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Journal of Bacteriology, April 2008, p. 2790-2803, Vol. 190, No. 8
0021-9193/08/$08.00+0     doi:10.1128/JB.01583-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Genome-Scale Metabolic Network Analysis of the Opportunistic Pathogen Pseudomonas aeruginosa PAO1 ^,

Matthew A. Oberhardt,^1, Jacek Puchaka,^2, Kimberly E. Fryer,¹ Vítor A. P. Martins dos Santos,^2,* and Jason A. Papin^1,*

Department of Biomedical Engineering, University of Virginia Health System, Box 800759, Charlottesville, Virginia 22908,¹ Helmholtz Center for Infection Research (HZI), Inhoffenstrasse 7, D-38124 Braunschweig, Germany²

Received 30 September 2007/ Accepted 3 January 2008

Pseudomonas aeruginosa is a major life-threatening opportunistic pathogen that commonly infects immunocompromised patients. This bacterium owes its success as a pathogen largely to its metabolic versatility and flexibility. A thorough understanding of P. aeruginosa's metabolism is thus pivotal for the design of effective intervention strategies. Here we aim to provide, through systems analysis, a basis for the characterization of the genome-scale properties of this pathogen's versatile metabolic network. To this end, we reconstructed a genome-scale metabolic network of Pseudomonas aeruginosa PAO1. This reconstruction accounts for 1,056 genes (19% of the genome), 1,030 proteins, and 883 reactions. Flux balance analysis was used to identify key features of P. aeruginosa metabolism, such as growth yield, under defined conditions and with defined knowledge gaps within the network. BIOLOG substrate oxidation data were used in model expansion, and a genome-scale transposon knockout set was compared against in silico knockout predictions to validate the model. Ultimately, this genome-scale model provides a basic modeling framework with which to explore the metabolism of P. aeruginosa in the context of its environmental and genetic constraints, thereby contributing to a more thorough understanding of the genotype-phenotype relationships in this resourceful and dangerous pathogen.

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* Corresponding author. Mailing address for Jason A. Papin: Department of Biomedical Engineering, University of Virginia Health System, Box 800759, Charlottesville, VA 22908. Phone: (434) 924-8195. Fax: (434) 982-3870. E-mail: papin{at}virginia.edu. Mailing address for Vítor A. P. Martins dos Santos: Helmholtz Center for Infection Research (HZI), Inhoffenstrasse 7, D-38124 Braunschweig, Germany. Phone: 49-531-6181-4008. Fax: 49-531-6181-5002. E-mail: vds{at}helmholtz-hzi.de

Published ahead of print on 11 January 2008.

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

M.A.O. and J.P. contributed equally to this study.

V.A.P.M.D.S. and J.A.P. contributed equally to this study.

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Journal of Bacteriology, April 2008, p. 2790-2803, Vol. 190, No. 8
0021-9193/08/$08.00+0     doi:10.1128/JB.01583-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

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