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Journal of Bacteriology, March 2009, p. 1656-1665, Vol. 191, No. 5
0021-9193/09/$08.00+0     doi:10.1128/JB.01555-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

sarZ, a sarA Family Gene, Is Transcriptionally Activated by MgrA and Is Involved in the Regulation of Genes Encoding Exoproteins in Staphylococcus aureus

Anand Ballal, Binata Ray, and Adhar C. Manna^*

Division of Basic Biomedical Sciences, University of South Dakota, Vermillion, South Dakota 57069, and Center for Infectious Disease Research and Vaccinology, South Dakota State University, Brookings, South Dakota 57007

Received 2 November 2008/ Accepted 9 December 2008

The expression of genes involved in the pathogenesis of Staphylococcus aureus is controlled by global regulatory loci, including two-component regulatory systems and transcriptional regulators (e.g., sar family genes). Most members of the SarA family have been partially characterized and shown to regulate a large numbers of target genes. Here, we describe the characterization of sarZ, a sarA paralog from S. aureus, and its regulatory relationship with other members of its family. Expression of sarZ was growth phase dependent with maximal expression in the early exponential phase of growth. Transcription of sarZ was reduced in an mgrA mutant and returned to a normal level in a complemented mgrA mutant strain, which suggests that mgrA acts as an activator of sarZ transcription. Purified MgrA protein bound to the sarZ promoter region, as determined by gel shift assays. Among the sarA family of genes analyzed, inactivation of sarZ increased sarS transcription, while it decreased agr transcription. The expression of potential target genes involved in virulence was evaluated in single and double mutants of sarZ with mgrA, sarX, and agr. Northern and zymogram analyses indicated that the sarZ gene product played a role in regulating several virulence genes, particularly those encoding exoproteins. Gel shift assays demonstrated nonspecific binding of purified SarZ protein to the promoter regions of the sarZ-regulated target genes. These results demonstrate the important role played by SarZ in controlling regulatory and virulence gene expression in S. aureus.

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* Corresponding author. Mailing address: Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, 414 E. Clark Street, Vermillion, SD 57069. Phone: (605) 677-6336. Fax: (605) 677-6381. E-mail: amanna{at}usd.edu

Published ahead of print on 19 December 2008.

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Journal of Bacteriology, March 2009, p. 1656-1665, Vol. 191, No. 5
0021-9193/09/$08.00+0     doi:10.1128/JB.01555-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

This article has been cited by other articles:

• Poor, C. B., Chen, P. R., Duguid, E., Rice, P. A., He, C. (2009). Crystal Structures of the Reduced, Sulfenic Acid, and Mixed Disulfide Forms of SarZ, a Redox Active Global Regulator in Staphylococcus aureus. J. Biol. Chem. 284: 23517-23524 [Abstract] [Full Text]  
• Ballal, A., Manna, A. C. (2009). Expression of the sarA family of genes in different strains of Staphylococcus aureus. Microbiology 155: 2342-2352 [Abstract] [Full Text]