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Molecular analysis of the role of streptococcal pyrogenic exotoxin A (SPEA) in invasive soft-tissue infection resulting from Streptococcus pyogenes
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Sriskandan, Shiranee, Unnikrishnan, Meera, Krausz, Thomas and Cohen, Jonathan (1999) Molecular analysis of the role of streptococcal pyrogenic exotoxin A (SPEA) in invasive soft-tissue infection resulting from Streptococcus pyogenes. Molecular Microbiology, Volume 33 (Number 4). pp. 778-790. doi:10.1046/j.1365-2958.1999.01525.x ISSN 0950-382X.
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Official URL: http://dx.doi.org/10.1046/j.1365-2958.1999.01525.x
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.
Item Type: | Journal Article | ||||
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Subjects: | Q Science > QR Microbiology | ||||
Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Microbiology & Infection Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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Library of Congress Subject Headings (LCSH): | Streptococcus pyogenes, Soft tissue injuries | ||||
Journal or Publication Title: | Molecular Microbiology | ||||
Publisher: | Wiley-Blackwell Publishing Ltd. | ||||
ISSN: | 0950-382X | ||||
Official Date: | August 1999 | ||||
Dates: |
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Volume: | Volume 33 | ||||
Number: | Number 4 | ||||
Page Range: | pp. 778-790 | ||||
DOI: | 10.1046/j.1365-2958.1999.01525.x | ||||
Status: | Peer Reviewed | ||||
Publication Status: | Published | ||||
Access rights to Published version: | Restricted or Subscription Access | ||||
Funder: | Medical Research Council (Great Britain) (MRC) |
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