This Article Full Text Full Text (PDF) Supplemental material Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sadykov, M. R. Articles by Somerville, G. A. Search for Related Content PubMed PubMed Citation Articles by Sadykov, M. R. Articles by Somerville, G. A.

 Previous Article  |  Next Article 

Journal of Bacteriology, December 2008, p. 7621-7632, Vol. 190, No. 23
0021-9193/08/$08.00+0     doi:10.1128/JB.00806-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Tricarboxylic Acid Cycle-Dependent Regulation of Staphylococcus epidermidis Polysaccharide Intercellular Adhesin Synthesis ^,

Marat R. Sadykov,¹ Michael E. Olson,² Steven Halouska,³ Yefei Zhu,¹ Paul D. Fey,² Robert Powers,³ and Greg A. Somerville^1*

Department of Veterinary and Biomedical Sciences, University of Nebraska—Lincoln, Lincoln, Nebraska 68583-0905,¹ Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska 68198-6280,² Department of Chemistry, University of Nebraska—Lincoln, Lincoln, Nebraska 68522-0304³

Received 9 June 2008/ Accepted 21 September 2008

Staphylococcus epidermidis is a major nosocomial pathogen primarily infecting immunocompromised individuals or those with implanted biomaterials (e.g., catheters). Biomaterial-associated infections often involve the formation of a biofilm on the surface of the medical device. In S. epidermidis, polysaccharide intercellular adhesin (PIA) is an important mediator of biofilm formation and pathogenesis. Synthesis of PIA is regulated by at least three DNA binding proteins (IcaR, SarA, and ^B) and several environmental and nutritional conditions. Previously, we observed the environmental conditions that increased PIA synthesis decreased tricarboxylic acid (TCA) cycle activity. In this study, S. epidermidis TCA cycle mutants were constructed, and the function of central metabolism in PIA biosynthesis was examined. TCA cycle inactivation altered the metabolic status of S. epidermidis, resulting in a massive derepression of PIA biosynthetic genes and a redirection of carbon from growth into PIA biosynthesis. These data demonstrate that the bacterial metabolic status is a critical regulatory determinant of PIA synthesis. In addition, these data lead us to propose that the TCA cycle acts as a signal transduction pathway to translate external environmental cues into intracellular metabolic signals that modulate the activity of transcriptional regulators.

---

* Corresponding author. Mailing address: Department of Veterinary and Biomedical Sciences, University of Nebraska—Lincoln, 155 VBS, Fair St. and East Campus Loop, Lincoln, NE 68583-0905. Phone: (402) 472-6063. Fax: (402) 472-9690. E-mail: gsomerville3{at}unl.edu

Published ahead of print on 26 September 2008.

Supplemental material for this article may be found at http://jb.asm.org/.

---

Journal of Bacteriology, December 2008, p. 7621-7632, Vol. 190, No. 23
0021-9193/08/$08.00+0     doi:10.1128/JB.00806-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

This article has been cited by other articles:

• Zhu, Y., Xiong, Y. Q., Sadykov, M. R., Fey, P. D., Lei, M. G., Lee, C. Y., Bayer, A. S., Somerville, G. A. (2009). Tricarboxylic Acid Cycle-Dependent Attenuation of Staphylococcus aureus In Vivo Virulence by Selective Inhibition of Amino Acid Transport. Infect. Immun. 77: 4256-4264 [Abstract] [Full Text]  
• Somerville, G. A., Proctor, R. A. (2009). At the Crossroads of Bacterial Metabolism and Virulence Factor Synthesis in Staphylococci. Microbiol. Mol. Biol. Rev. 73: 233-248 [Abstract] [Full Text]