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Updated: Aug 15, 2026

Implementation of a Permeable Membrane Insert-based Infection System to Study the Effects of Secreted Bacterial Toxins on Mammalian Host Cells
Published on: August 19, 2016
Complementation of a speA negative Streptococcus pyogenes with speA: effects on virulence and production of
M Unnikrishnan1, J Cohen, S Sriskandan
1Department of Infectious Diseases, Imperial College School of Medicine, Hammersmith Hospital, Du Can Road, London W12 0NN, UK.
Abstract:
We have shown previously that an isogenic SPEA-negative Streptococcus pyogenes strain did not attenuate virulence in a murine model of necrotizing fasciitis. The aim of this study was to confirm that streptococcal pyrogenic exotoxin A (SPEA) is not crucial for streptococcal invasiveness in murine invasive infection. The SPEA-negative S. pyogenes (H326) was complemented with speA extra-chromosomally to create strain H361 which produced 2.2-fold more SPEA compared with the parental speA(+)wild-type (H305). The growth phase-regulated expression of SPEA in vitro was unaffected in this strain. Complementation with speA resulted in reduced virulence and bacterial counts in invasive murine infection. SPEA production was quantitated from muscle tissue of infected mice. However, H361 did not produce more SPEA than H305 in vivo. We conclude that SPEA does not play a key role in invasive murine streptococcal infection.
Insights
Streptococcus pyogenes strains lacking streptococcal pyrogenic exotoxin A (SPEA) did not show reduced virulence. This study confirms SPEA is not crucial for invasive infections in mice.
Area of Science:
- Microbiology
- Infectious Diseases
- Toxicology
Background:
- Streptococcus pyogenes virulence is complex.
- Previous studies suggested SPEA might be important for invasive disease.
Purpose of the Study:
- To investigate the role of streptococcal pyrogenic exotoxin A (SPEA) in invasive Streptococcus pyogenes infections.
- To determine if SPEA is essential for bacterial invasiveness in a murine model.
Main Methods:
- Created a complemented strain (H361) with increased SPEA production compared to wild-type (H305).
- Inoculated mice with SPEA-negative, wild-type, and complemented strains.
- Quantified bacterial counts and SPEA levels in infected murine tissues.
Main Results:
- Complementation with speA in strain H361 led to reduced virulence and bacterial load in vivo.
- Despite higher in vitro production, strain H361 did not produce more SPEA than the wild-type in infected mouse tissues.
- SPEA production levels in vivo did not correlate with virulence.
Conclusions:
- Streptococcal pyrogenic exotoxin A (SPEA) does not appear to play a key role in the invasiveness of Streptococcus pyogenes in this murine model.
- Virulence in invasive streptococcal infections is likely mediated by factors other than SPEA.
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