Extracellular cysteine protease produced by Streptococcus pyogenes participates in the pathogenesis of invasive skin infection and dissemination in mice

The role of an extracellular cysteine protease encoded by the speB gene in group A Streptococcus (GAS) skin infection was studied with a mouse model. Mice were injected subcutaneously with a wild-type GAS serotype M3 strain o r a cysteine protease-inactivated isogenic derivative grown to stationary p hase. The mortality rate of mice injected with the M3 speB mutant strain wa s significantly decreased (P < 0.0008) compared to that of animals injected ,vith the wild-type parental organism. The abscesses formed in animals infe cted with the cysteine protease mutant strain were significantly smaller (P < 0.0001) than those caused by the wild-type organism and slowly regressed over 3 to 4 weeks. In striking contrast, infection with the wild-type GAS isolate generated necrotic lesions, and in some animals the GAS disseminate d widely from the injection site and produced extensive cutaneous damage. A ll of these animals developed bacteremia and died. GAS dissemination was ac companied by severe tissue and blood vessel necrosis. Cysteine protease exp ression in the infected tissue was identified by immunogold electron micros copy. These data demonstrate that cysteine protease expression contributes to soft tissue pathology, including necrosis, and is required for efficient systemic dissemination of the organism from the initial site of skin inocu lation.