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Updated: Jun 6, 2026

Implementation of a Permeable Membrane Insert-based Infection System to Study the Effects of Secreted Bacterial Toxins on Mammalian Host Cells
Published on: August 19, 2016
Antibacterial activity of the contact and complement systems is blocked by SIC, a protein secreted by Streptococcus
Inga-Maria Frick1, Oonagh Shannon, Per Åkesson
1Division of Infection Medicine, Department of Clinical Sciences, Lund University, SE-221 84 Lund, Sweden. Inga-Maria.Frick@med.lu.se
Abstract:
Recent studies have shown that activation of complement and contact systems results in the generation of antibacterial peptides. Streptococcus pyogenes, a major bacterial pathogen in humans, exists in >100 different serotypes due to sequence variation in the surface-associated M protein. Cases of invasive and life-threatening S. pyogenes infections are commonly associated with isolates of the M1 serotype, and in contrast to the large majority of M serotypes, M1 isolates all secrete the SIC protein. Here, we show that SIC interferes with the activation of the contact system and blocks the activity of antibacterial peptides generated through complement and contact activation. This effect promotes the growth of S. pyogenes in human plasma, and in a mouse model of S. pyogenes sepsis, SIC enhances bacterial dissemination, results which help explain the high frequency of severe S. pyogenes infections caused by isolates of the M1 serotype.
Insights
Streptococcus pyogenes M1 serotype infections are severe because the secreted SIC protein blocks antibacterial peptides. This allows the bacteria to grow and spread, explaining why M1 infections are often life-threatening.
Area of Science:
- Immunology
- Microbiology
- Molecular Biology
Background:
- Complement and contact systems generate antibacterial peptides.
- Streptococcus pyogenes has over 100 serotypes, with M1 isolates linked to severe infections.
- M1 isolates uniquely secrete the SIC protein.
Purpose of the Study:
- To investigate the role of SIC protein in S. pyogenes pathogenesis.
- To determine how SIC affects the host immune response, specifically complement and contact systems.
Main Methods:
- In vitro studies of contact system activation and antibacterial peptide activity.
- In vivo mouse model of S. pyogenes sepsis.
- Analysis of bacterial growth in human plasma.
Main Results:
- SIC protein inhibits contact system activation.
- SIC blocks the activity of antibacterial peptides.
- SIC promotes S. pyogenes growth in human plasma.
- SIC enhances bacterial dissemination in a mouse sepsis model.
Conclusions:
- SIC protein is a virulence factor for S. pyogenes M1 serotype.
- SIC contributes to the severity of S. pyogenes infections by evading host defenses.
- Targeting SIC may offer a strategy to combat severe S. pyogenes infections.
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