Superantigenic activity of emm3 Streptococcus pyogenes is abrogated by a conserved, naturally occurring smeZ mutation

Area of Science:

• Microbiology
• Immunology
• Genetics

Background:

• Streptococcus pyogenes emm3 strains are associated with severe infections and streptococcal toxic shock syndrome (STSS).
• STSS is triggered by superantigens that stimulate T cells.
• Previous observations suggested emm3 strains were less mitogenic than other emm types.

Purpose of the Study:

• To investigate the underlying cause of reduced superantigenic activity in emm3 Streptococcus pyogenes strains.
• To determine the role of the superantigen gene smeZ in the mitogenicity of emm3 strains.

Main Methods:

• Comparative analysis of smeZ gene sequences in various emm-types of Streptococcus pyogenes.
• In vitro and in vivo experiments to assess the mitogenic activity of different S. pyogenes strains and smeZ variants.
• Evaluation of cytokine induction in human tonsil and mouse models.

Main Results:

• A conserved 13 bp deletion in the smeZ gene of emm3 strains was identified, leading to a premature stop codon and a non-functional M3-smeZ protein.
• Expression of a functional smeZ gene restored mitogenic activity in emm3 strains and in other strains with disrupted smeZ.
• The mutated M3-smeZ could not restore or enhance mitogenicity in any tested S. pyogenes strain.
• The mutation reduced cytokine induction in human tonsil tissue but not in a mouse model.

Conclusions:

• The inherent poor superantigenicity of emm3 Streptococcus pyogenes strains is explained by a conserved, non-functional mutation in the smeZ gene.
• This genetic defect in smeZ contributes to the observed differences in virulence and STSS risk associated with emm3 strains.