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Strain-specific restriction of the antiphagocytic property of group A streptococcal M proteins
H Kotarsky1, A Thern, G Lindahl
1Institute for Laboratory Medicine, Lund University, Lund, Sweden.
Abstract:
Group A streptococcal M proteins are type-specific virulence factors that inhibit phagocytosis. We used two M proteins, M5 and Emm22, to analyze the influence of genetic background on the properties of M proteins. Mutant strains, engineered to lack these M proteins, were complemented with genes encoding the homologous or heterologous M protein, and the complemented strains were analyzed for phagocytosis resistance. Neither the M5 nor the Emm22 protein conferred phagocytosis resistance in the heterologous background, but they did do so in the homologous background. This was not due to lack of surface expression in the heterologous background. Moreover, the M5 and Emm22 proteins expressed in heterologous background appeared to have normal structure, since they were not affected in their ability to bind different human plasma proteins. In particular, M5 or Emm22 had normal ability to bind human complement inhibitors, a property that has been implicated in phagocytosis resistance. Results similar to those obtained with M5 and Emm22 were obtained in experiments with the M6 and Emm4 proteins. Together, these data suggest that the surface expression of M protein alone may not be sufficient to confer phagocytosis resistance and consequently that strain-specific factors other than M and Emm proteins may contribute to the ability of group A streptococci to resist phagocytosis.
Insights
Group A streptococcal M proteins are crucial for resisting phagocytosis. However, their effectiveness depends on the bacterial genetic background, not just surface expression, suggesting other strain-specific factors are involved.
Area of Science:
- Microbiology
- Immunology
- Molecular Biology
Background:
- Group A streptococcal M proteins are type-specific virulence factors.
- These proteins are known to inhibit phagocytosis, a key defense mechanism.
- Understanding M protein function is vital for combating streptococcal infections.
Purpose of the Study:
- To investigate the influence of genetic background on the antiphagocytic properties of M proteins.
- To determine if surface expression alone is sufficient for M proteins to confer phagocytosis resistance.
- To identify potential strain-specific factors contributing to bacterial defense.
Main Methods:
- Engineered mutant strains of Group A Streptococcus lacking specific M proteins (M5, Emm22).
- Complemented mutant strains with homologous or heterologous M protein genes.
- Assessed phagocytosis resistance in complemented strains.
- Analyzed M protein surface expression and binding to human plasma proteins.
Main Results:
- M proteins (M5, Emm22) conferred phagocytosis resistance only in their homologous genetic background.
- Lack of resistance in heterologous backgrounds was not due to reduced surface expression or altered protein structure.
- M proteins maintained normal binding to human complement inhibitors in heterologous backgrounds.
Conclusions:
- Surface expression of M protein is insufficient to guarantee phagocytosis resistance.
- Bacterial genetic background significantly impacts M protein function.
- Strain-specific factors beyond M and Emm proteins likely contribute to Group A Streptococcus's ability to evade phagocytosis.