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Coordinated Regulation by AgrA, SarA, and SarR To Control agr Expression in Staphylococcus aureus
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.
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“In addition, SarA activates the P2 promoter and promotes transcription by bending the DNA region of the agr promoter, thereby enhancing agr dimer interactions to upregulate agr expression [107].”
From A Review of Biofilm Formation of Staphylococcus aureus and Its Regulation Mechanism (2022) · cites this paper as [107]
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“Staphylococcus aureus is an opportunistic pathogen that causes a broad range of human infections in both community and hospital settings (17, 22).”
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Cited by
Arciola, C. R., Campoccia, D., Speziale, P., Montanaro, L., & Costerton, J. W. (2012) · Biomaterials · doi:10.1016/j.biomaterials.2012.05.031 · Cited by 1,047
Regulation of Staphylococcus aureus Virulence
Jenul, C., & Horswill, A. R. (2019) · Microbiology Spectrum · doi:10.1128/microbiolspec.gpp3-0031-2018 · Cited by 549
A Review of Biofilm Formation of Staphylococcus aureus and Its Regulation Mechanism
Peng, Q., Tang, X., Dong, W., Sun, N., & Yuan, W. (2022) · Antibiotics · doi:10.3390/antibiotics12010012 · Cited by 440
The Bicomponent Pore-Forming Leucocidins of Staphylococcus aureus
Alonzo, F., & Torres, V. J. (2014) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00055-13 · Cited by 276
Prevention and treatment of Staphylococcus aureus biofilms
Bhattacharya, M., Wozniak, D. J., Stoodley, P., & Hall-Stoodley, L. (2015) · Expert Review of Anti-infective Therapy · doi:10.1586/14787210.2015.1100533 · Cited by 265
Metadata
- Authors
- Reyes, D., Andrey, D. O., Monod, A., Kelley, W. L., Zhang, G., & Cheung, A. L.
- Affiliations
- Department of Microbiology, Dartmouth Medical School, Hanover, New Hampshire 03755
- Service of Infectious Diseases, University Hospital and Medical School of Geneva, 4 Rue Gabrielle-Perret-Gentil, CH-1211 Geneva 14, Switzerland
- Department of Immunology, National Jewish Hospital, Denver, Colorado
- Venue
- Journal of Bacteriology
- Publisher
- American Society for Microbiology
- Published
- 2011-11
- Volume
- 193
- Issue
- 21
- Pages
- 6020-6031
- ISSN
- 0021-9193
- 1098-5530
- Cited by
- 126
- References
- 1
- Language
- en
- Licence
- journals.asm.org/non-commercial-tdm-license (tdm)
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- Reyes, D., Andrey, D. O., Monod, A., Kelley, W. L., Zhang, G., & Cheung, A. L. (2011). Coordinated Regulation by AgrA, SarA, and SarR To Control agr Expression in Staphylococcus aureus. Journal of Bacteriology. https://doi.org/10.1128/jb.05436-11
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