Streptococcus pyogenes Superantigens: Studies Into Host Specificity and Functional Redundancy

Streptococcus pyogenes is a human-specific globally prominent bacterial pathogen that secretes extremely potent exotoxins known as superantigens. Superantigens function to overstimulate T lymphocytes, capable of inducing excessive cytokine responses, potentially leading to toxic shock syndrome. Each strain of S. pyogenes encodes multiple distinct superantigens, yet the reasons why S. pyogenes retains multiple superantigens has remained elusive. Using a murine model of acute nasopharyngeal infection, the role of each superantigen encoded by S. pyogenes MGAS5005 was evaluated using isogenic superantigen-deletion or -complemented strains, and passive immunization with superantigen-neutralizing antibodies. The superantigen SpeG, and likely SpeJ, were not required for infection. However, SpeA and SmeZ were both required for infection of HLA-DQ8 transgenic mice, and thus, are not functionally redundant. This supports the theory that S. pyogenes superantigen expression varies depending on host factors, and provides insight into superantigen function in non-severe infections