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Different alleles of the fcrA/mrp gene of Streptococcus pyogenes encode M-related proteins exhibiting an identical
B Krebs1, A Kaufhold, M D Boyle
1Institute of Medical Microbiology, Technical University (RWTH), Aachen, Germany. krebs@mzdmza.zdv.uni-mainz.de
Abstract:
The majority of group A streptococci (GAS, Streptococcus pyogenes) express immunoglobulin (Ig)-binding proteins. The genes encoding these proteins belong either to the emm or the emm-related (fcrA/mrp and enn) gene family and are located in close proximity on the GAS genome, where they form part of the vir regulon. In the present study analysis of sequence data of the 5' terminal portions of the fcrA/mrp genes from GAS isolates representing 37 different M serotypes led to a classification of six different types. Thus, although fcrA/mrp genes exhibit an allelic polymorphism, they do not display the high degree of N-terminal sequence diversity found among emm genes. The nucleotide sequences of the fcrA/mrp genes from 3 GAS isolates, belonging to serotypes M8, M9, and M13 and representing newly characterized fcrA/mrp gene types, are reported. Analysis of the Ig-binding properties of recombinant FcrA/Mrp8, 9, and 13 proteins, demonstrated a similar Ig-binding profile being reactive with human IgG subclasses 1, 2, and 4. This pattern is identical to that previously described for other recombinant fcrA/mrp4, 49, 64/14 and 76 gene products, indicating that this property is not affected by the N-terminal variability. Evidence for recombination between an fcrA/mrp and an mga gene was observed in an M-type 33 strain isolate providing further support for the concept of gene rearrangement contributing to the diversity of vir regulon gene products.
Insights
Group A Streptococcus (GAS) immunoglobulin-binding proteins, encoded by fcrA/mrp genes, show limited N-terminal sequence diversity across M serotypes. Recombinant proteins exhibit consistent IgG subclass binding, unaffected by allelic variations.
Area of Science:
- Microbiology
- Genetics
- Immunology
Background:
- Group A Streptococcus (GAS) possesses immunoglobulin (Ig)-binding proteins crucial for pathogenesis.
- These proteins are encoded by the emm, fcrA/mrp, and enn gene families within the vir regulon.
Purpose of the Study:
- To classify fcrA/mrp gene types based on N-terminal sequence diversity.
- To characterize the Ig-binding properties of newly identified FcrA/Mrp proteins.
- To investigate gene recombination within the GAS vir regulon.
Main Methods:
- Sequence analysis of 5' terminal portions of fcrA/mrp genes from 37 GAS M serotypes.
- Nucleotide sequencing of fcrA/mrp genes from M8, M9, and M13 serotypes.
- Analysis of Ig-binding profiles of recombinant FcrA/Mrp proteins using human IgG subclasses.
Main Results:
- Six distinct types of fcrA/mrp genes were identified based on N-terminal sequences.
- Recombinant FcrA/Mrp8, 9, and 13 proteins showed conserved binding to human IgG subclasses 1, 2, and 4.
- Evidence of recombination between fcrA/mrp and mga genes was observed in an M-type 33 isolate.
Conclusions:
- fcrA/mrp genes exhibit allelic polymorphism but less N-terminal sequence diversity compared to emm genes.
- Conserved Ig-binding properties of FcrA/Mrp proteins are independent of N-terminal variations.
- Gene rearrangement, including recombination events, contributes to the diversity of vir regulon products in GAS.