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Journal of Bacteriology, June 2009, p. 4015-4024, Vol. 191, No. 12
0021-9193/09/$08.00+0     doi:10.1128/JB.01743-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Comparative Genome-Scale Metabolic Reconstruction and Flux Balance Analysis of Multiple Staphylococcus aureus Genomes Identify Novel Antimicrobial Drug Targets{triangledown} ,{dagger}

Deok-Sun Lee,1,2,3 Henry Burd,4 Jiangxia Liu,5 Eivind Almaas,6 Olaf Wiest,7 Albert-László Barabási,1,2 Zoltán N. Oltvai,5 and Vinayak Kapatral4*

Center for Complex Network Research and Departments of Physics, Biology, and Computer Science, Northeastern University, Boston, Massachusetts 02215,1 Center for Cancer Systems Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215,2 Department of Natural Medical Sciences, Inha University, Incheon, 402-751, Republic of Korea,3 Integrated Genomics, Inc., Chicago, Illinois 60612,4 Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania 15261,5 Biosciences and Biotechnology Division, Lawrence Livermore National Laboratory, Livermore, California 94551,6 Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 465567

Received 12 December 2008/ Accepted 25 March 2009

Mortality due to multidrug-resistant Staphylococcus aureus infection is predicted to surpass that of human immunodeficiency virus/AIDS in the United States. Despite the various treatment options for S. aureus infections, it remains a major hospital- and community-acquired opportunistic pathogen. With the emergence of multidrug-resistant S. aureus strains, there is an urgent need for the discovery of new antimicrobial drug targets in the organism. To this end, we reconstructed the metabolic networks of multidrug-resistant S. aureus strains using genome annotation, functional-pathway analysis, and comparative genomic approaches, followed by flux balance analysis-based in silico single and double gene deletion experiments. We identified 70 single enzymes and 54 pairs of enzymes whose corresponding metabolic reactions are predicted to be unconditionally essential for growth. Of these, 44 single enzymes and 10 enzyme pairs proved to be common to all 13 S. aureus strains, including many that had not been previously identified as being essential for growth by gene deletion experiments in S. aureus. We thus conclude that metabolic reconstruction and in silico analyses of multiple strains of the same bacterial species provide a novel approach for potential antibiotic target identification.

* Corresponding author. Mailing address: Integrated Genomics, Inc., 2201 W. Campbell Park Drive, Chicago, IL 60612. Phone: (312) 850-0692 ext. 326. Fax: (312)491-0856. E-mail: vinayak{at}integratedgenomics.com

{triangledown} Published ahead of print on 17 April 2009.

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

Journal of Bacteriology, June 2009, p. 4015-4024, Vol. 191, No. 12
0021-9193/09/$08.00+0     doi:10.1128/JB.01743-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Msadek, T. (2009). Grasping at Shadows: Revealing the Elusive Nature of Essential Genes. J. Bacteriol. 191: 4701-4704 [Full Text]  


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