The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here: https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

Streptococcus pyogenes and its interactions with the human host

Author

  • Ulrika Ringdahl

Summary, in English

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.

Publishing year

2002

Language

English

Document type

Dissertation

Publisher

Ulrika Ringdahl, Bardisangränden 3 E, 226 48 Lund,

Topic

  • Immunology in the medical area
  • Microbiology in the medical area

Keywords

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

Status

Published

Supervisor

  • [unknown] [unknown]

ISBN/ISSN/Other

  • ISBN: 91-628-5207-8

Defence date

7 June 2002

Defence time

10:15

Defence place

Fernströmssalen, BMC, Sölveg 19, Lund

Opponent

  • Sven Bergström