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Infection and Immunity, July 2003, p. 3857-3865, Vol. 71, No. 7
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.7.3857-3865.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Combined Contributions of Streptolysin O and Streptolysin S to Virulence of Serotype M5 Streptococcus pyogenes Strain Manfredo

Michael C. Fontaine, Jeong Jin Lee, and Michael A. Kehoe^*

School of Cell and Molecular Biosciences, The Medical School, University of Newcastle upon Tyne, Newcastle upon Tyne NE2 4HH, United Kingdom

Received 7 August 2002/ Returned for modification 26 November 2002/ Accepted 27 March 2003

Streptolysin O (SLO) and streptolysin S (SLS) are potent cytolytic toxins produced by almost all clinical isolates of group A streptococci (GAS). Allele-replacement mutagenesis was used to construct nonpolar (in-frame) deletion mutations in the slo and sagB genes of the serotype M5 GAS strain Manfredo, producing isogenic single and double SLO- and SLS-defective mutants. In contrast to recent reports on SLS-defective insertion mutants (I. Biswas, P. Germon, K. McDade, and J. Scott, Infect. Immun. 69:7029-7038, 2001; Z. Li, D. Sledjeski, B. Kreikemeyer, A.Podbielski, and M. Boyle, J. Bacteriol. 181:6019-6027, 1999), none of the mutants described here had notable pleiotropic effects on the expression of other virulence factors examined. Comparison of isogenic parent and mutant strains in various virulence models revealed no differences in their abilities to multiply in human blood or in their 50% lethal doses (LD₅₀s) upon intraperitoneal infection of BALB/c mice. A single log unit difference in the LD₅₀s of the parent and SLS-defective mutant strains was observed upon infection by the subcutaneous (s.c.) route. Comparisons over a range of infective doses showed that both SLO and SLS contributed to the early stages of infection and to the induction of necrotic lesions in the murine s.c. model. Individually, each toxin made an incremental contribution to virulence that was not apparent at higher infective doses, although the absence of both toxins reduced virulence over the entire dose range examined. Interestingly, in some cases, the contribution of SLO to virulence was clear only from an analysis of the double-mutant strain, highlighting the value of not confining virulence studies to mutant strains defective in the expression of only single virulence factors.

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* Corresponding author. Mailing address: School of Cell and Molecular Biosciences, The Medical School, University of Newcastle upon Tyne, Framlington Place, Newcastle upon Tyne NE2 4HH, United Kingdom. Phone: 44 191 222 8143. Fax: 44 191 222 7736. E-mail: mike.kehoe{at}ncl.ac.uk.

Editor: V. J. DiRita

Present address: Moredun Research Institute, Penicuik EH26 0PZ, Scotland, United Kingdom.

Present address: LG Life Sciences Ltd., R&D, 104-1, Moonji-dong, Yusong-gu, Daejeon 305-308, Korea.

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Infection and Immunity, July 2003, p. 3857-3865, Vol. 71, No. 7
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.7.3857-3865.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

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