Molecular analysis of the role of streptococcal pyrogenic exotoxin A (SPEA) in invasive soft‐tissue infection resulting from Streptococcus pyogenes

Open Access
Publisher Website
Google Scholar
Abstract
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.
Keywords