title: Serotype 3 pneumococci sequester platelet-derived human thrombospondin-1 via the adhesin and immune evasion protein Hic.
abstract: Streptococcus pneumoniaeserotype 3 strains emerge frequently within clinical isolates of invasive diseases. Bacterial invasion into deeper tissues is associated with colonization and immune evasion mechanisms. Thus, pneumococci express a versatile repertoire of surface proteins sequestering and interacting specifically with components of the human extracellular matrix and serum. Hic, a PspC-like pneumococcal surface protein, possesses vitronectin and factor H binding activity. Here, we show that heterologously expressed Hic domains interact, similar to the classical PspC molecule, with human matricellular thrombospondin-1 (hTSP-1). Binding studies with isolated human thrombospondin-1 and various Hic domains suggest that the interaction between hTSP-1 and Hic differs from binding to vitronectin and factor H. Binding of Hic to hTSP-1 is inhibited by heparin and chondroitin sulfate A, indicating binding to the N-terminal globular domain or type I repeats of hTSP-1. Competitive inhibition experiments with other pneumococcal hTSP-1 adhesins demonstrated that PspC and PspC-like Hic recognize similar domains, whereas PavB and Hic can bind simultaneously to hTSP-1. In conclusion, Hic binds specifically hTSP-1; however, truncation in the N-terminal part of Hic decreases the binding activity, suggesting that the full length of the α-helical regions of Hic is required for an optimal interaction.
authors.affiliation: From the Department Genetics of Microorganisms, Interfaculty Institute for Genetics and Functional Genomics, University of Greifswald, 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, D-17487 Greifswald, Germany and kohlert@uni-greifswald.de.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Kohler
authors.affiliation: the Institute for Immunology and Transfusion Medicine, University Medicine Greifswald, 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, D-17487 Greifswald, Germany and.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Kohler
authors.affiliation: From the Department Genetics of Microorganisms, Interfaculty Institute for Genetics and Functional Genomics, University of Greifswald, D-17487 Greifswald, Germany and.
authors.forename: Johanna
authors.initials: J
authors.lastname: Habermeyer
authors.affiliation: the Institute for Immunology and Transfusion Medicine, University Medicine Greifswald, 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, D-17487 Greifswald, Germany and.
authors.forename: Sven
authors.initials: S
authors.lastname: Hammerschmidt
mesh_terms: D018829:Adhesins, Bacterial / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism*; D001792:Blood Platelets / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D006801:Humans; D011485:Protein Binding; D013296:Streptococcus pneumoniae / Q000378:metabolism*; D019700:Thrombospondin 1 / Q000378:metabolism*
chemical_list: D018829:Adhesins, Bacterial; D001426:Bacterial Proteins; D002352:Carrier Proteins; C417512:Hic protein, Streptococcus pneumoniae; C110344:SpsA protein, Streptococcus pneumoniae; D019700:Thrombospondin 1; C000611726:thrombospondin-1, human
keywords: Hic; Streptococcus pneumoniae; adhesion; bacterial pathogenesis; extracellular matrix protein; human serum; pneumococcal surface protein C; surface plasmon resonance (SPR); thrombospondin