Streptococcus pyogenes and its interactions with the human host
Author
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.
Department/s
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