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Infection and Immunity, December 2009, p. 5225-5232, Vol. 77, No. 12
0019-9567/09/$08.00+0 doi:10.1128/IAI.00636-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Department of Veterinary Molecular Biology, Montana State University, Bozeman, Montana 59717,1 Center for Molecular and Translational Human Infectious Diseases Research, the Methodist Hospital Research Institute, Houston, Texas 770302
Received 4 June 2009/ Returned for modification 29 June 2009/ Accepted 27 September 2009
Virulence factors regulated by the CovRS/CsrRS two-component gene regulatory system contribute to the invasive diseases caused by group A Streptococcus (GAS). To determine whether the streptococcal secreted esterase (Sse), an antigen that protects against subcutaneous GAS infection, is one of these virulence factors, we investigated the phenotype of a nonpolar sse deletion mutant strain (
sse). In addition, we examined the effects of covS mutation on sse expression. As assessed using a mouse model of subcutaneous infection, the virulence of the
sse strain is attenuated and the overall pathology is reduced. Furthermore, GAS was detected in the blood and spleens from mice subcutaneously infected with the parental strain, whereas mice subcutaneously infected with the
sse strain had no GAS present in their blood and spleens. The ability of the mutant to survive in the subcutis of mice appeared to be compromised. The growth of the
sse strain in rich and chemically defined media and nonimmune human blood and sera was slower than that of the wild-type strain. Complementation restored the phenotype of the
sse strain to that of the wild-type strain. The wild-type,
sse, and complement strains had no detectable SpeB activity. Expression of Sse is negatively controlled by CovRS. These findings suggest that Sse is a CovRS-regulated virulence factor that is important for the virulence of GAS in subcutaneous infection and plays an important role in severe soft tissue infections and systemic dissemination of GAS from the skin.
Published ahead of print on 5 October 2009.
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