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Journal of Bacteriology, February 2006, p. 863-873, Vol. 188, No. 3
0021-9193/06/$08.00+0     doi:10.1128/JB.188.3.863-873.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Domains Required for Transcriptional Activation Show Conservation in the Mga Family of Virulence Gene Regulators

Cheryl M. Vahling and Kevin S. McIver*

Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas 75390

Received 4 October 2005/ Accepted 8 November 2005

Mga, or the multigene regulator of the group A streptococcus (GAS) (Streptococcus pyogenes), is a transcriptional regulator of virulence genes important for colonization and immune evasion. All serotypes of the GAS possess one of two divergent mga alleles (mga-1 or mga-2), and orthologues of Mga have also been identified in other pathogenic streptococci. To date, the only functional motifs established within Mga are two amino-terminal DNA-binding domains (HTH-3 and HTH-4). To uncover novel domains, a random mutagenesis screen using an M6 Mga (mga-1) was undertaken to find mutations leading to a defect in transcriptional activation of the Mga-regulated emm gene. In addition to mutations in the established DNA-binding domains, the screen also revealed mutations in a region conserved among several Mga orthologues. Alanine scanning helped resolve the boundaries of this conserved Mga domain (CMD-1) spanning from residues 10 to 15 of the protein, with the two flanking amino acid residues likely involved in protein stability. Transcriptional reporter analyses demonstrated the importance of CMD-1 for activation of Pemm and autoactivation of Pmga in the serotype M6 Mga. Mutational analyses showed that both CMD-1 and HTH-4 are also necessary for activation of the promoter target Pmrp in a divergent serotype M4 Mga (mga-2), suggesting a conserved functionality. However, in contrast to M6, the M4 Mga mutants did not show a defect in autoregulation. Mutation of similar conserved residues in the Mga-like regulator DmgB from S. dysgalactiae subsp. dysgalactiae showed that CMD-1 and HTH-4 are critical for transcriptional activation in this orthologue, implying that a common mechanism of virulence gene activation may exist for members of the Mga family of regulators.

* Corresponding author. Mailing address: University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9048. Phone: (214) 648-1255. Fax: (214) 648-5907. E-mail: kevin.mciver{at}utsouthwestern.edu.

Journal of Bacteriology, February 2006, p. 863-873, Vol. 188, No. 3
0021-9193/06/$08.00+0     doi:10.1128/JB.188.3.863-873.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Almengor, A. C., Walters, M. S., McIver, K. S. (2006). Mga Is Sufficient To Activate Transcription In Vitro of sof-sfbX and Other Mga-Regulated Virulence Genes in the Group A Streptococcus. J. Bacteriol. 188: 2038-2047 [Abstract] [Full Text]  


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