Massive Bacterial Load and In Vivo Expression of Superantigen (SAg) in Patients with Severe Tissue Infections Caused by Group A Streptococci (GAS).

A. Norrby-Teglund¹, B.S. Gan², M. Kotb³, J. Andersson¹, A. McGeer², D.E. Low². ¹Karolinska Institute, Stockholm, Sweden; ²Mount Sinai Hospital, Toronto, ON, Canada; ³VA Medical Centre and University of TN-Memphis, Memphis, TN.

Background: SAg have been suggested to play a central role in the pathogenesis of GAS diseases. Here we analyzed in vivo bacterial load and SAg expression in context of severity of GAS tissue infection.

Methods: Snapfrozen tissue biopsies from patients with necrotizing fasciitis (n=3), and from the less severe forms of infection, cellulitis (n=1) and myositis (n=1) were sectioned, fixed and stained for GAS ans SpeF using specific antibodies. SpeF was used as a marker for SAg since it is present in all GAS strains. Detection was by intracellular immunohistochemistry or immunofluorescence.

Results: High amounts of extra- and intra-cellular GAS, and SpeF could be detected in tissue from all patients. Despite clinical differences, there was no difference in bacterial load or SpeF expression between the patients, or between severely or moderately involved tissue obtained from the same patient at the same time point. Consistently high amounts of GAS and SpeF could be detected in biopsies taken several days (3-14) after disease onset. Dual stainings revealed a strong colocalization of GAS and SpeF with T cells. SpeF showed an intense cytoplasmic staining pattern, and an increased expression with reduced extracellular GAS.

Conclusion: High bacterial load and excessive in vivo SAg production contributes to the inflammatory responses seen in these patients; however, the data suggest that also host factors are involved in regulating the level of response and consequently the severity of disease. The study indicates that there may be a relation between localization of GAS and SAg expression. Of major clinical importance is the finding that SAg expressing GAS can be found in tissue even after prolonged i.v. antibiotic therapy, which suggets that novel therapies may be required.

Key Words:

Pathogenesis
Streptococcus pyogenes
Superantigen

Presented at:

40^th INTERSCIENCE CONFERENCE ON ANTIMICROBIAL AGENTS AND CHEMOTHERAPY (ICAAC), Metro Toronto Convention Centre, Toronto, Ontario, Canada, September 17-20, 2000.