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SIC, a secreted protein of Streptococcus pyogenes that inactivates antibacterial peptides
Inga-Maria Frick1, Per Akesson, Magnus Rasmussen
1Department of Cell and Molecular Biology, Lund University, S-221 85 Lund, Sweden. Inga-Maria.Frick@medkem.lu.se
Abstract:
Some isolates of the significant human pathogen Streptococcus pyogenes, including virulent strains of the M1 serotype, secrete protein SIC. This molecule, secreted in large quantities, interferes with complement function. As a result of natural selection, SIC shows a high degree of variation. Here we provide a plausible explanation for this variation and the fact that strains of the M1 serotype are the most frequent cause of severe invasive S. pyogenes infections. Thus, protein SIC was found to inactivate human neutrophil alpha-defensin and LL-37, two major antibacterial peptides involved in bacterial clearance. This inactivation protected S. pyogenes against the antibacterial effect of the peptides. Moreover, SIC isolated from S. pyogenes of the M1 serotype was more powerful in this respect than SIC variants from strains of M serotypes 12 and 55, serotypes rarely connected with invasive infections.
Insights
Streptococcus pyogenes secretes protein SIC, which inactivates antibacterial peptides. M1 serotype strains, linked to severe infections, possess a more potent SIC, enhancing bacterial survival.
Area of Science:
- Microbiology
- Immunology
- Molecular Biology
Background:
- Streptococcus pyogenes is a significant human pathogen.
- Certain strains, particularly the M1 serotype, cause severe invasive infections.
- Protein SIC is secreted by S. pyogenes and interferes with the host immune system, specifically complement function.
Purpose of the Study:
- To explain the variation in protein SIC.
- To understand why M1 serotype strains are most frequent in severe infections.
- To investigate the mechanism by which SIC contributes to S. pyogenes virulence.
Main Methods:
- Analysis of protein SIC variation in different S. pyogenes serotypes.
- Testing the ability of SIC to inactivate human neutrophil alpha-defensin and LL-37.
- Comparing the potency of SIC from M1 serotype strains versus other serotypes (M12, M55).
Main Results:
- Protein SIC was found to inactivate human neutrophil alpha-defensin and LL-37.
- This inactivation protected S. pyogenes from the antibacterial effects of these peptides.
- SIC from M1 serotype strains demonstrated higher potency in inactivating these antibacterial peptides compared to SIC from M12 and M55 serotypes.
Conclusions:
- Protein SIC contributes to S. pyogenes virulence by neutralizing key antibacterial peptides.
- The enhanced potency of SIC in M1 serotype strains likely explains their association with severe invasive infections.
- Understanding SIC's function provides insights into S. pyogenes pathogenesis and potential therapeutic targets.