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Two-domain motif for IgG-binding activity by group A streptococcal emm gene products
D E Bessen1, M W Izzo, E J McCabe
1Yale University School of Medicine, Department of Epidemiology and Public Health (Microbiology Section), New Haven, CT 06520, USA. debra.bessen@yale.edu
Abstract:
A biological role for the non-immune binding of human IgG by group A streptococci is evidenced by its strong association with a subpopulation of strains giving rise to tissue-specific infection. IgG-binding activity lies within many of the M and M-like surface proteins (encoded by emm genes), and several structurally distinct IgG-binding sites are known to exist. In this report, two adjacent IgG-binding domains, differing in their specificity for human IgG subclasses, are localized within the M-like protein, protein H. The putative coding regions for the two IgG-binding domains were mapped for 82 epidemiologically unrelated strains. Both coding regions are associated with phylogenetically distant emm genes, supporting a role for horizontal transfer and intergenomic recombination in the evolution of emm genes. In most instances, the two coding regions are tightly linked, suggesting that there exist strong selective pressures to maintain a two-domain binding motif. Both coding regions are found among all strains bearing emm gene markers associated with impetigo lesions as the principal tissue reservoir, but are absent from most strains that exhibit markers for a predominant nasopharyngeal reservoir. The data support the hypothesis that the pathogenic potential of an isolate is dictated, at least in part, by its unique array of multifunctional emm gene products.
Insights
Group A Streptococcus non-immune binding of human immunoglobulin G (IgG) is linked to specific infections. Protein H
Area of Science:
- Microbiology and Immunology
- Bacterial Pathogenesis
- Molecular Evolution
Background:
- Group A Streptococcus (GAS) utilizes surface proteins, including M and M-like proteins encoded by emm genes, for non-immune binding of human immunoglobulin G (IgG).
- Distinct IgG-binding sites within these proteins are known, suggesting functional significance in GAS-host interactions.
Purpose of the Study:
- To investigate the biological role of non-immune IgG binding by GAS, specifically focusing on the M-like protein, Protein H.
- To map and characterize the IgG-binding domains within Protein H and their association with GAS infection types.
Main Methods:
- Localization of two adjacent IgG-binding domains within Protein H, differing in human IgG subclass specificity.
- Mapping of the putative coding regions for these domains across 82 epidemiologically distinct GAS strains.
- Analysis of the association of these coding regions with specific emm gene markers and tissue tropism (impentigo vs. nasopharyngeal).
Main Results:
- Two distinct, adjacent IgG-binding domains were identified in Protein H, each with specificities for different human IgG subclasses.
- The coding regions for these domains were found in phylogenetically diverse emm genes, suggesting horizontal gene transfer and recombination.
- Both coding regions were present in strains associated with impetigo but largely absent in strains with a nasopharyngeal reservoir, indicating a link to tissue-specific infection.
Conclusions:
- The presence and linkage of these two IgG-binding domains in Protein H are likely maintained by strong selective pressures.
- The distribution of these domains correlates with GAS tissue tropism, supporting their role in pathogenesis.
- The specific array of multifunctional emm gene products, including these IgG-binding domains, contributes to the pathogenic potential of GAS isolates.