Human immune response to streptococcal inhibitor of complement, a serotype M1 group A Streptococcus extracellular

N P Hoe1, P Kordari, R Cole

  • 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

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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