Coordinated Regulation by AgrA, SarA, and SarR To Control agr Expression in Staphylococcus aureus
- 1 November 2011
- journal article
- Published by American Society for Microbiology in Journal of Bacteriology
- Vol. 193 (21), 6020-6031
- https://doi.org/10.1128/jb.05436-11
Abstract
The agr locus of Staphylococcus aureus is composed of two divergent transcripts (RNAII and RNAIII) driven by the P2 and P3 promoters. The P2-P3 intergenic region comprises the SarA/SarR binding sites and the four AgrA boxes to which AgrA binds. We reported here the role of AgrA, SarA, and SarR on agr P2 and P3 transcription. Using real-time reverse transcription (RT)-PCR and promoter fusion studies with selected single, double, triple, and complemented mutants, we showed that AgrA is indispensable to agr P2 and P3 transcription, whereas SarA activates and SarR represses P2 transcription. In vitro runoff transcription assays revealed that AgrA alone promoted transcription from the agr P2 promoter, with SarA enhancing it and SarR inhibiting agr P2 transcription in the presence of AgrA or with SarA and AgrA. Electrophoretic mobility shift assay (EMSA) analysis disclosed that SarR binds more avidly to the agr promoter than SarA and displaces SarA from the agr promoter. Additionally, SarA and AgrA bend the agr P2 promoter, whereas SarR does not. Collectively, these data indicated that AgrA activates agr P2 and P3 promoters while SarA activates the P2 promoter, presumably via bending of promoter DNA to bring together AgrA dimers to facilitate engagement of RNA polymerase (RNAP) to initiate transcription.Keywords
This publication has 37 references indexed in Scilit:
- The Staphylococcus-Specific Gene rsr Represses agr and Virulence in Staphylococcus aureusInfection and Immunity, 2010
- Role of PknB Kinase in Antibiotic Resistance and Virulence in Community-Acquired Methicillin-Resistant Staphylococcus aureus Strain USA300Infection and Immunity, 2010
- Staphylococcus aureus SarA is a regulatory protein responsive to redox and pH that can support bacteriophage lambda integrase‐mediated excision/recombinationMolecular Microbiology, 2009
- SarZ Promotes the Expression of Virulence Factors and Represses Biofilm Formation by Modulating SarA and agr in Staphylococcus aureusInfection and Immunity, 2009
- The SarA protein family of Staphylococcus aureusThe International Journal of Biochemistry & Cell Biology, 2008
- MgrA Represses Biofilm Formation in Staphylococcus aureusInfection and Immunity, 2008
- Structure of the Staphylococcus aureus AgrA LytTR Domain Bound to DNA Reveals a Beta Fold with an Unusual Mode of BindingStructure, 2008
- Inhibition of rot translation by RNAIII, a key feature of agr functionMolecular Microbiology, 2006
- Activation and Transcriptional Interaction betweenagrRNAII and RNAIII inStaphylococcus aureusIn Vitro and in an Experimental Endocarditis ModelThe Journal of Infectious Diseases, 2002
- Molecular Interactions between Two Global Regulators, sar and agr, in Staphylococcus aureusPublished by Elsevier BV ,1998