Molecular analysis of the role of streptococcal pyrogenic Exotoxin A (SPEA) in invasive soft-tissue infection resulting from Streptococcus pyogenes.
Epidemiological studies strongly implicate the bacterial superantigen, streptococcal pyrogenic exotoxin A (SPEA), in the pathogenesis of necrotizing soft-tissue infection and toxic shock syndrome resulting from Streptococcus pyogenes. SPEA can act as a superantigen and cellular toxin ex vivo, but its role during invasive streptococcal infection is unclear. We have disrupted the wild-type spea gene in an M1 streptococcal isolate. Supernatants from toxin-negative mutant bacteria demonstrated a 50% reduction in pro-mitogenic activity in HLA DQ-positive murine splenocyte culture, and up to 20% reduction in activity in human PBMC culture. Mutant and wild-type bacteria were then compared in mouse models of bacteraemia and streptococcal muscle infection. Disruption of spea was not associated with attenuation of virulence in either model. Indeed, a paradoxical increase in mutant strain-induced mortality was seen after intravenous infection. Intramuscular infection with the SPEA-negative mutant led to increased bacteraemia at 24 h and a reduction in neutrophils at the site of primary muscle infection. Purified SPEA led to a dose-dependent increase in peritoneal neutrophils 6 h after administration. SPEA is not a critical virulence factor in invasive soft-tissue infection or bacteraemia caused by S. pyogenes, and it could have a protective role in murine immunity to pyogenic infection. The role of this toxin may be different in hosts with augmented superantigen responsiveness.
Sriskandan
S
S
Department of Infectious Diseases Imperial College School of Medicine aat Hammersmith Hospital, London,UK.
Unnikrishnan
M
M
Krausz
T
T
Cohen
J
J
D000818:Animals; D001426:Bacterial Proteins / Q000032:analysis / Q000235:genetics* / Q000633:toxicity; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005098:Exotoxins / Q000032:analysis / Q000235:genetics* / Q000633:toxicity; D006801:Humans; D007958:Leukocyte Count; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics* / Q000633:toxicity; D051379:Mice; D009154:Mutation; D009504:Neutrophils / Q000276:immunology; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger / Q000378:metabolism; D013194:Staining and Labeling; D013290:Streptococcal Infections / Q000276:immunology / Q000382:microbiology*; D013297:Streptococcus pyogenes / Q000235:genetics* / Q000472:pathogenicity; D014169:Transformation, Bacterial; D014774:Virulence / Q000235:genetics
D001426:Bacterial Proteins; D005098:Exotoxins; D008565:Membrane Proteins; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; C117980:SpeA protein, Streptococcus pyogenes