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Infection and Immunity, May 2001, p. 2943-2949, Vol. 69, No. 5
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.5.2943-2949.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Spa Contributes to the Virulence of Type 18 Group A Streptococci

Duncan G. J. McLellan,^1,2 Edna Y. Chiang,¹ Harry S. Courtney,^1,2 David L. Hasty,^1,3 Shirley C. Wei,^1,2 Mary C. Hu,⁴ Michael A. Walls,⁴ Jackie J. Bloom,⁴ and James B. Dale^1,2,*

VA Medical Center¹ and Departments of Medicine² and Anatomy and Neurobiology,³ University of Tennessee, Memphis, Tennessee 38104, and ID Biomedical Corporation, Bothell, Washington 98011⁴

Received 22 September 2000/Returned for modification 5 December 2000/Accepted 12 February 2001

Streptococcal protective antigen (Spa) is a newly described surface protein of group A streptococci that was recently shown to evoke protective antibodies (J. B. Dale, E. Y. Chiang, S. Liu, H. S. Courtney, and D. L. Hasty, J. Clin. Investig. 103:1261-1268, 1999). In this study, we have determined the complete sequence of the spa gene from type 18 streptococci. Purified, recombinant Spa protein evoked antibodies that were bactericidal against type 18 streptococci, confirming the presence of protective epitopes. Sera from patients with acute rheumatic fever contained antibodies against recombinant Spa, indicating that the Spa protein is expressed in vivo and is immunogenic in humans. To determine the role of Spa in the virulence of group A streptococci, we created a series of insertional mutants that were (i) Spa negative and M18 positive, (ii) Spa positive and M18 negative, and (iii) Spa negative and M18 negative. The mutants and the parent M18 strain (18-282) were used in assays to determine resistance to phagocytosis, growth in human blood, and mouse virulence. The results show that Spa is a virulence determinant of group A streptococci and that expression of both Spa and M18 is required for optimal virulence of type 18 streptococci.

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^* Corresponding author. Mailing address: VA Medical Center (11A), 1030 Jefferson Ave., Memphis, TN 38104. Phone: (901) 577-7207. Fax: (901) 448-8231. E-mail: JAMES.DALE{at}MED.VA.GOV.

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Infection and Immunity, May 2001, p. 2943-2949, Vol. 69, No. 5
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.5.2943-2949.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

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