Previous Article | Next Article 
Infection and Immunity, March 2005, p. 1423-1431, Vol. 73, No. 3
0019-9567/05/$08.00+0 doi:10.1128/IAI.73.3.1423-1431.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.
Rat/MgrA, a Regulator of Autolysis, Is a Regulator of Virulence Genes in Staphylococcus aureus
Susham Ingavale,1
Willem van Wamel,2
Thanh T. Luong,3
Chia Y. Lee,3 and
Ambrose L. Cheung1*
Department of Microbiology, Dartmouth Medical School, Hanover, New Hampshire,1
Department of Medical Microbiology, University of Utrecht, Utrecht, The Netherlands,2
Department of Microbiology, Molecular Genetics, and Immunology, University of Kansas Medical Center, Kansas City, Kansas3
Received 10 August 2004/
Returned for modification 8 October 2004/
Accepted 12 November 2004
We have previously identified mgrA (rat) as a regulator of autolysis in Staphylococcus aureus. Besides its effect on autolytic activity, we recently found alterations in the expression of regulator and target virulence genes in the mgrA mutant. Northern analysis and transcription fusion assays showed that inactivation of mgrA has led to the downregulation of RNAIII of agr and hla and upregulation of sarS and spa. Although both SarA and agr are activators of
-hemolysin and a repressors of protein A synthesis, we found that the transcription of sarA was not affected in the mgrA mutant and vice versa, indicating that MgrA likely regulates hla and spa in a SarA-independent manner. Previously we have shown that SarT, a SarA homolog, is a repressor of hla and an activator of spa, presumably by activating SarS, however, analysis of the double sarT mgrA mutant for hla and spa transcription indicated that the mgrA-mediated effect is not mediated via sarT. Our results further demonstrated that the mgrA gene product regulates hla and spa expression in a dual fashion, with the first being agr dependent and the second agr independent. In the agr-independent pathway, MgrA binds directly to hla and the sarS promoter to modulate
-hemolysin and protein A expression. Thus, our studies here have defined the nature of interaction of mgrA with other regulators such as agr, sarS, and sarT and its role in regulating hla and spa transcription within the virulence regulatory network of S. aureus.
* Corresponding author. Mailing address: Vail 206, Dartmouth Medical School, Hanover, NH 03755. Phone: (603) 650-1340. Fax: (603) 650-1362. E-mail:
ambrose.cheung{at}dartmouth.edu.
Editor: V. J. DiRita
Infection and Immunity, March 2005, p. 1423-1431, Vol. 73, No. 3
0019-9567/05/$08.00+0 doi:10.1128/IAI.73.3.1423-1431.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.
This article has been cited by other articles:
-
Rosenstein, R., Nerz, C., Biswas, L., Resch, A., Raddatz, G., Schuster, S. C., Gotz, F.
(2009). Genome Analysis of the Meat Starter Culture Bacterium Staphylococcus carnosus TM300. Appl. Environ. Microbiol.
75: 811-822
[Abstract]
[Full Text]
-
Tamber, S., Cheung, A. L.
(2009). SarZ Promotes the Expression of Virulence Factors and Represses Biofilm Formation by Modulating SarA and agr in Staphylococcus aureus. Infect. Immun.
77: 419-428
[Abstract]
[Full Text]
-
Trotonda, M. P., Tamber, S., Memmi, G., Cheung, A. L.
(2008). MgrA Represses Biofilm Formation in Staphylococcus aureus. Infect. Immun.
76: 5645-5654
[Abstract]
[Full Text]
-
Truong-Bolduc, Q. C., Ding, Y., Hooper, D. C.
(2008). Posttranslational Modification Influences the Effects of MgrA on norA Expression in Staphylococcus aureus. J. Bacteriol.
190: 7375-7381
[Abstract]
[Full Text]
-
Antignac, A., Sieradzki, K., Tomasz, A.
(2007). Perturbation of Cell Wall Synthesis Suppresses Autolysis in Staphylococcus aureus: Evidence for Coregulation of Cell Wall Synthetic and Hydrolytic Enzymes. J. Bacteriol.
189: 7573-7580
[Abstract]
[Full Text]
-
Lawrenz, M. B., Miller, V. L.
(2007). Comparative Analysis of the Regulation of rovA from the Pathogenic Yersiniae. J. Bacteriol.
189: 5963-5975
[Abstract]
[Full Text]
-
Bergman, N. H., Anderson, E. C., Swenson, E. E., Janes, B. K., Fisher, N., Niemeyer, M. M., Miyoshi, A. D., Hanna, P. C.
(2007). Transcriptional Profiling of Bacillus anthracis during Infection of Host Macrophages. Infect. Immun.
75: 3434-3444
[Abstract]
[Full Text]
-
Truong-Bolduc, Q. C., Hooper, D. C.
(2007). The Transcriptional Regulators NorG and MgrA Modulate Resistance to both Quinolones and {beta}-Lactams in Staphylococcus aureus. J. Bacteriol.
189: 2996-3005
[Abstract]
[Full Text]
-
Wei, K., Tang, D.-J., He, Y.-Q., Feng, J.-X., Jiang, B.-L., Lu, G.-T., Chen, B., Tang, J.-L.
(2007). hpaR, a Putative marR Family Transcriptional Regulator, Is Positively Controlled by HrpG and HrpX and Involved in the Pathogenesis, Hypersensitive Response, and Extracellular Protease Production of Xanthomonas campestris Pathovar campestris. J. Bacteriol.
189: 2055-2062
[Abstract]
[Full Text]
-
Renzoni, A., Barras, C., Francois, P., Charbonnier, Y., Huggler, E., Garzoni, C., Kelley, W. L., Majcherczyk, P., Schrenzel, J., Lew, D. P., Vaudaux, P.
(2006). Transcriptomic and Functional Analysis of an Autolysis-Deficient, Teicoplanin-Resistant Derivative of Methicillin-Resistant Staphylococcus aureus.. Antimicrob. Agents Chemother.
50: 3048-3061
[Abstract]
[Full Text]
-
Manna, A. C., Cheung, A. L.
(2006). Expression of SarX, a Negative Regulator of agr and Exoprotein Synthesis, Is Activated by MgrA in Staphylococcus aureus.. J. Bacteriol.
188: 4288-4299
[Abstract]
[Full Text]
-
Seidl, K., Stucki, M., Ruegg, M., Goerke, C., Wolz, C., Harris, L., Berger-Bachi, B., Bischoff, M.
(2006). Staphylococcus aureus CcpA Affects Virulence Determinant Production and Antibiotic Resistance.. Antimicrob. Agents Chemother.
50: 1183-1194
[Abstract]
[Full Text]
-
Roberts, C., Anderson, K. L., Murphy, E., Projan, S. J., Mounts, W., Hurlburt, B., Smeltzer, M., Overbeek, R., Disz, T., Dunman, P. M.
(2006). Characterizing the Effect of the Staphylococcus aureus Virulence Factor Regulator, SarA, on Log-Phase mRNA Half-Lives.. J. Bacteriol.
188: 2593-2603
[Abstract]
[Full Text]
-
Luong, T. T., Dunman, P. M., Murphy, E., Projan, S. J., Lee, C. Y.
(2006). Transcription Profiling of the mgrA Regulon in Staphylococcus aureus.. J. Bacteriol.
188: 1899-1910
[Abstract]
[Full Text]
-
Frees, D., Sorensen, K., Ingmer, H.
(2005). Global Virulence Regulation in Staphylococcus aureus: Pinpointing the Roles of ClpP and ClpX in the sar/agr Regulatory Network. Infect. Immun.
73: 8100-8108
[Abstract]
[Full Text]