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Streptococcus pyogenes and its interactions with the human host

Författare:
Publiceringsår: 2002
Språk: Engelska
Sidor: 112
Dokumenttyp: Doktorsavhandling
Förlag: Ulrika Ringdahl, Bardisangränden 3 E, 226 48 Lund,
Ytterligare information: Article: I Carlsson Wistedt A, Ringdahl U, Müller-Esterl W, Sjöbring U. (1995) Identification of a plasminogen-binding motif in PAM, a bacterial surface protein. Molecular Microbiology 18:569-578 Article: II Ringdahl U, Svensson M, Carlsson Wistedt A, Renné T, Keller R, Müller-Esterl W, and Sjöbring U. (1998) Molecular co-operation between protein PAM and streptokinase for plasmin acquisition by Streptococcus pyogenes. Journal of Biological Chemistry 273:6424-6430 Article: III Ringdahl U, Svensson H, Kotarsky H, Gustafsson M, Weineisen M, and Sjöbring U. (2000) A role for the fibrinogen-binding regions of streptococcal M proteins in phagocytosis resistance. Molecular Microbiology 37(6):1318-1326 Article: IV Sjöbring U, Ringdahl U, and Ruggeri ZM. (2002) Induction of platelet thrombi by bacteria and antibodies. Submitted.

Sammanfattning

We have found that a set of group A streptococcal strains, primarily associated with skin infections, express surface-associated M proteins that bind plasminogen and plasmin with high affinity. The binding is mediated by a common 13 amino acid internal repeated sequence located in the NH2-terminal surface-exposed portion of these M proteins. It could be demonstrated that plasminogen, absorbed by the bacteria when grown in plasma, could be activated by exogenous and endogenous streptokinase, a potent plasminogen activating protein that is secreted by group A streptococci, thereby providing the bacteria with a surface-associated enzyme that could act on fibrin films or other tissue barriers in the infected host. While only a subset of these bacteria bind plasminogen, almost all group A streptococcal strains bind fibrinogen. It is known that this property is coupled to members of the M protein family. We first identified the fibrinogen-binding region in the type M1 and M5 proteins and then generated an isogenic strain expressing an M5 protein lacking the fibrinogen-binding region. This strain had lost the ability to resist phagocytosis in human blood, a feature that is characteristic for group A streptococci. Furthermore, streptococcal mutants expressing versions of the fibrinogen non-binding M4 protein grafted with the fibrinogen-binding regions from M1 or M5 were generated. The manipulation converted these strains from phagocytosis sensitive to phagocytosis resistant, demonstrating the importance of the fibrinogen-binding capacity for bacterial survival. The ability to bind fibrinogen also gives the bacteria the ability to interact with platelets. Fibrinogen serves as a link between the bacteria and the platelet and the subsequent binding of antibodies directed against the bacteria to the FcgRIIa receptor can induce platelet activation and aggregation, a property that may contribute to acute complications in severe group A streptococcal infection.

Disputation

2002-06-07
10:15
Fernströmssalen, BMC, Sölveg 19, Lund
  • Sven Bergström

Nyckelord

  • Medicine and Health Sciences
  • Biology and Life Sciences
  • Infections
  • mykologi
  • virologi
  • bakteriologi
  • M protein
  • Streptococcus pyogenes
  • plasminogen
  • fibrinogen
  • phagocytosis
  • platelet
  • Microbiology
  • bacteriology
  • virology
  • Mikrobiologi
  • mycology
  • Infektioner
  • Immunology
  • serology
  • transplantation
  • Immunologi
  • serologi

Övriga

  • ISBN: 91-628-5207-8

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