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Infection and Immunity, January 2003, p. 446-455, Vol. 71, No. 1
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.1.446-455.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Cytotoxic Effects of Streptolysin O and Streptolysin S Enhance the Virulence of Poorly Encapsulated Group A Streptococci

Gabriele Sierig,1,{dagger} Colette Cywes,1 Michael R. Wessels,1,2 and Cameron D. Ashbaugh1*

Channing Laboratory and Division of Infectious Diseases, Brigham and Women's Hospital,1 Division of Infectious Diseases, Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts 021152

Received 4 June 2002/ Returned for modification 8 August 2002/ Accepted 15 October 2002

Although the toxicity of streptolysin O (SLO) and streptolysin S (SLS) in purified group A streptococci (GAS) has been established, the effect of these molecules in natural infection is not well understood. To identify whether biologically relevant concentrations of SLO and SLS were cytotoxic to epithelial and phagocytic cells that the bacteria would typically encounter during human infection and to characterize the influence of cell injury on bacterial pathogenesis, we derived GAS strains deficient in SLO or SLS in the background of an invasive GAS M3 isolate and determined their virulence in in vitro and in vivo models of human disease. Whereas bacterial production of SLO resulted in lysis of both human keratinocytes and polymorphonuclear leukocytes, GAS expression of SLS was associated only with keratinocyte injury. Expression of SLO but not SLS impaired polymorphonuclear leukocyte killing of GAS in vitro, but this effect could only be demonstrated in the background of acapsular organisms. In mouse invasive soft-tissue infection, neither SLO or SLS expression significantly influenced mouse survival. By contrast, in a mouse model of bacterial sepsis after intraperitoneal inoculation of GAS, SLO expression enhanced the virulence of both encapsulated and acapsular GAS, whereas SLS expression increased the virulence only of acapsular GAS. We conclude that the cytotoxic effects of SLO protect GAS from phagocytic killing and enhance bacterial virulence, particularly of strains that may be relatively deficient in hyaluronic acid capsule. Compared to SLO, SLS in this strain background has a more modest influence on GAS pathogenicity and the effect does not appear to involve bacterial resistance to phagocytosis.

* Corresponding author. Mailing address: Channing Laboratory, 181 Longwood Ave., Boston, MA 02115. Phone: (617) 525-2242. Fax: (617) 731-1541. E-mail: cashbaugh{at}channing.harvard.edu.

Editor: V. J. DiRita

{dagger} Present address: Department of Pediatric Cardiology, Heart Centre Leipzig, Leipzig, Germany.

Infection and Immunity, January 2003, p. 446-455, Vol. 71, No. 1
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.1.446-455.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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