JBC

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Chien, Y.-t.
Right arrow Articles by Cheung, A. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chien, Y.-t.
Right arrow Articles by Cheung, A. L.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

J Biol Chem, Vol. 274, Issue 52, 37169-37176, December 24, 1999

SarA, a Global Regulator of Virulence Determinants in Staphylococcus aureus, Binds to a Conserved Motif Essential for sar-dependent Gene Regulation*

Yueh-tyng ChienDagger §, Adhar C. MannaDagger , Steven J. Projan∥, and Ambrose L. CheungDagger **

From the Dagger  Laboratory of Bacterial Pathogenesis and Immunology, The Rockefeller University, New York, New York 10021 and ∥ Wyeth-Ayerst Research, Lederle Laboratories, Pearl River, New York 10965

The expression of many virulence determinants in Staphylococcus aureus including alpha -hemolysin-, protein A-, and fibronectin-binding proteins is controlled by global regulatory loci such as sar and agr. In addition to controlling target gene expression via agr (e.g. alpha -hemolysin), the sar locus can also regulate target gene transcription via agr-independent mechanisms. In particular, we have found that SarA, the major regulatory protein encoded within sar, binds to a conserved sequence, homologous to the SarA-binding site on the agr promoter, upstream of the -35 promoter boxes of several target genes including hla (alpha -hemolysin gene), spa (protein A gene), fnb (fibronectin-binding protein genes), and sec (enterotoxin C gene). Deletion of the SarA recognition motif in the promoter regions of agr and hla in shuttle plasmids rendered the transcription of these genes undetectable in agr and hla mutants, respectively. Likewise, the transcription activity of spa (a gene normally repressed by sar), as measured by a XylE reporter fusion assay, became derepressed in a wild type strain containing a shuttle plasmid in which the SarA recognition site had been deleted from the spa promoter region. However, DNase I footprinting assays demonstrated that the SarA-binding region on the spa and hla promoter is more extensive than the predicted consensus sequence, thus raising the possibility that the consensus sequence is an activation site within a larger binding region. Because the sar and agr regulate an assortment of virulence factors in S. aureus, we propose, based on our data, a unifying hypothesis for virulence gene activation in S. aureus whereby SarA is a regulatory protein that binds to its consensus SarA recognition motif to activate (e.g. hla) or repress (e.g. spa) the transcription of sar target genes, thus accounting for both agr-dependent and agr-independent mode of regulation.

* This work was supported in part by National Institutes of Health Grants AI30061 and AI37142.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

§ Supported by a New York Heart Participatory Laboratory Award. Present address: Scriptgen Pharmaceuticals Inc. 610 Lincoln St., Waltham, MA 02451.

Present address: Dept. of Microbiology, Dartmouth Medical School, Hanover, NH 03755.

** Recipient of the Irma T. Hirschl Career Scientist Award as well as the Genentech Established Investigator Award from the American Heart Association. To whom correspondence should be addressed. Present address: Dept. of Microbiology, Dartmouth Medical School, Hanover, NH 03755.

Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 Infect. Immun.Home page
R. M. Q. Shanks, M. A. Meehl, K. M. Brothers, R. M. Martinez, N. P. Donegan, M. L. Graber, A. L. Cheung, and G. A. O'Toole
Genetic Evidence for an Alternative Citrate-Dependent Biofilm Formation Pathway in Staphylococcus aureus That Is Dependent on Fibronectin Binding Proteins and the GraRS Two-Component Regulatory System
Infect. Immun., June 1, 2008; 76(6): 2469 - 2477.
[Abstract] [Full Text] [PDF]

Home page
 J. Bacteriol.Home page
A. L. Cheung, K. Nishina, and A. C. Manna
SarA of Staphylococcus aureus Binds to the sarA Promoter To Regulate Gene Expression
J. Bacteriol., March 15, 2008; 190(6): 2239 - 2243.
[Abstract] [Full Text] [PDF]

Home page
 Bioscience HorizonsHome page
M. J. H. Goldsworthy
Gene expression of Pseudomonas aeruginosa and MRSA within a catheter-associated urinary tract infection biofilm model
Bioscience Horizons, March 1, 2008; 1(1): 28 - 37.
[Abstract] [Full Text] [PDF]

Home page
 J. Bacteriol.Home page
N. Harraghy, D. Homerova, M. Herrmann, and J. Kormanec
Mapping the Transcription Start Points of the Staphylococcus aureus eap, emp, and vwb Promoters Reveals a Conserved Octanucleotide Sequence That Is Essential for Expression of These Genes
J. Bacteriol., January 1, 2008; 190(1): 447 - 451.
[Abstract] [Full Text] [PDF]

Home page
 MicrobiologyHome page
A. C. Manna and B. Ray
Regulation and characterization of rot transcription in Staphylococcus aureus
Microbiology, May 1, 2007; 153(5): 1538 - 1545.
[Abstract] [Full Text] [PDF]

Home page
 J. Bacteriol.Home page
J. Oscarsson, A. Kanth, K. Tegmark-Wisell, and S. Arvidson
SarA Is a Repressor of hla ({alpha}-Hemolysin) Transcription in Staphylococcus aureus: Its Apparent Role as an Activator of hla in the Prototype Strain NCTC 8325 Depends on Reduced Expression of sarS
J. Bacteriol., December 15, 2006; 188(24): 8526 - 8533.
[Abstract] [Full Text] [PDF]

Home page
 MicrobiologyHome page
J. Cassat, P. M. Dunman, E. Murphy, S. J. Projan, K. E. Beenken, K. J. Palm, S.-J. Yang, K. C. Rice, K. W. Bayles, and M. S. Smeltzer
Transcriptional profiling of a Staphylococcus aureus clinical isolate and its isogenic agr and sarA mutants reveals global differences in comparison to the laboratory strain RN6390.
Microbiology, October 1, 2006; 152(Pt 10): 3075 - 3090.
[Abstract] [Full Text] [PDF]

Home page
 J. Bacteriol.Home page
L. N. Shaw, J. Aish, J. E. Davenport, M. C. Brown, J. K. Lithgow, K. Simmonite, H. Crossley, J. Travis, J. Potempa, and S. J. Foster
Investigations into {sigma}B-Modulated Regulatory Pathways Governing Extracellular Virulence Determinant Production in Staphylococcus aureus.
J. Bacteriol., September 1, 2006; 188(17): 6070 - 6080.
[Abstract] [Full Text] [PDF]

Home page
 MicrobiologyHome page
K. Sambanthamoorthy, M. S. Smeltzer, and M. O. Elasri
Identification and characterization of msa (SA1233), a gene involved in expression of SarA and several virulence factors in Staphylococcus aureus.
Microbiology, September 1, 2006; 152(Pt 9): 2559 - 2572.
[Abstract] [Full Text] [PDF]

Home page
 J. Bacteriol.Home page
A. C. Manna and A. L. Cheung
Expression of SarX, a Negative Regulator of agr and Exoprotein Synthesis, Is Activated by MgrA in Staphylococcus aureus.
J. Bacteriol., June 1, 2006; 188(12): 4288 - 4299.
[Abstract] [Full Text] [PDF]

Home page
 J. Bacteriol.Home page
C. Roberts, K. L. Anderson, E. Murphy, S. J. Projan, W. Mounts, B. Hurlburt, M. Smeltzer, R. Overbeek, T. Disz, and P. M. Dunman
Characterizing the Effect of the Staphylococcus aureus Virulence Factor Regulator, SarA, on Log-Phase mRNA Half-Lives.
J. Bacteriol., April 1, 2006; 188(7): 2593 - 2603.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
Y. Liu, A. C. Manna, C.-H. Pan, I. A. Kriksunov, D. J. Thiel, A. L. Cheung, and G. Zhang
Structural and function analyses of the global regulatory protein SarA from Staphylococcus aureus
PNAS, February 14, 2006; 103(7): 2392 - 2397.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
D. Frees, K. Sorensen, and H. Ingmer
Global Virulence Regulation in Staphylococcus aureus: Pinpointing the Roles of ClpP and ClpX in the sar/agr Regulatory Network
Infect. Immun., December 1, 2005; 73(12): 8100 - 8108.
[Abstract] [Full Text] [PDF]

Home page
 J. Bacteriol.Home page
M. P. Trotonda, A. C. Manna, A. L. Cheung, I. Lasa, and J. R. Penades
SarA Positively Controls Bap-Dependent Biofilm Formation in Staphylococcus aureus
J. Bacteriol., August 15, 2005; 187(16): 5790 - 5798.
[Abstract] [Full Text] [PDF]

Home page
 J. Bacteriol.Home page
C. W. Tseng and G. C. Stewart
Rot Repression of Enterotoxin B Expression in Staphylococcus aureus
J. Bacteriol., August 1, 2005; 187(15): 5301 - 5309.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
A. L. Cheung and A. C. Manna
Role of the Distal sarA Promoters in SarA Expression in Staphylococcus aureus
Infect. Immun., July 1, 2005; 73(7): 4391 - 4394.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
P. J. McNamara and A. S. Bayer
A rot Mutation Restores Parental Virulence to an agr-Null Staphylococcus aureus Strain in a Rabbit Model of Endocarditis
Infect. Immun., June 1, 2005; 73(6): 3806 - 3809.
[Abstract] [Full Text] [PDF]

Home page
 J. Bacteriol.Home page
M. A. Tormo, M. Marti, J. Valle, A. C. Manna, A. L. Cheung, I. Lasa, and J. R. Penades
SarA Is an Essential Positive Regulator of Staphylococcus epidermidis Biofilm Development
J. Bacteriol., April 1, 2005; 187(7): 2348 - 2356.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
S. Ingavale, W. van Wamel, T. T. Luong, C. Y. Lee, and A. L. Cheung
Rat/MgrA, a Regulator of Autolysis, Is a Regulator of Virulence Genes in Staphylococcus aureus
Infect. Immun., March 1, 2005; 73(3): 1423 - 1431.
[Abstract] [Full Text] [PDF]

Home page
 J. Bacteriol.Home page
J. E. Cassat, P. M. Dunman, F. McAleese, E. Murphy, S. J. Projan, and M. S. Smeltzer
Comparative Genomics of Staphylococcus aureus Musculoskeletal Isolates
J. Bacteriol., January 15, 2005; 187(2): 576 - 592.
[Abstract] [Full Text] [PDF]

Home page
 MicrobiologyHome page
B. Fournier and A. Klier
Protein A gene expression is regulated by DNA supercoiling which is modified by the ArlS-ArlR two-component system of Staphylococcus aureus
Microbiology, November 1, 2004; 150(11): 3807 - 3819.
[Abstract] [Full Text] [PDF]

Home page
 J. Bacteriol.Home page
A. C. Manna, S. S. Ingavale, M. Maloney, W. van Wamel, and A. L. Cheung
Identification of sarV (SA2062), a New Transcriptional Regulator, Is Repressed by SarA and MgrA (SA0641) and Involved in the Regulation of Autolysis in Staphylococcus aureus
J. Bacteriol., August 15, 2004; 186(16): 5267 - 5280.
[Abstract] [Full Text] [PDF]

Home page
 J. Bacteriol.Home page
J. Gao and G. C. Stewart
Regulatory Elements of the Staphylococcus aureus Protein A (Spa) Promoter
J. Bacteriol., June 15, 2004; 186(12): 3738 - 3748.
[Abstract] [Full Text] [PDF]

Home page
 MicrobiologyHome page
L. Shaw, E. Golonka, J. Potempa, and S. J. Foster
The role and regulation of the extracellular proteases of Staphylococcus aureus
Microbiology, January 1, 2004; 150(1): 217 - 228.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
K. A. Schmidt, A. C. Manna, and A. L. Cheung
SarT Influences sarS Expression in Staphylococcus aureus
Infect. Immun., September 1, 2003; 71(9): 5139 - 5148.
[Abstract] [Full Text] [PDF]

Home page
 Antimicrob. Agents Chemother.Home page
J. Rossi, M. Bischoff, A. Wada, and B. Berger-Bachi
MsrR, a Putative Cell Envelope-Associated Element Involved in Staphylococcus aureus sarA Attenuation
Antimicrob. Agents Chemother., August 1, 2003; 47(8): 2558 - 2564.
[Abstract] [Full Text] [PDF]

Home page
 J. Bacteriol.Home page
K. M. Sterba, S. G. Mackintosh, J. S. Blevins, B. K. Hurlburt, and M. S. Smeltzer
Characterization of Staphylococcus aureus SarA Binding Sites
J. Bacteriol., August 1, 2003; 185(15): 4410 - 4417.
[Abstract] [Full Text] [PDF]

Home page
 J. Bacteriol.Home page
R. Li, A. C. Manna, S. Dai, A. L. Cheung, and G. Zhang
Crystal Structure of the SarS Protein from Staphylococcus aureus
J. Bacteriol., July 15, 2003; 185(14): 4219 - 4225.
[Abstract] [Full Text] [PDF]

Home page
 J. Bacteriol.Home page
T. T. Luong, S. W. Newell, and C. Y. Lee
mgr, a Novel Global Regulator in Staphylococcus aureus
J. Bacteriol., July 1, 2003; 185(13): 3703 - 3710.
[Abstract] [Full Text] [PDF]

Home page
 J. Bacteriol.Home page
B. Said-Salim, P. M. Dunman, F. M. McAleese, D. Macapagal, E. Murphy, P. J. McNamara, S. Arvidson, T. J. Foster, S. J. Projan, and B. N. Kreiswirth
Global Regulation of Staphylococcus aureus Genes by Rot
J. Bacteriol., January 15, 2003; 185(2): 610 - 619.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
A. C. Manna and A. L. Cheung
sarU, a sarA Homolog, Is Repressed by SarT and Regulates Virulence Genes in Staphylococcus aureus
Infect. Immun., January 1, 2003; 71(1): 343 - 353.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
P. Vaudaux, P. Francois, C. Bisognano, W. L. Kelley, D. P. Lew, J. Schrenzel, R. A. Proctor, P. J. McNamara, G. Peters, and C. Von Eiff
Increased Expression of Clumping Factor and Fibronectin-Binding Proteins by hemB Mutants of Staphylococcus aureus Expressing Small Colony Variant Phenotypes
Infect. Immun., October 1, 2002; 70(10): 5428 - 5437.
[Abstract] [Full Text] [PDF]

Home page
 J. Bacteriol.Home page
M. J. Horsburgh, J. L. Aish, I. J. White, L. Shaw, J. K. Lithgow, and S. J. Foster
{sigma}B Modulates Virulence Determinant Expression and Stress Resistance: Characterization of a Functional rsbU Strain Derived from Staphylococcus aureus 8325-4
J. Bacteriol., October 1, 2002; 184(19): 5457 - 5467.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
B. D. Shepard and M. S. Gilmore
Differential Expression of Virulence-Related Genes in Enterococcus faecalis in Response to Biological Cues in Serum and Urine
Infect. Immun., August 1, 2002; 70(8): 4344 - 4352.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
T. Luong, S. Sau, M. Gomez, J. C. Lee, and C. Y. Lee
Regulation of Staphylococcus aureus Capsular Polysaccharide Expression by agr and sarA
Infect. Immun., February 1, 2002; 70(2): 444 - 450.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
G. Heyer, S. Saba, R. Adamo, W. Rush, G. Soong, A. Cheung, and A. Prince
Staphylococcus aureusagr and sarA Functions Are Required for Invasive Infection but Not Inflammatory Responses in the Lung
Infect. Immun., January 1, 2002; 70(1): 127 - 133.
[Abstract] [Full Text] [PDF]

Home page
 J. Bacteriol.Home page
P. M. Dunman, E. Murphy, S. Haney, D. Palacios, G. Tucker-Kellogg, S. Wu, E. L. Brown, R. J. Zagursky, D. Shlaes, and S. J. Projan
Transcription Profiling-Based Identification of Staphylococcus aureus Genes Regulated by the agr and/or sarA Loci
J. Bacteriol., December 15, 2001; 183(24): 7341 - 7353.
[Abstract] [Full Text] [PDF]

Home page
 J. Bacteriol.Home page
M. Bischoff, J. M. Entenza, and P. Giachino
Influence of a Functional sigB Operon on the Global Regulators sar and agr in Staphylococcus aureus
J. Bacteriol., September 1, 2001; 183(17): 5171 - 5179.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
K. A. Schmidt, A. C. Manna, S. Gill, and A. L. Cheung
SarT, a Repressor of {alpha}-Hemolysin in Staphylococcus aureus
Infect. Immun., August 1, 2001; 69(8): 4749 - 4758.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
Y. Liu, A. Manna, R. Li, W. E. Martin, R. C. Murphy, A. L. Cheung, and G. Zhang
Crystal structure of the SarR protein from Staphylococcus aureus
PNAS, May 24, 2001; (2001) 121013398.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
A. L. Cheung, K. Schmidt, B. Bateman, and A. C. Manna
SarS, a SarA Homolog Repressible by agr, Is an Activator of Protein A Synthesis in Staphylococcus aureus
Infect. Immun., April 1, 2001; 69(4): 2448 - 2455.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
A. Manna and A. L. Cheung
Characterization of sarR, a Modulator of sar Expression in Staphylococcus aureus
Infect. Immun., February 1, 2001; 69(2): 885 - 896.
[Abstract] [Full Text] [PDF]

Home page
 J. Bacteriol.Home page
S. K. Chakrabarti and T. K. Misra
SarA Represses agr Operon Expression in a Purified In Vitro Staphylococcus aureus Transcription System
J. Bacteriol., October 15, 2000; 182(20): 5893 - 5897.
[Abstract] [Full Text]

Home page
 Proc. Natl. Acad. Sci. USAHome page
Y. Liu, A. Manna, R. Li, W. E. Martin, R. C. Murphy, A. L. Cheung, and G. Zhang
Crystal structure of the SarR protein from Staphylococcus aureus
PNAS, June 5, 2001; 98(12): 6877 - 6882.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 1999 by the American Society for Biochemistry and Molecular Biology.