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Infection and Immunity, April 1999, p. 1779-1788, Vol. 67, No. 4
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Extracellular Cysteine Protease Produced by Streptococcus pyogenes Participates in the Pathogenesis of Invasive Skin Infection and Dissemination in Mice

Slawomir Lukomski,1 Charles A. Montgomery,2 Jacqueline Rurangirwa,1 Robert S. Geske,2 James P. Barrish,3 Gerald J. Adams,1 and James M. Musser1,*

Institute for the Study of Human Bacterial Pathogenesis, Department of Pathology,1 and Center for Comparative Medicine,2 Baylor College of Medicine, and Electron Microscopy Laboratory, Texas Children's Hospital,3 Houston, Texas 77030

Received 9 October 1998/Returned for modification 11 December 1998/Accepted 12 January 1999

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 or a cysteine protease-inactivated isogenic derivative grown to stationary phase. The mortality rate of mice injected with the M3 speB mutant strain was significantly decreased (P < 0.0008) compared to that of animals injected with the wild-type parental organism. The abscesses formed in animals infected 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 disseminated widely from the injection site and produced extensive cutaneous damage. All of these animals developed bacteremia and died. GAS dissemination was accompanied by severe tissue and blood vessel necrosis. Cysteine protease expression in the infected tissue was identified by immunogold electron microscopy. 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 inoculation.

* Corresponding author. Mailing address: Institute for the Study of Human Bacterial Pathogenesis, Department of Pathology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030. Phone: (713) 798-4198. Fax: (713) 798-4595. E-mail: jmusser{at}bcm.tmc.edu.

Infection and Immunity, April 1999, p. 1779-1788, Vol. 67, No. 4
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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