory, Departments of Human Pathology and Medicine, University of Messina, Messina, Italy.|Scylla Biotech Srl, Messina, Italy.
authors.forename: Concetta
authors.initials: C
authors.lastname: Beninati
mesh_terms: D018829:Adhesins, Bacterial / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001422:Bacterial Adhesion / Q000502:physiology; D002473:Cell Wall / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism; D005341:Fibrinolysin / Q000378:metabolism; D006801:Humans; D051379:Mice; D010958:Plasminogen / Q000378:metabolism*; D011485:Protein Binding; D013290:Streptococcal Infections / Q000382:microbiology; D013291:Streptococcus / Q000378:metabolism; D013292:Streptococcus agalactiae / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D014774:Virulence
chemical_list: D018829:Adhesins, Bacterial; D010958:Plasminogen; D005341:Fibrinolysin