PavB is a surface-exposed adhesin of Streptococcus pneumoniae contributing to nasopharyngeal colonization and airways infections

Authors

  • Inga Jensch,

    1. Department Genetics of Microorganisms, Institute for Genetics and Functional Genomics, University of Greifswald, D-17487 Greifswald, Germany.
    2. Max von Pettenkofer Institute, Ludwig-Maximilians University München, D-80336 München, Germany.
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    • These authors contributed equally to this work.

  • Gustavo Gámez,

    1. Department Genetics of Microorganisms, Institute for Genetics and Functional Genomics, University of Greifswald, D-17487 Greifswald, Germany.
    2. Max von Pettenkofer Institute, Ludwig-Maximilians University München, D-80336 München, Germany.
    3. School of Microbiology, University of Antioquia, Medellín, Colombia.
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    • These authors contributed equally to this work.

  • Michael Rothe,

    1. Research Center for Infectious Diseases, University of Würzburg, D-97070 Würzburg, Germany.
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  • Sandra Ebert,

    1. Department of Neurology, University of Göttingen, D-37073 Goettingen, Germany.
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  • Marcus Fulde,

    1. Department of Microbial Pathogenesis, Helmholtz Centre for Infection Research, D-38124 Braunschweig, Germany.
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  • Daniela Somplatzki,

    1. Research Center for Infectious Diseases, University of Würzburg, D-97070 Würzburg, Germany.
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  • Simone Bergmann,

    1. Max von Pettenkofer Institute, Ludwig-Maximilians University München, D-80336 München, Germany.
    2. Research Center for Infectious Diseases, University of Würzburg, D-97070 Würzburg, Germany.
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  • Lothar Petruschka,

    1. Department Genetics of Microorganisms, Institute for Genetics and Functional Genomics, University of Greifswald, D-17487 Greifswald, Germany.
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  • Manfred Rohde,

    1. Department of Microbial Pathogenesis, Helmholtz Centre for Infection Research, D-38124 Braunschweig, Germany.
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  • Roland Nau,

    1. Department of Neurology, University of Göttingen, D-37073 Goettingen, Germany.
    2. Department Geriatrics, Evangelisches Krankenhaus Göttingen-Weende, D-37075 Göttingen, Germany.
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  • Sven Hammerschmidt

    Corresponding author
    1. Department Genetics of Microorganisms, Institute for Genetics and Functional Genomics, University of Greifswald, D-17487 Greifswald, Germany.
    2. Max von Pettenkofer Institute, Ludwig-Maximilians University München, D-80336 München, Germany.
    3. Research Center for Infectious Diseases, University of Würzburg, D-97070 Würzburg, Germany.
      E-mail sven.hammerschmidt@uni-greifswald.de; Tel. (+49) 3834 864161; Fax (+49) 3834 864172.
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E-mail sven.hammerschmidt@uni-greifswald.de; Tel. (+49) 3834 864161; Fax (+49) 3834 864172.

Summary

The genomic analysis of Streptococcus pneumoniae strains identified the Pneumococcal adherence and virulence factor B (PavB), whose repetitive sequences, designated Streptococcal Surface REpeats (SSURE), interact with human fibronectin. Here, we showed the gene in all tested pneumococci and identified that the observed differences in the molecular mass of PavB rely on the number of repeats, ranging from five to nine SSURE. PavB interacted with fibronectin and plasminogen in a dose-dependent manner as shown by using various SSURE peptides. In addition, we identified PavB as colonization factor. Mice infected intranasally with ΔpavB pneumococci showed significantly increased survival times compared with wild-type bacteria. Importantly, the pavB-mutant showed a delay in transmigration to the lungs as observed in real-time using bioluminescent pneumococci and decreased colonization rates in a nasopharyngeal carriage model. In co-infection experiments the wild-type out-competed the pavB-mutant and infections of epithelial cells demonstrated that PavB contributes to adherence to host cell. Blocking experiments suggested a function of PavB as adhesin, which was confirmed by direct binding of SSURE peptides to host cells. Finally, PavB may represent a new vaccine candidate as SSURE peptides reacted with human sera. Taken together, PavB is a surface-exposed adhesin, which contributes to pneumococcal colonization and infections of the respiratory airways.

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