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Updated: May 13, 2026

Invasion of Human Cells by a Bacterial Pathogen
Published on: March 21, 2011
Coiled-coil irregularities of the M1 protein structure promote M1-fibrinogen interaction and influence group A
Satoshi Uchiyama1, Federica Andreoni, Claudia Zürcher
1Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Rämistr 100, 8091 Zürich, Switzerland.
Abstract:
Group A Streptococcus (GAS) is a human pathogen causing a wide range of mild to severe and life-threatening diseases. The GAS M1 protein is a major virulence factor promoting GAS invasiveness and resistance to host innate immune clearance. M1 displays an irregular coiled-coil structure, including the B-repeats that bind fibrinogen. Previously, we found that B-repeat stabilisation generates an idealised version of M1 (M1) characterised by decreased fibrinogen binding in vitro. To extend these findings based on a soluble truncated version of M1, we now studied the importance of the B-repeat coiled-coil irregularities in full length M1 and M1 expressed in live GAS and tested whether the modulation of M1-fibrinogen interactions would open up novel therapeutic approaches. We found that altering either the M1 structure on the GAS cell surface or removing its target host protein fibrinogen blunted GAS virulence. GAS expressing M1 showed an impaired ability to adhere to and to invade human endothelial cells, was more readily killed by whole blood or neutrophils and most importantly was less virulent in a murine necrotising fasciitis model. M1-mediated virulence of wild-type GAS was strictly dependent on the presence and concentration of fibrinogen complementing our finding that M1-fibrinogen interactions are crucial for GAS virulence. Consistently blocking M1-fibrinogen interactions by fragment D reduced GAS virulence in vitro and in vivo. This supports our conclusion that M1-fibrinogen interactions are crucial for GAS virulence and that interference may open up novel complementary treatment options for GAS infections caused by the leading invasive GAS strain M1.
Insights
Altering the Group A Streptococcus M1 protein structure or blocking its interaction with fibrinogen significantly reduces bacterial virulence. This finding suggests new therapeutic strategies for invasive Group A Streptococcus infections.
Area of Science:
- Microbiology
- Infectious Diseases
- Structural Biology
Background:
- Group A Streptococcus (GAS) is a significant human pathogen.
- The GAS M1 protein is a key virulence factor enhancing invasiveness and immune evasion.
- M1 protein's coiled-coil structure, including B-repeats, mediates fibrinogen binding.
Purpose of the Study:
- To investigate the role of M1 protein's coiled-coil irregularities in full-length M1 virulence.
- To assess the impact of modulating M1-fibrinogen interactions on GAS virulence.
- To explore novel therapeutic approaches targeting M1-fibrinogen interactions.
Main Methods:
- Studied full-length M1 and M1 expressed on live GAS.
- Assessed GAS adherence and invasion of human endothelial cells.
- Evaluated GAS killing by whole blood and neutrophils.
- Tested GAS virulence in a murine necrotising fasciitis model.
- Investigated the effect of fibrinogen concentration and fragment D on GAS virulence.
Main Results:
- Altering M1 structure or removing fibrinogen reduced GAS virulence.
- GAS expressing M1 exhibited impaired adherence, invasion, and increased susceptibility to immune clearance.
- M1-mediated virulence was dependent on fibrinogen concentration.
- Blocking M1-fibrinogen interactions with fragment D reduced GAS virulence in vitro and in vivo.
Conclusions:
- M1-fibrinogen interactions are critical for GAS virulence.
- Modulating these interactions offers potential complementary therapeutic strategies for invasive GAS infections.
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