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Infection and Immunity, October 1999, p. 5298-5305, Vol. 67, No. 10
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

A Two-Component Regulatory System, CsrR-CsrS, Represses Expression of Three Streptococcus pyogenes Virulence Factors, Hyaluronic Acid Capsule, Streptolysin S, and Pyrogenic Exotoxin B

Andrew Heath,1 Victor J. DiRita,2,3 Neil L. Barg,1 and N. Cary Engleberg1,2,*

Departments of Internal Medicine1 and Microbiology and Immunology,2 and the Unit for Laboratory Animal Medicine,3 University of Michigan Medical School, Ann Arbor, Michigan 48109

Received 22 February 1999/Returned for modification 15 June 1999/Accepted 28 July 1999

Certain Tn916 insertions in the chromosome of an M1-type, nonmucoid Streptococcus pyogenes isolate (MGAS166) were previously shown to result in stable mucoidy with increased expression of the capsular synthetic genes. The transposon insertions in these strains are directly upstream of an apparent operon encoding a two-component regulatory system, designated csrR-csrS. Compared with MGAS166, these mucoid mutants are more hemolytic and cause significantly more tissue damage in a murine model of skin infection. To extend these observations, we constructed an in-frame deletion in the gene encoding the response regulator, csrR, and we evaluated the expression of other known S. pyogenes virulence factors. We discovered that csrR mutants have enhanced transcription of sagA, a gene associated with streptolysin S (SLS) and speB, the gene encoding pyrogenic exotoxin B (SpeB). The mutants also express substantially higher SLS activity and SpeB antigen in late-exponential-phase cultures. There is no change in expression of emm, scpA, sic, or cpa (genes encoding other S. pyogenes virulence factors). CsrR- strains but not the wild-type parental strain produce necrotizing lesions in a mouse model of subcutaneous infection. A double mutant with deletions in both csrR and the capsular synthesis genes caused fewer and smaller necrotic skin lesions than the csrR mutants. However, this nonmucoid csrR strain was more likely than the wild type to yield necrotic lesions, suggesting that mucoidy contributes to virulence in this model of infection but that there are other csrR-regulated factors involved in the production of necrotic lesions.

* Corresponding author. Mailing address: Division of Infectious Diseases, Department of Internal Medicine, University of Michigan Hospitals, 3116B Taubman Center, Box 0378, Ann Arbor, MI 48109. Phone: (734) 936-5205. Fax: (734) 936-2737. E-mail: cengleb{at}umich.edu.

Infection and Immunity, October 1999, p. 5298-5305, Vol. 67, No. 10
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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