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Analysis of plasminogen-binding M proteins of Streptococcus pyogenes
1Institute for Laboratory Medicine, Section for Microbiology, Immunology and Glycobiology, Lund University, Sölvegatan 23, Lund, S-223 62, Sweden. Ulrika.Ringdahl@mig.lu.se
Abstract:
Group A streptococci are common human pathogens that cause a variety of infections. They express M proteins which are important cell wall-bound type-specific virulence factors. We have found that a set of strains, associated primarily with skin infections, express M proteins that bind plasminogen and plasmin with high affinity. The binding is mediated by a 13-amino-acid internal repeated sequence located in the N-terminal surface-exposed portion of these M proteins. This sequence binds to kringle 2 in plasminogen, a domain that is not involved in the interaction with streptokinase, a potent group A streptococcal activator of plasminogen. It could be demonstrated that plasminogen, absorbed from plasma by growing group A streptococci expressing the plasminogen-binding M proteins, could be activated by exogenous and endogenous streptokinase, thereby providing the bacteria with a surface-associated enzyme that could act on the tissue barriers in the infected host.
Insights
Group A streptococci M proteins bind plasminogen, aiding skin infection spread. This interaction facilitates bacterial enzyme activation, enhancing tissue barrier penetration in hosts.
Area of Science:
- Microbiology
- Molecular Biology
- Biochemistry
Background:
- Group A streptococci (GAS) are significant human pathogens.
- M proteins are key GAS virulence factors involved in host-pathogen interactions.
- Specific M protein variants facilitate plasminogen binding, particularly in skin infection strains.
Purpose of the Study:
- To investigate the mechanism of plasminogen binding by GAS M proteins.
- To identify the specific M protein region responsible for plasminogen interaction.
- To elucidate how plasminogen binding contributes to GAS virulence and pathogenesis.
Main Methods:
- Bacterial protein analysis
- Plasminogen binding assays
- Amino acid sequence analysis
- Enzyme activity assays
Main Results:
- GAS M proteins from skin infection strains exhibit high-affinity binding to human plasminogen.
- A 13-amino-acid internal repeat in the M protein N-terminus mediates plasminogen binding.
- This binding site interacts with the kringle 2 domain of plasminogen, distinct from streptokinase interaction sites.
- Bound plasminogen can be activated by streptokinase, generating surface-associated proteolytic activity.
Conclusions:
- The plasminogen-binding capability of specific M proteins is a crucial virulence mechanism for GAS.
- This mechanism allows bacteria to harness host plasminogen, converting it into a surface-bound enzyme.
- This surface enzyme aids in degrading host tissue barriers, facilitating infection progression and spread.