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Infect Immun, April 1998, p. 1671-1679, Vol. 66, No. 4
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Reduced Virulence of Group A Streptococcal Tn916 Mutants That Do Not Produce Streptolysin S

Stephen D. Betschel,1 Sergio M. Borgia,1 Neil L. Barg,2 Donald E. Low,1 and Joyce C. S. De Azavedo1,*

Department of Microbiology, Mount Sinai and Princess Margaret Hospitals, and University of Toronto, Toronto, Ontario, Canada M5G 1X5,1 and Division of Infectious Diseases, Department of Veterans' Affairs Medical Center, and University of Michigan, Ann Arbor, Michigan 481052

Received 20 June 1997/Returned for modification 18 August 1997/Accepted 14 January 1998

Streptolysin S (SLS) is a potent cytolytic toxin produced by nearly all group A streptococci (GAS). SLS-deficient Tn916 insertional mutants were generated from two clinical isolates of GAS, MGAS166s and T18Ps (M serotypes 1 and 18, respectively), by transposon mutagenesis using Tn916 donor strain Enterococcus faecalis CG110. Representative nonhemolytic transconjugants SBNH5 and SB30-2 each harbored a single Tn916 insertion in identical loci. The insertion in SBNH5 was located in the promoter region of an open reading frame, designated sagA, rendering it transcriptionally inactive. Protease, streptolysin O, and DNase activities and the production of M protein remained the same in the nonhemolytic mutants and the wild-type strains, as did the growth rates and exoprotein profiles. Transconjugants were evaluated in an established murine model by injecting the organisms subcutaneously and monitoring the mice for alterations in weight and the development of necrotic lesions. Animals infected with SBNH5, compared to those infected with MGAS166s, gained weight during the first 24 h (+1.15 versus -1.16 g; P < 0.05) and had fewer necrotic lesions (0 versus 7; P = 0.0007). Animals infected with SB30-2, compared to those infected with T18Ps, also gained weight within the first 24 h (+0.54 versus -0.66 g; P < 0.05) and produced fewer necrotic lesions (1 versus 8; P = 0.001). Revertants of the mutants in which Tn916 had been excised regained the hemolytic phenotype and the virulence profile of the wild-type strains. This study demonstrates that SLS-deficient mutants of GAS, belonging to different M serotypes and containing identical Tn916 mutations, are markedly less virulent than their isogenic parents.

* Corresponding author. Mailing address: Mount Sinai Hospital, Department of Microbiology, 600 University Ave., Toronto, Ontario, Canada M5G 1X5. Phone: (416) 586-8459. Fax: (416) 586-8746. E-mail: jdazavedo{at}mtsinai.on.ca.




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