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A secreted streptococcal cysteine protease can cleave a surface-expressed M1 protein and alter the immunoglobulin
R Raeder1, M Woischnik, A Podbielski
1Department of Microbiology and Immunology, Medical College of Ohio, Toledo 43699-0008, USA.
Abstract:
Previous studies of recent clinical isolates of serotype M1 group A streptococci indicated that they display two patterns of non-immune human IgG subclass binding reactivity associated with their M1 protein. One group reacted with all four IgG subclasses (type IIo), while the second group expressed an M1 protein reacting preferentially with human IgG3 (type IIb). In this study, we have demonstrated that a cysteine protease, SpeB, present in culture supernatants of M1 serotype group A streptococcal isolates expressing type IIb IgG binding protein, can convert a recombinant Emm1 protein from a type IIo functional profile to a type IIb profile by removal of 24 amino acids from the N-terminus of the mature M1 protein. Furthermore, SpeB can convert bacteria expressing IgG binding proteins of the type IIo phenotype into those expressing type IIb proteins. The role of the cysteine protease as the central bacterial enzyme in this posttranslational modification event was confirmed by generation of an isogenic SpeB-negative mutant.
Insights
Group A Streptococcus M1 protein exhibits two IgG binding patterns. A cysteine protease, SpeB, modifies the M1 protein, converting type IIo to type IIb IgG binding, revealing a key posttranslational modification mechanism.
Area of Science:
- Microbiology
- Immunology
- Biochemistry
Background:
- Serotype M1 group A streptococci (GAS) clinical isolates show distinct human IgG subclass binding patterns.
- These patterns are linked to the M1 protein's interaction with IgG subclasses, specifically type IIo (all subclasses) and type IIb (preferential IgG3 binding).
Purpose of the Study:
- To investigate the mechanism behind the two IgG binding phenotypes observed in M1 GAS.
- To determine the role of the cysteine protease SpeB in modifying the M1 protein's IgG binding properties.
Main Methods:
- Utilized recombinant Emm1 protein to study M1 protein modification.
- Generated a SpeB-negative mutant of M1 GAS to confirm the protease's role.
- Assessed changes in IgG subclass binding profiles before and after SpeB treatment.
Main Results:
- Demonstrated that the cysteine protease SpeB converts a type IIo recombinant Emm1 protein to a type IIb profile by cleaving 24 N-terminal amino acids.
- Showed that SpeB can alter M1 protein phenotype directly on the bacterial surface.
- Confirmed SpeB's essential role in this posttranslational modification by using an isogenic SpeB-negative mutant.
Conclusions:
- SpeB is the central enzyme responsible for the posttranslational modification of the M1 protein in type IIb strains.
- This modification alters the M1 protein's interaction with human IgG subclasses, potentially impacting GAS virulence and immune evasion.