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Updated: Jul 28, 2026

Invasion of Human Cells by a Bacterial Pathogen
Published on: March 21, 2011
Human immune response to streptococcal inhibitor of complement, a serotype M1 group A Streptococcus extracellular
1Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA. nhoe@niaid.nih.gov
Abstract:
Streptococcal inhibitor of complement (Sic) is a highly polymorphic extracellular protein made by serotype M1 group A Streptococcus strains that contributes to bacterial persistence in the mammalian upper respiratory tract. New variants of the Sic protein arise very rapidly by positive selection in human populations during M1 epidemics. The human antibody response to Sic was analyzed. Of 636 persons living in diverse localities, 43% had anti-Sic serum antibodies, but only 16.4% had anti-M1 protein serum antibody. Anti-Sic antibody was also present in nasal wash specimens in high frequency. Linear B cell epitope mapping showed that serum antibodies recognized epitopes located in structurally variable regions of Sic and the amino terminal hypervariable region of the M1 protein. Phage display analyses confirmed that the polymorphic regions of Sic are primary targets of host antibodies. These results support the hypothesis that selection of Sic variants occurs on mucosal surfaces by a mechanism that involves acquired host antibody.
Insights
Group A Streptococcus M1 strains produce a polymorphic protein, Streptococcal inhibitor of complement (Sic), which aids bacterial persistence. Host antibodies target variable Sic regions, suggesting immune selection drives Sic evolution during epidemics.
Area of Science:
- Microbiology
- Immunology
- Molecular Biology
Background:
- Streptococcal inhibitor of complement (Sic) is an extracellular protein from M1 group A Streptococcus.
- Sic exhibits high polymorphism and contributes to bacterial persistence in the upper respiratory tract.
- Rapid emergence of Sic variants suggests positive selection in human populations during M1 epidemics.
Purpose of the Study:
- To analyze the human antibody response to the Streptococcal inhibitor of complement (Sic) protein.
- To investigate the role of host antibodies in the evolution of Sic variants.
Main Methods:
- Analysis of serum and nasal wash specimens from 636 individuals.
- Linear B cell epitope mapping.
- Phage display analyses to identify antibody targets on Sic.
Main Results:
- 43% of individuals possessed anti-Sic serum antibodies, compared to 16.4% with anti-M1 protein antibodies.
- Anti-Sic antibodies were frequently detected in nasal secretions.
- Antibodies targeted structurally variable regions and hypervariable regions of Sic and M1 protein.
Conclusions:
- Host antibodies recognize polymorphic regions of Sic, indicating they are key targets.
- Acquired host immunity likely drives the selection of new Sic variants on mucosal surfaces.
- This immune pressure contributes to the rapid evolution of Sic during M1 epidemics.
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