Abstract
Superantigens are ubiquitous within the Streptococcus pyogenes genome, which suggests that superantigen-mediated T-cell activation provides a significant selective advantage. S. pyogenes can carry a variable complement of the 11 known superantigens. We have identified two novel S. pyogenes superantigens, denoted speQ and speR, adjacent to each other in the core-chromosome of isolates belonging to eleven different emm-types. Although distinct from other superantigens, speQ and speR were most closely related to speK and speJ, respectively. Recombinant SPEQ and SPER were mitogenic towards human peripheral blood mononuclear cells at ng/ml concentrations, and SPER was found to be more mitogenic than SPEQ.
Highlights
The human pathogen, Streptococcus pyogenes, produces numerous virulence factors, including the extracellular superantigen toxins which are associated with the development of streptococcal toxic shock syndrome and scarlet fever
We identified two potential superantigen genes present in the chromosomes of two 1930s S. pyogenes emm[60] isolates and subsequently identified the same genes in isolates belonging to 10 other emm-types in modern international isolates
We tested the genomes over 4000 different isolates representing 86 emm-types and detected speQR in strains belonging to emm[9, 15, 18, 42, 53, 58, 60, 77, 87, 94] and 169, both speQR positive and negative lineages existed within these genotypes (Supplementary Figure 2)
Summary
The human pathogen, Streptococcus pyogenes, produces numerous virulence factors, including the extracellular superantigen toxins which are associated with the development of streptococcal toxic shock syndrome and scarlet fever. There are 14 known streptococcal superantigens, 11 of which have been found in S. pyogenes; speA, speC, speG-speM, smeZ and ssa. The other eight identified S. pyogenes superantigens are associated with prophages which have the potential to be mobile, introducing variability among isolates. As there is variability in the complement of superantigens carried by S. pyogenes isolates, along with mobility and sharing across other streptococcal species, there may be streptococcal superantigens that are yet to be identified. Whilst testing for the presence of the 11 known superantigens in whole genome sequence (WGS) data from two S. pyogenes isolates from the pre-antibiotic era, we identified two new adjacent potential superantigen genes. The two new potential superantigen genes were not associated with recognised mobile genetic elements but were limited to certain emm-types. We have termed the genes speQ and speR, to follow the proposed nomenclature, and confirmed that they are mitogenic towards human mononuclear cells
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