title: Pneumococcal Adhesins PavB and PspC Are Important for the Interplay with Human Thrombospondin-1.
abstract: The human matricellular glycoprotein thrombospondin-1 (hTSP-1) is released by activated platelets and mediates adhesion of Gram-positive bacteria to various host cells. In staphylococci, the adhesins extracellular adherence protein (Eap) and autolysin (Atl), both surface-exposed proteins containing repeating structures, were shown to be involved in the acquisition of hTSP-1 to the bacterial surface. The interaction partner(s) on the pneumococcal surface was hitherto unknown. Here, we demonstrate for the first time that pneumococcal adherence and virulence factor B (PavB) and pneumococcal surface protein C (PspC) are key players for the interaction of Streptococcus pneumoniae with matricellular hTSP-1. PavB and PspC are pneumococcal surface-exposed adhesins and virulence factors exhibiting repetitive sequences in their core structure. Heterologously expressed fragments of PavB and PspC containing repetitive structures exhibit hTSP-1 binding activity as shown by ELISA and surface plasmon resonance studies. Binding of hTSP-1 is charge-dependent and inhibited by heparin. Importantly, the deficiency in PavB and PspC reduces the recruitment of soluble hTSP-1 by pneumococci and decreases hTSP-1-mediated pneumococcal adherence to human epithelial cells. Platelet activation assays suggested that PavB and PspC are not involved in the activation of purified human platelets by pneumococci. In conclusion, this study indicates a pivotal role of PavB and PspC for pneumococcal recruitment of soluble hTSP-1 to the bacterial surface and binding of pneumococci to host cell-bound hTSP-1 during adhesion.
authors.affiliation: From the Department Genetics of Microorganisms, Interfaculty Institute for Genetics and Functional Genomics, University of Greifswald, Friedrich-Ludwig-Jahn-Strasse 15a, D-17487 Greifswald, Germany and.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Binsker
authors.affiliation: From the Department Genetics of Microorganisms, Interfaculty Institute for Genetics and Functional Genomics, University of Greifswald, Friedrich-Ludwig-Jahn-Strasse 15a, D-17487 Greifswald, Germany and kohlert@uni-greifswald.de.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Kohler
authors.affiliation: Institute for Immunology and Transfusion Medicine, University Medicine Greifswald, Ferdinand-Sauerbruch-Strasse, D-17489 Greifswald, Germany.
authors.forename: Krystin
authors.initials: K
authors.lastname: Krauel
authors.affiliation: From the Department Genetics of Microorganisms, Interfaculty Institute for Genetics and Functional Genomics, University of Greifswald, Friedrich-Ludwig-Jahn-Strasse 15a, D-17487 Greifswald, Germany and.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Kohler
authors.affiliation: Institute for Immunology and Transfusion Medicine, University Medicine Greifswald, Ferdinand-Sauerbruch-Strasse, D-17489 Greifswald, Germany.
authors.forename: Hansjörg
authors.initials: H
authors.lastname: Schwertz
authors.affiliation: From the Department Genetics of Microorganisms, Interfaculty Institute for Genetics and Functional Genomics, University of Greifswald, Friedrich-Ludwig-Jahn-Strasse 15a, D-17487 Greifswald, Germany and.
authors.forename: Sven
authors.initials: S
authors.lastname: Hammerschmidt
mesh_terms: D018829:Adhesins, Bacterial / Q000032:analysis / Q000378:metabolism*; D001422:Bacterial Adhesion; D002460:Cell Line; D004847:Epithelial Cells / Q000382:microbiology; D054884:Host-Pathogen Interactions; D006801:Humans; D011008:Pneumococcal Infections / Q000378:metabolism*; D011485:Protein Binding; D013296:Streptococcus pneumoniae / Q000502:physiology*; D019700:Thrombospondin 1 / Q000378:metabolism*; D037521:Virulence Factors / Q000032:analysis / Q000378:metabolism
chemical_list: D018829:Adhesins, Bacterial; D019700:Thrombospondin 1; D037521:Virulence Factors
keywords: MSCRAMMs; adhesin; bacterial pathogenesis; extracellular matrix protein; platelet; pneumococci; thrombospondin