Superantigen Interactions in Streptococcal Tonsillitis

Streptococcus pyogenes is the major cause of bacterial tonsillitis worldwide, and is also responsible for severe invasive infections such as necrotising fasciitis and toxic shock syndrome. Although it can cause severe infections, S. pyogenes can also be carried asymptomatically in the throat, and transferred from person to person. It is known that S. pyogenes produces a number of highly potent toxins (superantigens), which have the ability to create a massive inflammatory response, and can even overwhelm the immune system. However, it is unclear why or when these are produced by the bacteria.
This research will investigate the role of the superantigens produced by S. pyogenes in tonsillitis. Using a variety of laboratory techniques we will see if the superantigens alone are responsible for the inflammatory changes which occur during tonsil infections, and whether their production is increased in bacteria cultured from people with clinical disease when compared to their relatives who have asymptomatic carriage of the same bacterial strain.
The results of this study will not only provide important information about the mechanisms employed by S. pyogenes to cause disease, but can also be applied to other bacteria which produce superantigens, especially Staphylococcus aureus.

Streptococcus pyogenes causes both mucosal and severe invasive infections and the pharynx represents the major human reservoir for disease. S. pyogenes produces potent superantigenic exoproteins, though the advantage conferred by these to the bacterium is unknown. We aim to investigate whether superantigens confer specific advantage to S. pyogenes during infection of the nasopharynx as follows:
Superantigen expression during bacterial growth in tonsil co-cultures and during tonsillitis will be evaluated by transcription and protein analysis.
To evaluate cellular and cytokine responses that are evoked by superantigens in tonsil, techniques will include co-culture of human tonsil lymphoid cells with a panel of isogenic bacterial strains differing only in superantigenicity.
Finally, to determine the impact of streptococcal superantigens on mucosal immune responses and clearance of infection, we will employ an HLA class II humanised system that is uniquely sensitive to streptococcal superantigens. The influence of superantigen production on cellular and cytokine responses in nasal associated lymphoid tissue (NALT) will be investigated and the impact of superantigen exposure on clearance of bacteria will be measured.
The range of approaches proposed will reveal the significance of superantigens to streptococcal pathogenesis and will provide a strong foundation for research training.