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Journal of Bacteriology, February 2009, p. 851-861, Vol. 191, No. 3
0021-9193/09/$08.00+0     doi:10.1128/JB.01357-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

The Mevalonate Pathway of Staphylococcus aureus{triangledown} ,{dagger}

Carl J. Balibar, Xiaoyu Shen, and Jianshi Tao*

Department of Infectious Diseases, Novartis Institutes for BioMedical Research, 500 Technology Square, Cambridge, Massachusetts 02139

Received 29 September 2008/ Accepted 9 November 2008

Isoprenoids are a class of ubiquitous organic molecules synthesized from the five-carbon starter unit isopentenyl pyrophosphate (IPP). Comprising more than 30,000 known natural products, isoprenoids serve various important biological functions in many organisms. In bacteria, undecaprenyl pyrophosphate is absolutely required for the formation of cell wall peptidoglycan and other cell surface structures, while ubiquinones and menaquinones, both containing an essential prenyl moiety, are key electron carriers in respiratory energy generation. There is scant knowledge on the nature and regulation of bacterial isoprenoid pathways. In order to explore the cellular responses to perturbations in the mevalonate pathway, responsible for producing the isoprenoid precursor IPP in many gram-positive bacteria and eukaryotes, we constructed three strains of Staphylococcus aureus in which each of the mevalonate pathway genes is regulated by an IPTG (isopropyl-β-D-thiogalactopyranoside)-inducible promoter. We used DNA microarrays to profile the transcriptional effects of downregulating the components of the mevalonate pathway in S. aureus and demonstrate that decreased expression of the mevalonate pathway leads to widespread downregulation of primary metabolism genes, an upregulation in virulence factors and cell wall biosynthetic determinants, and surprisingly little compensatory expression in other isoprenoid biosynthetic genes. We subsequently correlate these transcriptional changes with downstream metabolic consequences.

* Corresponding author. Mailing address: Department of Infectious Diseases, Novartis Institutes for BioMedical Research, 500 Technology Square, Cambridge, MA 02139. Phone: (617) 871-7431. Fax: (617) 871-5791. E-mail: jianshi.tao{at}novartis.com

{triangledown} Published ahead of print on 21 November 2008.

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

Journal of Bacteriology, February 2009, p. 851-861, Vol. 191, No. 3
0021-9193/09/$08.00+0     doi:10.1128/JB.01357-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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