Alternate complement pathway activation by group A streptococci: role of M-protein
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Updated: Aug 12, 2026

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Published on: August 19, 2016
Abstract:
Avirulent strains of group A streptococci readily activate the complement system in normal human serum via the alternate complement pathway (ACP). Virulent M-positive group A streptococci are much less potent as activators of the ACP. The ability of M-positive streptococci to activate the ACP is enhanced by trypsinization or mild peptic digestion. The latter treatment removes the serologically active and antiphagocytic type-specific moieties of M protein, but retains the surface fuzzy layer. The phagocytosis of avirulent streptococci is markedly enhanced by preopsonization in serum chelated with Mg-ethylene glycol tetraacetic acid (classic complement pathway blocked) but not in serum devoid of heat-labile factors. These studies suggest that the function of M protein as a virulence factor may be mediated, at least in part, by its ability to retard interaction of ACP components with structures present on the streptococcal cell surface.
Insights
Virulent M-protein strains of Group A Streptococcus are poor activators of the alternate complement pathway (ACP). M protein may hinder ACP activation, contributing to bacterial virulence.
Area of Science:
- Microbiology
- Immunology
- Bacteriology
Background:
- Group A Streptococcus (GAS) is a significant human pathogen.
- The alternate complement pathway (ACP) is crucial for innate immunity against bacterial infections.
- M protein is a key virulence factor in GAS, associated with resistance to phagocytosis.
Purpose of the Study:
- To investigate the role of M protein in the activation of the alternate complement pathway (ACP) by Group A Streptococcus.
- To elucidate the mechanism by which M protein influences complement-mediated immune responses.
Main Methods:
- Comparative analysis of ACP activation by virulent (M-positive) and avirulent streptococcal strains.
- Treatment of M-positive strains with trypsin or mild peptic digestion to assess the role of M protein moieties.
- Assessment of opsonophagocytosis in serum with blocked classic complement pathway (Mg-EGTA) versus serum deficient in heat-labile factors.
Main Results:
- Avirulent streptococci efficiently activate the ACP in normal human serum.
- Virulent M-positive streptococci exhibit reduced ACP activation.
- Trypsinization or mild peptic digestion of M-positive strains enhances ACP activation.
- Phagocytosis of avirulent streptococci is enhanced by opsonization via the classic complement pathway, but not the ACP.
Conclusions:
- M protein likely functions as a virulence factor by inhibiting the interaction of ACP components with the streptococcal cell surface.
- This inhibition of the ACP may contribute to immune evasion and pathogenesis of Group A Streptococcus infections.
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